publicação oficial do conselho brasileiro de oftalmologia ... · a r q u i v o s br a s i l e i r...

A r q u i v o s b r a s i l e i r o s d e

77 06publicação oficial do conselho brasileiro de oftalmologia

noVembro/deZembro 2014

issn 0004-2749versão impressa

Tonic pupil in leprosy

Ocular torsion after superior oblique tenectomy

Conjunctival microbiota in brazilian diabetic patients

Safety of intracameral trypan blue

Pattern-reversal electroretinogram and glaucoma

indexada nas bases de dados

medline | embase | isi | scielO

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Frequency of publication: Bimonthly Arq Bras Oftalmol. São Paulo, v. 77, issue 6, pages 345-426, Nov/Dec. 2014

Continuous publication since 1938

Publisher: Ipsis Gráfica e Editora S.A. Divulgation: Brazilian Council of OphthalmologyCirculation: 7.900 copies

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PUBLICAÇÃO OFICIAL DOCONSELHO BRASILEIRO

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OffiCiAl PuBliCAtiON Of thE BrAziliAN COuNCil Of OPhthAlmOlOgy (CBO) iSSN 0004-2749(Printed version)


Frequency of publication: Bimonthly Arq Bras Oftalmol. São Paulo, v. 77, issue 6, pages 345-426, Nov/Dec. 2014

PUBLICAÇÃO OFICIAL DOCONSELHO BRASILEIRO

DE OFTALMOLOGIA

EditorialV vision 2020: on the home stretch Visão 2020: na reta final Jayter Silva Paula, João Marcello Furtado, João Paulo Souza, Van Charles Lansingh

Original Articles345 Comparison of central corneal thickness measurements using optical low-coherence reflectometry, Fourier domain optical

coherence tomography, and Scheimpflug camera Comparação entre medidas de espessura central da córnea com reflectometria óptica de baixa coerência, tomografia de coerência óptica de domínio Fourier,

e câmera Scheimpflug Saban Gonul, Bengu Ekinci Koktekir, Berker Bakbak, Sansal Gedik

351 Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in Brazil

Microbiota bacteriana aeróbica conjuntival em pacientes diabéticos com hemoglobina glicada normal e alterada em duas regiões brasileiras Natalia Pimentel Moreno, Renaldo Duarte Moreno, Luciene Barbosa Sousa

355 Outcomes of cataract surgery in diabetic patients: results of the Pan American Collaborative retina Study group Resultados da cirurgia de catarata em pacientes diabéticos: resultados do Pan-American Collaborative Retina Study Group Roberto Gallego-Pinazo, Rosa Dolz-Marco, Maria Berrocal, Lihteh Wu, Mauricio Maia, Martín Serrano, Arturo Alezzandrini, J. Fernando Arévalo, Manuel Díaz-Llopis,

for the Pan-American Collaborative Retina Study Group (PACORES)

360 Non-pupillary block angle-closure mechanisms: a comprehensive analysis of their prevalence and treatment outcomes Mecanismos de fechamento angular sem bloqueio pupilar: análise de prevalência e resultados terapêuticos Daniela L. M. Junqueira, Vitor G. Prado, Flavio S. Lopes, Luis Gustavo Biteli, Syril Dorairaj, Tiago S. Prata

364 Measurement of ocular torsion variation following superior oblique tenectomy Medida da variação da torção ocular após a tenectomia do oblíquo superior Bruna Lana Ducca, Carlos Ramos de Souza-Dias, Aline Cristina Fioravanti Lui, Mauro Goldchmit

368 Evaluation of peripapillary choroidal and retinal nerve fiber layer thickness in eyes with tilted optic disc Avaliação espessura da camada de fibras nervosas peripapilares da retina e coroide em olhos com disco óptico inclinado Muammer Ozcımen, Yasar Sakarya, Sertan Goktas, Rabia Sakarya, Ismail S. Ivacık, Halil I. Yener, Erkan Erdogan

373 influence of aspheric intraocular lens on frequency doubling technology and contrast sensitivity: a fellow eye study Influência da lente intraocular asférica na perimetria de frequência dupla e sensibilidade ao contraste: estudo contralateral Rodrigo França de Espíndola, Marcony R. Santhiago, Mário Luiz Ribeiro Monteiro, Newton Kara-Junior

377 Palpebral position interdependence in blepharoptosis: comparison of the effect of instillation of 10% phenylephrine drop and digital lifting

Interdependência na posição palpebral em ptose palpebral: comparação do efeito de instilação de colírio de fenilefrina 10% e o teste de elevação digital da pálpebra Ivana Cardoso Pereira, Suzana Matayoshi

382 ultrasound biomicroscopy after palliative surgical procedures for bullous keratopathy: a descriptive comparative study Biomicroscopia ultrassônica após procedimentos cirúrgicos paliativos na ceratopatia bolhosa: estudo comparativo descritivo Fabiana dos Santos Paris, Eliana Domingues Gonçalves, Maira Saad Ávila Morales, Liliane Andrade Almeida Kanecadan, Mauro Silveira de Queiroz Campos,

José Álvaro Pereira Gomes, Norma Allemann, Elcio Hideo Sato

388 Evaluation of the safety of intracameral trypan blue injection on corneal tissue using oxidative stress parameters and apoptotic activity: an experimental study

Avaliação da segurança de injeção de azul de tripan intracameral no tecido da córnea utilizando parâmetros de estresse oxidativo e atividade apoptótica: um estudo experimental

Ali Akal, Turgay Ulas, Tugba Goncu, Mehmet Fatih Adibelli, Sezen Kocarslan, Muhammet Emin Guldur, Muslum Guler, Ufuk Ozkan, Mehmet Dusunur, Tuncer Demir

Case Reports392 ultrasound biomicroscopy confirmation of corneal overriding due to improper suturing of full-thickness corneal laceration Confirmação por biomicroscopia ultrassônica de encavalamento corneano devido à sutura inadequada de laceração de espessura total da córnea Murat Kucukevcilioglu, Volkan Hurmeric

395 Tonic pupil in leprosy Pupila tônica em doença de Hansen Marco Aurélio Lana-Peixoto, Wesley Ribeiro Campos, Pedro Augusto Costa Reis, Christian Marcellus Camargo Campos, Carlos Alberto Rodrigues

397 hemorrhagic retinopathy in an infant with hemolytic-uremic syndrome Retinopatia hemorrágica em lactente com síndrome hemolítico-urêmica João Caetano Ávila Geraissate, Rafael Eidi Yamamoto, David Leonardo Cruvinel Isaac, Marcos Pereira de Ávila

400 Autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytoma Autofluorescência e tomografia de coerência óptica de domínio espectral do melanocitoma do disco óptico Ricardo Luz Leitão Guerra, Eduardo Ferrari Marback, Igor Sandes Pessoa da Silva, Otacílio de Oliveira Maia Jr., Roberto Lorens Marback

Review Articles403 The role of pattern-reversal electroretinography in the diagnosis of glaucoma Importância do eletroretinograma de padrão reverso no diagnóstico do glaucoma André Carvalho Kreuz, Maria Kiyoko Oyamada, Marcelo Hatanaka, Mário Luiz Ribeiro Monteiro1

Letters to the Editor411 Metallic corneal foreign bodies: an occupational health hazard Corpos estranhos metálicos na córnea: um problema de saúde ocupacional Saban Gonul, Banu Bozkurt, Suleyman Okudan

413 Instructions to Authors

417 Index v. 77 - 2014

V

Editorial

http://dx.doi.org/10.5935/0004-2749.20140086

Vision 2020: on the home stretchVisão 2020: na reta final

Jayter Silva Paula1, João Marcello Furtado1, João Paulo Souza2, van charleS lanSingh3

Submitted for publication: October 13, 2014 Accepted for publication: October 14, 20141 Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto

Medical School, Universidade de São Paulo, São Paulo, SP, Brazil.2 Department of Social Medicine, Ribeirão Preto Medical School, Universidade de São Paulo, São

Paulo, SP, Brazil. 3 International Agency for the Prevention of Blindness, Queretaro, Mexico and Instituto Mexicano de

Oftalmologia, Queretaro, Mexico.

Funding: No specific financial support was available for this study.

Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of interest to disclose.

Corresponding author: Jayter Silva Paula. Departamento de Oftalmologia. Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo. Av. Bandeirantes, 3900/12º andar - Ribeirão Preto - SP - 14049-900 - Brazil - E-mail: [email protected]

Current efforts for strengthening ocular care worldwide are evident but still not sufficient to provide equita-ble eye care in many places around the world, particularly in under-resourced countries. Despite the decrease on the global prevalence of visual impairment in the last two decades(1), the main cause of blindness (cataract) as well as the main cause of moderate or severe visual impairment (uncorrected refractive errors) could be averted or treated(2). The VISION 2020: The Right to Sight initiative, created by the World Health Organization (WHO) and the International Agency for Prevention of Blindness (IAPB), is the main global program to eliminate avoidable blindness since its launch, in 1999.

Through the analysis of key indicators, VISION 2020 has been monitoring continuously eye health interven-tions. Its targets were updated in the 66th World Health Assembly, based on lessons learnt from 2009 to 2013, when the most recent action plan was released: the WHO Global Action Plan 2014-2019 - Towards Universal Eye Health(3,4). Also, specific regional strategies have been proposed, such as the VISION 2020 Latin America (V2020LA) Strategic Plan for 2013-2016 and the Pan American Health Organization Action Plan 2014-2019. These regional plans are important because they provide local members from global and regional organizations a common strategy towards implementing the WHO objectives and optimize their collaboration regionally(5).

Initial analyses had projected 76 million blind people in 2020 throughout the world(6), but this number would be hardly reached because recent compiling results have shown a number of 32.4 million blind individuals(1). Since the relative and absolute older population has grown worldwide, the fact that the number of blind people remained almost stable during the last decade(1) is an indicator of success of the measures.

Considering the advances observed but the large underserved population, a review of actions and an evalua-tion of cost-effectiveness must be made in countries supported or not by any branch of VISION 2020 program. Fortunately, actions targeting control of sight-threatening diseases have been constantly revised by health care providers, government, and global institutions such as the WHO and IAPB. As an example, in the 1980’s, infectious diseases such as trachoma and onchocerciasis played a major role in blindness prevention, and in recent years the importance of chronic eye conditions such as glaucoma, diabetic retinopathy and age-related macular de-generation has increased(2). These chronic eye conditions present more difficult public health interventions and the success in controlling them depends especially on adequate national policies. In countries where avoidable blindness had been increasingly controlled and is no longer considered an issue, new concerns have been focused on visual impairment strategies (e.g. Uruguay)(5,7).

Vision 2020, in its first 12 years proved to be effective in delivering equitable eye health services in remote locations, with economic rates of return of 20%(3). However, considering those changes in the social and health profiles, VISION 2020 must “scale up” with focus on closer alignment and integration with local primary health system and advocacy with major government health programs. The WHO Global Action Plan 2014-2019 was developed around 3 main objectives: (1) generate evidence on the regional or local magnitude and causes of visual impairment and eye care services in order to enhance advocacy; (2) implementation of national health policies and programs aligned with WHO’s framework for improving local health systems; (3) stimulation of effective multisectoral partnerships to strengthen eye health(3,4).

A very important lesson learnt is that VISION 2020 initiative cannot depend on a sole contact in each country to effectively implement its program goals and objectives. In Latin America, VISION 2020 has been especially effective in establishing national committees with representation and participation of private and public stakeholders. Collaboration between both sectors was encouraged and helped the development of many national plans in the region(5). However, in recent years, the concept and importance of committees have unfor-tunately diminished in this region, where some countries could not establish committees for some time, or they have been dormant. The approval of those new WHO plans and the global indicators data collection proposal, which are now required by member states, has resulted in a re-awakening of the national committee concept in Latin America. For example, committees have been reactivated in Peru, Mexico and Uruguay.

Vision 2020: on the home stretch

VI

Other important accomplishment of VISION 2020 Latin America is a push for evidence-based medicine to guide national policies and programs on eye care(5), such as some Rapid Assessment of Avoidable Blindness (RAAB) studies performed in the last three years(8). New ideas aimed at the current VISION 2020 Latin America challenges should be carried through in most regional countries, especially those based on the development and continuous maintenance of technical local teams or subcommittees acting as manager of eye care activities as well as the achievement of funding resources to keep members engaged and productive.

While elimination of avoidable blindness by 2020 may not be possible as originally planned, the VISION 2020 initiative has identified bottlenecks and a roadmap to strengthening local health systems and improve ophthal-mological services around the world. Even considering discrepancies among Latin American countries, the next actions should involve mechanisms to distribute and decentralize human resources with adequate quality at the subnational level in order to overcome barriers to eye care. The upcoming year can be an important year for the international public health since it marks the end of the first cycle of coordinated actions to eliminate hunger, reduce extreme poverty and foster better health and social development around the world. International eye care community should be able to mobilize and bring the control of blindness to the set of actions that are being prepared for the WHO second cycle of development of this millennium (2015-2035)(9). VISION 2020 actions on its home stretch can provide the initial backbone for this mobilization to make the world free of avoidable blindness in decades to come.

RefeRenCeS 1. Stevens GA, White RA, Flaxman SR, Price H, Jonas JB, Keeffe J, Leasher J, Naidoo K,

Pesudovs K, Resnikofgf S, taylor H, Bourne RR; Vision Loss Expert Group. Global preva-lence of vision impairment and blindness: magnitude and temporal trends, 1990-2010. Ophthalmology. 2013;120(12):2377-84.

2. Bourne RR, Stevens GA, White RA, Smith JL, Flaxman SR, Price H, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, Resnikoff S, Taylor HR; Vision Loss Expert Group. Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health. 2013;1(6):e339-49. Comment in: Lancet Glob Health. 2013;1(6):e311-2; Lancet Glob Health. 2014;2(2):e76-7.

3. Ackland P. The accomplishments of the global initiative VISION 2020: The Right to Sight and the focus for the next 8 years of the campaign. Indian J Ophthalmol. 2012; 60(5):380-6.

4. World Health Organization. Universal eye health: a global action plan 2014-2019 [Internet]. Geneva: WHO; 2013. [cited 2014 Jun 21]. Available from: http://www.who.int/blindness/AP2014_19_English.pdf?ua=1

5. Pan American Health Organization. Plan de acción para la prevención de la ceguera

y de las deficiencias visuales [Internet]. Wahington: PAHO; 2014. [cited 2014 Oct 1]. Available at: https://vision2020la.files.wordpress.com/2014/07/plan-de-accic3b3n.pdf

6. Thylefors B, Négrel AD, Pararajasegaram R, Dadzie KY. Global data on blindness. Bull World Health Organ. 1995;73(1):115-21.

7. Furtado JM, Lansingh VC, Carter MJ, Milanese MF, Peña BN, Ghersi HA, et al. Causes of blindness and visual impairment in Latin America. Surv Ophthalmol. 2012;57(2):149-77.

8. Yaacov-Peña F, Jure D, Ocampos J, Samudio M, Furtado JM, Carter M, et al. Prevalence and causes of blindness in an urban area of Paraguay. Arq Bras Oftalmol. 2012;75(5): 341-3.

9. Jamison DT, Summers LH, Alleyne G, Arrow KJ, Berkley S, Binagwaho A, Bustreo F, Evans D, Feachem RG, Frenk J, Ghosh G, Goldie SJ, Guo Y, Gupta S, Horton R, Kruk ME, Mahmoud A, Mohohlo LK, Ncube M, Pablos-Mendez A, Reddy KS, Saxenian H, Soucat A, Ulltveit-Moe KH, Yamey G. Global health 2035: a world converging within a generation. Lancet. 2013;382(9908):1898-955. Erratum in: Lancet. 2014;383(9913):218. Comment in: Lancet. 2014;383(9921):949; Lancet. 2014;383(9921):949-50; Lancet. 2014;383(9921):950-1; Lancet. 2013;382(9908):e38-9; Lancet. 2013;382(9908):e34-5; Lancet. 2013; 82(9908):e36-7; Lancet. 2013;382(9908):e33-4; Lancet. 2013;382(9908): 1859-61; Lancet. 2013;382(9908):1861-4.

Original Article

345Arq Bras Oftalmol. 2014;77(6):345-50http://dx.doi.org/10.5935/0004-2749.20140087

InTRODUCTIOnAccurate determination of central corneal thickness (CCT) has

be come increasingly important in ophthalmic applications. CCT mea surement is crucial in preoperative ocular evaluations, particular-ly when performing laser in situ keratomileusis because the amount of correction is limited by the corneal thickness(1). Moreover, this parameter is important in the risk assessment for glaucoma progres-sion in patients with ocular hypertension and glaucoma(2). Corneal thickness measurements are also extensively used in the diagnosis of keratoconus and other corneal disorders(3).

There are several techniques used for CCT measurement. One of these, an ultrasound-based technique, is considered to be the gold standard. However, this is limited because it is a contact technique with the potential drawbacks of causing discomfort to patients and introducing measurement errors secondary to probe misplacement or corneal compression. Furthermore, this contact technique does not enable investigators to obtain a corneal pachymetry map, and the thinnest point of the cornea cannot be determined, although this is very important for decision-making in refractive surgery. Therefore, new non-contact CCT measurement techniques have been develo-

Comparison of central corneal thickness measurements using optical low-coherence reflectometry, Fourier domain optical coherence tomography, and Scheimpflug cameraComparação entre medidas de espessura central da córnea com reflectometria óptica de baixa coerência, tomografia de coerência óptica de domínio Fourier, e câmera Scheimpflug

Saban gonul1, bengu ekinci koktekir1, berker bakbak1, SanSal gedik1

Submitted for publication: August 4, 2014 Accepted for publication: September 22, 2014

Study conducted at Selcuk University Faculty of Medicine, Department of Ophthalmology, Konya, Turkey.

1 Selcuk University Faculty of Medicine, Department of Ophthalmology, Konya, Turkey.

Funding: No specific financial support was used for this study.


Corresponding author: Saban Gonul. Selcuk University Faculty of Medicine - Department of Ophthal-mology. Konya - Turkey - E-mail: [email protected]

ABSTRACTPurpose: To compare the results of central corneal thickness (CCT) measurements obtained using optical low-coherence reflectometry (OLCR), Fourier domain optical coherence tomography (FD-OCT), and a Scheimpflug camera (SC), combined with Placido corneal topography. Methods: A total of 25 healthy subjects were enrolled in the present study, and one eye of each subject was included. A detailed ophthalmic examination was performed in all cases following CCT measurements with OLCR, FD-OCT, and SC. The results were compared using an ANOVA test. Bland-Altman analysis was used to demonstrate agreement between methods. Intra-examiner repeatability was assessed by using intraclass correlation coefficients (ICCs). Results: Statistically significant differences were observed between the results of the CCT measurements obtained using the three different devices (p=0.009). Significant correlations were found between OLCR and FD-OCT (r=0.97; p<0.0001), FD-OCT and SC (r=0.91; p<0.0001), and OLCR and SC (r=0.95; p<0.0001). The 95% limits of agreement (LOA) obtained from Bland-Altman plots were from -7.2 μm to 28.7 μm for OLCR versus FD-OCT, from -19.2 μm to 30.4 μm for OLCR versus SC, and from -42.6 to 32.3 μm for FD-OCT versus SC. Intra-examiner repeatability was excellent for each method, with ICCs >0.98. Conclusions: Although the results of CCT measurements obtained from these three devices were highly correlated with one another and the mean differences between instruments were comparable with the reported diurnal CCT fluctuation, the measurements are not directly interchangeable in clinical practice because of the wide LOA values.

Keywords: Cornea/anatomy & histology; Corneal topography/methods; Tomo-graphy, optical coherence/methods; Fourier analysis; Comparative study; Obser ver variation

RESUMO Objetivo: Comparar os resultados de medições de espessura corneana central (CCT ) obtidos com reflectometria óptica de baixa coerência (OLCR), tomografia de coerência óptica de domínio Fourier (FD-OCT ), e uma câmera Scheimpflug (SC), combinada com topografia corneana de placido. Métodos: Um olho de cada de 25 indivíduos saudáveis foram incluídos neste estudo. Um exame oftalmológico detalhado foi realizado em todos os casos após as medidas de CCT com OLCR, FD-OCT, e SC. Os resultados foram comparados por meio do teste ANOVA. Análise de Bland-Altman foi utilizada para demonstrar concordância entre os métodos. A repetibilidade intra-examinador foi avaliada por meio de coeficientes de correlação intraclasse (ICCs). Resultados: Foram observadas diferenças estatisticamente significativas entre os resultados das medidas de CCT obtidas a partir de três dispositivos diferentes (p=0,009). Foram encontradas correlações significativas entre OLCR e FD-OCT (r=0,97, p<0,0001), FD-OCT e SC (r=0,91, p<0,0001), e OLCR e SC (r=0,95; p<0,0001). Os limites de 95% de confiança (LOA) obtidos a partir de gráficos de Bland-Altman foram de -7,2 a 28,7 μm para OLCR contra FD-OCT, de -19,2 a 30,4 μm para OLCR contra SC, e de -42,6 a 32,3 μm para FD-OCT contra SC. A repetibilidade intra-examinador foi excelente para cada método com ICCs>0,98. Conclusões: Apesar de os resultados das medições CCT obtidos a partir destes três dispositivos terem sido altamente correlacionados entre si e as diferenças médias entre os instrumentos serem comparáveis à flutuação relatado da CCT diurna, as medições não são diretamente intercambiáveis na prática clínica em razão da largura dos valores limites de confiança.

Descritores: Córnea/anatomia & histologia; Topografia da corneana/métodos; To-mografia de coerência óptica/métodos; Análise de Fourier; Variações dependentes do observador; Estudo comparativo

Comparison of central corneal thickness measurements using optical low-coherence reflectometry, fourier domain optical coherence tomography, and Scheimpflug camera

346 Arq Bras Oftalmol. 2014;77(6):345-50

ped. At present, various non-contact imaging technologies are avai-lable for CCT measurement. Interferometry has been proposed to be more precise and reliable than ultrasound for CCT measurement(4,5). The relatively new Lenstar LS900 (Haag-Streit, Switzerland) instru-ment uses an interferometry technique to perform biometry of the whole eye in approximately 20 s per measurement(6).

Optical coherence tomography (OCT) is another imaging mo-dality that provides noncontact measurement of CCT. Recently, Fourier domain OCT (FD-OCT) has demonstrated greater speed, shor-ter acqui sition time, high resolution, and less motion error compared with a time-domain OCT (TD-OCT)(7). The commercially available FD-OCT (RTvue-100, Optovue Inc, Fremont, CA) has a scan rate of 26,000 A-scans per second and an axial resolution of 5 µm. It obtains high-resolution, cross-sectional images of the cornea and provides a pachymetry map(8,9).

The Scheimpflug camera (SC) combined with Placido corneal to -pography (Sirius; CSO Inc, Firenze, Italy) is a new topography device that enables rapid acquisition of cross-sectional images of the cor-nea. It can measure 35,632 points on the anterior corneal surface and 30,000 on the posterior corneal surface, in high-resolution mode, in approximately 5-6 s. A pachymetric map is then reconstructed using the point-by-point anterior and posterior corneal surface data(10).

These non-contact instruments have been shown to have good repeatability in normal eyes(3,6,9-15). However, there are limited data available regarding the agreement among CCT measurements obtai-ned using OLCR, FD-OCT, and SC. The aim of the present study was to evaluate the level of agreement among CCT measurements acquired by these instruments.

MeTHODSTwenty-five healthy subjects (15 females and 10 males) admitted

for routine ophthalmic examination at Selcuk University Faculty of Medicine Ophthalmology Department were recruited for the present study. This study adhered to the tenets of the Declaration of Helsinki, and all subjects provided informed consent for participation. Inclu-sion criteria were a negative history of chronic ocular or systemic disease and ocular surgery and no signs of previous or present ocular disease; subjects with refractive errors over ±1 diopter spherical or cylindrical values were excluded. The age of the subjects ranged from 12 to 52 years (mean, 27.8 ± 7.2 years). CCT was measured in both

eyes using OLCR, FD-OCT, and SC following a complete ophthalmic examination, but only the right eye of each subject was included in the study. The same examiner sequentially obtained the measure-ments using OLCR, FD-OCT, and SC. Three consecutive scans were obtained using each device. The mean values of these three readings was used for analysis.

In the examination using OLCR, the subjects were asked to gaze at the round circle in front of them. The CCT measurements, which were automatically calculated by the internal software of the device, recorded, and interpreted. For the SC examination, the investigator observed the image of the eye on the monitor, brought the image into focus, and centralized it on the monitor. When the image was in focus, the CCT measurements were taken and assessed using the pachymetry map. For the FD-OCT examination, infrared lights were temporally placed to the subject’s eye to provide illumination of the ocular surface. CCT measurements, which were automatically assessed using the pachymetry map, were recorded and interpreted (Figure 1).

For optimal scan quality, the patients were instructed to blink completely just before each measurement to achieve proper ocular surface, to stare at the target, and not to blink during the measure-ment. Moreover, images were only obtained after a bright, centered corneal apex reflection during the SC and FD-OCT measurements. Repeat scans were performed if the signal strength index of the image was <30 during FD-OCT measurements and if poor acquisition quality was observed during SC measurements. Improper images were automatically excluded during OLCR measurements. Therefore, the study included only centered and proper scans.

Statistical analysis was performed using SPSS version 11.5 (SPSS Inc., Chicago, IL) for Windows (Microsoft Corporation, Redmond, WA). The descriptive statistics were presented as mean ± standard de-viation. To ascertain the association between the three methods of evaluation, Spearman’s rank correlation coefficient (r) was calculated. The results of CCT measurements obtained using each device were compared by using a repeated-measures analysis of variance (ANOVA) test, and pair-wise comparisons were performed using Bonferroni adjustment tests. A p value <0.05 was considered to be statistically significant. Bland-Altman(16) analysis was used to demonstrate agree-ment between methods, and 95% limits of agreement (LOA) were calculated. Intra-examiner repeatability was determined using intra-class correlation coefficients (ICCs).

figure 1. Optical low-coherence reflectometry output, Scheimpflug camera and Fourier domain optical coherence tomography pachymetry maps demonstrating central corneal thickness measurements obtained from a subject.

Gonul S, et al.

347Arq Bras Oftalmol. 2014;77(6):345-50

ReSULTSTable 1 summarizes the mean CCT values measured using OLCR,

SC, and FD-OCT. Significant correlations were found between all pair-wise comparisons (p<0.0001) (Table 2). In comparing the three instruments using repeated-measures ANOVAs, a statistically sig-nificant difference was observed between the results of the CCT measurements (p=0.009). There was a significant difference in the measurements between OLCR and FD-OCT; hovewer, no statistically significant differences were observed between the results of the CCT measurements in the other pair-wise comparisons (OLCR ver-sus SC and FD-OCT versus SC) obtained using ANOVAs with Bonferroni adjustment tests (Table 2). The respective Bland-Altman plots bet ween each pair of the three devices are shown in figures 2 through 4. The plots show that the OLCR measurement was higher than the FD-OCT measurement (mean difference, 10.8 μm) (Figure 2). The OLCR mea-surement was also higher than the SC measurement, with a mean difference of 5.6 μm (Figure 3), and the FD-OCT measurement was thinner than the SC measurement (mean difference, 5.2 μm) (Figure 4). Considering the 95% LOA obtained from Bland-Altman plots for these comparisons, the OLCR and FD-OCT measurement displayed the smallest range of LOA (35.9 μm). The other LOA ranges were 49.6 μm between OLCR and SC, and 74.9 μm between FD-OCT and SC.

Intra-examiner repeatability of each method showed that the ICCs were excellent for each method, ranging from 0.98 to 0.99 (Table 3).

DISCUSSIONCorneal thickness measurements can be performed using ultra-

sound-based or optical-based techniques. Traditional ultrasound pa-chymetry has been the gold standard method of measuring CCT for many years(17). However, ultrasound pachymetry is a contact method, which requires topical anesthesia and may carry a risk of infection or mechanical trauma unless proper precautions are taken(18). Moreover, the instillation of topical anesthesia may cause the overestimation of CCT measurements in this technique(19). Thus, there are several advan-tages in using a non-contact procedure for CCT measurements(17,20).

In the current study, FD-OCT had a slightly lower mean CCT mea-surement (by a mean of 5.16 µm) compared with the SC CCT mea-surement, although this difference was not statistically significant. In contrast, significantly higher CCT measurements using TD-OCT (Stratus) were described by Ceylan et al.(21) when comparing TD-OCT values to SC (Pentacam). In their study, CCT measurements were ob-tained manually with the TD-OCT device, unlike in our study. Thus, in their study, the CCT measurements could have been overestimated during manual measurement because of misalignment of the central

cornea. On the other hand, Ishibazawav et al.(11) showed that the CCT measurement obtained using FD-OCT (RTVue-100) was significantly thinner than that obtained with SC (Pentacam). They proposed that the higher resolution of FD-OCT compared with SC could have led to better corneal edge detection, resulting in underestimation of the CCT. In our study, another topography system, also based on the SC (Sirius), was used, and its CCT measurements were, on average, 5.16 ± 8.08 µm thicker than the FD-OCT measurements; however, the difference was not statistically significant.

In several studies, the CCT measurements acquired with OCT were substantially lower than those obtained with SC and OLCR(8-11,22-24). A possible explanation for this difference was described by Li et al.(25) They used TD-OCT (Visante) in their study; this device uses software analysis that places boundary lines on the anterior and posterior corneal surface to automatically measure CCT. The anterior boundary line is often placed slightly below the anterior corneal surface. This results in slightly lower CCT values when using the automatic CCT measurements, which we used for our comparative analysis. Howe-ver, the FD-OCT was used in our study. Because FD-OCT has greater speed, shorter acquisition time, high resolution, and less motion error compared with TD-OCT, detection of the anterior boundary line could be improved. Therefore, the mean difference in CCT mea-surements between FD-OCT and SC was small and not statistically sig nificant in our study.

In the current study, we found that the results of CCT measure-ments obtained from these three devices were highly correlated with one another (95.0%, 91.0%, and 97% in pair-wise comparisons; Table 2). However, it has been shown that a high correlation coefficient does not always reflect a high agreement between two compared ins-truments. Therefore, mean differences between instruments should be first considered, while considering the agreements between instruments to conclude whether these instruments could be used interchangeably for CCT measurements. In our study, these values were not statistically significant except for the difference between FD-OCT and OLCR measurements. In addition, the mean differences in all pair-wise comparisons were comparable with the reported diur nal CCT fluctuation(26). In order to assess the agreement among the instruments, we used the Bland-Altman plots that describe the range in which 95% of all differences are anticipated to fall. Although the OLCR and FD-OCT measurements displayed the smallest range of LOA (35.9 μm), it ranged from 28.70 to -7.20, meaning that these ins-truments might measure the CCT as far as 28.7 mm higher or 7.2 mm lower than one another. These values were not comparable with the diurnal CCT fluctuation. Thus, we conclude that the measurements are not directly interchangeable for all comparisons in clinical practi-ce because of the wide LOA values.

Table 4 summarizes the previous studies comparing the three methods in CCT measurements. Chen et al.(9) also investigated the agreement between another SC (Pentacam) and the same FD-OCT used in our study. In their study, the range of 95% LOA was 23.2 μm, which is considerably narrower than those found in our study (74.9 μm). They concluded that measurements with both instruments could be used interchangeably despite statistically significant difference between devices because the difference was comparable with the reported diurnal CCT fluctuation(26). Conversely, Milla et al.(10) sho-

Table 1. Mean ± SD values for central corneal thickness (CCT) measures obtained with the three devices

OLCR SC fD-OCT p-value

CCT, µm 531.88 ± 29.10 526.28 ± 25.51 521.12 ± 30.92 0.009

OLCR= optical low coherence reflectometry; SC= Scheimpflug camera; FD-OCT= Fou-rier-domain optical coherence tomography.

Table 2. Pairwise comparison of central corneal thickness measurements using optical low coherence reflectometry (OLCR), Scheimpflug camera (SC) and fourier-domain optical coherence tomography (fD-OCT)

Pairwise comparison Mean difference ± SD, μm Spearman rank correlation coefficient *, r 95% limits of agreement, μm p-value**

OLCR/SC -5.60 ± 12.65 0.95 30.40 to -19.20 <0.110

FD-OCT/SC -5.16 ± 19.09 0.91 32.30 to -42.60 <0.568

OLCR/FD-OCT 10.76 ± 09.16 0.97 28.70 to -7.20 <0.001

SD= standard deviation; *= all with P<0.001; **= pair-wise comparison.



wed poor agreement between the pachymetric maps provided by TD-OCT system (Visante) and the same SC used in our study. In their study, the range of the 95% LOA was 40.7 μm. They inferred that the range of the 95% LOA was too broad to interchange the measure-ments with both instruments. As the measurements obtained using the SC were always higher than those obtained using TD-OCT in their study, they emphasized that this difference is important, especially when screening candidates for excimer laser refractive surgery. In addition, several studies that compared the agreement between TD-OCT (Visante) and SC (Pentacam) for CCT measurement showed that these devices should not be used interchangeably in a clinical setting because of poor agreement(6,22,27). Similarly, Ishibazawa et al.(11) showed that the 95% LOA for the CCT measurement between ano-

ther SC (Pentacam) and the same FD-OCT used in our study was 44 μm, which was not wider than those found in our study (74.9 μm). They concluded that CCT measurements with these devices should not be used interchangeably in a clinical setting. Similarly, in our study, the ranges of 95% LOA between FD-OCT and SC were broad and in accordance with literature, as stated above.

In our study, considering the 95% LOA obtained from Bland-Altman plots for these comparisons, the OLCR and FD-OCT measurement displayed the smallest range of LOA (35.9 μm). López-Miguel et al.(14) observed that the 95% LOA for the CCT measurement between another FD-OCT (Cirrus) and the same OLCR used in our study was 44.93 μm, which was slightly wider than those found in our study. They suggested that CCT measurements obtained with these devices could be used interchangeably, with minimum calibration adjust-ment. Nevertheless, they mentioned that these small differences between devices might be clinically relevant, especially in patients considering refractive surgery and patients with glaucoma.

Cruysberg et al.(23) reported that the 95% LOA for the CCT measu-rement between TD-OCT (Visante) and the same OLCR used in our study was 26 μm, which was slightly narrower than those observed in our study. In their study, the difference between the CCT measu-rements of the OLCR and the TD-OCT was statistically significant, resulting in higher CCT values using OLCR compared with TD-OCT. The OLCR measurement was also higher than the FD-OCT measure-ment in our study. O’Donnell et al.(6) also reported that the 95% LOA for the CCT measurement between TD-OCT (Visante) and the same OLCR used in our study was 65.52 μm, which was much wider than those observed in our study. They suggested that CCT measures from these instruments should not be used interchangeably because of poor agreement between these instruments. In our study, reasonable agreement was found between the OLCR and the FD-OCT, in contrast with their study.

In the current study, we found that the range of 95% LOA between OLCR and SC was 49.6 μm. On the other hand, Chen et al.(28) reported that the 95% LOA for the CCT measurement between the same devi-ces used in our study was 22.33 μm, which was considerably narrower than those observed in our study. They suggested that CCT measure-ments from these instruments can be used interchangeably, because of good agreement between these instruments. This discrepancy might be caused by the difference of the mean CCT values between the two studies. In our study, the mean CCT values measured by OLCR and SC were 531.88 µm and 526.28 ± 25.51 µm, respectively. In their study, the mean CCT values were not mentioned. For these reason, further studies on a larger range of CCT thicknesses are warranted.

In conditions with statistically non-significant mean differences between two devices, the agreement between the devices can be determined using the magnitude of the LOA. In addition, whether the range of LOA includes zero mean difference between devices on Bland-Altman plots is also important to draw conclusions regarding the agreement between two devices. All these factors can determine the agreement between two devices and whether both devices can be used interchangeably. On the other hand, whether this agreement is clinically satisfactory depends on the clinical situation. In patients undergoing refractive surgery, for instance, overestimation of CCT could lead to serious complications, whereas underestimation of CCT could lead to the exclusion of eligible patients from refractive surgery procedures(1). Similarly, these faulty measurements may be misleading with regard to the diagnosis and treatment of glaucoma cases(2). In such cases, the range of LOA should not only be narrow, but the zero mean difference between the devices should also be in the middle of that narrow range on Bland-Altman plots in order to use the two devices interchangeably. In the current study, the zero mean difference falls in the middle of the range of LOA for all device pairs. However, the ranges of LOAs for all the device pairs were too broad to use both devices interchangeably.

Interestingly, there were a few participants who were obvious outliers in Bland-Altman plots, causing larger differences in CCT

figure 3. A Bland-Altman plot comparing the central corneal thickness measurements obtained using optical low-coherence reflectometry and the Scheimpflug camera.

figure 2. A Bland-Altman plot comparing the central corneal thickness measurements obtained using optical low-coherence reflectometry and Fourier domain optical cohe-rence tomography.

Table 3. Intra-examiner repeatability of each method of central corneal thickness measurements

Methods ICC 95% CI

OLCR 0.9874 0.9715-0.9945

SC 0.9838 0.9632-0.9928

FD-OCT 0.9901 0.9776-0.9956

ICC= intraclass correlation coefficient; CI= confidence interval; OLCR= optical low cohe rence reflectometry; SC= Scheimpflug camera; FD-OCT= Fourier-domain optical coherence tomography.

Gonul S, et al.


Table 4. Previous studies comparing three methods in central corneal thickness measurements

Author Devices Mean difference ± SD, μm 95% limits of agreement, μm p value

Chen et al.(9) SC (Pentacam) - FD-OCT (RTVue) 10.90 ± 5.93 22.5 to -0.7 <0.001

Milla et al.(10) SC (Sirius) - FD-OCT (Visante) 22.4 ± 10.4 42.7 to 2.0 <0.016

Ishibazawa et al.(11) SC (Pentacam) - FD-OCT (RTVue) 22.0 ± 9 5 to -39.0 <0.001

López-Miguel et al.(14) OLCR- FD-OCT (Cirrus) 5.68 ± 11.46 21.28 to -23.99 <0.001

Cruysberg et al.(23) OLCR- FD-OCT (Visante) 11.1 ± 6.5 24.1 to -1.9 <0.001

O’Donnell et al.(6) OLCR- FD-OCT (Visante) Not available 40.78 to -21.74 <0.005

O’Donnell et al.(6) OLCR-SC (Pentacam) Not available 15.53 to -24.40 <0.005

SD= standard deviation; FD-OCT= Fourier-domain optical coherence tomography; SD OCT= spectral-domain optical coherence tomography; OLCR= optical low coherence reflectometry; SC= Scheimpflug camera.

measurements between devices, which induced poor agreement between the devices. We were unable to determine which device caused these different CCT measurements because our study did not include any ultrasound-based CCT measurements, which is the gold standard in CCT measurement. However, this might have been caused by some subjects with CCT values at the upper/lower limit of normal. Therefore, further studies including a larger number of subjects with extreme values of CCT as well as ultrasound-based CCT measurements are warranted.

The results of the present study demonstrated that all devices have high repeatability in healthy subjects and were in accordance with the literature(3,6,9-15). In addition, the FD-OCT exhibited slightly better repeatability compared with the other devices. A possible explanation for this is that FD-OCT measures CCT with greater speed and shorter acquisition time, reducing error due to eye motion. Also, FD-OCT has high resolution, which enables the precise delineation of the boundaries of the cornea. These factors reduce the variability of measurements acquired with FD-OCT.

There are some limitations that must be addressed. In our study, ultrasound pachymetry, the gold standard in CCT measurement, was not included because our main purpose was to evaluate the level of agreement among CCT measurements acquired by three non-in-vasive techniques. In addition, these measurements were acquired only from healthy subjects. Therefore, further studies are needed to assess the agreement of measurements in patients with conditions such as cataract, keratoconus, ocular hypertension, and other corneal disorders.

In conclusion, the results of CCT measurements obtained using these three devices are correlated with one another, and the mean differences are comparable with the reported diurnal CCT fluctua-

tion; however, the agreement expressed by the 95% LOA values is broad for all the device pairs. This suggests that clinicians should be aware of the differences between these noncontact devices, and that they should not be used interchangeably for CCT measurements in the evaluation of patients with glaucoma or in patients who are candidates for refractive procedures.

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figure 4. A Bland-Altman plot comparing the central corneal thickness measurements between the Fourier domain optical coherence tomography and the Scheimpflug camera.



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40o Congresso da Sociedade Brasileira de Retina e Vítreo

18 a 20 de abril de 2015Costão do Santinho

Florianópolis - SC

informações: Site: www.retina2015.com.br

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Original Article


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teraction of organism and environment(1-3). Enabling factors, such as diabetes mellitus, may affect the growth of human conjunctival microbiota, increasing the risk of eye infection(4).

Diabetes mellitus is a group of metabolic diseases resulting from defects in insulin action and secretion, leading to a hyperglycemic

ABSTRACTPurpose: To study the aerobic bacterial microbiota of the conjunctiva in diabetic patients with regard to the management of diabetes, assessed using glycated hemoglobin levels.Methods: A cross-sectional study was conducted using conjunctival smears of diabetic patients from both sexes and with different ages, residing in two different Brazilian cities (Sorocaba and Rio Branco). A control group of non-diabetic patients was also included. The diabetic patients were considered to have controlled dia-betes when their glycated hemoglobin level was ≤7% and blood glucose level was ≤126 mg/dL. Patients with non-controlled diabetes were those with glycated hemoglobin levels >7% and blood glucose levels >126 mg/dL. The samples obtained were inoculated in Brain-Heart Infusion broth and in culture media for aerobic bacteria (blood and chocolate agars); bacterial growth was evaluated in a microbiology laboratory. Results: A total of 120 eyes of 120 patients were included in the present study. The percentage of cultures in which bacterial growth was observed was greater in diabetic patients, although the difference was not statistically significant (p=0.103). There was a greater trend toward bacterial growth in the conjunctiva of diabetic patients with altered fasting blood glucose. There was no difference in the frequency of bacterial growth on the conjunctiva between diabetic patients with normal or altered glycated hemoglobin levels. In Sorocaba, conjunctival bacterial growth was similar to that observed in Rio Branco. The microorganism most frequently detected in the present study was Staphylococcus epidermidis, followed by Staphylococcus aureus, Proteus mirabilis, and Escherichia coli. Conclusions: There was no difference between diabetic patients with normal or altered glycated hemoglobin levels. The microorganisms found were similar to those found in studies investigating the conjunctival bacterial flora of diabetic and non-diabetic patients.

Keywords: Conjunctiva; Microbiota; Diabetes mellitus; Hemoglobin A, glycosylated

RESUMOObjetivo: Estudar a microbiota conjuntival bacteriana aeróbica dos pacientes dia-béticos em relação ao controle glicêmico, verificado através da hemoglobina glicada, em duas cidades distintas. Métodos: Foi realizado um estudo transversal utilizando raspados de conjuntiva de indivíduos diabéticos de ambos os sexos e idades variáveis de duas cidades: So-rocaba e Rio Branco. O grupo controle foi constituído de pacientes não diabéticos. A amostra foi constituída de pacientes diabéticos que foram considerados controlados com hemoglobina glicada ≤7% e glicemia de jejum ≤126 mg/dl e não controlados com hemoglobina glicada >7% e glicemia de jejum >126 mg/dl. O material obtido foi semeado em meio líquido Brain Heart Infusion (BHI) e em meios de cultivo para bactérias aeróbicas (ágar sangue e ágar chocolate). O crescimento bacteriano foi avaliado em laboratório de microbiologia. Resultados: Foram incluídos 120 olhos de 120 pacientes. A porcentagem de culturas nas quais houve crescimento bacteriano foi maior em pacientes diabéticos, sendo a diferença não estatisticamente significante (p=0,103). Não houve diferença entre o crescimento bacteriano em pacientes com hemoglobina glicada normal e alterada. Houve uma tendência maior de crescimento bacteriano em conjuntivas de pacientes diabéticos com glicemias de jejum elevada. Em Sorocaba houve crescimento bacteriano conjuntival semelhante a Rio Branco. O microrganismo mais frequente encontrado neste estudo foi Staphylococcus epidermidis, seguido de Staphylococcus aureus, Proteus mirabilis e Escherichia coli. Conclusões: Não ocorreu diferença entre pacientes diabéticos com hemoglobina gli cada normal e alterada. Os microrganismos encontrados foram semelhantes aos estudos da flora bacteriana de conjuntivas normais e de diabéticos.

Descritores: Conjuntiva; Microbiota; Diabetes mellitus; Hemoglobina A glicosilada

state(5). Measurement of glycated hemoglobin is the gold-standard test in the assessment of glycemic control in patients with diabetes mellitus and is a useful test in the follow-up of diabetic patients, as well as in the assessment of the status of blood glucose over the previous 3 months(6,7). The correlation of glycated hemoglobin values with fasting blood sugar values is still not well defined(8,9). Values of fasting blood sugar have a better association with glycated hemoglo-

Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in BrazilMicrobiota bacteriana aeróbica conjuntival em pacientes diabéticos com hemoglobina glicada normal e alterada em duas regiões brasileiras

natalia PiMentel Moreno1, renaldo duarte Moreno2, luciene barboSa SouSa3

Submitted for publication: August 4, 2014 Accepted for publication: October 6, 2014

Study conducted at Department of Ophthalmology and Visual Sciences, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

1 Department of Ophthalmology and Visual Sciences, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

2 Department of Ophthalmology, Federal University of Acre (UFAC), Acre, AC, Brazil.3 Cornea and External Diseases Section, Department of Ophthalmology and Visual Sciences, Federal

University of São Paulo (UNIFESP), São Paulo, SP, Brazil.



Corresponding author: Natalia Pimentel Moreno. Rua Floriano Peixoto, 335 - Rio Branco, AC 69900-025 - Brazil - E-mail: [email protected]

Approved by the following Research Ethics Committee: Federal University of São Paulo (UNIFESP) (0115/09).

Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in Brazil


bin values when they are higher, i.e., in situations of poor glycemic control(7,8).

Studies show that the bacterial flora of healthy individuals is for-med by Staphylococcus epidermidis(4,10,11), S. aureus, Corynebacterium sp, and Propineobacterium acne(13). S. epidermidis, S. aureus, and Cory-nebacterium sp have also been found in diabetic patients(4).

Variations in conjunctival microbiota may occur due to both intrinsic and extrinsic changes in the body, such as geographical di-versity and different socioeconomic characteristics(4,10,12-14). Therefore, the conjunctival aerobic microbiota of diabetic patients was studied in two different Brazilian cities: Rio Branco, in the state of Acre, in north Brazil; and Sorocaba, in the state of São Paulo, in southeastern Brazil. Rio Branco has a largely equatorial climate, while Sorocaba has a subtropical climate. They are significantly different in terms of social and economic development, as Rio Branco has an agriculture-based economy, while Sorocaba is located in a burgeoning industrial sec-tor(15,16). Based on such climate and socioeconomics differences, the bacterial flora of diabetic and non-diabetic patients was studied in these two regions.

Although the literature also demonstrates the presence of anae-robic bacteria and fungi, the object of the current study was to eva-luate the aerobic bacteria in this context(13,14).

The main aim of the current study was to study aerobic bacterial microbiota in the conjunctiva of diabetic patients in terms of the level of control of diabetes, assessed using glycated hemoglobin levels. It also aimed to analyze the influence of fasting blood sugar on conjunctival bacterial growth in diabetic patients and to study the influence of environmental variations on the aerobic bacterial microbiota in the conjunctiva of diabetic and non-diabetic patients.

MeTHODSA cross-sectional study was performed using smears from the

con junctiva of diabetic patients of both sexes and of different ages, living in the urban areas of two cities, Sorocaba (São Paulo) and Rio Branco (Acre). The study was approved by the Ethics Committee at the Federal University of São Paulo (São Paulo, Brazil) and patients signed an Informed Consent form.

The patients in the present study included individuals with diag -nostic confirmation of type 2 diabetes as well as non-diabetic indivi-duals based on clinical history and laboratory tests (previously per-formed blood glucose test results included in their medical records). The groups were matched according to sex and age. Patients were selected from two different regions (the Acre Teaching Hospital in Rio Branco and the Ophthalmology Hospital of Sorocaba in São Paulo), and were chosen according to sex and age.

The exclusion criteria for both groups were as follows: the presen-ce of eye disease not related to diabetes, such as anatomical or func-tional lesions of the eyelids, lacrimal system, cornea or conjunctiva, hyperemia and/or conjunctival secretion; use of topical medication or contact lenses within the previous 30 days; or patients with other diseases that could alter the immune response. Patients underwent a review of clinical history and an eye examination via slit lamp biomi-croscopy prior to the sample collection for the evaluation of inclusion and exclusion criteria.

A total of three main groups were created: controlled diabetic; non-controlled diabetic and control groups. The diabetic sample consisted of patients who were considered to have controlled dia-betes, with glycated hemoglobin levels (hemoglobin A1c fraction) ≤7% and blood glucose levels ≤126 mg/dL (DMc group; controlled diabetic patients); and patients with non-controlled diabetes, with glycated hemoglobin >7% and blood glucose >126 mg/dL (DMnc group; considered to be non-controlled diabetic patients), according to the American Diabetes Association(17), based on the results of the Diabetes Control and Complications Trial(17) and the United Kingdom Prospective Diabetes Study(18). Patients without diabetes mellitus

for med the control group (group C). The group of non-controlled diabetic patients was also evaluated according to the range of fas-ting blood sugar values: 126 to 140 mg/dL; 141 to 160 mg/dL; and >160 mg/dL. Individuals with glycated hemoglobin levels >7% and fasting blood glucose levels < 126 mg/dL were not selected, nor were individuals with glycated hemoglobin levels <7% and fasting blood glucose levels >126 mg/dL. After collecting blood from the patients in order to evaluate glycated hemoglobin and fasting blood sugar, the collection of eye secretions was performed in all patients from each city, under similar environmental conditions, maintaining the same temperature and humidity and without the use of air conditio-ning. Data collection was performed by the same researcher.

Swabs were used to collect the content from the bottom of the lower conjunctival sac of the right eye using a rotating and gliding motion on the surface of the lower eyelid conjunctiva and at the bottom of the lower conjunctival sac, without touching the eyelid margins and eyelashes, and without the use of anesthetic eye drops. Sterile gloves were used. The samples were inoculated in liquid Brain Heart Infusion medium and in culture media for aerobic bacteria (blood and chocolate agars).

The samples were stored at room temperature and immediately sent to the Microbiology Laboratory of the Santa Casa hospital in Sorocaba, and the Microbiology Laboratory at the Acre Teaching Hospital. Samples were labeled so that the technician had no access to the patients’ clinical information. The plates were incubated at 35°C for 48 h and, in the event of bacterial growth, identification was pro-cessed in accordance with the criteria established by the Clinical and Laboratory Standards Institute in 2006)(19). Growth of aerobic bacteria was observed. Samples were considered to be negative when no growth was observed in the medium after a period of seven days. For the statistical analysis, SPSS® (Statistical Package for Social Sciences) version 15.0 (SPSS Inc, Chicago, IL, USA) was used and groups were compared using the χ2 test. The null hypothesis was accepted for all analyses at p≥0.05.

ReSULTSA total of 120 eyes from 120 patients were included in the study:

60 patients (20 controlled diabetic patients, 20 non-controlled dia-betic patients and 20 non-diabetic patients) in each city (Rio Branco and Sorocaba). The mean age in the three groups was 68 years (range 50 to 82 years).

With regard to gender, on evaluating the three study groups (120 patients), the proportion of males and females was 54 (45%) and 66 (55%), respectively. No statistically significant difference between the groups was found when they were compared according to gender (p=0.807).

As for the conjunctival culture, it was found that, in the group of diabetic patients, 50 of the 80 diabetic patients (65%) had a positive culture for aerobic bacteria, whereas this number was 24 (60%) in the 40 non-diabetic patients, with no statistically significant difference (p=0.103).

Table 1 shows bacterial growth in the three groups.Figure 1 shows the age distribution according to the positive

culture results.With regard to fasting blood glucose levels, three ranges of values

were evaluated: 126 to 140 mg/dL, 141 to 160 mg/dL and >160 mg/dL (Table 2).

The distribution of microorganisms found in positive cultures of diabetic and non-diabetic patients is presented in table 3.

DISCUSSIOnIn the present study, the percentage of cultures in which bacterial

growth was observed was higher among diabetic patients (83.3%) compared with non-diabetic patients (80%), but this difference was not statistically significant (p=0.103).

Moreno NP, et al.


In previous studies, bacterial growth was observed in at least one eye in 94.18% of the cultures obtained from diabetic patients and in 73.33% of those obtained from non-diabetic patients(4). The presen-ce of pathogenic microorganisms in the conjunctival microbiota of patients without any evident clinical infection, as observed in the present study, which is associated with the presence of immunolo-gical alterations described in this group of individuals, could have the effect of increasing the risk of developing infection following intraocular procedures(20).

When performing an assessment according to age group, a greater number of diabetic and non-diabetic patients were found between 61 and 70 years of age and older than 70 years of age, regardless of glycemic control (patients with controlled and non-controlled diabetes) in the two regions studied, although the difference was not statistically significant. Eyelid changes, poor tear drainage, fragi lity of the corneal epithelium, decrease in corneal sensitivity and asso ciated comorbidities are only a few of the ocular and systemic features des -cribed(21).

In a previous study, the bacterial flora of 579 patients was ana-lyzed preoperatively before cataract surgery, along with the isolated bacteria and the percentage of bacterial resistance, and was compa-red among age groups and according to the presence or absence of diabetes mellitus. In this study, bacterial isolation was lower in pa-tients younger than 40 years of age compared with those older than 60 years of age (61 to 70 years of age; 71 to 80 years of age; and older than 80 years of age), with advanced age being the only significant risk factor in the detection of bacterial growth(22).

Despite immunity, changes described in diabetic patients are related to hyperglycemia(19). In the present study, no differences

were observed in the bacterial growth of the conjunctival flora when com paring patients with controlled and non-controlled glycated hemoglobin levels.

When the bacterial flora of the conjunctival sac of patients before cataract surgery was assessed, no significant difference was observed in the rate of bacterial detection among diabetic patients (a total of 197 patients) with regard to glycated hemoglobin levels as well as glycosuria and diabetic retinopathy. The reason for this is unclear, but it is possible that these factors have little influence on conjunctival microbiota. As the microorganisms isolated from the eye, especially from the cornea and conjunctiva, come into direct contact with the environment and originate from the skin of the eyelid, they are in-fluenced by the meibomian glands and endogenous flora; therefore, multiple sources may be responsible(22).

Although glycated hemoglobin level did not have an influence on greater bacterial growth in the samples collected, it was noted that diabetic patients with higher fasting blood glucose levels were more likely to have bacterial growth in their cultures compared with diabetic patients with lower blood glucose levels and with non-dia-betic patients. The difference was not statistically significant (p>0.05), likely due to the small sample size in the present study.

With the data obtained in the present study, it is possible to ap-preciate the importance of fasting blood glucose levels to bacterial growth because the collection of blood occurred at the same time as the collection of eye secretion. The presence of glucose in the skin, urine, mucous and tears creates a favorable environment for the growth of microrganisms(12) and may also be responsible for the most significant bacterial growth observed in this study.

Any alteration in skin integrity could provide a gateway to infec-tion because of the microbiota that typically colonizes the surface of the human body. The changes found in the microbiota may depend on social and personal factors, on the predominant geographical area, as well as on the resistance that may be present against the em-pirically administered antibiotics(23). The profile of the ocular micro-biota undergoes constant change, influenced by seasonal variations, temperature, age, environmental exposure factors, surgical trauma and host immunity(4,10,12-14).

The characteristics of the two cities studied are, respectively, an equatorial climate with hot and rainy weather in Rio Branco(15), and a subtropical and temperate climate in Sorocaba(16). Located in diffe-rent regions of Brazil, Sorocaba has a population of 500,000 and large economic diversity(16), in contrast to the city of Rio Branco, which has a population of approximately 350,000 and a barely sustainable economy based on agricultural activities(15). Despite the fact that the literature shows the possible influence of climate and socioeconomic conditions on conjunctival microbiota (bacterial and fungal)(4,10,12-14), no significant differences were observed in the regions studied with regard to bacterial growth.

The most common microorganism found in this study was Sta-phylococcus epidermidis, followed by Staphylococcus aureus, Proteus mirabilis and Escherichia coli; no significant differences were observed

Table 1. Result from conjunctival cultures comparing patients with controlled diabetes, patients with non-controlled diabetes and non-diabetic patients from samples collected in Sorocaba (São Paulo) and Rio Branco (Acre), Brazil, 2010 and 2011

Controlled diabetes non-controlled diabetes non-diabetic Total

pn (%) n (%) n (%) n (%)

Sorocaba

Positive culture 15 (18.75%) 14 (17.5%) 10 (8.33%) 39 (32.5%) 0.910

Negative culture 05 (06.25%) 06 (07.5%) 10 (8.33%) 21 (17.5%) 0.910

Rio Branco

Positive culture 11 (13.75%) 10 (12.5%) 14 (11.66%) 35 (29.16%) 0.639

Negative culture 09 (11.25%) 10 (12.5%) 06 (05.00%) 25 (20.83%) 0.639

figure 1. Distribution by age group according to results of a conjunctival culture in diabetic and non-diabetic patients evaluated in Sorocaba (São Paulo) and Rio Branco (Acre), Brazil, 2010 and 2011.

Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in Brazil


between patients with controlled and non-controlled diabetes and patients without diabetes in the two regions examined (Sorocaba and Rio Branco).

A study performed on patients with diabetes mellitus showed that the species most commonly found in the microbiota of diabetic patients, in descending order, were: coagulase-negative Staphylo-coccus (mainly Staphylococcus epidermidis), Corynebacterium sp and Staphylococcus aureus(4). In the present study, the species of bacteria isolated in the cultures of the conjunctiva of diabetic patients were no different from those identified in the conjunctiva of non-diabetic patients, as was also observed in the study by Martins et al.(4) In nor -mal bacterial flora, the aerobic agents most commonly found are Staphylococcus epidermidis, Staphylococcus aureus, Corynebacterium spp and Propionibacterium acne(4,12). Most studies agree that Staphylo-coccus epidermidis is the microorganism most commonly found in aerobic bacterial flora of normal conjunctivas(4,10,11,24).

Greater aerobic bacterial growth was also observed in the con-junctivas of the older patients, regardless of gender or the presence or absence of diabetes. An increased aerobic bacterial growth was observed in patients with altered fasting blood glucose levels at the time of examination, and no difference was observed in aerobic bac-terial growth in diabetic patients in relation to glycated hemoglobin levels at the time of collection. There was no difference between the two regions evaluated in any aspect of the study. The microorganisms found were similar to those found in studies on bacterial flora of nor mal conjunctivas and of diabetic patients, and Staphylococcus epidermidis was the main aerobic bacteria found.

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Table 2. Results of conjunctival cultures from diabetic patients with altered glycated hemoglobin levels according to fasting glycemia, in Sorocaba (São Paulo) and Rio Branco (Acre), Brazil, 2010 and 2011

fasting glycemia p

126-140 mg/dL 141-160 mg/dL >160 mg/dL

Positive culture 5 (20.83%) 7 (29.16%) 12 (50%) 0.158

Negative culture 6 (37.50%) 6 (37.50%) 04 (25%) P=0.688

Table 3. Distribution of microorganisms comparing positive cultures of diabetic and non-diabetic patients evaluated in Sorocaba (São Paulo) and Rio Branco (Acre), Brazil, 2010 and 2011

Diabetic non-diabeticCfU (%) CfU (%)

Staphylococcus epidermidis 41 (82%) 22 (91.6%)

Staphylococcus aureus 07 (14%) 01 (04.2%)

Proteus mirabilis and S. epidermidis 02 (04%) -

Escherichia coli and S. epidermidis - 01 (04.2%)

CFU= colony forming unit.

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Original Article


InTRODUCTIOnDiabetic retinopathy (DR) represents a leading cause of moderate

and severe vision loss within the working-age population in develo-ped countries(1). Advanced proliferative DR complicated by vitreous hemorrhage or tractional retinal detachment is responsible for most

ABSTRACTPurpose: This study was designed to evaluate the visual and anatomical out co mes after cataract surgery in diabetic patients with different intraoperative therapeutic strategies. Methods: The research design comprised of a multicentric, retrospective, inter-ventional study conducted at 6 centers in Argentina, Brazil, Costa Rica, Puerto Rico, Spain, and Venezuela. We included 138 diabetic patients with at least 6-month follow-up following phacoemulsification and intraocular lens implantation. Best-corrected visual acuity (BCVA) and central subfield thickness were collected at baseline and at 1-, 2-, 3-, and 6-month follow-up. Of these, 42 cases were not treated with any intraoperative coadjuvant medication (Group 1), 59 patients received intraoperative bevacizumab (Group 2) and 37 patients received intrao-perative triamcinolone (4 mg/0.1 ml) (Group 3). Results: The mean logMAR [± standard deviation (SD)] BCVA improved from 0.82 (± 0.43) at baseline, to 0.14 (± 0.23) at 6-month follow-up (p<0.001) in Group 1; from 0.80 (± 0.48) to 0.54 (± 0.45) (p<0.001) in Group 2; and from 1.0 (± 0.40) to 0.46 (± 0.34) (p<0.001) in Group 3. The mean central subfield thickness increased from 263.57 µm (± 35.7) at baseline to 274.57 µm (± 48.7) at 6-month follow-up (p=0.088) in Group 1; from 316.02 µm (± 100.4) to 339.56 µm (± 145.3) (p=0.184) in Group 2; and from 259.18 µm (± 97.9) to 282.21 µm (± 87.24) (p=0.044) in Group 3. Conclusions: Diabetic patients may significantly benefit from cataract surgery. This study provides evidence to support the use of intravitreal triamcinolone or bevaci-zumab at the time of cataract surgery in cases with pre-existent diabetic macular edema or moderate-severe non-proliferative diabetic retinopathy.

Keywords: Diabetic retinopathy; Macular edema; Cataract extraction; Intraope-rative care; Phacoemulsification; Lens implantation, intraocular; Antibodies, mo-no clonal; Multicenter study

RESUMO Objetivo: Avaliar os resultados visuais e anatômicos após a cirurgia de catarata em pacientes diabéticos com estratégias terapêuticas intraoperatórias diferentes. Métodos: Estudo multicêntrico, retrospectivo, de intervenção realizado em 6 centros da Argentina, Brasil, Costa Rica, Porto Rico, Espanha e Venezuela. Foram incluídos 138 pacientes diabéticos com pelo menos 6 meses de seguimento após facoemulsifi-cação com implante de lente intraocular. Acuidade visual melhor corrigida (BCVA) e a espessura subcampo central (CST ) foram coletadas no início e em 1, 2, 3 e 6 meses de seguimento. Destes, 42 casos não foram tratadas com qualquer co-adjuvante de medicamentos intra-operatório (Grupo 1), 59 pacientes receberam bevacizumab intraoperatório (Grupo 2), e 37 pacientes receberam triancinolona intraoperatória (4 mg/0,1 ml) (Grupo 3).Resultados: A média logMAR (± desvio-padrão [DP]) BCVA melhorou de 0,82 (± 0,43) no início do estudo, para 0,14 (± 0,23) aos 6 meses de seguimento (p<0,001) no Grupo 1; de 0,80 (± 0,48) para 0,54 (± 0,45) (p<0,001) no Grupo 2; e de 1,0 (± 0,40) para 0,46 (± 0,34) (p<0,001) no Grupo 3. A CST média aumentou de 263,57 µm (± 35,7) na linha de base para 274,57±48,7 µm em 6 meses acompanhamento (p=0,088) no Grupo 1; de 316,02 µm (± 100,4), para 339,56 µm (± 145,3) (p=0,184) no Grupo 2; e de 259,18 µm (± 97,9), para 282,21 µm (±87,24) (p=0,044) no grupo 3. Conclusões: Pacientes diabéticos podem se beneficiar significativamente da cirur gia de catarata. Este estudo parece fornecer evidências para apoiar o uso de triancinolona intravítrea ou bevacizumab no momento da cirurgia de catarata em casos com ede-ma macular diabético preexistente (DME) ou retinopatia diabética não-proliferativa moderada a grave.

Descritores: Retinopatia diabética; Edema macular; Extração de catarata; Cuidados intraoperatórios; Facoemulsificação; Implante de lente intraocular; Anticorpos mono-clonais; Estudo multicêntrico

cases of severe loss of vision, but diabetic macular edema (DME) is the most prevalent cause of moderate vision loss(2). It is known that hyper-glycemia causes damage to the retinal vascular endothelium, resulting in increased vascular permeability, exudation, and accumulation of extracellular fluid and proteins within the macula, hemorrhages,

Outcomes of cataract surgery in diabetic patients: results of the Pan American Collaborative Retina Study Group Resultados da cirurgia de catarata em pacientes diabéticos: resultados do Pan-American Collaborative Retina Study Group

roberto gallego-Pinazo1, roSa dolz-Marco1, Maria berrocal2, lihteh Wu3, Mauricio Maia4, Martín Serrano5, arturo alezzandrini6, J. Fernando arévalo7,8, Manuel díaz-lloPiS1,9, For the Pan-aMerican collaborative retina Study grouP (PacoreS)*

Submitted for publication: June 30, 2014 Accepted for publication: October 6, 2014

Multicentric, study conducted at different centers in Argentina, Brazil, Costa Rica, Puerto Rico, Spain and Venezuela.

1 Department of Ophthalmology, University and Polytechnic Hospital La Fe, Valencia, Spain.2 Department of Ophthalmology, University of Puerto Rico, San Juan, Puerto Rico.3 Instituto de Cirugía Ocular, San Jose, Costa Rica.4 Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina (EPM), Universidade

Federal de São Paulo (UNIFESP), São Paulo, Brazil.5 Clinica Oftalmologica Centro Caracas and the Arevalo-Coutinho Foundation for Research in Oph-

thalmology, Caracas, Venezuela.6 Cátedra de Oftalmologia, Universidad de Buenos Aires, Buenos Aires, Argentina.7 Vitreoretinal Division, The King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.8 Retina Division, The Wilmer Eye Institute, Johns Hopkins University, Baltimore, USA.9 Faculty of Medicine, University of Valencia, Valencia, Spain.* For a complete listing of participating members of PACORES see Appendix.



Corresponding author: Rosa Dolz-Marco. Department of Ophthalmology - University and Polytechnic Hospital La Fe. Bulevar Sur - s/n - Valencia - 46026 - Spain - E-mail: [email protected]

Outcomes of cataract surgery in diabetic patients: results of the Pan American Collaborative Retina Study Group


microaneurysm formation, and capillary closure(3,4). Hypoxia has been linked to retinal neovascularization but has also been associated with DME(3).

Focal or grid macular laser photocoagulation (MLP) were pre-viously the mainstay of treatment for DME, but the advent of intra-vitreal inhibitors of the vascular endothelial growth factor (VEGF) has recently changed the therapeutic strategies for DME. Several stu -dies have demonstrated significantly better visual outcomes with in travitreal injections of ranibizumab alone or in combination with MLP(3-6). Intravitreal injections of corticosteroids (triamcinolone and dexamethasone implant) have also achieved positive functional and anatomical results in the treatment of DME; however, local safety issues, such as cataract progression or intraocular pressure increase, must be considered for this treatment(5,7).

Visual outcomes following cataract surgery in diabetic patients have been correlated with the presence of DME and the severity of DR at the time of the surgery. It is controversial whether phacoemul-sification may trigger the progression of DR and DME compared with the natural history of the disease(8-9).

The purpose of the present study was to evaluate the functional and anatomical outcomes after cataract surgery in diabetic patients managed with different therapeutic approaches.

MeTHODSThis retrospective, multicentric, interventional study was conduc-

ted at 6 different centers in Argentina, Brazil, Costa Rica, Puerto Rico, Spain and Venezuela between December 2009 and December 2012. The clinical charts of all diabetic patients who underwent cataract surgery were retrospectively reviewed after obtaining institutional review board approval.

The inclusion criteria were patients over 18 years old diagnosed with diabetes mellitus who had undergone uncomplicated phacoe-mulsification with intraocular lens implantation and had at least 6 months of follow-up after phacoemulsification and intraocular lens implantation. Patients were excluded if there was evidence of any retinal disease other than diabetic retinopathy. Patients showing su bretinal fibrosis or fibrous metaplasia of the retinal pigment epi-thelium, or vitreo-macular traction that may limit the visual function, were also excluded.

Patients were classified into 3 groups depending on the use of co-adjutant medications during cataract surgery. The decisions about whether to administer any co-adjuvant therapy, and the choice of the drug if administered, were left to the discretion of the treating surgeon. Patients in Group 1 did not receive any co-adjuvant therapy; patients in Group 2 received an intraoperative intravitreal injection of bevacizumab (1.25 mg/0.05 ml); and patients in Group 3 received an intravitreal injection of triamcinolone (4 mg/0.1 ml) intraoperatively.

Best-corrected visual acuity (BCVA) measured by Early Treatment Diabetic Retinopathy Study (ETDRS) charts expressed in a logari-thm of minimum angle of resolution (logMAR) and central subfield thickness (CST) automatically measured by optical coherence tomo-graphy (OCT) were collected at baseline and 1-, 2-, 3- and 6-months follow-up visits. The types of OCT used were Cirrus HD-OCT (Carl Zeiss, Dublin, CA, USA) and Spectralis OCT (Heidelberg Engineering, Hei delberg, Germany). In all cases, a quality of the OCT scans of at least 7/10 was required, and all the images were reviewed in order to avoid any misalignment. The presence of DME was defined as the evidence of retinal thickening in the OCT images, and it was classified as cystoid, diffuse macular thickening (DMT) or neurosensory deta-chment. A fluorescein angiography was performed and analyzed at baseline to assess the presence of focal or diffuse macular edema and to rule out the presence of macular ischemia.

The data were collected in a Microsoft Office Excel 2007 spread-sheet (Microsoft Corporation, Unterschleissheim, Germany) and sta-tistically analyzed by SPSS Software version 21.0 (SPSS Inc, Chicago, IL, USA).

ReSULTSBaSelINe CharaCterIStICS

The clinical charts of 138 eyes of 138 patients (72 male, 66 female) were reviewed. The mean age was 66.8 years (standard deviation [SD ± ] 8.59; range: 38-96). We found coexistence of systemic arterial hypertension in 21 patients (14.2%), a prior history of stroke in 6 pa-tients (4%) and myocardial infarction in 10 patients (6.8%). The mean time since the initial diagnosis of diabetes had been established was 16.4 years (SD ± 8.32; range: 38-96). Fifty-two patients (35.1%) were receiving treatment with insulin, 45 patients (30.4%) with oral hypoglycemic agents, 34 patients (23%) used insulin in combination with oral hypoglycemic agents and 7 patients (4.7%) were controlled only with diet.

The baseline retinal status was normal in 26 patients (18.8%); mild non-proliferative diabetic retinopathy (NPDR) was found in 24 pa-tients (17.4%); moderate NPDR in 18 patients (13%); and severe NPDR in 21 patients (15.2%). On the other hand, inactive proliferative dia-betic retinopathy (PDR) without laser therapy treated with anti-VEGF therapy(10) was present in 18 patients (13%); inactive PDR treated with laser was present in 10 patients (7.2%); 5 patients (3.6%) presented with active PDR without previous laser therapy and 16 patients (11.6%) presented with active PDR with laser treatment. Pre vious treatments received by the 138 patients included in the study were intravitreal bevacizumab (46 patients, 33.3%), with a mean number of 3.1 injections (range: 1-13); intravitreal triamcinolone injections (21 patients, 15.2%); MLP (48 patients, 34.8%); and 9 patients (6.5%) had previous pars plana vitrectomy (PPV) with internal limiting mem-brane peeling (6 patients, 4.3%) or without it (3 patients, 2.2%). The baseline characteristics by groups are summarized in table 1.

Overall we found a statistically significant and positive correlation between the final BCVA with the baseline BCVA (p<0.001, r=0.33). In addition, we report a statistically significant but negative correlation between the final BCVA and the duration of diabetes (p=0.002, r=-0.31), level of hemoglobin A1c (HbA1c) (p=0,044; r=-0.18), grade of diabetic retinopathy at baseline examination (p<0.001, r=-0.44) and prior treatment with triamcinolone (p=0.001, r=-0.19) or anti-VEGF drugs (p=0.027, r=-0.28). Final CST in the OCT was significantly and positively correlated with baseline CST (p<0.001, r=0.39), history of myocardial infarction (p=0.018, r=0.20), level of HbA1c (p=0,042, r=0.19), prior treatment with triamcinolone (p=0.003; r=0.43) and prior treatment with anti-VEGF drugs (p<0.001, r=0.25) or MLP (p=0.04, r=0.17).

No co-adjuvant intraoperative treatment was administered to 42 patients (Group 1). Fifty-nine patients were treated with intravitreal bevacizumab intraoperative (Group 2), and 37 patients were injected intraoperatively with triamcinolone (Group 3).

GrOUp 1: WIthOUt CO-aDjUvaNt therapy

Forty-two cases were included in this group. At baseline, 3 pa-tients (7.1%) showed DMT, but no signs of cystoid DME or neurosen-sory detachment were found in the other 39 patients (92.9%). The FA images showed focal edema in two patients (4.7%) and diffuse edema in one patient (2.4%). No signs of retinal or macular ischemia were reported in these patients. The retinal status was normal in 23 patients (54.8%); mild NPDR was found in 6 patients (14.3%); mode-rate NPDR in 3 patients (7.1%); severe NPDR in two patients (4.8%); and PDR was present in 8 patients (19%).

The mean logMAR BCVA improved significantly from 0.82 (SD ± 0.43, median: 0.75) at baseline, to 0.20 (SD ± 0.26, median: 0.10) at 1-month of follow-up (p<0.001); and maintained the significant visual gain compared with baseline at 2 months of follow-up (mean: 0.16, SD ± 0.25, median: 0.05; p<0.001), and at 3 months of follow-up (Mean: 0.14, SD ± 0.23, median: 0.0; p<0.001). At 6 months of follow-up, the mean BCVA was 0.14 (SD ± 0.23, median: 0.0), still showing statistically significant differences from baseline (p<0.001).

Gallego-Pinazo R, et al.


The mean CST significantly increased from 263.57 microns (SD ± 35.7, median: 275 microns) at baseline to 276.9 microns (SD ± 52.9, median: 280) at 1 month of follow-up (p=0.049); and it remained stable compared with baseline at 2 months of follow-up (mean: 275.1 mi-crons, SD ± 39.3, median: 279; p=0.157) and at 3 months of follow-up (mean: 275.4 microns, SD ± 35.6, median: 280; p=0.064). At 6 months of follow-up, the mean CST remained stable in 274.57 microns (SD ± 48.7, median: 277 microns) without significant differences from ba seline data (p=0.088).

The time to the first postoperative treatment indicated for DME since cataract surgery was 106.7 days (SD ± 70.6, median: 120). Eleven patients (26.2%) received intravitreal bevacizumab, two patients (3.8%) received intravitreal triamcinolone, 3 patients (7.1%) received MLP, in 1 patient (2.3) a YAG capsulotomy was performed, and 11 pa tients (26.2%) did not receive any further treatment during the follow-up.

GrOUp 2: CO-aDjUvaNt therapy WIth INtraOperatIve BevaCIzUmaB

At baseline, 35 patients (59.3%) showed DMT in the OCT images; 15 patients (25.4%) presented with cystic DME; and 6 patients (10.1%) showed neurosensory detachment. In the FA images, focal edema was present in 27 patients (45.8%) and diffuse in 25 patients (42.4%). Macular ischemia was observed in 5 patients (8.5%). No evidence of DME was found in two patients (3.4%). Retinal status was normal in 3 patients (5.1%); mild NPDR in 15 patients (25.4%); moderate NPDR in 10 patients (16.9%); severe NPDR in 10 patients (16.9%); and PDR in 11 patients (18.6%).

The mean logMAR BCVA improved significantly from 0.80 (SD ± 0.48, median: 0.70) at baseline to 0.54 (SD ± 0.42, median: 0.50) at 1 month of follow-up (p<0.001); and maintained the significant visual gain compared with baseline at 2 months of follow-up (mean: 0.52, SD ± 0.42, median: 0.50; p<0.001), and at 3 months of follow-up (mean: 0.49, SD ± 0.42, median: 0.40; p<0.001). At 6 months of follow-up, the mean BCVA was 0.54 (SD ± 0.45, median: 0.50), showing signifi-cant differences from baseline data (p<0.001).

The mean CST increased from 316.02 microns (SD ± 100.4, me-dian: 309 microns) at baseline to 334.63 microns (SD ± 130.8, median: 279.5) at 1 month of follow-up (p=0.039); and remained stable when compared with baseline at 2 months of follow-up (mean: 334.36 microns, SD ± 174.1, median, 242; p=0.248), and at 3 months of follow-up (mean: 286.63 microns, SD ± 98.3, median: 248; p=0.852). At 6 months of follow-up, the mean CST remained stable in 339.56 microns (SD ± 145.3, median: 278 microns) (p=0.184) without signifi-cant differences from baseline data.

The time to the first postoperative treatment indicated for DME since cataract surgery was 150.6 days (SD ± 137.4, median: 160). Twenty-eight patients (42.4%) received intravitreal treatment with bevacizumab, 7 patients (11.9%) with triamcinolone, and 5 patients (8.5%) with dexamethasone implant (Ozurdex®). Two patients (3.4%) received MLP, and 24 patients (40.6%) did not receive any treatment during the follow-up.

GrOUp 3: CO-aDjUvaNt therapy WIth INtraOperatIve trIamCINOlONe

At baseline 25 patients (67.6%) showed DMT in the OCT images; 5 patients (13.5%) cystoid DME; and two patients (5.4%) neurosensory detachment. In the FA images, DME corresponded with focal edema in 14 patients (37.8%) and diffuse edema in 13 patients (35.1%). Ma-cular ischemia was observed in 5 patients (13.5%). No signs of DME were found in 5 patients (13.5%). No patient showed a normal retinal status at baseline; mild NPDR was found in 3 patients (8.1%); modera-te NPDR in 5 patients (13.5%); severe NPDR in 9 patients (24.3%); and PDR in 20 patients (54.1%).

The mean logMAR BCVA improved significantly from 1.0 (SD ± 0.40, median: 1.0) at baseline to 0.48 (SD ± 0.37, median: 0.40) at 1 month of follow-up (p<0.001); and maintained the significant visual gain compared with baseline at 2 months of follow-up (mean: 0.45, SD ± 0.38, median: 0.35; p<0.001); and at 3 months of follow-up (mean: 0.42, SD ± 0.31, median: 0.40; p<0.001). At 6 months of follow-up, the mean BCVA was 0.46 (SD ± 0.34, median: 0.40), showing significant differences from baseline data (p<0.001).

The mean CST significantly decreased from 259.18 microns (SD ± 97.9; median, 239 microns) at baseline to 243.97 microns (SD ± 69.6; median, 236) at 1 month of follow-up (p=0.038); and remained stable when compared with preoperative data at 2 months of follow-up (mean: 251.42 microns, SD ± 63, median: 246; p=0.478) and at 3 months of follow-up (266.97 microns, SD ± 66.7, median: 253; p=0.340). At 6-month follow-up, the CST increased to 282.21 microns (SD ± 87.24, median: 257 microns) with significant differences from baseline (p=0.044).

The time to the first postoperative treatment indicated for DME since cataract surgery was 191.05 days (SD ± 118.4; median, 189). Four patients (10.8%) received intravitreal treatment with bevacizumab, 1 patient (2.7%) received intravitreal treatment with triamcinolone, 15 patients (40.5%) received macular laser therapy, two patients recei-

Table 1. Baseline characteristics

Group 1 Group 2 Group 3 p

Number of patients 42 59 37

Sex, n(%) 0.911

Male 21 (50) 32 (54.2) 19 (51.4)

Female 21 (50) 27 (45.7) 18 (48.6)

Age (mean + SD), years 68.1±8.3 65.5±10.1 65+5.8 0.433

Mean BCVA: baseline 0.21 0.25 0.14 0.008

Mean OCT scores: baseline, microns 263.57 316.01 259.2 0.001

Hypertension, n (%) 16 (38.1) 12 (20.3) 2 (5.4) <0.001

History of stroke, n (%) 3 (7.1) 03 (05.1) 0 (0) 0.284

History of myocardial infarction, n (%) 3 (7.1) 06 (10.7) 1 (2.7) 0.395

Systemic glycemic control, n (%) <0.001

Diet 6 (14.3) 1 (1.7) 0 (0)

Oral hypoglycemiants 8 (19) 37 (62.7) 07 (18.9)

Insulin 18 (42.9) 16 (27.1) 11 (29.7)

Combined therapy 10 (23.8) 5 (8.5) 19 (51.4)

Time to diagnosis of DM, years 12.1 16.1 21 <0.001

HbA1c, % 7.13 8.14 8.36 0.004

Grade of DR, n (%) <0.001

Normal 23 (45.8) 3 (5.1) 0 (0)

Mild NPDR 06 (14.3) 15 (25.4) 3 (08.1)

Moderate NPDR 03 (07.1) 10 (16.9) 5 (13.5)

Severe NPDR 02 (04.8) 10 (16.9) 9 (24.3)

Inactive PDR, no laser 8 (19) 5 (8.5) 5 (13.5)

Inactive PDR, laser 0 (00) 0 (0) 0 (0)

Active PDR, no laser 0 (00) 1 (1.7) 04 (10.8)

Active PDR, laser 0 (00) 5 (8.5) 11 (29.7)

Prior treatment, n (%)

Anti VEGF injection 7 (16.7) 36 (55.9) 3 (8.1) <0.001

Triamcinolone injection 1 (02.4) 19 (32.2) 1 (2.7) <0.001

Macular laser therapy 4 (09.5) 41 (69.5) 2 (5.4) <0.001

PPV 5 (11.9) 04 (06.8) 1 (2.7) <0.475

ANOVA test.SD=standard deviation; BCVA= best-corrected visual acuity; OCT= optical coherence tomography; DM= diabetes mellitus; Hb= hemoglobin; DR= diabetic retinopathy; NPDR= non-proliferative diabetic retinopathy; PDR= proliferative diabetic retinopathy; VEGF= vascular endothelial growth factor; PPV= pars plana vitrectomy.

Outcomes of cataract surgery in diabetic patients: results of the Pan American Collaborative Retina Study Group


ved pan-retinal photocoagulation therapy and 16 patients (43.2%) did not receive any treatment during the follow-up.

INterGrOUp COmparISON There were no significant differences between the 3 groups in gen-

der (p=0.911), age (p=0.433), and previous history of stroke (p=0.284) or myocardial infarction (p=0.395). However, there were statistically significant differences between the 3 groups regarding the presence of systemic arterial hypertension (p<0.001); systemic glycemic con-trol therapy (p<0.001); duration of diabetes (p<0.001); level of HbA1c (p=0.004); baseline DR grading (p<0.001); the frequency of previous treatment with anti-VEGF (p<0.001), triamcinolone (p<0.001) and MLP (p<0.001); and prevalence of DME evaluated by OCT and FA (p<0.001). There were significant differences in the intergroup com-parison in the number of untreated patients prior to the cataract removal between Group 2 and Groups 1 and 3 (p<0.001), but no sig-nificant difference was observed between Groups 1 and 3 (p=0.156).

Statistically significant differences in the baseline BCVA between the 3 groups were evidenced (p=0.008). These significant differences were also present in the final BCVA outcomes (p<0.001). The mean visual gain was 0.68 (SD ± 0.41; median: 0.60) in Group 1; 0.26 (SD ± 0.46; median: 0.10) in Group 2; and 0.51 (SD ± 0.43; median: 0.50) in Group 3. We found significant differences in the intergroup compa-rison between the 3 groups (p<0.001), and between Group 2 and Groups 1 and 3 (p<0.001 and p=0.009 respectively), but no significant differences were observed between Groups 1 and 3 (p=0.79).

There were also statistically significant differences in the baseline CST between the 3 groups (p=0.001), which were also present in the final CST (p=0.005).

Finally there were no significant differences in the time when the physicians indicated the first treatment for DME after cataract surgery between the 3 groups (p=0.121).

No ocular adverse event or significant ocular inflammatory reac-tion was reported in any of the 3 groups. Functional and anatomical results are summarized in table 2.

DISCUSSIOnThe presence of postoperative macular edema after cataract sur -

gery in diabetic patients may be related to the cataract surgery itself (so called pseudophakic cystoid macular edema, PCME) or to the un-derlying diabetic condition. The differentiation between both types is challenging. Whereas PCME tends to resolve spontaneously, DME frequently persists or increases following surgery(9,11).

The incidence of clinical significant PCME after uncomplicated cataract surgery in the healthy population has been reported to be 0.1-2% of cases(12,13), whereas in diabetic patients the incidence of macular thickening after cataract surgery may rise to 10-81%(8,9,12,14). Factors reported to be associated with an increased risk for deve-loping macular thickening after uneventful phacoemulsification in diabetic patients are DR stage, presence of DME, history of previous

treatments, level of HbA1c and duration of diabetes of more than 10 years(8). Our results are consistent with these data, as we found a significant correlation between all those characteristics and both the final BCVA and CST.

Prophylaxis of macular thickening following cataract extraction in diabetic patients is a controversial issue. Intravitreal anti-VEGF (be -vacizumab or ranibizumab)(15-20) and intravitreal steroids (triamcino-lone acetonide or dexamethasone implant)(20-22) have been reported to achieve positive anatomical and functional results when injected immediately after the surgical procedure. More recently, the efficacy of topical non-steroidal anti-inflammatory drugs has also been re-ported(23).

In the present study, we found a significant postoperative retinal thickness decrease in the group treated with 4 mg/0.1 ml of intrao-perative triamcinolone, but during the follow-up these patients sho-wed a significant increase in CST. On the other hand, the group with no co-adjuvant treatment and that with co-adjuvant therapy with 1.25 mg/0.05 ml of bevacizumab showed a significant increase in the CST during the follow-up. We hypothesize that intravitreal triamcino-lone administration may play a positive role in controlling the acute inflammatory factors that are released following cataract removal. The increase in the CST in the group of patients injected intraope-ratively with bevacizumab is consistent with the results achieved by Rauen et al.(17), who did not find a positive anatomical response with intraoperative ranibizumab, in contrast to other similar studies(15-19). These results may be related to the high percentage of patients (84.7%) previously treated for DME in this group, as it is known that the presence of DME before the cataract removal is a risk factor for developing macular thickening with this surgical procedure. Never-theless, we found dissociation between anatomical and functional outcomes, as we found significant BCVA improvement after cataract extraction in all the study groups.

The results of the present study may suggest that patients with lower DR severity and absence of preoperative DME achieve the better visual outcomes. These results are consistent with previous reports(8,9). On the other hand, patients with a higher grade of DR and previously treated DME showed less visual gain but the increase in BCVA was still statistically significant. We hypothesize that due to the baseline differences between groups, patients without co-adjuvant treatment or treated intraoperatively with triamcinolone achieved significant higher visual gain. Finally, all the patients included in the present study significantly improved BCVA, thus the cataract surgery may be a relevant approach to be considered in such cases.

The patients with DME at baseline and previous history of diffe-rent treatments for DME were preferably injected intraoperatively with bevacizumab by the responsible physician, whereas patients with previously untreated DME were preferably treated with intrao-perative triamcinolone. Otherwise, in patients with no DME at ba seline and no previous treatments the physicians preferred not to provide any co-adjuvant therapy. We cannot offer an accurate intergroup comparison, but we did identify these preferred practice patterns

Table 2. Intergroup comparison of the functional and anatomic results

Group 1 Group 2 Group 3 p

Mean baseline BCVA (logMAR) 000.82 (SD ± 0.43) 000.80 (SD ± 0.48) 001.0 (SD ± 0.40) p=0.008

Mean final BCVA (logMAR) 000.14 (SD ± 0.23) 000.54 (SD ± 0.45) 000.46 (SD ± 0.34) p<0.001

Mean visual gain 000.68 (SD ± 0.41) 000.26 (SD ± 0.46) 000.51 (SD ± 0.43) p<0.001

Mean baseline CST (microns) 263.57 (SD ± 35.70) 316.02 (SD ± 100.4) 259.18 (SD ± 69.6) p=0.001

Mean final CST (microns) 274.57 (SD ± 48.70) 339.56 (SD ± 145.3) 282.21 (SD ± 87.24) p=0.005

ANOVA test.SD= standard deviation; BCVA= best-corrected visual acuity; CST= central subfield thickness; logMAR= logarithm of minimum angle of resolution.

Gallego-Pinazo R, et al.


depending on the presence of previous DME and treatment adminis-tration before cataract extraction.

COnCLUSIOnThe limitations of the present study include its uncontrolled, re -

trospective and non-randomized nature. This has led to important differences in epidemiological and clinical factors between the diffe-rent groups. The differences the presence of systemic arterial hyper-tension, systemic glycemic control therapy, duration of diabetes and level of HbA1c at baseline may influence our results. However, our results are consistent with previous reports showing that DR grading and the presence of DME before cataract extraction may be related to a higher rate of DME after phacoemulsification. The relatively short-term follow-up is another limiting factor of the present study. Further prospective, randomized studies are warranted in order to analyze the efficacy of the different approaches.

In summary, our results suggest that cataract surgery in diabetic patients is an efficient procedure, resulting in highly significant BCVA improvement. This study may provide evidence to support the use of intravitreal triamcinolone or bevacizumab at the time of cataract sur-gery in cases with preexistent DME or moderate-severe NPDR. We can conclude that the visual outcomes after cataract surgery in diabetic patients may depend on the previous DR stage and the presence of DME, and the use of intravitreal co-adjuvants as triamcinolone or bevacizumab may optimize functional outcomes in these cases.

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16. Takamura Y, Kubo E, Akagi Y. Analysis of the effect of intravitreal bevacizumab injection on diabetic macular edema after cataract surgery. Ophthalmology. 2009;116(6):1151-7. Comment in: Ophthalmology. 2010;117(4):849; author reply 849-50.

17. Rauen PI, Ribeiro JA, Almeida FP, Scott IU, Messias A, Jorge R Intravitreal injection of ranibizumab during cataract surgery in patients with diabetic macular edema. Retina. 2012;32(9):1799-803.

18. Fard MA, Yazdanei Abyane A, Malihi M. Prophylactic intravitreal bevacizumab for diabetic macular edema (thickening) after cataract surgery: prospective randomized study. Eur J Ophthalmol. 2011;21(3):276-81. Comment in: Eur J Ophthalmol. 2012;22(3): 513; author reply 514.

19. Akinci A, Batman C, Ozkilic E, Altinsoy A. Phacoemulsification with intravitreal bevaci-zumab injection in diabetic patients with macular edema and cataract. Retina. 2009; 29(10):1432-5.

20. Akinci A, Muftuoglu O, Altınsoy A, Ozkılıc E. Phacoemulsification with intravitreal be-vacizumab and triamcinolone acetonide injection in diabetic patients with clinically significant macular edema and cataract. Retina. 2011;31(4):755-8.

21. Takata C, Messias A, Folgosa MS, Lucena LR, Lucena DR, Scott IU, Jorge R. Intravitreal injection versus subtenon infusion of triamcinolone acetonide during cataract surge-ry in patients with refractory diabetic macular edema. Retina. 2010;30(4):562-9.

22. Agarwal A, Gupta V, Ram J, Gupta A. Dexamethasone intravitreal implant during pha-coemulsification. Ophthalmology. 2013;120(1):211.

23. Singh R, Alpern L, Jaffe GJ, Lehmann RP, Lim J, Reiser HJ, et al. Evaluation of nepafenac in prevention of macular edema following cataract surgery in patients with diabetic retinopathy. Clin Ophthalmol. 2012;6:1259-69.

appeNDIx

The following investigators belong to the Pan-American Collabo-rative Retina Study Group (PACORES):

The Pan-American Collaborative Retina Study Group (PACORES)*-L. Wu (PI), Instituto de Cirugia Ocular, San Jose, Costa Rica; J. F.

Arevalo (PI), I Kozak,V. Gupta, S. Al-Rashaed, E. Al-Kahtani, The King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia, and the Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA; M. A. Serrano (PI), A. F. Lasave, Clinica Oftalmologica Centro Caracas and the Arevalo-Coutinho Foundation for Research in Ophthalmology, Caracas, Venezuela; M. Farah (PI), M. Maia, F. M. Penha, E. B. Rodrigues, Universidade Federal de São Paulo - Depar-ta mento de Oftalmologia - Instituto da Visão - Sao Paulo, Brazil; V. Mo rales-Canton (PI), J. Fromow-Guerra, J.L. Guerrero-Naranjo, J. Dal-ma-Weiszhausz, M. A. Martinez-Castellanos, Asociación para Evitar la Ceguera en México, Mexico City, Mexico; H. Quiroz-Mercado (PI), R. Velez-Montoya, University of Colorado, School of Medicine, Denver, Colorado, USA; F. J. Rodriguez (PI), F. E. Gomez, A. C. Brieke, Fundacion Oftalmologica Nacional, Universidad del Rosario, Bogota, Colombia; M.H. Berrocal (PI), V. Cruz-Villegas, University of Puerto Rico, San Juan, Puerto Rico; F. Graue-Wiechers (PI), D. Lozano-Rechy, E. Ariza-Ca-macho, Fundacion Conde Valenciana, Mexico City, Mexico; J.A. Roca (PI), R.G. Chico, Clínica Ricardo Palma, Lima, Peru; M. J. Saravia (PI), A. Schlaen, A. Lupinacci, M. N. Gabin, Hospital Universitario Austral, Buenos Aires, Argentina; M. Avila (PI), L. Carla, Universidade Federal de Goiás - Departamento de Oftalmologia - Goiânia, Brazil; J. Cardillo (PI), Hospital de Olhos de Araraquara, and the Universidade de Sao Paulo, Sao Paulo, Brazil; C. Carpentier (PI), J. Verdaguer T., J.I. Verdaguer D., G. Sepúlveda, Fundacion Oftalmologica Los Andes, Santiago de Chile, Chile; A. Alezzandrini (PI), B. Garcia, G. Bregliano, OFTALMOS, Catedra de Oftalmologia, Universidad de Buenos Aires, Buenos Aires, Argentina; G. Alvira (PI), P. Flor, F, Jaramillo, Hospital Metropolita-no, Quito, Ecuador; M. Diaz-Llopis (PI), R. Gallego-Pinazo, D. Salom, R. Dolz-Marco, S. Martínez-Castillo, Hospital La Fe, Universidad de Valencia, Spain; M. Figueroa (PI), I. Contreras, D. Ruiz-Casas, Hospital Universitario Ramón y Cajal, Departamento de Retina, and VISSUM Madrid Mirasierra de Oftalmología Integral, Madrid, Spain.

*PI=Principal Investigator

Original Article

360 Arq Bras Oftalmol. 2014;77(6):360-3 http://dx.doi.org/10.5935/0004-2749.20140090

InTRODUCTIOnRelative pupillary block (PB) is considered to be the primary me -

chanism for angle closure(1-3). Although laser peripheral iridotomy (LPI) remains the cornerstone of angle-closure management, it does not widen the angle in all cases, as approximately 20%-30% of these patients continue to exhibit appositional angle closure in the pre-sence of a patent iridotomy(1-3). In these cases, non-PB mechanisms, such as lens-induced, plateau iris, and peripheral angle crowding,

may be involved(4-7). Argon laser peripheral iridoplasty (ALPI) and lens extraction have been proposed as effective procedures to manage eyes with persistent occludable angles(8-10).

While dealing with cases of primary angle closure (with or without glaucoma), identification of the underlying mechanism is of the utmost importance because each may follow a different course and require a different treatment approach. Although there is extensive informa-tion in the literature regarding the main etiologies and guidelines

Non-pupillary block angle-closure mechanisms: a comprehensive analysis of their prevalence and treatment outcomes Mecanismos de fechamento angular sem bloqueio pupilar: análise de prevalência e resultados terapêuticos

daniela l. M. Junqueira1, vitor g. Prado1,2, Flavio S. loPeS1,2, luiS guStavo biteli1,2, Syril dorairaJ3, tiago S. Prata1,2

Submitted for publication: May 12, 2014 Accepted for publication: October 21, 2014

Study conducted at Universidade Federal de São Paulo.1 Glaucoma Unit, Hospital Medicina dos Olhos, Osasco, SP, Brazil.2 Universidade Federal de São Paulo, São Paulo, SP, Brazil. 3 Mayo Clinic, Jacksonville, Florida.



Corresponding author: Tiago Santos Prata. Departamento de Oftalmologia - UNIFESP/EPM - Rua Botucatu, 821- São Paulo, SP - 04023-062 - Brazil - E-mail: [email protected]

Approved by the following Research Ethics Committee: Sociedade Brasileira e Japonesa de Beneficência/Hospital Santa Cruz, São Paulo, sob o número (178.759).

ABSTRACTPurpose: To assess the prevalence and treatment outcomes of angle-closure mechanisms other than pupillary block in a population of Brazilian patients. Methods: A retrospective chart review was conducted to evaluate patients who had undergone laser peripheral iridotomy (LPI) due to occludable angles at a single institution between July 2009 and April 2012. An occludable angle was defined as an eye in which the posterior trabecular meshwork was not visible for ≥180° on dark-room gonioscopy. Key exclusion criteria were any form of secondary glaucoma and the presence of >90° of peripheral anterior synechiae. Collected data were age, race, gender, angle-closure mechanism (based on indentation goniocopy and ultrasound biomicroscopy), intraocular pressure (IOP), number of antiglaucoma medications and subsequent management during follow-up. If both eyes were eligible, the right eye was arbitrarily selected for analysis. Results: A total of 196 eyes of 196 consecutive patients (mean age 58.3 ± 11.6 years) who underwent LPI were included. In most of the patients [86% (169 pa-tients; 133 women and 36 men]), LPI sucessfully opened the angle. Mean IOP was reduced from 18.3 ± 6.4 mmHg to 15.4 ± 4.5 mmHg after LPI (p<0.01). Among the 27 patients with persistent occludable angles, the most common underlying mechanisms were plateau iris (56%) and lens-induced component (34%). Most of these patients (85%) were treated with argon laser peripheral iridoplasty (ALPI); approximately 90% showed non-occludable angles following the laser procedure (mean IOP reduction of 18.9%), with no significant differences between patients with plateau iris and lens-induced components (p=0.34; mean follow-up of 11.4 ± 3.6 months). Conclusions: Our findings suggest that, in this population of Brazilian patients, several eyes with angle closure were not completely treated with LPI. In the pre-sent large case series involving middle-age patients, plateau iris was the leading cause of persistent angle closure and was effectively treated with ALPI. A detailed eye examination with indentation gonioscopy should always be performed after LPI to rule out persistent angle closure due to non-pupillary block mechanisms.

Keywords: Angle closure; Non-pupillary block mechanisms; Iris diseases; Iris/pathology; Iridectomy; Treatment outcome

RESUMOObjetivo: Reportar a prevalência e os resultados terapêuticos em casos de fechamento angular por outros mecanismos além de bloqueio pupilar em uma população de pacientes brasileiros. Método: Realizou-se um estudo retrospectivo para avaliar pacientes apresentando ângulo oclusível submetidos à iridotomia periférica a laser (LPI), em uma única insti-tuição, entre julho/2009 e abril/2012. Ângulo oclusível foi definido pela não observação do trabeculado posterior em mais de 180° à gonioscopia sem identação. Olhos com glaucomas secundários ou >90º de sinéquia anterior periférica foram excluídos. Fo ram coletados os seguintes dados: idade, raça, sexo, mecanismo de fechamento angu-lar (com base na gonioscopia e biomicroscopia ultrassônica), pressão intraocular (PIO), número de medicações antiglaucomatosas e manejo subsequente durante o seguimento. Sempre que ambos os olhos eram elegíveis, o olho direito foi escolhido arbitrariamente para análise. Resultados: Foram incluídos 196 olhos de 196 pacientes (58,3 ± 11,6 anos) que foram submetidos à LPI. Na maioria dos casos [86% (169 pacientes; 133 mulheres e 36 homens), a LPI foi capaz de abrir o ângulo. A PIO média foi reduzida de 18,3 ± 6,4 para 15,4 ± 4,5 mmHg após a LPI (p<0,01). Entre os 27 casos que persistiram com ângulo oclusível, os mecanismos mais comuns envolvidos foram íris em platô (56%) e induzido por componente cristaliniano (34%). A maioria desses casos (85%) foram tratados com iridoplastia periférica a laser (ALPI). Aproximadamente 90% tornaram-se não oclusíveis após a ALPI (redução média da PIO de 18,9%), não havendo diferença significativa entre os pacientes com componentes de íris em platô ou cristaliniano (p=0,34; seguimento médio de 11,4 ± 3,6 meses). Conclusões: Nossos resultados sugerem que, nessa população de pacientes brasileiros, parte dos olhos com fechamento angular não foi completamente tratada com LPI. Nesta série de pacientes de meia-idade, a presença de íris em platô foi a principal causa de fechamento angular persistente, sendo efetivamente tratada com ALPI. Acreditamos que um exame gonioscópico detalhado deva ser realizado após a LPI para descartar fechamento angular persistente por outros mecanismos que não bloqueio pupilar.

Descritores: Fechamento angular; Bloqueio pupilar; Doenças da íris; Irís/patologia; Iridectomia; Resultado de tratamento

Junqueira DLM, et al.


for management of primary angle closure in Asian, North American, and European populations, there are scant data with regard to South American patients(2,11-16). In the present study, we investigated the prevalence and treatment outcomes of angle-closure mechanisms other than pupillary block in a population of Brazilian patients.

MeTHODSpatIeNtS

After Institutional Review Board approval, a comprehensive chart review was conducted to evaluate consecutive patients who un-derwent LPI due to occludable angles at a single institution between July 2009 and April 2012. An occludable angle was defined as an eye in which the posterior trabecular meshwork was not visible for ≥180° without indentation on dark-room gonioscopy. Because some eyes may not have irido-trabecular contact even when the trabecular meshwork is not visible, an additional requirement was that corneal and iris beams of light should merge during non-indentation gonios-copy (in order to confirm the presence of irido-trabecular contact). Eyes with previous incisional surgery, with >90° of peripheral anterior synechiae (PAS), ocular trauma, uveitis, or any other form of seconda-ry glaucoma were excluded.

Data COlleCtION aND prOCeDUreS

Data collected were age, gender, race, presence of glaucoma, pre- and post-laser intraocular pressure (IOP), number of antiglauco-ma medications, angle status and underlying angle-closure mecha-nisms as determined by gonioscopy and subsequent management during follow-up. All laser procedures, pre- and post-laser goniosco-py assessments and IOP measurements were performed by two ex-perienced glaucoma specialists (LGB and TSP). In all cases, dark-room gonioscopy was performed with and without indentation using a Posner four-mirror lens (Ocular Instruments Inc., Bellevue, WA, USA). The light beam was set at 1-2 mm to avoid illuminating the pupil, and the most posterior region of the anterior chamber angle that was visible without indentation was determined. The angle was classified as occludable or non-occludable based on the previously mentioned definition. Regarding ALPI parameters, a 500 micron spot, 500 ms duration and 250 mW power were routinely used, which could vary according to iris pigmentation and tissue response. The center of a Goldmann 3 mirror lens was used and, after the procedure, predniso-lone acetate 1% was administered four times per day for one week.

In brief, the main mechanisms of angle closure could be descri-bed as follows: (1) relative pupillary block, which results from increa-sed resistance to the flow of aqueous humor between the pupillary portion of the iris and the anterior lens surface; (2) plateau iris (Figure 1 A), which results from an abnormal anatomical configuration/rela-tionship of the anterior chamber angle and ciliary body and is usually confirmed after a LPI failure; and (3) lens induced (Figure 1 B), which involves a normal or large lens pushing the iris forward and resulting in a reduced anterior chamber volume and angle-closure(4-7).

On indentation gonioscopy, eyes with a relatively deep central anterior chamber and irido-trabecular contact after LPI in which the “double hump sign” was identified were considered to exhibit plateau

iris component. On the other hand, those with a shallower central anterior chamber in which the iris appeared to drape the anterior surface of the lens, giving rise to a “volcano-like” configuration were considered to exhibit the lens-induced component(5,8). Ultrasound biomicroscopy was used in most cases of persistent occludable angles following LPI.

StatIStICal aNalySIS Descriptive analysis was used to present demographic and cli-

nical data. D’Agostino-Pearson’s test was performed to determine whether the data had a normal distribution. The paired-samples T-test was used to compare continuous normally distributed variables, while the Wilcoxon signed-rank test was used to compare those that were non-normally distributed. Baseline IOP was determined as the average of three measurements prior to the laser procedures. Post-laser IOP was based on a single measurement (IOP measurement on each patient’s last visit). The treatment regimen was not altered until the final follow-up visit. If both eyes were eligible for inclusion, the right eye was arbitrarily chosen for analysis. Statistical significance was set at p<0.05. Computerized analysis was performed using MedCalc software (MedCalc Inc., Mariakerke, Belgium).

ReSULTSA total of 196 eyes of 196 consecutive patients (mean age 58.3

± 11.6 years; 133 women and 36 men) who underwent LPI were included. Primary angle-closure suspects/primary angle closure constituted 54% of the cases, primary angle-closure glaucoma 40% and acute angle-closure glaucoma 6%. In most of the cases (86%), LPI successfully opened the angle. Mean IOP was reduced from 18.3 ± 6.4 to 15.4 ± 4.5 mmHg after LPI (p<0.01).

Forty-one eyes (27 patients) had persistent occludable angles after LPI, comprising approximately 14% of the cases that had pre-viously undergone iridotomy. Among these cases, the most common angle-closure mechanisms were plateau iris (56%) and lens-induced component (34%). Regarding the remaining 10% of the cases of persistent occludable angles (without characteristics of plateau iris or lens-induced component), most eyes had a thick peripheral iris with prominent circumferential folds, occupying a large proportion of the angle, and were classified as thick peripheral iris roll (or peripheral iris crowding)(4,5). Patients with plateau iris were mostly women (75%) and younger (mean age 55.3 years) than those with lens-induced component (mean age 64.8 years; 30% women; p≤0.03). None of the patients were taking pilocarpine prior to the laser procedures. Table 1 summarizes the clinical characteristics of these patients.

Most of these cases of persistent occludable angles following LPI were treated with laser iridoplasty (85%). Regarding the four other patients, two had cataracts associated with low visual acuity and

A B

figure 1. Ultrasound biomicroscopy images of two patients with persistent occlu-dable angles following laser peripheral iridotomy due to plateau iris (A) and lens-induced component (B).

Table 1. Characteristics of patients with persistent occludable angle due to non-pupillary mechanisms*

Variables Patients (n=27)

Mean age (years) 58.9 ± 11.8

Gender % (men/women) 44/56

Race % (white/black/asian) 78/15/7

Presence of glaucoma (%) 63%

Angle-closure mechanisms % (PIC/LIAC/others) 56/34/10

Mean IOP before ALPI (mmHg) 17.9 ± 4.9

Mean IOP after ALPI (mmHg) 14.5 ± 4.2

*Data are presented as mean ± standard deviation whenever indicated.ALPI= argon laser peripheral iridoplasty; IOP= intraocular pressure; LIAC= lens-induced angle closure; PIC= plateau iris component.

Non-pupillary block angle-closure mechanisms: a comprehensive analysis of their prevalence and treatment outcomes


underwent phacoemulsification with intraocular lens implantation, and two were treated with pilocarpine at night-time. Treatment regi-mens were not changed until the final follow-up visit (mean length of follow-up, 11.4 ± 3.6 months; mean number of antiglaucoma medications, 1.7 ± 1.3). Approximately 90% of the cases showed non-occludable angles following ALPI. Intraocular pressure was sig -nificantly reduced from 17.9 ± 4.9 to 14.5 ± 4.2 (p<0.01) with no sig nificant differences between patients with plateau iris and lens-in-duced components (p=0.34). Although some cases of photophobia were noted, there were no cases of peripheral anterior synechiae formation.

DISCUSSIOnRecent estimates show that >67 million individuals around the

world have glaucoma. Although open-angle glaucoma comprises approximately two-thirds of these cases, angle-closure glaucoma is present in one-half of patients who are blind from the disease(17,18). In addition, in populations such as Chinese, Indian and Mongolian, the prevalence of angle-closure glaucoma is as high or even higher than that of open-angle glaucoma(16,17,19-22). Therefore, angle-closure glaucoma has a considerable impact on daily clinical practice. Evalua-ting a large series of patients with primary angle closure (with and without glaucoma), we determined the most frequent underlying angle-closure mechanisms and the outcomes of laser treatment (both iridotomy and iridoplasty). To the best of our knowledge, the present study is the first to report on such findings in a large sample of Brazilian patients.

At this point, we believe it is important to discuss the clinical im-plications of our findings. Treatment of primary angle-closure is directed toward two goals: to eliminate the mechanism of angle closure and to control IOP elevation(14). Previous studies have shown that following LPI, approximately 20%-30% of these patients conti-nue to exhibit appositional angle closure in the presence of a patent iridotomy(1-3). In our study, we found a slightly higher success rate, as 86% of the eyes showed non-occludable angles following LPI. Although these differences may be the result of a lower prevalence of non-pupillary block mechanisms in our study population, we believe that age (the mean age of our study population was <60 years and, thus, the prevalence of lens-induced component was likely low) and the fact we excluded patients with >90° of PAS should be taken into consideration.

Although laser iridotomy is currently the first line of treatment, many eyes will continue to exhibit appositional angle-closure, and an additional treatment option may be necessary(2,3). In the present large consecutive series, ALPI was highly effective in eliminating re-sidual appositional angle closure caused by mechanisms other than pupillary block. In addition, we documented a 20% IOP reduction on average. Our results not only confirm the important role of ALPI in cases of plateau iris(8), but also suggest that it may be an effective alternative in cases involving lens-induced component. We believe that this is clinically meaningful, as not every case of lens-induced angle closure necessarily coexists with a symptomatic cataract. In fact, this appears to be the case of our study population, which is mostly composed of middle-aged patients. It is noteworthy that ALPI has also been successfully used as an initial treatment to break acute phacomorphic attacks(23). Regarding the few cases in which ALPI was not effective in our series, the proportion was similar between eyes with plateau iris and lens-induced component, and we could not identify any predictors of success or failure. As additional findings, our plateau iris patients tended to be women and younger than those with lens-induced component, and ALPI effectiveness was similar in both angle-closure mechanisms during an average follow-up period of almost one year.

We believe it is important to stress some specific characteristics and limitations of our study. First, our study is based on retrospective

data and had a relative short follow-up period. Therefore, success ra-tes, especially related to ALPI, may have been positively influenced. Second, a subjective gonioscopic criterion was adopted for each angle-closure mechanism. Moreover, ultrasound biomicroscopy images were available for most patients with persistent occludable angles following LPI, but not for every patient. These missing ultra-sound biomicroscopy data could have added useful information (such as anterior chamber depth measurements) to our results. Third, ideally, different examiners should have performed pre- and post-laser gonioscopic examinations. However, the present study was retros-pective, and each glaucoma specialist performed not only the laser procedure, but also baseline and post-laser gonioscopy assessments. This potential bias of data collection should be considered while in-terpreting our results. Fourth, although Brazil is a multiracial country, our patients were enrolled from just one center (in the city of Osasco, São Paulo). Therefore, our results may not be representative of the en-tire Brazilian population. However, it should be emphasized that São Paulo has a high rate of immigration and, as a result, its population is composed of individuals from all over the country.

In conclusion, our findings suggest that, in this population of Bra-zilian patients, several eyes with angle closure were not completely treated with LPI. In the present large series of middle-aged patients, plateau iris was the leading cause of persistent angle closure and was effectively treated with ALPI. A detailed eye examination with indentation gonioscopy should always be performed after LPI to rule out persistent angle closure due to non-pupillary block mechanisms.

RefeRenCeS 1. He M, Friedman DS, Ge J, Huang W, Jin C, Lee PS, et al. Laser peripheral iridotomy in

primary angle-closure suspects: biometric and gonioscopic outcomes: the Liwan Eye Study. Ophthalmology. 2007;114(3):494-500.

2. Thomas R, Arun T, Muliyil J, George R. Outcome of laser peripheral iridotomy in chronic primary angle closure glaucoma. Ophthalmic Surg Lasers. 1999;30(7):547-53.

3. Chandler PA. Narrow-angle glaucoma. Arch Ophthalmol. 1952;47(6):695-716. 4. Prata TS, Biteli LG, Dorairaj S. Angle closure associated with a cobblestone iris confi-

guration: clinical and imaging description. J Glaucoma. 2013;22(9):36-7. 5. Shabana N, Aquino MC, See J, Ce Z, Tan AM, Nolan WP, et al. Quantitative evaluation

of anterior chamber parameters using anterior segment optical coherence tomography in primary angle closure mechanisms. Clin Experiment Ophthalmol. 2012;40(8):792-801.

6. Tornquist R. Angle-closure glaucoma in an eye with a plateau type of iris. Acta Oph-thalmol (Copenh). 1958;36(3):419-23.

7. Prata TS, Dorairaj S, De Moraes CG, Tello C, Liebmann JM, Ritch R. Indentation slitlamp-adapted optical coherence tomography technique for anterior chamber angle assessment. Arch Ophthalmol. 2010;128(5):646-7.

8. Ritch R, Tham CC, Lam DS. Long-term success of argon laser peripheral iridoplasty in the management of plateau iris syndrome. Ophthalmology. 2004;111(1):104-8.

9. Ming Zhi Z, Lim AS, Yin Wong T. A pilot study of lens extraction in the management of acute primary angle-closure glaucoma. Am J Ophthalmol. 2003;135(4):534-6.

10. Gunning FP, Greve EL. Lens extraction for uncontrolled angle-closure glaucoma: long-term follow-up. J Cataract Refract Surg. 1998; 24(10):1347-56.

11. Sakata K, Sakata LM, Sakata VM, Santini C, Hopker LM, Bernardes R, et al. Prevalence of glaucoma in a South brazilian population: Projeto Glaucoma. Invest Ophthalmol Vis Sci. 2007;48(11):4974-9.

12. Nolan WP, Foster PJ, Devereux JG, Uranchimeg D, Johnson GJ, Baasanhu J. YAG laser iridotomy treatment for primary angle closure in east Asian eyes. Br J Ophthalmol. 2000;84(11):1255-9.

13. Cumba RJ, Nagi KS, Bell NP, Blieden LS, Chuang AZ, Mankiewicz KA, et al. Clinical outcomes of peripheral iridotomy in patients with the spectrum of chronic primary angle closure. ISRN Ophthalmol. 2013 26;2013:828972.

14. American Academy of Ophthalmology. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern Guidelines: Primary Angle Closure. San Francisco, Calif, USA: American Academy of Ophthalmology; 2010.

15. See JL, Aquino MC, Aduan J, Chew PT. Management of angle closure glaucoma. Indian J Ophthalmol. 2011;59 Suppl:S82-7.

16. Foster PJ, Johnson GJ. Glaucoma in china: how big is the problem? British Journal of Ophthalmology. 2001;85(11):1277-82.

17. Congdon N, Wang F, Tielsch JM. Issues in the epidemiology and population-based screening of primary angle-closure glaucoma. Surv Ophthalmol. 1992;36(6):411-23.

18. Day AC, Baio G, Gazzard G, Bunce C, Azuara-Blanco A, Munoz B, et al. The prevalence of primary angle closure glaucoma in european derived populations: A systematic review. Br J Ophthalmol. 2012;96(9):1162-7.

19. Quigley HA, Congdon NG, Friedman DS. Glaucoma in China (and worldwide): chan-

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ges in established thinking will decrease preventable blindness. Br J Ophthalmol. 2001;85(11):1271-2.

20. Shen SY, Wong TY, Foster PJ, Loo JL, Rosman M, Loon SC, et al. The prevalence and types of glaucoma in malay people: the Singapore Malay eye study. Invest Ophthal-mol Vis Sci. 2008;49(9):3846-51.

21. Tarongoy P, Ho CL, Walton DS. Angle-closure glaucoma: the role of the lens in the pathogenesis, prevention, and treatment. Surv Ophthalmol. 2009; 54(2):211-25.

22. Amerasinghe N, Zhang J, Thalamuthu A, He M, Vithana EN, Viswanathan A, et al. The heritability and sibling risk of angle closure in Asians. Ophthalmology. 2011;118(3): 480-5.

23. Tham CC, Lai JS, Poon AS, Chan JC, Lam SW, Chua JK, et al. Immediate argon laser pe-ripheral iridoplasty (ALPI) as initial treatment for acute phacomorphic angle-closure (phacomorphic glaucoma) before cataract extraction: a preliminary study. Eye (Lond). 2005;19(7):778-83.

XXII Curso Regional Pan-Americano de Oftalmologia

21 a 22 de março de 2015 Hard Rock Hotel

Cidade do Panamá - Panamá

informações: Site: http://www.paao.org/index.php?component=com_articles&id_art=90#registration

Original Article


InTRODUCTIOn Eye torsion can be measured both subjectively and objectively.

Sub jective measurement is obtained using the Maddox rod test, which corresponds to the patient’s perception of image torsion. Objec-ti ve measurement is performed using funduscopy or fundus photo-graphy (retinography)(1-5).

Superior oblique overaction is recognized by some authors as a major factor in the genesis of A-pattern and in the intorsion obser-ved in the fundus(6,7). Correction is obtained using superior oblique surgical weakening, which can be performed through the medial approach (lengthening, tenotomy(8) or Berke tenectomy(9)), or by the lateral approach to the superior rectus muscle (posterior partial te-nectomy(10), disinsertion(7), or tenectomy(11)). Procedures that weaken anterior fibers result in a greater excycloduction(6,7).

The cycloduction that results from weakening surgeries of the in ferior oblique muscle is widely reported in the literature(2,5,12,13). However, few studies have evaluated the torsional effect resulting from weakening procedures involving the superior oblique muscle. Sharma et al.(14) studied objective and subjective torsion variation in 15 patients with superior oblique overaction who underwent partial posterior tenectomy. Mean preoperative torsion was 6.46° ± 3.44° in

ABSTRACT Purposes: To objectively evaluate the torsional effect of the superior oblique muscle-weakening surgery using the tenectomy technique proposed by Souza-Dias. Methods: The present prospective study included 10 patients (20 eyes) with ho-rizontal strabismus, bilateral superior oblique overaction and A-pattern of 15 to 30 prism diopters who underwent superior oblique tenectomy. Objective assessment of ocular torsion was performed by retinography immediately before and one month after surgery. The amount of ocular torsion was determined by measuring the angle formed by a horizontal line drawn across the geometric center of the optic disc and a second line connecting this point to the fovea. Results: The median preoperative angle was 5.56° in the right eyes and -3.43° in the left eyes. The median postoperative angle was 1.84° in the right eyes and -3.12° in the left eyes. The angle variation was statistically significant in both eyes (p=0.012 and p=0.01, respectively). Conclusion: The present study suggests that superior oblique tenectomy has an extorter effect, decreasing the intorsion detected on overaction of this muscle.

Keywords: Strabismus; Oculomotor muscles; Torsion abnormality; Ophthalmologic surgical procedures/methods

RESUMOObjetivo: Avaliar, de forma objetiva, a torção ocular após a tenectomia do oblíquo superior, proposta por Souza-Dias.Métodos: Estudo prospectivo de dez pacientes (20 olhos) com estrabismo horizontal, hiperfunção bilateral dos oblíquos anisotropia em A de 15 a 30 dioptrias prismáticas,

submetidos à tenectomia bilateral dos oblíquos superiores. A avaliação objetiva da torção foi realizada com a retinografia antes e após a cirurgia, determinando-se o ângulo de torção formado entre a linha horizontal que passa pelo centro do disco óptico e a linha que passa pelo centro da fóvea. Resultados: A mediana dos ângulos de torção pré-operatória foi de 5,56° nos olhos direitos e de 3,43° nos esquerdos. Após a cirurgia, o ângulo mediano foi de 1,84° nos olhos direitos e de -3,12° nos esquerdos. Em ambos os olhos, a variação absoluta foi estatisticamente significativa (p=0,012/p=0,01).Conclusão: O presente estudo demonstrou que a tenectomia do oblíquo superior tem ação extorsora, reduzindo de forma significante a intorção encontrada nos casos de hiperfunção deste músculo.Descritores: Estrabismo/cirurgia; Músculos oculomotores; Anormalidade torcional; Procedimentos cirúrgicos oftalmológicos/métodos

the right eyes and 7.13° ± 2.56° in the left eyes. At the postoperative evaluation, the mean correction was found to be 0.06° ± 1.10° in the right eyes and 0.46° ± 0.91° in the left eyes. Roizen et al.(15) performed a subjective evaluation (Maddox rod test) of five patients with intorsion and diplopia who underwent superior oblique anterior tenectomy; the mean correction of torsion was 5.2°.

No studies were found that included an objective evaluation of the cycloduction obtained with superior oblique full tenectomy. The aim of the present study was to evaluate eye torsion after weakening surgery of the superior oblique muscle using the tenectomy techni-que proposed by Souza-Dias(11).

MeTHODS The protocol of the present study was approved by the Commit-

tee on Ethical Research of the Irmandade da Santa Casa de Misericór-dia Hospital of São Paulo (protocol #044/10). Informed consent was obtained from patients or their responsible caretaker before surgery.

A prospective study was performed that included 10 patients with strabismus and bilateral superior oblique overaction (2+-3+ in a scale of 1+-4+) whose surgical planning included bilateral superior

Measurement of ocular torsion variation following superior oblique tenectomyMedida da variação da torção ocular após a tenectomia do oblíquo superior

bruna lana ducca1,2, carloS raMoS de Souza-diaS3, aline criStina Fioravanti lui4, Mauro goldchMit1,2

Submitted for publication: February 6, 2014 Accepted for publication: September 12, 2014

Study conducted at Department of Ophthalmology, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.

1 Strabismus Section, Department of Ophthalmology, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.

2 Strabismus Section, Cema Hospital, São Paulo, SP, Brazil.3 Ophthalmology Department, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.4 Uveitis Section, Department of Ophthalmology, Santa Casa de Misericórdia de São Paulo, São

Paulo, SP, Brazil.



Corresponding author: Bruna Lana Ducca. Rua Brás Cardoso, 85/101 - São Paulo, SP - 04510-030 - Brazil - E-mail: [email protected]

Ducca BL, et al.


oblique tenectomy; in this technique proposed by Souza-Dias(11), 6 mm of the SO tendon was resected from its insertion. Patients with nystagmus, those who did not permit the performance of the retinography and/or those submitted to a previous eye surgery were excluded from the present study. The mean age of the study group was 21.3 years (range four to 28 years). Four patients were male (40%) and six were female (60%). Eight patients had esotropia (80%) and two had exotropia (20%).

All patients underwent ophthalmological examination that inclu-ded visual acuity measurement (Snellen table), cycloplegic refracto-metry, biomicroscopy, and fundus examination. Measurement of the deviation was performed using the alternate cover test with prisms for distance in the primary, superior and inferior positions, and for near. All had A-pattern varying from 15 prism diopters (PD) to 30 PD. The Titmus stereopsis test was performed and none of the patients recognized it. Fusion was also not detected. The same examiner, who was masked to the diagnosis and to the planned surgical procedure, performed all measurements.

Objective evaluation of eye torsion was performed by retinogra-phy one week before and one month after the surgery. Mydriasis was achieved with instillation of one drop of tropicamide 1% in each eye. The head of the patient was stabilized in the chin and forehead rests and eye height was regulated according to the markings in the reti-nographer. The examiner took care to observe that the patient’s head was straight while being photographed; however, no special head brace or leveling device was used. The patient was asked to look at the internal target of the instrument. With the help of a circle-shaped device on the screen of the instrument, the examiner established the position of the optic disc and of the macula in relation to the posterior pole, placing the fovea at the center of the device. The image obtai-ned was used to measure the torsion angle with a software applied in architecture, Autocad 2009® (Autodesk, Inc. San Rafael, California). Four lines were drawn tangent to the upper, medial, lower and lateral extremities of the optic disc, forming a rectangle, and two diagonal lines crossing the internal angles of the figure. This was the manner to determine the center of the disc, through which a horizontal line was drawn parallel to the upper and lower horizontal lines of the rectan-gle (Figure 1 A). Then, another line was drawn connecting the center of the optic disc to the center of the fovea, and the angle formed by the two lines was measured, which was called the “torsion angle” (Figure 1 B). The normal location of the fovea was considered to be between the center of the optic disc and a 7.25° angle below the ho-rizontal line that crosses the center, according to the study performed by Bixenman and Von Noorden(2). For the sake of convention, positive angles were established to be those located above the horizontal line that crosses the center of the optic disc, and negative angles were

those located below that line. Pre- and postoperative results were com pared. The examiner responsible for the performance of the measurements was blinded to the diagnosis or to the performance of a previous surgery.

The non-parametric Wilcoxon test as used for statistical analysis, for the purpose of comparing the values observed before and after the surgery for each patient. The test was applied separately in the right eye and in the left eye. The same test was applied to compare the right and the left eye for absolute variations observed between the values of the angles measured before and after the surgery. The significance level was established as 0.05 or 5%. Because the current study presented non-parametric data, medians were used.

ReSULTS Patients presented visual acuity with optical correction varying

from 20/30 to 20/20 in both eyes, and no changes were observed with regard to biomicroscopy and fundus examination.

There was a statistically significant difference (p<0.05) between the preoperative torsion angles in the right eyes and in the left eyes; thus, statistical analysis was performed separately for each eye. Table 1 shows the results of angle analyses, and figures 2 A, B, C, and D repre-sent an illustrative example of the results.

Despite the decrease in the angles, six of the 10 right eyes remai-ned in intorsion, three remained within the normal range (0° to 7.25°), and one presented extorsion (-13,16°). In the left eyes, three remained in intorsion, four presented extorsion (-8.29°, -9.19°, -15.80°, -16.86°) and three remained within normal limits.

The median A-pattern before surgery was 22.5 PD, and zero after surgery, indicating a mean correction of 22.5 PD (p=0.01). The change in superior oblique muscle overaction was statistically significant in both right and left eyes (p=0.01); however, there was no difference with regard to inferior oblique underaction (p=0.06/p=0.12).

There was no correlation between the values of A-pattern, supe-rior oblique overaction, inferior oblique underaction and the degree of preoperative torsion.

DISCUSSIOnObjective evaluation of eye torsion may be performed with fun-

duscopy and eye fundus photography; the latter has been shown to be effective for quantitative analysis of the angle between the fovea and the optic disc center in a study performed by Morton et al.(5).

In our study, patients were photographed in a primary gaze po -sition, in monocular vision, with a fixating gaze being photographed. According to Kushner et al.(3) there was no significant clinical diffe-

figure 1. A) Determination of the optic disc center: horizontal line crossing the intersection of the diagonal lines to the center of the optic disc. B) Torsion angle between the centers of the fovea and of the optic disc.

A B

Measurement of ocular torsion variation following superior oblique tenectomy


Table 1. Patients submitted to bilateral tenectomy of the superior oblique muscle (SO) according to the A-pattern, SO overaction, inferior oblique underaction values, to the torsion angles measured in degrees in the pre and postoperative periods, and according to the absolute variation values of these anglesRight eyes Pre-operative Post-operativepatients A (Δ) SO IO Torsion angle A (Δ) OS IO Torsion angle Torsion angle variation01 25 +1 0 4.31 -15 -1.5 +2 -13.16 17.47

02 20 +2 0 4.87 0 0 0 -1.57 6.44

03 25 +3 0 7.57 0 0 0 4.22 3.35

04 20 +2 -1.5 11.53 13 +2 -1 6.78 4.75

05 30 +1 -2 11.83 0 0 0 2.64 9.19

06 25 +3 -2.5 19.36 0 0 0 5.97 13.39

07 30 +3 -3 1.36 -5 +3 -1.5 -3.61 4.97

08 20 +2 -2 4.05 5 +1 -1 1.04 3.01

09 15 +1.5 0 -2.82 -12 +1 0 -6.59 3.77

10 15 +1.5 0 6.26 0 +1 0 3.75 2.61

Median 22.5 +2 -0.75 5.56 0 0.5 1.84 4.86

P 0.012

Left eyes Pre-operative Post-operativepatients A (Δ) SO IO Torsion angle A (Δ) OS IO Torsion angle Torsion angle variation01 25 +2 0 7.21 -15 +2 0 -15.80 23.01

02 20 +2 0 1.43 0 0 0 -8.29 9.72

03 25 +3 0 0.66 0 0 0 -1.50 2.16

04 20 +2 0 8.43 13 +1 0 2.65 5.78

05 30 +2 -2 10.61 0 0 0 -1.48 12.09

06 25 +3 -2.5 2.53 0 0 0 -4.73 7.26

07 30 +3 -3 -3.43 -5 +1 0 -9.19 5.76

08 20 +2 -2 -1.51 5 +1 -1 -16.86 15.30

09 15 +2 0 5.91 -12 0 0 1.29 4.62

10 15 +1.5 0 4.33 0 +2 0 2.23 2.10

Median 22.5 +2 0 3.43 0 -3.12 6.52

P 0.01

A= A-pattern in prism dioptries; OS= superior oblique muscle action (+= over; -= underaction); IO= inferior oblique muscle (+= over; -= underaction); Preop= preoperative; Postop= postope-rative; (-)= angles above the horizontal line that crosses the optical disk center; values without a signal mean that the angles are below that line. Wilcoxon Test; p= statistical significance (<0,05).

figure 2. A) Right eye: preoperative torsion angle. B) Left eye: preoperative torsion angle. C) Right eye: postoperative torsion angle. D) Left eye: postoperative torsion angle.

A

C

B

D

Ducca BL, et al.


rence when the photograph was taken with the contralateral eye looking at the external target. Consequently, objective torsion may be studied with either of the eyes looking fixedly at a target.

The Maddox rod test was not performed in the present study because the subjective test results may show absence of torsion due to sensorial adaptations, even if objective tests show changes in eye torsion(9,12,16-18). This is because spatial adaptation offsets the torsion of the image, particularly in patients with congenital torsion alterations or changes acquired very early in life(18).

Among superior oblique weakening techniques, those perfor-med medially to the superior rectus provide greater effect compared with the lateral approach technique, and may cause complications such as superior oblique palsy(6). Scleral disinsertion and tenectomy performed laterally to the superior rectus are the preferred techni-ques for small and medium overactions of the superior oblique(9). In our study, patients had bilateral superior oblique overaction, varying from 2+ to 3+, and the technique used was tenectomy, performed laterally to the superior rectus(11) in both eyes, which acts on both anterior and posterior fibers, thus reducing intorsion. This procedure did not involve risk of permanent diplopia, although some patients ended up with significant excyclotorsion and inferior oblique overac-tion, since no patients exhibited stereopsis or fusion.

Before surgery, the ocular torsion angles varied from 0.66° to 19.36° above the horizontal line that crosses the geometric center of the optic disc, which is a sign of intorsion according to the study performed by Bixenman and Von Noorden(2), who found that the normal location of the fovea is between the center of the optic disc and a 7.25° angle below the center. As we considered the angles below the horizontal line that crosses the center of the optic disc to be negative, normal values for the position of the fovea are between zero and -7.25°; extorsion is present when the angle is greater than that value. Bixenman and Von Noorden(2) also established the normal position of the fovea, located at one-third of the disk diameter below the horizontal line that crosses the optic disc center, creating a mean angle of 7.25° with that line. Guyton(12) described a grading method that classifies the torsion with respect to the optic disc divided into eight parts. In this case, the normal position of the fovea is located 9° below the optic disc center, which corresponds to the union between the central and the lower thirds.

Our results show that full superior oblique tenectomy acted as an extorsional surgery on the torsion fibers of this muscle, as all of the eyes exhibited a statistically significant difference between the angles before and after surgery. Even eyes that remained in intorsion after surgery were considerably extorted after the tenectomy; for example, the right eye of patient 6 presented a torsion angle variation of 13.39°; however, considering that the final angle was 5.97°, it still remained in intorsion. The mean correction of intorsion was 4.86° and 6.52° in the right and left eyes, respectively; these results are similar to those obtained by Roizen et al.(15), who found that anterior fibers te-nectomy corrected 5.2° of intorsion. Sharma et al.(14), in turn, showed that the posterior tenectomy technique did not change eye torsion, with non-statistically significant postoperative results (p=0.81 in the right eye and p=0.09 in the left eye), and concluded, therefore, that selective weakening of posterior fibers of the superior oblique mus-cle only affects the functions of downgaze and abduction of the eye.

In our study, there was considerable variation in surgical torsion changes. This could be correlated with the severity of pre-operative torsion; however, if patient 1 (right eye: pre-operative torsion angle +4.31, post-operative torsion angle -13.16; variation: 17.47) is compa-red with patient 6 (right eye: pre-operative torsion angle +19.36, post-o perative torsion angle +5.97; variation: 13.39), the former hypothesis becomes invalid. This variation may be due to the lack of knowledge of the position of reinsertion of the tendon after tenecto-my. According to Souza-Dias and Prieto-Diaz(7), the closer to the tro chlea the superior oblique weakening is performed, the greater the effect. If the tendon is sectioned adjacent to the medial margin of the superior rectus, the weakening effect is smaller. In addition, there are other, unknown factors in the creation of A-patterns that may be related to this variation.

The present study was limited by a small sample size. In addition, it would be interesting to consider a longer follow-up period in future studies.

In conclusion, superior oblique tenectomy caused a mean ex-torsion of 4.86° (p=0.12) in the right eyes and 6.52° (p=0.1) in the left eyes, thus reducing the incycloduction observed with overaction of this muscle.

RefeRenCeS 1. Felius J, Locke KG, Hussein MA, Jr DRS, Stager DR. Photographic assessment of chan-

ges in torsional strabismus. JAAPOS. 2009;13(6):593-5. 2. Bixenman WW, Von Noorden GK. Apparent foveal displacement in ciclotropia.

Ophthalmology. 1982;89(1):58-63. 3. Kushner BJ, Hariharan L. Observations about objective and subjective ocular torsion.

Ophthalmology. 2009;116(10):2001-9. 4. Kushner BJ: Effect of ocular torsion on A and V patterns and apparent oblique muscle

overaction. Arch Ophthalmol. 2010;128(6):712-18. 5. Morton GV, Lucchese N, Kushner BJ. The role of fundoscopy and fundus photography

in strabismus diagnosis. Ophthalmology. 1983;90(10)1189-92. 6. Prieto-Diaz J, Souza-Dias C. Estrabismo. 4th ed. São Paulo: Santos; 2002. 7. Souza-Dias C. Coleção de manuais básicos CBO/Estrabismo. São Paulo: Cultura Mé-

dica;1999. 8. Berke RN. Tenotomy of the superior oblique muscles for hypertropia. Arch Ophthal-

mol. 1947;38(5):605-44. 9. Scott WE, Jampolsky J, Redmond MR. Superior oblique tenotomy: indications and

complications. Int Ophthalmol Clin. 1976;16(3):151-9. 10. Prieto-Diaz J. Posterior tenectomy of the superior oblique. J Pediatr Ophthalmol Stra-

bismus. 1979;16(5):321-3. 11. Souza-Dias C. Full tenectomy of the superior oblique muscle close to the scleral

insertion for the correction of “A” anisotropia. Proceedings of the Fifth Meeting. ISA-V-Rome. 1986. p.429-36.

12. Guyton DL. Clinical assessment of ocular torsion. Am Orthoptic J. 1983;33:7-15. 13. Santiago AP, Isenberg SJ, Apt L, Roh YB. The effect of anterior transposition of the

inferior oblique muscle on ocular torsion. JAAPOS. 1997;1(4):191-6. 14. Sharma P, Saxena R, Rao BV, Menon V. Effect of posterior tenectomy of the superior

oblique on objective and subjective torsion in cases of superior oblique overaction. J Pediatr Ophthalmol Strabismus. 2005;42(5):284-9.

15. Roizen A, Velez FG, Rosenbaum AL: Superior oblique anterior tenectomy. JAAPOS. 2008;12(1):54-7.

16. Guyton DL. Ocular torsion reveals the mechanisms of cyclovertical strabismus - the Weisenfeld Lecture. Invest Ophthalmol Vis Sci. 2008;49(3):847-57.

17. Gobin MH. Desinsertion of the superior oblique in “A” pattern strabismus. Doc Oph-thal mol. 1997;44(1):193-202.

18. Von Noorden GK. Binocular vision and ocular motility. St Louis: Mosby; 2002.

Original Article


InTRODUCTİOnThe tilted optic disc is a congenital, nonhereditary condition in

which the optic nerve enters the eye at an oblique angle. Its preva-lence has been reported to be 1%-2% in the general population(1). In clinical practice, the diagnosis of tilted disc is based on ophthalmos-copic appearance. Clinically, tilted discs appear as an exaggerated oval or D-shaped optic nerve head with one hemisphere of the disc more elevated than the contralateral half(2). The elevated margin of the disc is usually adjacent to an intact neurosensory retina, pigment epithelium, and choroid and the depressed portion of the disc is commonly associated with a thinned choroid and thinned retinal pigment epithelium (RPE) that may be visible as fundus depigmen-tation on ophthalmoscopic evaluation(3-5).

The most common form of optic disc tilt consists of superotemporal rim elevation, often with inferonasal depression(5). Subretinal neovas-cularization and chorioretinal degenerative changes in the tilted disc syndrome have been reported(6-8).

ABSTRACTPurpose: This study was performed to evaluate the retinal nerve fiber layer (RNFL) and peripapillary choroidal thickness in eyes with tilted optic disc in order to identify characteristic RNFL and peripapillary choroid patterns verified by optical coherence tomography (OCT). Method: Twenty-nine eyes of 29 patients with tilted optic discs were studied with spectral-domain (SD)-OCT and compared with age and sex-matched control subjects in a prospective design. The imaging of RNFL was performed using circular scans of a diameter of 3.4 mm around the optic disc using OCT. For measurements of peripapillary choroidal thickness, the standar d protocol for RNFL assessment was performed. Results: SD-OCT indicated significantly lower superotemporal (p<0.001), supe-ronasal (p=0.001), and global (p=0.005) RNFL thicknesses in the tilted disc group than those of the control group. Peripapillary choroid was significantly thicker at the site of the elevated rim of eyes with tilted disc (p<0.001). Conclusions: This study demonstrated a clinical characterization of the main tilted disc morphologies that may be helpful in differentiating a tilted disc from other altered disc morphologies. Further studies are recommended to study the comparison between glaucoma and tilted disc groups.

Keywords: Choroid/pathology; Nerve fibers; Tomography, optical coherence; Optic disc/abnormalities

RESUMOObjetivo: Avaliar camada de fibras nervosas da retina (RNFL) e a espessura da coroide peripapilar em olhos com disco óptico inclinado a fim de identificar as características da RNFL e os padrões de coroide peripapilar verificados pela tomografia de coerência óptica (OCT ). Método: Vinte e nove olhos de 29 pacientes com discos ópticos inclinadas foram estudados prospectivamente com OCT de domínio espectral (SD) e comparados com controles pareados por sexo e idade. As imagens da RNFL foi obtidas por meio de varreduras circulares com um diâmetro de 3,4 mm em torno do disco óptico usando OCT. Para as medições de espessura da coroide peripapilar, o protocolo padrão para avaliação da RNFL foi realizado. Resultados: O OCT SD indicou diminuição das espessuras significativas da RNFL superotemporal (p<0,001), superonasal (p=0,001), e global (p=0,005) no grupo disco inclinado em relação aos do grupo controle. A coroide peripapilar foi significativamente mais espessa no local da borda elevada dos olhos com disco inclinado (p<0,001). Conclusões: Este estudo demonstrou que a caracterização clínica das principais morfologias disco inclinado pode ser útil na diferenciação entre um disco inclinado de outras alterações morfológicas de disco. Seria importante a comparação entre grupos com glaucoma e com discos inclinados, estudos futuros.

Descritores: Coroide/patologia; Fibras nervosas; Tomografia de coerência óptica; Disco óptico/anormalidades

In most of the cases, RNFL thickness was found to be thinned on the sectors close to the elevated disc rim. Many studies have discus-sed altered RNFL patterns in cases of tilted disc, but the results did not reflect the same results. Law et al.(9) found significant lower RNFL in eyes with tilted optic disc, whereas Rauscher et al.(10) found no as-sociation between optic disc tilt and RNFL. Controversially, the study by Hwang et al.(11) using a Cirrus HD OCT found a significantly thicker RNFL in eyes with tilted disc.

The characteristics of tilted optic disc make the diagnosis and mo-nitoring of glaucoma difficult due to the similarities with glaucoma-tous discs. Moreover, tilted disc is associated with visual field defects, which also leads to diagnostic difficulties.

With the advent of OCT, all retinal layers can now be measured objectively, and the technique is widely used to assess the status of the RNFL in patients with glaucoma and other optic neuropathies(12). Spai-de et al. recently described a technique (enhanced depth imaging) in which SD-OCT was used to measure choroidal thickness(13).

Evaluation of peripapillary choroidal and retinal nerve fiber layer thickness in eyes with tilted optic discAvaliação espessura da camada de fibras nervosas peripapilares da retina e coroide em olhos com disco óptico inclinado

MuaMMer ozciMen1, yaSar Sakarya1, Sertan goktaS1, rabia Sakarya1, iSMail S. ivacik1, halil i. yener2, erkan erdogan1

Submitted for publication: April 10, 2014 Accepted for publication: September 18, 2014

Study conducted at Konya Training and Research Hospital, Konya, Turkey.1 Department of Ophthalmology, Konya Training and Research Hospital, Konya, Turkey.2 Konya Eye Clinic, MD, Konya, Turkey.



Corresponding author: Muammer Ozcımen. Konya Egitim ve Arastirma Hastanesi - Goz Klinigi - Meram/Konya 42090 - Turkey - E-mail: [email protected]

Approved by the following Research Ethics Committee: Selcuk University, Faculty of Medicine, Konya, Turkey (2013/373).

Ozcımen M, et al.


Our aim was to study RNFL and peripapillary choroidal thickness in individuals with tilted disc and compare the values obtained from the control group in order to identify characteristic RNFL and choroi-dal thickness patterns.

MeTHODSThis prospective study included 35 eyes of 35 patients with tilted

disc syndrome (14 men and 21 women). Records from the Ophthal-mology Department at Konya Training and Research Hospital were scanned. Patients who were diagnosed with tilted optic disc were invited to participate in the study from December 2013 to February 2014. The control group included 29 eyes of 29 age- and sex-matched control subjects. All patients underwent a complete ophthalmic exa-mination including slit-lamp biomicroscopy, Goldman applanation tonometry, color vision test (Ishihara test), fundoscopy, optic disc photograph imaging and computerized perimetry. Subjects were evaluated by a 24.2 program with SITA standard algorithm of the Humprey Visual Field analyser II model 750i (Humphrey Instruments, San Leandro, CA, USA). Only the reliable visual field parameters (fi-xation loss, <20%; false positive rate, <33%; and false negative rate, <33%) were included in the study. Global indices (mean deviation [MD] and pattern standard deviation [PSD]) were evaluated. Tilted disc cases underwent two reliable visual fields, with a minimum time in-terval of 1 month, and control cases received only one reliable visual field test after the perimetric learning effect.

Best-corrected visual acuity (BCVA) was measured by means of the standard Snellen chart. The values of visual acuity were converted to the logMAR scale for statistical analysis. Exclusion criteria included history of glaucoma and intraocular trauma, optic neuropathy, axial length measurement other than 22-26 mm and a spherical equiva-lent higher than -6.00 D. Subjects with unstable and uncontrolled

cardiovascular, renal or pulmonary diseases, diabetes and pregnancy were also excluded. A tilted disc was defined as anteroposterior rotation (tilt) and sagittal plane rotation (torsion) based on a review of tilted disc syndrome by Witmer et al.(2). These characteristics were easily evaluated by fundoscopy or optic disc photographs.

Choroidal thickness measurements were performed using an SD-OCT device (λ=870 nm, 40000A-scans/s and 3.9 μm axial resolu-tion) with software version 5.3 (Spectralis; Heidelberg Engineering, Heidelberg, Germany). RNFL imaging was performed using circular scans of a diameter of 3.4 mm around the optic disc. The scans were well centered at the optic nerve head. Spectralis OCT included RNFL thickness in six sectors: nasal (N), superonasal (NS), superotemporal (TS), temporal (T), inferotemporal (TI) and inferonasal (NI), as well as global RNFL thickness (G) (Figure 1).

For measurements of peripapillary choroidal thickness, a 360-de-gree 3.4 mm diameter peripapillary circle scan was performed using the standard protocol for RNFL assessment. Choroidal thickness was measured manually from the outer portion of the hyperreflective line corresponding to the RPE to the inner surface of the sclera (Figure 2). Peripapillary choroidal thicknesses adjacent to the elevated disc rim and the depressed sector directly opposite to the elevated disc rim were evaluated. In the control group, measurements were taken of the superotemporal and inferonasal peripapillary choroidal thickness in which the superotemporal choroid region corresponded to the choroid adjacent to elevated disc rim in the tilted disc group and the inferonasal choroid corresponded to the choroid adjacent to the depressed disc rim, which is directly opposite the elevated disc rim location, in the tilted disc group (Figure 1). The choroid was measured by two independent graders (MO, SI) using the tools found on the Spectralis OCT analysis software. The intraclass correlation coeffi-cients for overall peripapillary choroidal thickness were used to assess agreement between both graders.

TS= superotemporal; NI= inferonasal.

figure 1. Inferior nasal crescent and superotemporal disc rim elevation with loss of superior retinal nevre fiber layer thickness verified in OCT.

Evaluation of peripapillary choroidal and retinal nerve fiber layer thickness in eyes with tilted optic disc


The study was conducted under a protocol approved by the Konya Selcuk University Medical Faculty Ethics Committee and was in accor-dance with the ethical standards stated in the 1964 Declaration of Helsinki. Informed consent was obtained from all the patients after explanation of the procedures.

All statistical analysis of the data were performed using commer-cial software (Statistical Package for Social Science, version 15.0; SPSS Inc., Chicago, IL, USA). Statistical analysis was performed by using the Independent t-test (parametric). Pearson correlation coefficient was used to evaluate the correlation between the RNFL thickness and the global indices of visual field. Results were considered statistically significant when p<0.05. Results are represented as mean ± SD.

ReSULTSThe recordings of 35 patients were assessed and six were exclu-

ded from the study. Four cases were excluded because the sclera was invisible in OCT, and two cases were excluded due to unreliability for visual field analysis. A total of 58 subjects were included in the study. The tilted disc group included 29 eyes of 29 individuals, aged between 19 and 67 years (mean age, 45.3 ± 13.2). The control group included 29 eyes of 29 individuals aged between 21 and 64 years (mean age, 48.3 ± 12.1).

Fundus examination in all eyes showed the existence of tilted optic disc with mainly inferior nasal crescent (Figure 1). The most common form of tilted disc we found was superotemporal rim eleva-tion (n=17, 58.6%), followed by temporal rim elevation (n=7, 24.1%). None of our cases had evident posterior staphylomas on fundoscopic examination.

Mean best-corrected visual acuity was 0.15 ± 0.13 logMAR for the tilted disc group and 0.08 ± 0.06 logMAR for the control group. The axial length value for the tilted disc group was 25.1 ± 2.3 mm and 24.8 ± 3.4 mm for the control group. There were no differences between the tilted disc and control groups in regard to mean BCVA and axial lenght (p=0.09 and p=0.087, respectively). The mean sphe-rical equivalent for the tilted disc group was -1.94 ± 2.56 D, whereas the control group mean was -0.86 ± 1.96 D (p=0.076). All patients had normal color vision.

The RNFL thickness analysis showed that the superotemporal and superonasal sectors were significantly thinner in the tilted disc group than those of the control group (p<0.001 and p=0.001, respectively; Table 1). The RNFL thickness of the nasal sector was significantly higher in the tilted disc group (p=0.013); however, the global RNFL was signi-ficantly lower in the tilted disc group (p=0.005).

Peripapillary choroidal thicknesses are presented in table 2. The analysis showed that the mean choroidal thickness next to the eleva-ted disc rim was 193.75 ± 37.87 µm and the mean choroidal thickness opposite this location was 125.48 ± 24.68 µm; the difference was statistically significant between these topographical regions in the same eye (p<0.001). The control group had a mean superotemporal peripapillary choroidal thickness of 209.37 ± 27.98 µm and an infe-ronasal choroidal thickness of 198.34 ± 17.08 µm; the difference was not significant between these topographical regions in the same eye

(p=0.075). There was no significant difference in superotemporal cho-roidal thickness between the tilted disc and control groups (p=0.079); however, inferonasal choroidal thickness was significantly lower in the tilted disc group (p<0.001).

Eighteen eyes (62%) presented visual field defects, most frequen-tly found on the superotemporal quadrant (n=10), whereas 11 eyes had normal visual fields. There was generalized reduction in retinal sensitivity in all quadrants. Visual field analysis revealed a pattern standard deviation (PSD) of 4.20 ± 1.47 for the tilted disc group, which was significantly higher (p<0.001) than the control group (1.65 ± 0.60). Mean deviation (MD) was significantly lower (p<0.001) in the tilted disc group than the control group, with a mean value of -7.09 ± 3.45, whereas the control group had a MD of -2.63 ± 1.29. There was no significant correlation (correlation coefficient, p value) for MD and the RNFL thicknesses at all quadrants except TI (0.373, p=0.046) and for PSD and the RNFL thicknesses at all quadrants except TI (0.458, p=0.013). There was a significant correlation for PSD the global RNFL thickness (0.428, p=0.020).

Regarding the manual measurement of peripapillary choroidal thickness, the intraclass correlation coefficients showed agreement between the two observers (p<0.001) and ranged from moderate (0.67, next to the elevated disc rim) to very high (0.96, superotemporal).

DİSCUSSİOnThis study used SD-OCT to demonstrate that tilted optic disc is

asso ciated with abnormal patterns of both peripapillary RNFL and choroidal thickness. The most common form of tilted disc in our stu-dy was inferonasal disc rotation with superotemporal rim elevation, which is similar to previous reports(1,5,14). We found that a significant difference exists in the choroidal thickness between the elevated and depressed sectors of the optic disc, in which there is a thinner cho -roid next to the depressed part of the disc. Furthermore, we found that eyes with inferior tilted disc show superior RNFL defects when analyzed by OCT imaging. We also confirmed that global RNFL was significantly lower in the tilted disc group. These findings show that OCT technology may be more sensitive for the detection of RNFL defects in abnormal optic disc morphologies.

The choroid inferior to the optic disc and the choroid nasal to the macula were reported to be thinner than all other sectors, and those variations were attributed to the natural anatomical architecture of normal eyes(15). This regional difference observed in choroidal thickness may be imputable to the development of the eye. Evidence from embryology indicates that the optic fissure is located in the inferior aspect of the optic cup, which is the last part of the globe to close during eye formation. A thinner choroid may be important because it may make this area more susceptible to retinal and choroidal disea-ses(15). This idea is favored by eyes with glaucoma wherein the choroid was reported to be thinner and the observation of more severe field defects in the thinner hemifield in glaucomatous eyes(16). Reported disorders such as subretinal neovascularization and chorioretinal de-generative changes in the tilted disc syndrome(3) may be associated with thinner choroid next to the depressed part of the optic disc. It

CTER= peripapillary choroidal thickness adjacent to elevated disc rim; CTDR= peripapillary choroidal thickness adjacent to depressed disc rim.

figure 2. Peripapillary choroidal thickness image showing thinner choroid in the inferior sector of the optic disc.

Ozcımen M, et al.


is unclear why the choroid is thinner in the discoloration area than in the other quadrants. However, it may correspond to the absence of retinal pigment epithelium and photoreceptors and attenuation of the choroid(17).

Brito et al.(14) reported that the most common RNFL defect was lo cated on the superotemporal sector of the Spectralis OCT, and the most commonly involved perimetric quadrant was also supero-temporal. They speculated that this was the opposite of what would be expected. We likewise found superotemporal visual field defects in cases with superotemporal RNFL defect; however, the results of analysis of correlations between MD and PSD were not completely consistent. We therefore concluded that visual field defects in indivi-duals with tilted optic disc might be multifactorial in origin. Further-more, it would be beneficial to study visual fields and document the factors influencing the test parameters in subjects with tilted optic disc.

In this study, OCT examination found that RNFL thickness was significantly thinned in the superior quadrant in patients with tilted disc syndrome. This may be attributed to the fact that the density of nerve fibers entering the optic disc in tilted disc syndrome is lower in this sector(18).

The differences may be due to hypoplasia associated with tilted disc. There is little knowledge regarding the underlying etiology of the embryonic aberrations(19). Simon et al.(20) reported that intraute-rine injury to the retina, optic nerve, chiasm or posterior visual pa-thway may cause hypoplasia of the optic nerve. Similarly Apple et al.(5) speculated that localized absence of ganglion cells and their failure to make synaptic connections in the lateral geniculate body might result in hypoplastic development of other supportive tissue. Consequently, the disc becomes tilted because of the imbalance in the number of ganglion cells and supportive tissue within the optic nerve. In addition, when the visual fields of eyes with tilted optic disc were compared to control groups, there was generalized reduction in retinal sensitivity in all quadrants(21). This generalized reduction in sensitivity has lead to the opinion that tilted disc may represent a diffusely hypoplastic optic nerve(22).

It is an uneasy issue whether a patient with tilted disc and ocular hypertension has glaucomatous optic neuropathy and RNFL dama-ge. A commonly observed problem with tilted disc is the detection of early glaucomatous damage. Both are associated with visual

field defects, and tilted disc morphology is a finding in optic disc rim eva luation; its presence makes identification of the usual signs of glaucomatous damage, such as pathological cupping, difficult to detect(23,24). We may say that the presence of a small visual field defect in a patient with an inferior tilted disc and superior RNFL loss is most probably related to tilted disc morphology instead of glaucomatous optic neuropathy; however, this argument needs to be proven by large-scale studies comparing visual fields in both glaucoma and til-ted disc groups. In addition to clinical examination, realization of OCT in conjunction with perimetry can help in the diagnosis and monito-ring of glaucoma in cases of concomitant optic disc tilt. OCT appears to have the ability to distinguish normal from glaucomatous optic nerve heads, but it is not clear that these findings can be generalized to tilted disc and glaucoma(25). Witmer et al.(2) partly supported this notion as they reported that new technologies for imaging the optic nerve head and RNFL currently had a limited role in diagnosing and monitoring tilted disc. There could be OCT error due to the abnormal anatomy of the nerve, as tilted discs can mimic other conditions; however, this diagnostic error is best prevented by clinicians who are familiar with the clinical manifestations of the anomaly. Nevertheless, in a study of patients with glaucoma and tilted discs, OCT was shown to be accurate in measuring the RNFL thickness and corresponded well to Humphrey visual field defects(26).

Eyes with tilted discs were more miopic than controls. However, none of our cases had evident posterior staphylomas on fundoscopic examination. Furthermore, we recruited cases with a spherical equi-valent lower than 6.00 D of myopia to reduce the possible effects of myopic chorioretinopathy on peripapillary RNFL. To avoid RNFL changes due to mechanical tissue stretching, we included cases with an axial length measurement within a certain range (22-26 mm).

OCT imaging of the optic nerve head and RNFL rely on validated normative data; however, validated normative datasets for tilted disc do not currently exist. Therefore, considering these data, imaging the optic disc with OCT could be a limitation of our study.

This study demonstrated a clinical characterization of the main tilted disc morphologies that may be helpful in differentiating a tilted disc from other altered disc morphologies. Additionally, the presence of optic disc tilt should be taken into account when interpreting peripapillary RNFL and choroidal thicknesses by SD-OCT. It would be beneficial to explore the comparison between glaucoma and tilted disc groups in additional studies.

ACKnOWLeDGMenTSThe authors thank Mehmet Yemenici and Zehra Yalcin for techni-

cal assistance in obtaining OCT images

RefeRenCeS 1. Young SE, Walsh FB, Knox DL. The tilted disc syndrome. Am J Ophthalmol. 1976;82(1):

16-23. 2. Witmer MT, Margo CE, Drucker M. Tilted optic disks. Surv Ophthalmol. 2010;55(5):403-28. 3. Giuffre G. Chorioretinal degenerative changes in the tilted disc syndrome. Int Oph-

thalmol. 1991;15(1):1-7. 4. Stur M. Congenital tilted disc syndrome with parafoveal subretinal neovascularization.

Am J Ophthalmol. 1988;105(1):98-9. 5. Apple DJ, Rabb MF, Walsh PM. Congenital anomalies of the optic disc. Surv Ophthalmol.

1982;27(1):3-41. 6. Prost M, DeLaey JJ. Choroidal neovascularization in tilted disc syndrome. Int Ophthal-

mol.1988;12(2):131-5. 7. Leys AM, Cohen SY. Subretinal leakage in myopiceyes with a posterior staphyloma

or tilted disc syndrome. Retina. 2002;22(5):659-65. 8. Moschos MM, Margetis I, Papadimitriou S, Tzeni Z, Moschos MN. Clinical and multifo-

cal-electroretinographic findings of congenital tilted disc syndrome associated with choroidal neovascularization: a case report. Doc Ophthalmol. 2007;115(2):121-4.

9. Law SK, Tamboli DA, Giaconi J, Caprioli J. Characterization of retinal nerve fiber layer in nonglaucomatous eyes with tilted discs. Arch Ophthalmol. 2010;128(1):141-2.

10. Rauscher FM, Sekhon N, Feuer WJ, Budenz DL. Myopia affects retinal nerve fiber layer measurements as determined by optical coherence tomography. J Glaucoma. 2009; 18(7):501-5.

Table 1. RnfL thickness: tilted disc and control group

SD-OCT RnfL (µm)Tilted disc group

(n=29)Control group

(n=29) Significance

Superotemporal 109.24 ± 09.98 126.44 ± 09.45 p<0.001

Superonasal 085.37 ± 13.34 106.68 ± 09.99 P=0.001

Inferonasal 113.72 ± 08.87 118.24 ± 12.27 p=0.114

Inferotemporal 129.27 ± 15.36 133.72 ± 13.25 p=0.243

Temporal 067.10 ± 09.67 071.58 ± 10.19 p=0.091

Nasal 081.44 ± 09.48 074.82 ± 10.20 p=0.013

Global 087.62 ± 10.37 096.06 ± 11.44 p=0.005

Table 2. Average peripapillary choroidal thickness (µm)

Sectors Tilted disc group Control group p-value

Superotemporal (CTER) 193.75 ± 37.87 209.37 ± 27.98 p=0.079

Inferonasal (CTDR) 125.48 ± 24.68 198.34 ± 17.08 p<0.001

p-value p<0.001 p=0.075

CTER= peripapillary choroidal thickness adjacent to elevated disc rim; CTDR= peripapillary choroidal thickness adjacent to depressed disc rim.

Evaluation of peripapillary choroidal and retinal nerve fiber layer thickness in eyes with tilted optic disc


11. Hwang YH, Yoo C, Kim YY. Characteristics of peripapillaryretinal nerve fiber layer thickness in eyes with myopic optic disctilt and rotation. J Glaucoma. 2012;21(6):394-400.

12. Pasol J. Neuro-ophthalmic disease and optical coherence tomography: glaucoma look alikes. Curr Opin Ophthalmol. 2011;22(2):124-32.

13. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146(4):496-500.

14. Brito PN, Vieira MP, Falcao MS, Olinda FS, Fernando RF. Optical coherence tomography study of peripapillary retinal nerve fiber layer and choroidal thickness in eyes with tilted optic disc. J Glaucoma. 2013 Feb 19 [Ahead of print].

15. Tanabe H, Ito Y, Terasaki H. Choroid is thinner in inferior region of optic disks of normal eyes. Retina. 2012;32(1):134-9.

16. Yin ZQ, Vaegan, Millar TJ, Beaumont P, Sarks S. J Glaucoma. Widespread choroidal insufficiency in primary open-angle glaucoma. 1997;6(1):23-32.

17. Dorrell D. The tilted disc. Br J Ophthalmol. 1978;62(1):16-20. 18. Moschos MM, Triglianos A, Rotsos T, Papadimitriou S, Margetis I, Minogiannis P, et al.

Tilted disc syndrome: an OCT and mfERG study. Doc Ophthalmol. 2009;119(1):23-8. 19. Giuffre G. Hypothesis on the pathogenesis of the papillary dysversion syndrome. J Fr

Ophtalmol. 1985;8(8-9):565-72.

20. Simon J, Aaby A, Drack A. Optic nerve hypoplasia. In: American Academy of Ophthal-mology, Basic and Clinical Science Course, Section 6, Pediatric Ophthalmology and Strabismus. San Francisco: AAO; 2008-2009. p.362-3.

21. Gurlu VP, Alimgil ML, Benian O. Topographical analysis of the visual field in tilted disk syndrome. Retina. 2002;22(3):366-8.

22. Tay E, Seah SK, Chan SP, Lim AT, Chew SJ, Foster PJ, et al. Optic disk ovality as an index of tilt and its relationship to myopia and perimetry. Am J Ophthalmol. 2005;139(2):247-52.

23. Brazitikos PD, Safran AB, Simona F, Zulauf M. Threshold perimetry in tilted disc syn-drome. Arch Ophthalmol. 1990;108(12):1698-700.

24. Vuori ML, Mantyjarvi M. Tilted disc syndrome may mimic false visual field deteriora-tion. Acta Ophthalmol. 2008;86(6):622-5.

25. Medeiros F, Zangwill L, Bowd C, Weinreb RN. Comparison of the GDx VCC scanning laser polarimeter, HRT II confocal scanning laser ophthalmoscope, and stratus OCT optical coherence tomography for the detection of glaucoma. Arch Ophthalmol. 2004;122(6):827-37.

26. Yu S, Tanabe T, Hangai M, Morishita S, Kurimoto Y, Yoshimura N. Scanning laser pola-rimetry with variable corneal compensation and optical coherence tomography in tilted disk. Am J Ophthalmol. 2006;142(3):475-82.

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Original Article


InTRODUCTIOnMany studies have contributed to the development of foldable

IOLs of different materials and designs, and have been performed to help cataract surgeons to select an IOL that could provide the best quality of vision for pseudophakic patients(1). Some of those studies have shown that the human cornea has a positive value of spherical aberration (SA), which is stable throughout the entire life(2).

Implantation of a spherical IOL could theoretically increase the positive SA of the eye and subsequently degrade the quality of vi-sion(3-5). The aspheric IOLs were developed as an option to generate less higher-order aberration (HOAs) after cataract surgery, providing patients a better contrast sensitivity (CS) and, therefore, enhancing patients’ quality of life(6-10).

Frequency-doubling technology (FDT) testing for the detection of glaucomatous visual field (VF) loss consists of determining CS

mea sures for detecting the frequency-doubled stimulus(11). Maddess et al.(12) proposed that a CS test based on the frequency-doubling illusion should be effective in the detection of early glaucomatous VF loss. However, previous studies have yielded divergent views regarding the diagnostic performance of FDT perimetry to standard automatic white-on-white perimetry (SAP) for the detection of glaucoma(13-15).

Because previous studies have demonstrated an improvement in CS in eyes implanted with aspheric IOLs(6-10), is important to inves-tigate its influence on the results of FDT. As the number of aspheric IOLs implanted all over the world increases and the FDT is progressi-vely incorporated in clinical practice, understanding the effect of aspheric IOLs on this mode of perimetry is of considerable clinical importance. A possible improvement in the perimetry values with such lenses may mask the diagnosis of glaucoma or lead to other dia g nostic confusions.

Influence of aspheric intraocular lens on frequency doubling technology and contrast sensitivity: a fellow eye studyInfluência da lente intraocular asférica na perimetria de frequência dupla e sensibilidade ao contraste: estudo contralateral

rodrigo França de eSPíndola1, Marcony r. Santhiago1, Mário luiz ribeiro Monteiro1, neWton kara-Junior1

Submitted for publication: July 31, 2014 Accepted for publication: October 12, 2014

Study conducted at Division of Ophthalmology, University of São Paulo, São Paulo, SP, Brazil.1 Division of Ophthalmology, University of São Paulo, São Paulo, SP, Brazil.



Corresponding author: Rodrigo F. Espindola. Praça das Hortências, 70 - Itu - SP - 13301-690 - Brazil - E-mail: [email protected]

ABSTRACTPurpose: To evaluate whether implantation of an aspheric intraocular lens (IOL) results in reduced ocular aberrations and improved contrast sensitivity after cataract surgery and, therefore, changes on frequency-doubling technology (FDT) testing. Methods: The present prospective clinical study enrolled 25 patients with bila-teral cataract (50 eyes), who randomly received either an aspheric (Akreos AO) or a spherical (Akreos Fit) IOL in one eye and the other IOL in the second eye. Assessment 12 months postoperatively included photopic and mesopic contrast sensitivity testing. Higher-order aberrations (HOAs) were computed. FDT testing was divided into four areas to evaluate the variation of the values at different points. The median values of the local pattern thresholds (median area contrast sensitivity [MACS]) obtained with that division were calculated. Results: The Akreos AO group obtained statistically significantly lower values of HOAs and spherical aberration compared with the Akreos Fit group. There was a statistically significant between-group difference in contrast sensitivity under mesopic conditions at all spatial frequencies. No statistically significant differences were observed in mean deviation and pattern standard deviation. The aspheric IOL exhibited higher MACS in all areas, although a statistically significant difference was reached only in the 20-degree field area (P=0.043). Conclusions: Aspheric IOLs significantly reduced spherical aberration and HOAs, improving mesopic contrast sensitivity. Although there was a trend toward slightly improved FDT in the aspheric IOL group, it was not statistically significant.

Keywords: Cataract; Phacoemulsification; Contrast sensitivity; Lenses, intraocular

RESUMOObjetivo: Avaliar se o implante de uma lente intraocular (LIO) asférica reduz a aberra ção ocular (alta ordem e esférica), melhora a sensibilidade ao contraste e consequen-temente, provoca mudanças nos valores da perimetria de frequência dupla (FDT ). Métodos: Trata-se de um estudo prospectivo envolvendo 25 pacientes com catarata bilateral (50 olhos) que foram randomizados para receberem uma LIO asférica (Akreos AO) em um olho e uma LIO esfércia (Akreos Fit) no olho contralateral. Com 12 meses de pós-operatório a sensibilidade ao contraste (condições fotópicas e mesópicas) e a aberração de alta ordem foram computados. A FDT foi dividida em 4 áreas para análise da variação dos valores em diferentes localizações. Os valores médios dos limiares locais (área média de sensibilidade ao contraste [MACS]) obtidos com essa divisão foram calculados. Resultados: O grupo da Akreos AO apresentou menores valores de aberração de alta ordem e aberração esférica. Houve diferença estatisticamente significativa na sensibilidade ao contraste em condições mesópicas em todas frequências. Não houve diferença estatística nos valores do mean deviation e pattern standard deviation da FDT. A LIO asférica apresentou maiores MACS em todas as áreas, embora diferença estatística foi encontrada apenas na área de 20 graus de campo visual (P=0,043). Conclusão: A lente asférica reduziu significativamente a quantidade de aberração de alta ordem e esférica, melhorando a sensibilidade ao contraste em condições mesópicas. Embora houve uma melhora nos valores da FDT no grupo da LIO asférica, essa diferença não foi estatisticamente significativa.

Descritores: Catarata; Facoemulsificação; Sensibilidade ao contraste; Lentes intrao-culares

Influence of aspheric intraocular lens on frequency doubling technology and contrast sensitivity: a fellow eye study


The aim of the present prospective randomized clinical study was to investigate whether implantation of an aspheric IOL results in re-duced ocular aberrations and improved CS (measured using the VCTS 6000) after cataract surgery and, therefore, changes in FDT values.

MeTHODSThe present prospective, randomized double-blinded study

included 25 patients with bilateral cataracts. Patients randomly recei-ved an aspheric IOL Akreos AO in one eye (25 eyes; Bausch & Lomb, Inc), and a spherical IOL Akreos Fit (25 eyes; Bausch & Lomb, Inc.) in the other eye. The present study was conducted in adherence with the tenets of the Declaration of Helsinki, and approval of the study was obtained from the institutional review board of the Clinical Hos-pital, São Paulo, Brazil. All patients received a detailed explanation of the study, including the necessity for an examination, after which they provided written informed consent.

Patients without any kind of glaucoma observed during the ophthalmologic examination were eligible for inclusion in the study. The optic discs were evaluated and the retinal nerve fiber layers were examined using Cirrus optical coherence tomography (OCT; Carl Zeiss Meditec) and fundus photography. Exclusion criteria were any other ocular disease, such as corneal opacities or irregularity, am blyopia, retinal abnormalities, surgical complications, posterior capsule opacification or incomplete follow-up. Ocular evaluations (vi-sual acuity, intraocular pressure measurements, gonioscopy, central corneal thickness and fundus examination) were performed in each study visit as a basic visual care parameter to avoid bias of low visual acuity on FDT perimetry and to ensure that glaucomatous patients were not included.

Patients were examined before surgery and at one, seven and 30 days, and three, six and 12 months after surgery. At 12 months, best-corrected visual acuity (BCVA), distance uncorrected visual acuity (UCVA), CS, wavefront analysis and FDT values were measured.

Visual acuity was measured using the Early Treatment of Diabetic Retinopathy Study charts under photopic conditions (target lumi-nance of 85 cd/m2). The values were converted to the logarithm of the minimal angle resolution scale (logMAR).

CS was measured using the VCTS 6000 (Vistech Consultants Inc, Dayton, Ohio, USA) with best-spectacle correction under photopic (85 cd/m2) and mesopic (3 cd/m2) conditions. Light conditions were controlled using a luxometer (Gossen-Starlite, Nürnberg, Germany). The log base 10 CS values were used to construct a graphic for each spatial frequency tested and then presented in the original test scale.

Wavefront analysis was performed using the OPD-Scan aberro-meter (Nidek Co, Gamagori, Japan), which uses dynamic retinoscopy technology to obtain wavefront data. Measurements were repeated at least three times to obtain a well-focused and aligned image of the eye, and analyzed for 5 mm and 6 mm pupils. All aberrations were measured up to the sixth Zernike order.

Pupils were dilated using two drops of cyclopentolate 1% gi-ven 15 min apart, and the size measurements (in millimeters) were obtained 45 min after the last cyclopentolate drop was administered (under scotopic [1.5 cd/m2], mesopic [3 cd/m2], and photopic [85 cd/m2] conditions). Pupil diameter was measured using the Colvard pupillo-meter (Oasis Medical, Glendora, California, USA).

FDT perimetry (Carl Zeiss Meditec, Dublin, CA, USA) was per-for med using best-spectacle correction in a darkened room (target lu minance of 3 cd/m2). Patients were assessed using the N-30 full-threshold program. The strategy tested four locations in each qua-drant (10º × 10º squares), one central location (10º of the arc of a central circle) totaling 17 locations tested in the central 20º and two in the lateral 30o VF. In each area, the FDT device presents frequency-doubling stimuli with low spatial frequency, co-sinusoidal grating (0.25 cycles/degree) and high temporal frequency (25 Hz counter-phase flicker) on a square background.

The N-30 full-threshold protocol determines the minimum con -trast necessary to detect the stimulus for each of the 19 target lo-cations in the stimulus display. This is accomplished by means of a modified binary search (MOBS) type of staircase. If the stimulus is detected, the contrast is decreased in the following presentation; if the stimulus is not detected, the contrast is increased. Thus, the test is continued until the stimulus with the lowest contrast is detected(16).

Parameters on FDT included in the analysis were mean deviation (MD) and pattern standard deviation (PSD). Only reliable fields were accepted in the study (<33% false-positive or false-negative respon-ses and <20% fixation losses).

A screening test (C-20-5) was first performed to minimize the learning curve. An interval of at least 5 min was allowed between the screening test and the full-threshold test in order to improve reliability, as suggested by previous studies(17). These tests were not included in the analysis.

In addition, the VF was also divided into four areas (Figure 1) to evaluate the variation of the values in different areas: the central area (A1); the 10o field area (A2); the 20o field area (A3) and the 30o lateral field area (A4). The median thresholds for each of the four areas were calculated; each of these medians are referred to as the median area CS (MACS).

Statistical analysis was performed using SPSS for Windows (ver sion 15; SPSS, Inc, Chicago, Illinois, USA). For primary outcome measures, P<0.05 was considered to be statistically significant. The normality of the quantitative variables was verified using the Kol-mogorov-Smirnov test. The nonparametric Wilcoxon paired test was used to compare data between the two IOL groups. The differences between MD, PSD and MACS were compared using an unpaired t test.

ReSULTSA total of 25 patients (50 eyes; 12 men [48.0%] and 13 women

[52.0%]) were enrolled in the present study. The mean age of the pa-tients was 57.80 ± 6.48 years. No significant difference was observed between the IOL groups with regard to mean IOL power (P=0.736) and mean axial length (P=0.431) (Table 1).

No significant difference was observed between the aspheric and spherical groups for distance-corrected vision (0.00 ± 0.11 and 0.01± 0.07 logMAR, respectively) (P=0.432).

The mean pupil diameter was similar between Akreos AO and Akreos Fit under photopic (P=0.083), mesopic (P=0.066), and scotopic conditions (P=0.180) (Table 2).

figure 1. Representation of the frequency-doubling technology division in four areas: central (A1); paracentral (A2); peripheral (A3); and lateral (A4).

Espíndola RF, et al.


At 12 months, the spherical equivalent was 0.03 ± 0.29 in the Akreos AO group and 0.06 ± 0.43 in other group (P=0.296). There was no significant difference between the IOL groups with regard to distance UCVA (P=0.379) and distance BCVA (P=0.331). The UCVA was 0.08 ± 0.05 in the Akreos AO group and 0.09 ± 0.06 in the Akreos Fit group. The BCVA was 0.01 ± 0.10 in the Akreos AO group and 0.02 ± 0.09 in the Akreos Fit group.

Figures 2 and 3 present the CS results. Under photopic conditions, the Akreos AO IOL was associated with significantly better CS than the Akreos Fit IOL only at the spatial frequency of 12 cycles per de-gree (cpd) (P=0.028). Under mesopic conditions, the Akreos AO IOL was associated with significantly better CS than the Akreos Fit IOL at all spatial frequencies (1.5, 3, 6, 12, and 18 cpd; P=0.004, P=0.042, P=0.017, P=0.0017, and P=0.001, respectively).

Table 2 shows wavefront data after cataract surgery. The Akreos AO group had statistically significantly lower values of mean HOA and SA compared with the Akreos Fit group (P=0.004 and P<0.001, respectively). There were no statistically significant differences in coma values between the two IOL groups (P=0.412).

The average MDs of eyes implanted with aspheric and spherical IOLs were -1.01 ± 1.68 dB and -3.15 ± 3.78 dB, respectively, on FDT testing. There was no significant difference in either MD (P=0.051) or PSD (P=0.233) between the groups (Table 3).

Considering the VF division, the MACS of the aspheric IOL had higher values than the spherical IOL in all areas (A1 to A4), although the difference was statistically significant only in the peripherical area (A3) (P=0.043).

DISCUSSIOn Functional and structural changes associated with glaucoma

require special consideration in the patient who is undergoing ca-taract/IOL surgery. The decreased CS observed in glaucoma may be improved by the use of aspheric IOLs(18).

Contrast is one of the most important parameters activating cor-tical cells involved in vision processing(19). The perception of median arcuate ligament frequency doubling may be mediated by a group of retinal ganglion cells called My cells or by cortical mechanisms(20-23).

Given the similarities between the frequency-doubling illusion and CS, one might deduce that cataract extraction results in recovery of sensitivity in FDT(29). Previous studies showed that the MD of FDT and SITA-fast perimetry were improved after cataract extraction but PSD remained unchanged(24,25).

Similarly, we suspected that changes after aspheric IOL implanta-tion may influence CS and its thresholds. Therefore, the present con-tralateral eye study was conducted to analyze the theoretical benefits of aspheric IOL in improving CS and its consequences in FDT parame-ters. To our knowledge, no previous study comparing the effect of an aspheric IOL on FDT perimetry has been published to date.

Table 1. Demographic characteristics of patients enrolled in the study

Characteristics Akreos AO Akreos fit p-value

No. of eyes 25 25

Age (years) 57.80 ± 6.48 57.80 ± 6.48

Sex (M/F) 12/13 12/13

Eye (OD/OS) 11/14 14/11

IOL power (D) 21.48 ± 2.23 21.51 ± 2.20 0.878

Axial length (mm) 22.35 ± 2.20 22.20 ± 2.43 0.630

M= male; F= female; OD= right eye; OS= left eye; lOL= intraocular lens; D= diopters.

Table 2. Wavefront data and pupil size of eyes implanted with Akreos AO and Akreos fit

Wavefront dataAkreos AO

(Mean ± SD)Akreos fit

(Mean ± SD) p-value

HOA RMS 0.96 ± 0.19 1.39 ± 0.39 0.004*

Coma 0.51 ± 0.19 0.57 ± 0.28 0.412

Spherical aberration 0.26 ± 0.08 0.45 ± 0.17 <0.001*

Pupil size (mm)

Scotopic 4.48 ± 0.46 4.54 ± 0.40 0.180

Mesopic 4.01 ± 0.45 4.04 ± 0.41 0.066

Photopic 3.48 ± 0.42 3.42 ± 0.40 0.083

HOA= higher-order aberration; RMS= root mean square; SD= standard deviation; mm= millimeters; *= statistically significant.

figure 2. Graph showing contrast sensitivity under photopic conditions in the aspheric and spherical groups.

figure 3. Graph showing contrast sensitivity under mesopic conditions in the aspheric and spherical groups.

Table 3. frequency doubling technology (fDT) data of eyes implanted with Akreos AO and Akreos fit at 12 months postoperatively

fDT dataAkreos AO

(Mean ± SD)Akreos fit

(Mean ± SD) p-value

MD (dB) -1.01 ± 1.68 -3.15 ± 3.78 0.051

PSD (dB) -5.05 ± 1.21 -6.30 ± 3.39 0.233

MD= mean deviation; PSD= pattern standard deviation; SD= standard deviation.

Influence of aspheric intraocular lens on frequency doubling technology and contrast sensitivity: a fellow eye study


In the present study, under mesopic conditions, postoperative VCTS CS testing revealed significant differences between the two groups at all spatial frequencies, indicating that the Akreos AO IOL group performed better than the Akreos Fit group in larger pupil sizes. However, under photopic conditions, the Akreos AO IOL per-formed better than Akreos Fit only at 12 cpd (P=0.028). In addition, we found that the amount of HOAs was significantly lower in the aspheric group.

Although previous studies comparing aspheric and spherical IOLs have also reported the reduction of SA in patients implanted with aspheric IOLs, its influence in improved CS results is still contro-versial. Some studies show improvement in CS with aspheric IOLs(6-10), while others have showed no improvement(26,27).

The increase in optical quality obtained with aspheric IOLs in our study does not play a significant role in changing FDT parameters. Our results showed that both MD (P=0.051) and PSD (P=0.233) did not differ significantly between groups.

A previous study by Ueda et al.(25) reported findings that were similar to those in the present study. They analyzed the effect of clear (VA60BB, HOYA) and yellow-tinted lenses (YA60BB, HOYA) on FDT values, and concluded that both MD and PSD did not differ sig-nificantly. It is important to notice that this study was not conducted with aspherical IOLs.

Others studies have analyzed the influence of IOLs on short-wa-velength automated perimetry (SWAP)(28,29). Jang et al analyzed clear (AcrySof SA60AT; Alcon Laboratories) and yellow-tinted lenses (AcrySof SN60AT or SN60WF; Alcon Laboratories) on SWAP(28). The SN60WF IOL is designed with negative SA to compensate for the positive aberration of the average cornea. The authors demonstrated that yellow-tinted IOLs may affect the SWAP results, although they did not separately analyze the effect of the aspheric IOL used (SN60WF) on perimetry.

Kara-Junior et al.(29) reported different results than Jang et al.(28). They suggested that yellow-tinted IOLs (AcrySof SN60AT) did not interfere with the results of SWAP. It should be noted that both IOLs studied generated a considerable amount of SA.

With respect to mean sensitivities of the different zones as defi-ned in the present study, FDT testing resulted in improved CS after aspheric IOL implantation. We found higher mean values in the eye with Akreos AO in all areas (A1 to A4), but a statistical difference (P=0.043) was found only in the 20o field area (A3). Although the chan ges were not statistically significant, it is noteworthy that an improvement in the perimetry values with such lenses could mask the diagnosis of glaucoma or lead to other diagnostic confusions, especially considering that the functional abnormalities detected by FDT perimetry were shown to be predictive of the future onset and location of VF loss among suspected glaucoma patients(13-15).

The results of the present study indicate that MD values were higher in the Akreos AO group, and the PSD was higher in the Akreos Fit group. Note that a more negative MD indicates a worse visual per-formance than expected from the normative database, and a higher PSD indicates greater changes in sensibility. Previous studies in pa-tients with yellow-tinted IOLs and patients with clear IOLs have also showed higher MD values in patients with yellow-tinted IOLs(25,28,29). However, both indices in our study were not statistically significant.

The present study had several limitations, including the absence of preoperative FDT perimetry data, the small number of cases and the absence of concurrent standard automated perimetry. A larger number of cases (approximately 100 cases in each group) could make a difference in the findings between each group, or confirm the result observed in the present study.

In addition, the present study specifically investigated these effects in patients without glaucoma. It stands to reason that in a disease process that decreases CS, an attempt to increase CS would be beneficial to the patient.

In summary, aspheric IOLs significantly reduced SA and HOAs, improving mesopic CS. Although there was a trend toward slightly

improved FDT in the aspheric IOL group, it was not statistically signi-ficant. Further studies with large sample sizes should be performed to confirm or reject this hypothesis.

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Original Article


InTRODUCTIOnAfter surgical correction of unilateral blepharoptosis, a decrease

in the height of the contralateral upper eyelid may be observed(1-3). Gay et al.(4) suggested that the phenomenon may be explained by Hering’s law, which states that the muscles responsible for eye mo-vement in each eye are innervated equally as observed in the lateral and medial rectus muscles during horizontal version. Hering’s law posits that the same amount of stimulus is transmitted to each of the two muscles in a pair. Thus, eyelid position in patients with ptosis

would be analogous to the secondary deviation seen in paralytic strabismus(5).

Therefore, in the correction of unilateral ptosis, the innervational stimulus for that eyelid will be lower, causing the fall of the contrala-teral eyelid and demonstrating an interdependence of eyelid height between both eyelids.

Phenylephrine, a selective α-adrenergic receptor agonist, elevates the upper eyelid, simulating the effect of corrective surgery for ble-pharoptosis(6). Digital lifting and closure of the ptotic eyelid is also

Palpebral position interdependence in blepharoptosis: comparison of the effect of instillation of 10% phenylephrine drop and digital liftingInterdependência na posição palpebral em ptose palpebral: comparação do efeito de instilação de colírio de fenilefrina 10% e o teste de elevação digital da pálpebra

ivana cardoSo Pereira1, Suzana MatayoShi1

Submitted for publication: June 17, 2014 Accepted for publication: November 4, 2014

Study conducted at Department of Ophthalmology, Faculdade de Medicina, University of São Paulo (USP), São Paulo, SP, Brazil.

1 Department of Ophthalmology, Faculdade de Medicina, University of São Paulo (USP), São Paulo, SP, Brazil.



Corresponding author: Ivana Cardoso Pereira. Rua Suriname, 430/131 - Americana, SP - 13465-790 - Brazil - E-mail: [email protected]

Approved by the following research ethics committee: CAPPesq da Diretoria Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (0213/11).

ABSTRACTPurpose: To quantify and compare the effects of instillation with 10% phenylephrine and digital lifting on the contralateral upper eyelid of patients with involutional bilateral blepharoptosis. Methods: The present prospective clinical study involved patients with involu-tional bilateral blepharoptosis who underwent two tests: 1) digital lifting of the more ptotic eyelid and observation of the effect on the contralateral eyelid and 2) instillation of two drops of 10% phenylephrine in the more ptotic eye and obser-vation of the effect on the contralateral eyelid. Patients were filmed before and 5, 10, and 15 min after instillation, and the resulting images were analyzed to obtain eyelid measurements. The results were tested using a linear mixed-effects model. Results: A total of 27 patients, ranging from 52 to 82 years of age (mean age 68.51 ± 8.21 years), 24 (88.88%) of whom were women, were included in the present study. In eyes that received instillation, the marginal distance reflex-1 (MDR1) va-lues increased from baseline (1.21 ± 0.60 mm) until 10 min after instillation, then remained statistically unchanged until 15 min after instillation (2.42 ± 0.90 mm). Significant differences were observed in the contralateral eye of the group that underwent digital lifting (1.51 ± 0.53 mm - 1.63 ± 0.56 mm) and in the contralateral eye of the group that underwent 10% phenylephrine instillation (1.38 ± 0.54 mm - 1.63 ± 0.56 mm); p=0.02 and p<0.01, respectively. Conclusions: In all eyes, 10% phenylephrine elevated the upper eyelid, with improved eyelid height at 10 min after instillation. Significant differences were observed in the height of the contralateral eyelid when compared before and after each intervention in each group; however, this difference was very small and nearly undetectable by conventional clinical evaluation in the digital lifting group. However, the 10% phenylephrine eye-drop test resulted in substantial changes in MDR1 values in the treated and contralateral eyes, indicating clinical and statistical efficiency.

Keywords: Blepharoptosis; Eyelids/innervations; Phenylephrine; Ophthalmic so lu-tions; Lifting; Laws of cure in homeopathy

RESUMOObjetivo: Quantificar e comparar o efeito da instilação do colírio de fenilefrina 10% com o levantamento manual da pálpebra superior contralateral de pacientes com ptose palpebral bilateral involucional. Método: Estudo clínico e prospectivo de pacientes com ptose palpebral bilateral involucional submetidos a dois testes: 1) elevação manual da pálpebra mais ptótica e observação do efeito da intervenção na pálpebra contralateral; e 2) a instilação de duas gotas de colírio de fenilefrina 10% no olho mais ptótico e observação do efeito da intervenção na pálpebra contralateral. Os pacientes foram filmados antes e 5, 10 e 15 minutos após a instilação. Os resultados foram analisados estatisticamente com o modelo linear de efeitos mistos. Resultados: O estudo incluiu 27 pacientes com idade entre 52-82 anos (68,51 ± 8,21), 24 dos quais eram do sexo feminino (88,88%). Em olhos submetidos a instilação do colírio, os valores da DMR1 (distância marginal reflexo) aumentaram da linha de base (1,21 ± 0,60 mm) até os 10 min, em seguida, manteve-se estatisticamente estável até 15 min (2,42 ± 0,90 mm). Diferenças significativas foram observadas nos olhos contralaterais, independentemente do levantamento manual da pálpebra (1,51 ± 0,53 mm - 1,63 ± 0,56 milímetros) e da instilação do colírio de fenilefrina 10% (1,38 ± 0,54 mm - 1,63 ± 0,56 mm), p=0,02 e p<0,01 respectivamente. Conclusões: Em todos os olhos, a instilação do colírio de fenilefrina 10% mostrou um aumento gradual do valor de distância marginal reflexo até os 10 min. Nos olhos contralaterais houve diminuição do valor de distância marginal reflexo, independen-temente do teste realizado, porém as mudanças que ocorrem na posição da pálpebra contralateral, durante o teste da elevação manual, são muito pequenas e difíceis de serem detectadas no exame clínico convencional. Enquanto isso, o teste de colírio de fenilefrina 10% produziu mudanças substanciais nos valores distância marginal reflexo nos olhos tratados e contralateral, o que indica a eficiência clínica e estatística.

Descritores: Blefaroptose; Pálpebras/inervação; Fenilefrina; Soluções oftálmicas; Remoção; Leis de cura em homeopatia

Palpebral position interdependence in blepharoptosis: comparison of the effect of instillation of 10% phenylephrine drop and digital lifting


used to simulate the effect of corrective surgery and observe the compensatory change in the position of the contralateral eyelid. This digital lift test is useful in the preoperative assessment, as demonstra-ted in a study by Kratky and Harvey, in which 46.7% of the patients had positive test results(5).

Few studies have explored the changes in the contralateral upper eyelid produced by phenylephrine instillation in one eye. Similarly, there is a paucity of evidence in the literature regarding the efficacy of digital lift compared with instillation of phenylephrine drops to induce a decrease in the height of the contralateral upper eyelid.

The objective of the present study was to compare instillation of 10% phenylephrine drops with digital lifting of the ptotic eyelid with regard to changes in upper eyelid position in patients with bilateral senile blepharoptosis.

MeTHODSThe present prospective clinical study included patients with

bilateral senile involutional blepharoptosis, and was conducted between June 2011 and September 2012. All patients provided infor-med written consent. The study was approved by the Ethics Committee for Analysis of Projects and Research at the Clinic Hospital of University of São Paulo Medical Center (HC-FMUSP) under protocol #0213/11.

Subjects presenting with bilateral blepharoptosis with a marginal reflex distance-1 (MDR1) of <2.6 mm were eligible. The exclusion criteria were: corneal changes precluding accurate measurements, use of sympathomimetic drugs or eyedrops, previous eyelid surgery, other types of ptosis (traumatic, mechanical or post-contact lens ptosis), myopathies, and untreated and/or decompensated cardio-vascular disease.

At baseline, the patients underwent a complete ophthalmolo-gical evaluation, including assessment of visual acuity, pupillary re-fle xes, MDR1, levator palpebrae superioris muscle (LPSM) function, biomicroscopy, intraocular pressure and fundoscopy.

Subsequently, the patients underwent the following tests: • Test1:Digitalliftingofthemoreptoticeyelidandobservation

of the effect of the intervention on the contralateral eyelid (Figure 1).

• Test2:Instillationoftwodropsof10%phenylephrine(Allergan;standardized at HC-FMUSP) in the more ptotic eye and obser-vation of the effect of the intervention on the contralateral eyelid.

Patients were filmed using a Sony HDR-CX150 digital video ca mera for 1 min before the tests, during digital lifting, and 5, 10 and 15 min after phenylephrine instillation. The patient’s head was placed on a chin rest at a predetermined distance, with a ruler measuring length in millimeters across the forehead for the calibration of eyelid posi-

tion measurement. The five video frames in which the patient pre-sented the greatest eyelid elevation were selected and the average of the measurements was calculated. The images were analyzed to de-termine MDR1 (Imovie software [version 8.0.6] and Image J software [version 1.43r]). The central corneal light reflex was used as reference.

A linear mixed-effects model was used in the statistical analysis because data from the same individuals were grouped and the assumption of independence among observations in the same group was not adequate (Schall, 1991; Littel, 1996). The residue was assumed to have normal distribution with a mean value of zero and constant variance (σ2). The analysis was performed with the SAS software (version 9.2) using the MIXED procedure.

ReSULTSA total of 27 patients, ranging from 52 to 82 years of age (mean

68.51 ± 8.21 years), 24 (88.88%) of whom were women, were included in the present study.

As shown in figure 2 and table 1, which present the MDR1 values of eyes instilled with 10% phenylephrine according to the time of observation, the differences in MDR1 values were significant for all comparisons, except between 10 and 15 min.

Table 1 shows the distribution of MDR1 values for the eyes that underwent phenylephrine instillation.

Table 2 shows the distribution of MDR1 values for the eyes con-tralateral to the eyes that underwent digital lifting or phenylephrine instillation.

As suggested by table 3 and figure 3, the contralateral eyelid tended to be lower after phenylephrine instillation compared with after digital lifting (MDR1=1.38 versus 1.51 mm), and statistically significant differences were observed in both groups (p<0.01 and p=0.02, respec-tively).

DISCUSSIOnIn blepharoptosis, one or both upper eyelids droop below the

normal position. According to the most widely accepted definition, the condition is diagnosed when the border of the upper eyelid

figure 2. Boxplot showing marginal distance reflex-1 (MRD1) measures of eyes that underwent instillation with 10% phenylephrine according to time of observation.figure 1. Digital lifting of the more ptotic eyelid (Test 1).

Pereira IC, Matayoshi S


between the center of the pupillary light reflex and the upper eyelid margin (MDR1), which is clinically equivalent to the distance between the upper eyelid margin and the center of the pupil. Since MDR1 ranges from 2.6 to 4.4 mm in normal individuals, values <2.6 mm are suggestive of blepharoptosis(9). However, other factors, such as facial and/or eyelid asymmetry, facial proportions and racial characteristics, should be taken into account.

Blepharoptosis may present as a simple esthetic change, or as a functional problem if the eyelid covers the visual axis or causes sight impairment in the upper peripheral field.

Patients often unconsciously attempt to compensate the droop by contracting the frontal muscles and the corrugator supercilii, or by tilting the head backwards.

The outcome of corrective surgery for blepharoptosis is difficult to predict and patients often require reoperation, even when treated by experienced surgeons(10). One of the most delicate issues is the descent of the contralateral eyelid following surgical correction of unilateral blepharoptosis.

Several tests have been proposed to predict eyelid position after correction of unilateral blepharoptosis, including digital lifting and closure of the ptotic eyelid, and instillation of phenylephrine.

Table 1. Distribution of marginal distance reflex (MRD1) and results of the linear mixed-effects model in eyes that underwent instillation with 10% phenylephrine according to time of observation

Comparison MRD1 mean values (mm) estimate p-value LL UL

Pre-instillation vs 5 min 1.21 vs 1.84 -0.64 <0.01 -0.82 -0.45



5 min vs 10 min 1.84 vs 2.27 -0.42 <0.01 -0.61 -0.24

5 min vs 15 min 1.84 vs 2.42 -0.57 <0.01 -0.76 -0.39

10 min vs 15 min 2.27 vs 2.42 -0.15 <0.11 -0.33 -0.03

LL= lower limit; UL= upper limit (95% confidence interval).

Table 2. Marginal distance reflex-1 (MRD1) values for contralateral (non-intervention) eyes according to intervention and time

Intervention Mean SD Minimum 1st quartile Median 3rd quartile Maximum

Before test 1.63 0.56 0.56 1.20 1.57 2.08 2.68

DL 1.51 0.53 0.10 1.19 1.57 1.86 2.61

PI -5 min 1.52 0.55 0.50 1.20 1.53 1.94 2.68

PI-10 min 1.44 0.56 0.36 1.15 1.37 1.79 2.63

PI-15 min 1.38 0.54 0.36 0.99 1.38 1.79 2.56

SD= standard deviation; DL= digital lifting; PI= phenylephrine instillation.

Table 3. Results of the linear mixed-effects model for contralateral (non-intervention) eyes according to intervention and time of observation

95% CI

MRD1 mean values (mm) Comparison estimate p-value LL UL

1.51 vs 1.63 DL vs before DL 0.13 <0.02 -0.02 0.23

1.63 vs 1.52 Pre-instillation vs 5 min 0.12 <0.01 -0.04 0.19



1.52 vs 1.44 5 min vs 10 min 0.08 0.04 -0.01 0.15

1.52 vs 1.38 5 min vs 15 min 0.14 <0.01 -0.06 0.21

1.44 vs 1.38 10 min vs 15 min 0.06 <0.14 -0.02 0.13

DL= digital lifting; LL= lower limit; UL= upper limit; CI= confidence interval; MDR1= marginal distance reflex-1.

covers >2 mm of the corneal limbus at the 12 o’clock position in the primary position of gaze(7). When the droop is quantified by digital elevation, eyelid measurements tend to be inaccurate. Thus, Sarver and Putterman(8) proposed to detect ptosis based on the distance

figure 3. Boxplot of marginal distance reflex-1 (MRD1) values for contralateral (non-in-tervention) eyes according to intervention and time (A) after phenylephrine instillation; B) after digital lifting).

A B

Palpebral position interdependence in blepharoptosis: comparison of the effect of instillation of 10% phenylephrine drop and digital lifting


Bodian(1) observed the appearance of ptosis in the contralateral eye in 9.6% of 115 patients submitted to surgical correction for uni-lateral blepharoptosis. Likewise, Averbuch-Heller et al.(3) observed the descent of the contralateral eyelid following the elevation of the pto-tic eyelid in patients with neuromuscular blepharoptosis. To explain this phenomenon, Gay et al.(4) cited Hering’s law, which states that the muscles responsible for eye movement in each eye are innervated equally (as observed for the lateral and medial rectus muscles during horizontal version) and the same amount of stimulus is transmitted to each of the two muscles in a pair. However, in his original study, Hering did not specify whether the law of motor correspondence applies to the LPSM (Hering apud Gay et al.)(4).

Erb et al.(2) observed no significant difference between patients testing positive and negative for Hering’s test prior to surgery. The test involved the digital lifting of the ptotic eyelid and observation of the contralateral eye. Patients were considered to be Hering-positive when a descent of the contralateral eyelid was observed. In both groups, the MDR1 value of the contralateral eye decreased by 0.2 ± 0.8 mm following surgical correction of unilateral blepharoptosis. In other words, negativity for Hering’s effect prior to surgery was not predictive of the absence of postoperative ptosis in the contralateral eye. According to the authors, 5% of the patients required a second intervention(2).

Digital lifting and closure of the ptotic eyelid is also used to si-mulate the effect of surgical correction of unilateral blepharoptosis and its repercussion on the contralateral upper eyelid. Kratky and Harvey(5) evaluated two tests with the patient looking straight ahead at a distant point: the lift test, in which the examiner digitally lifts the ptotic eyelid as far as the upper limbus while observing the descent of the contralateral upper eyelid; and the closure test, in which the examiner digitally occludes the ptotic eyelid while observing the elevation of the contralateral upper eyelid. The tests may be com-plemented by rapid release of the position, occluding or elevating the eyelid, respectively. According to the authors, the return to the original position is more easily observed in the contralateral upper eyelid. In their study, changes in the contralateral upper eyelid were observed in 66.7% of the patients with the closure test, and in 46.7% with the lift test(5).

These observations may be explained by the fact that when the ptotic eyelid is corrected in patients with bilateral asymmetric blepharoptosis, the nervous stimulus transmitted to the LPSM on both sides decreases, causing the previously compensated eyelid to droop.

The 10% phenylephrine test is commonly used in the semiology of blepharoptosis. If the eyelid is elevated following instillation, the test is considered to be positive and the patient is referred to surgical correction with müllerectomy(6). In the present study, 10% phenyle-phrine drops were instilled in only one eye of each patient in order to analyze the effect of the medication on the upper eyelids of both eyes. The choice of medication and concentration was based on the commercial availability of 10% phenylephrine eyedrops and on the fact that the medication is more efficient at 10% than at 2.5%, with an average difference in eyelid elevation of + 0.2 mm, as demonstrated by other authors(11).

Both concentrations have been associated with adverse ocular and/or systemic reactions. Phenylephrine eyedrops are contrain-dicated in patients with closed-angle glaucoma, children with low body weight and patients potentially hypersensitive to the drug (for example, patients with insulin-dependent diabetes or individuals with a history of cerebral aneurysm, cardiovascular disease or idiopa-thic orthostatic hypotension)(12,13). Nevertheless, a recent study found no significant difference between the two concentrations (2.5% and 10%) with regard to systemic blood pressure or heart rate. In ano-ther study, no clinical problems were observed following the use of phenylephrine eyedrops(14). Likewise, in the present study, none of our patients experienced any local and/or systemic adverse reactions to the medication during or after the intervention.

In the present study, each case was documented using digital images, which were analyzed using a computer for greater accuracy. Eyelid position is not static; thus, to minimize image capture bias, patients were filmed rather than photographed. The method, which has been described in other studies evaluating the eyelid and related structures(15,16), was simple to apply. The semiology employed in the study is the most widely used in the evaluation of blepharoptosis and was based on the measurement of the distance between the center of the pupillary light reflex and the upper eyelid margin (MDR1) and on the 10% phenylephrine instillation test.

In our sample, patients were predominantly female (88.88%). The mean age was 68.51 years.

In eyes treated with 10% phenylephrine eyedrops, MDR1 increa-sed from baseline to the 10 min mark, then remained stable up to 15 min after baseline (Table 1; Figure 2).

With regard to the contralateral eye, a tendency toward descent of the contralateral eyelid following digital lifting was observed, which was statistically significant (p=0.02; 95%CI=0.02-0.23) (Table 3).

As shown in table 3, the difference between the time-points was statistically significant for contralateral eyes regardless of the 10% phenylephrine instillation (p<0.01).

In other words, while changes do occur in the position of the contralateral eyelid during the digital lift test, the difference is very difficult to detect by conventional clinical evaluation.

These findings are supported by Nunes(15) who found contralate-ral eyelid changes to be detectable solely with the aid of digital image processing due to the greater accuracy of automated measurements. Very small differences detected in this manner may not be percepti-ble on ectoscopy(15).

In addition, changes in the contralateral eyelids of our patients may have been negligible because the eyelid position, MDR1 values, LPSM function and innervational stimuli tend to be similar on both sides in bilateral senile blepharoptosis.

However, the 10% phenylephrine eye drop test produced subs-tantial changes in MDR1 values in the treated and contralateral eye, indicating clinical and statistical efficiency.

In the clinical context, Hering positivity indicates the presence of blepharoptosis in the contralateral eye as well(17). The cut-off value for bilateral surgery has not yet been defined, but it would be interesting to correlate the changes observed in the present study with Hering test results after surgical correction of unilateral blepharoptosis. However, two previous studies failed to demonstrate a correlation between preoperative Hering positivity and postoperative contrala-teral upper eyelid position(2,18).

In the present study, we quantified the interaction between eyeli-ds in response to instillation with phenylephrine eyedrops and digital lifting of one of the eyelids, with focus on the effect produced on the contralateral eyelid. In theory, the existence of a feedback effect of the contralateral eyelid on the eyelid submitted to instillation may be postulated, since the palpebral descent resulting from the Hering effect could cause the upper eyelid of the tested eye to rise, thereby indirectly adding to the effect of the medication. This theory is not applicable to the digital lift test because the lifting is performed ma-nually and cannot be measured.

COnCLUSIOnSThe 10% phenylephrine eye drop test is more useful than the

digital lift test in patients with bilateral senile blepharoptosis because changes in eyelid position in the contralateral eyelid are barely detec-table using the digital lift test.

The currently available diagnostic tests for blepharoptosis require further study and development before they can be adequately used in the semiology and treatment of blepharoptosis in the quest for improved palpebral symmetry.

Pereira IC, Matayoshi S


RefeRenCeS 1. Bodian M. Lip droop following contralateral ptosis repair. Arch Ophthalmol 1982;

100(7):1122-4. 2. Erb MH, Kersten RC, Yip CC, Hudak D, Kulwin DR, McCulley TJ. Effect of unilateral

blepharoptosis repair on contralateral eyelid position. Ophthal Plast Reconstr Surg 2004;20(6):418-22. Comment in: Ophthal Plast Reconstr Surg. 2005;21(4):323; author reply 324; Ophthal Plast Reconstr Surg. 2005;21(4):323-4; author reply 323.

3. Averbuch-Heller L, Poonyathalang A, von Maydell RD, Remler BF. Hering’s law for eyelids: still valid. Neurology. 1995;45(9):1781-3. Comment in: Neurology. 1996;47(5):1352.

4. Gay AJ, Salmon ML, Windsor CE. Hering’s law, the levators, and their relationship in disease states. Arch Ophthalmol. 1967;77(2):157-60.

5. Kratky V, Harvey JT. Tests for contralateral pseudoretraction in blepharoptosis. Ophthalmol Plast Reconstr Surg. 1992;8(1):22-5.

6. Putterman AM, Urist MJ. Müller muscle-conjunctiva resection. Technique for treatment of blepharoptosis. Arch Ophthalmol. 1975;93(8):619-23.

7. Beard C. Examinaton of ptosis patient. 3rd.ed. St. Louis: Mosby; 1981. 8. Sarver BL, Putterman AM. Margin limbal distance to determine amount of levator re-

section. Arch Ophthalmol. 1985;103(3):354-6. 9. Frueh BR. Graves’ eye disease: orbital compliance and other physical measurements.

Trans Am Ophthalmol Soc. 1984;82:492-598.

10. Mustarde JC. Experiences in ptosis correction. Trans Am Acad Ophthalmol Otolaryn-gol. 1968;72(2):173-85.

11. Glatt HJ, Fett DR, Putterman AM. Comparison of 2.5% and 10% phenylephrine in the elevation of upper eyelids with ptosis. Ophthalmic Surg. 1990;21(3):173-6.

12. Wilensky JT, Woodward HJ. Acute systemic hypertension after conjunctival instillation of phenylephrine hydrochloride. Am J Ophthalmol. 1973;76(1):156-7.

13. Fraunfelder FT, Scafidi AF. Possible adverse effects from topical ocular 10% phenyle-phrine. Am J Ophthalmol. 1978;85(4):447-53.

14. Diniz Filho A, Frasson M, Merula RV, Morais PR, Cronemberger S. [Cardiovascular and pupillary effects of topical ophthalmic 2.5 and 10.0% phenylephrine in healthy vo-lunteers]. Arq Bras Oftalmol. 2007;70(6):961-6. Portuguese.

15. Nunes TP, Matayoshi S. [Phenylephrine 10% eye drop action in the eyelid position in healthy subjects]. Arq Bras Oftalmol. 2008;71(5):639-43. Portuguese.

16. Cruz AA, Coelho RP, Baccega A, Lucchezi MC, Souza AD, Ruiz EE. Digital image pro-cessing measurement of the upper eyelid contour in Graves disease and congenital blepharoptosis. Ophthalmology. 1998;105(5):913-8.

17. Putterman AM, Fett DR. Müller ‘s muscle in the treatment of upper eyelid ptosis: a ten-year study. Ophthalmic Surg. 1986;17(6):354-60.

18. Wladis EJ, Gausas RE. Transient descent of the contralateral eyelid in unilateral ptosis surgery. Ophthal Plast Reconstr Surg. 2008;24(5):348-51. Comment in: Ophthal Plast Reconstr Surg. 2009; 25(5):419-20;author reply 420.

VII Congresso Brasileiro da SOBLeC

10 a 12 de abril de 2015Maksoud Plaza Hotel

São Paulo - SP

informações: Site: www.congressosoblec.com.br

E-mail: [email protected]

Original Article


InTRODUCTIOn

Bullous keratopathy (BK) is a disorder of the corneal endothelium in which the cell density is not sufficient to regulate corneal hydration and maintain corneal clarity(1). Clinically, BK presents with stromal edema and epithelial blisters, leading to decreased visual acuity and

ABSTRACTPurpose: To describe quantitative and qualitative features of eyes with advanced bullous keratopathy assessed using ultrasound biomicroscopy, before and after anterior stromal puncture (ASP) or amniotic membrane transplantation (AMT) procedures to relieve chronic pain. Methods: The present descriptive comparative study included 40 eyes of 40 patients with chronic intermittent pain due to bullous keratopathy who were randomly assigned to one of the two treatments (AMT or ASP). Ultrasound bio-microscopy (Humphrey, UBM 840, 50 MHz transducer, immersion technique) was used, and a questionnaire about pain intensity was completed preoperatively and postoperatively at days 90 and 180, respectively. Exclusion criteria were age<18 years, presence of concurrent infection, ocular hypertension, and absence of pain. Results: In a 180-day follow-up, the AMT group exhibited mean central corneal thickness (CCT), 899.4 µm preoperatively and 1122.5 µm postoperatively (p<0.001); mean epithelial thickness (ET), 156.4 µm preoperatively and 247.8 µm postope-ratively (p<0.001); and mean stromal thickness (ST), 742.9 µm preoperatively and 826.3 µm postoperatively (p=0.005). The ASP group exhibited mean CCT, 756.7 µm preoperatively and 914.8 µm postoperatively (p<0.001); mean ET, 102.1 µm preoperatively and 245.2 µm postoperatively (p<0.001); and mean ST, 654.6 µm preoperatively and 681.5 µm postoperatively (p<0.999). Correlations between CCT and pain intensity in the AMT group (p=0.209 pre- and postoperatively) and the ASP group (p=0.157 preoperatively and p=0.426 at the 180-day follow-up) were not statistically significant. Epithelial and stromal edema, Descemet’s membrane folds, epithelial bullae, and the presence of interface fluid were frequently obser-ved qualitative features. Conclusion: CCT increased over time in both groups. The magnitude of CCT did not correlate with pain intensity in the sample studied. The presence of interface fluid was a qualitative feature specifically found in some patients who underwent AMT.

Keywords: Corneal edema; Corneal endothelial cell loss; Corneal pachymetry; Cor nea/ultrasound; Amnion/transplantation; Biological dressings; Palliative care

RESUMOObjetivo: Descrever as características quantitativas e qualitativas da biomicrosco-pia ultrassônica (UBM) em olhos com ceratopatia bolhosa avançada, antes e após os procedimentos de punção estromal anterior (ASP) ou transplante de membrana amniótica (AMT ) para alívio de dor crônica. Métodos: Estudo comparativo descritivo incluindo 40 olhos de 40 pacientes com dor crônica intermitente devido a ceratopatia bolhosa, randomizados em duas mo-dalidades de tratamento (AMT e ASP). Biomicroscopia ultrassônica (Humphrey, UBM 840, transdutor de 50 MHz, técnica de imersão) foi utilizada, e um questionário de avaliação da intensidade da dor foi aplicado no pré-operatório, e após 90 e 180 dias de pós-operatório. Critérios de exclusão foram: idade abaixo de 18 anos, presença de infecção, hipertensão ocular, e ausência de dor. Resultados: No seguimento de 180 dias, o grupo Transplante de membrana amniótica apresentou: média da espessura corneana central (CCT ): 899,4 µm (pré), 1.122,5 µm (pós-operatório) (p<0,001); média da espessura epitelial (ET ): 156,4 µm (pré), 247,8 µm (pós-operatório) (p<0,001); média da espessura estromal (ST ): 742,9 µm (pré), 826,3 µm (pós-operatório) (p=0,005), e, grupo ASP apresentou: CCT média: 756.7 µm (pré), 914,8 µm (pós-operatório) (p<0,001); ET média: 102,1 µm (pré), 245,2 µm (pós-operatório) (p<0,001); ST média: 654,6 µm (pré), 681.5 µm (pós-operatório) (p<0,999). A correlação entre intensidade da dor e espessura corneana central no grupo AMT (p=0,209 pré e pós-operatórios) e no grupo ASP (p=0,157 pré-operatório e p=0,426 aos 180 dias de seguimento) não foi significativa. Edema epitelial e estromal, dobras na membrana de Descemet, bolhas epiteliais, e presença de fluido na interface foram características qualitativas frequentemente observadas. Conclusão: A espessura corneana central aumentou ao longo do tempo em ambos os grupos. A magnitude da espessura corneana central não interfere na intensidade da dor na amostra estudada. Presença de fluido na interface foi uma característica qualitativa especificamente encontrada em alguns pacientes submetidos a transplante de membraa amniótica.

Descritores: Edema da córnea; Perda de células endoteliais da córnea; Paquimetria corneana; Córnea/ultrassonografia; Amnio/transplante; Curativos biológicos; Cuida-dos paliativos

pain(2,3). The main causes of BK are related to advanced age; trauma; absolute glaucoma; primary corneal endotheliopathies, such as Fu-chs’ endothelial dystrophy; and endothelial cell loss following surgical interventions, such as cataract surgery with or without intraocular lens implantation (anterior or posterior chamber pseudophakic im-plants), vitreoretinal surgery (particularly when silicone oil is used),

Ultrasound biomicroscopy after palliative surgical procedures for bullous keratopathy: a descriptive comparative studyBiomicroscopia ultrassônica após procedimentos cirúrgicos paliativos na ceratopatia bolhosa: estudo comparativo descritivo

Fabiana doS SantoS PariS1, eliana doMingueS gonçalveS1, Maira Saad ávila MoraleS1, liliane andrade alMeida kanecadan1, Mauro Silveira de queiroz caMPoS1, JoSé álvaro Pereira goMeS1, norMa alleMann1, elcio hideo Sato1

Submitted for publication: August 12, 2014 Accepted for publication: September 29, 2014

Study was conducted at Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.1 Department of Ophthalmology and Visual Sciences, Federal University of São Paulo (UNIFESP), São

Paulo, SP, Brazil.

Funding: This study was supported by Foundation for Support to Research of São Paulo State, (FAPESP) grant number 2001/07036-3.


Corresponding author: Fabiana dos Santos Paris. Av. Pedro de Toledo, 760/94 - Marília - SP - 17509-020 - Brazil - E-mail: [email protected]

Approved by the following research ethics committee: Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil (0728/02).

Clinical trials registration: The study was registered at clinicaltrials.gov (Identifier: NCT 00659308).

Paris FS, et al.


and penetrating keratoplasty (PK) following graft failure or immune rejection(1,3-7).

Corneal graft is the definitive treatment for BK, restoring vision (when possible) and providing pain relief. Other treatments can be used for patients with no potential for vision restoration or while patients are waiting for a corneal graft. Such treatments include the use of topical 5% NaCl hypertonic solution, non-steroidal anti-inflam-matory agents, antiglaucomatous medications, therapeutic contact lenses, conjunctival flaps, electrocauterization, annular keratotomy, phototherapeutic keratectomy, anterior stromal puncture (ASP), and amniotic membrane transplantation (AMT)(3,8-12).

In order to compare the effectiveness of ASP and AMT for the relief of pain in patients with advanced BK(3), central corneal thickness (CCT) was considered to be an important variable, although it exceeded the upper limit for ultrasound pachymetry. Ultrasound biomicroscopy (UBM) is considered to be an alternative method for measuring CCT because it is an imaging method that provides cross-sections of the intact anterior segment of the eye at microscopic resolution. UBM has been used as an aid in diagnoses of ocular disease, as predicted by Pavlin et al. in 1991, when the method was first described(13-16) and provides highly detailed images of the cornea, allowing the characte-rization of structural changes of the corneal layers.

In the present study, we assessed quantitative and qualitative fea tures of eyes with advanced BK using UBM, and its association with pain intensity before and after patients underwent ASP or AMT.

MeTHODSThe present descriptive comparative study was conducted over

18 months and was part of a randomized prospective study com-

paring ASP and AMT in the management of pain in patients with symptomatic BK. The inclusion criteria were chronic pain related to BK in patients on the waiting list for a corneal transplant or in patients whose affected eye had no or minimal visual potential and no indi-cation for corneal transplant. Written consent was obtained from all enrolled patients. Exclusion criteria were age <18 years, presence of concurrent infection, increased eye pressure, and absence of pain.

A detailed history was obtained from each patient, including the administration of a questionnaire for assessing pain. Patients were asked to score the maximum intensity of pain experienced in the preceding one-month period on a scale of 1 to 10 (1=minimal pain and 10=unbearable pain)(3,8). Clinical ophthalmologic examinations were conducted, including best corrected visual acuity, slit-lamp exa-mination and photographic documentation with and without fluo-rescein staining, and Goldman tonometry(3). Quantitative (CCT) and qualitative aspects of the cornea with BK were evaluated using UBM.

The same ophthalmologist (FSP) implemented randomization (using a computer-generated list of random numbers) as follows: 45 patients were considered, of whom 40 patients (40 eyes) were enrolled in the present study. Five patients were excluded: three of whom had previously undergone ASP, one had presented with herpes virus corneal infection, and one had raised intraocular pressure. At the outset, there were 20 patients in each group (AMT and ASP). After randomization, two patients in the ASP group were excluded from the analysis, as described in figure 1.

The causes of BK were endothelial lesion related to previous cata-ract surgery in 17 (85%) patients in the AMT group, and in 14 (77.7%) patients in the ASP group (p=0.102). Of the 17 patients enrolled in the AMT group, nine had additional surgical procedures: trabeculectomy

AMT= amniotic membrane transplantation; ASP= anterior stromal puncture; UBM= ultrasound bio-microscopy.

figure 1. Study flow diagram.

Ultrasound biomicroscopy after palliative surgical procedures for bullous keratopathy: a descriptive comparative study


(three patients; one underwent reoperation), intraocular lens remo-val (three patients, two with associated vitrectomy), intraocular lens fixation (one patient), glaucoma valve implant associated with PK (one patient) and vitreoretinal surgery (one patient). Moreover, of the 14 patients in the ASP group, three underwent additional procedures: trabeculectomy (one patient underwent reoperation) and intraocu-lar lens removal (two patients)(3,17). Demographic characteristics and other clinical features are presented in table 1.

Both ASP and AMT procedures were performed by the same ophthalmologist (FSP) as previously described by Paris et al.(3) Patients were followed up on days 1, 14, 30, 90, and 180 postoperatively.

UBM was performed preoperatively and at 90 and 180 days’ follow-up. At the time of the study, the available equipment was a Humphrey UBM Model 840, 50-MHz transducer, and the examination was conducted under topical anesthesia with the aid of an immer-sion cup filled with 2% methylcellulose solution and 0.9% saline solution. To evaluate the central cornea, an axial scan was utilized, with 60 dB gain and 5.0 mm width x 5.0 mm depth in a vertical scan of the central cornea. If the patient was wearing a therapeutic contact lens, it was maintained during the UBM examination. Images were acquired and posteriorly analyzed, providing A-mode measurements of thickness (quantitative analysis) and B-mode features (reflectivity and anatomy; qualitative analysis). Parameters evaluated were the presence of epithelial bullae, epithelial thickening, stromal thickening, stromal reflectivity, and Descemet’s membrane regularity. In the AMT group, the amniotic membrane thickness was included in the CCT measurement. In stored images for which posterior editing was not possible, a National Institute of Health (NIH)-approved software for measurements (ImageJ64) that allows users to scale according to a given reference in the image and, subsequently, to measure the pa-

rameter of interest. ImageJ is a public-domain, Java-based imag-pro-cessing program developed at NIH. The total thickness of tissue was considered in the measurements. If there was fluid in the interface, this fluid was not included in the measurement.

StatIStICal aNalySIS

Data were presented as mean, standard deviation (SD), median, minimum and maximum values, or absolute and relative frequencies (%), as appropriate. Patient characteristics and baseline variables were compared with respect to the quantitative variables using Student’s t test or the Mann-Whitney test for independent samples, and with respect to categorical variables using the χ2 test or Fisher’s exact test. Spearman’s correlation coefficient was used to measure the correlation of CCT with pain intensity preoperatively and at 90 and 180 days postoperatively(18).

Nonparametric analysis of ordered categorical data in study de signs with longitudinal observation, as described by Brunner and Langer, was performed to compare CCT, epithelial and stromal thickness (ST) distributions in both groups, and to compare preoperative and at 180-day follow-up within each group(19). When differences were asssessed in ST analysis, p values were corrected by Bonferroni ine-qualities(20). Non-parametric analysis was required because assump-tions for using a model of analysis of variance for repeated measures were not satisfied(20). p<0.05 (α=5%) was considered to be statistically significant.

ReSULTSIn the 180-day follow-up, CCT and epithelial thickness (ET) in -

creased (p<0.001) in both groups. The results for the AMT group were CCT mean value, 899.4 µm preoperatively and 1122.5 µm pos-toperatively; ET mean value, 156.4 µm preoperatively and 247.8 µm postoperatively. The results for the ASP group were CCT mean value, 756.7 µm preoperatively and 914.8 µm postoperatively; ET mean value, 102.1 µm preoperatively and 245.2 µm postoperati-vely. ST measurements increased at the 180-day follow-up in the AMT group [ST mean value, 742.9 µm preoperatively and 826.3 µm postoperatively (p=0.005)], while the ASP group did not exhibit di-fferences in ST following the intervention [ST mean value, 654.6 µm preoperatively and 681.5 µm postoperatively (p>0.999)]. Details are presented in table 2 and figure 2.

The correlations between CCT and pain intensity in the AMT group (p=0.209 pre- and postoperatively) and the ASP group (p=0157 preoperatively and 0.426 at 180-day follow-up) were not significant, as seen in table 3.

The main features observed in UBM were: epithelial and stromal edema, 32 patients (100%) preoperatively and 29 (100%) in the 180-day follow-up in both the AMT and ASP groups; Descemet’s membrane folds, four patients (23.5%) preoperatively and four patients (25.0%) at the 180-day follow-up in the AMT group, and three patients (20.0%) preoperatively and two patients (15.4%) at the 180-day follow-up in the ASP group; epithelial bullae, five patients (29.4%) preoperatively and five patients (31.3%) at the 180-day follow-up in the AMT group, and four patients (26.7%) preoperatively and two patients [15.4%] at the 180-day follow-up in the ASP group); and presence of fluid at the interface in three (17.6%) patients in the AMT group. See figure 3.

DISCUSSIOnGlobal trends show that after the advent of phacoemulsification,

BK has become the leading indication of corneal and endothelial transplantation, particularly in developed countries(7,17,21-26). Because patients with BK can experience severe pain, many clinical and sur-gical interventions intending to improve the quality of life for these patients can be attempted while they are waiting for a donor cornea or when visual potential is poor and transplant is contraindicated.

Table 1. Demographics and clinical features of patients with sympto-matic bullous keratopathy divided in the two groups: anterior stromal puncture (ASP) and amniotic membrane transplantation (AMT)

Variable

Group

pAMT (n=20) ASP (n =18)

Age (years)

0.656Mean (SD) 64.1 (15.1) 66.2 (13.9)

Range 23-81 42-85

Gender n (%)

0.076Male 10 (50%) 04 (22.2%)

Female 10 (50%) 14 (77.8%)

Affected eye

0.758Right 11 (55.0%) 9 (50%)

Left 09 (45.0%) 9 (50%)

Disease duration (years)

0.624Mean (SD) 2.2 (1.5) 2.3 (2.4)

Median 2.0 1.8

Range 0.17 - 5 0.25 - 8

Etiology

0.102

Unknown 00 (00.0%) 03 (16.7%)

Cataract surgery 17 (85.0%) 14 (77.7%)

Vitreorretinal surgery 01 (05.0%) 00 (00.0%)

Fuchs’ endothelial dystrophy 02 (10.0%) 01 (05.6%)

AMT= amniotic membrane transplantation; ASP= anterior stromal puncture; statistical tests used were student’s t test or the Mann-Whitney test for independent samples, and χ2= test or Fisher’s exact test.

Paris FS, et al.


Previous studies suggested that ASP and AMT are efficient treatments for pain relief in patients with advanced BK(3,8-12). Frequently, UBM is important for planning the surgical approach when there is potential for restoring vision in eyes with advanced BK and corneal opacity due to severe edema. Therefore, we believe that the increasing number of aphakic and pseudophakic BK associated with the use of palliative treatments, such as AMT and ASP, will be a common finding on UBM examination.

The definitive treatment to control edema with enlarged corneal thickness in BK is a penetrating or endothelial corneal graft. It is not surprising that, at the 180-day follow-up of the present study, CCT and ET showed significantly (p<0.001) increased values in both the AMT and ASP groups because endothelial cell count was still reduced after the palliative treatments were proposed. In addition, the physical presence of the amniotic membrane contributes to the increase in CCT and ET values in the AMT group. Subepithelial fibrosis is described after AMT and ASP(3,8,27). This can constitute a barrier to fluid movement from the continuously hydrated stroma to the epi-thelium and can also decrease tissue evaporation, leading to stromal enlargement. This effect could be observed in the 180-day follow-up, when ST was significantly increased in the AMT group (p=0.005).

Despite this, in the 180-day follow-up, ST did not significantly change in the ASP group (p<0.999); thus, CCT increased at the expense of ET enlargement in the ASP group. Technically, an increase in ST could be a negative factor in a future corneal transplantation in the AMT group compared with the ASP group, considering that suturing a very thick receptor cornea might add technical difficulty due to the difference between donor and receptor corneal thickness.

The role of the amount of edema, here expressed by CCT, in pain intensity in patients with BK is uncertain. The presence of aberrant regeneration of stromal nerves may be a factor leading to pain in patients with BK, as demonstrated by Al-Aqaba in a histological and laser scanning confocal microscopy study. Al-Aqaba et al could not reach a conclusion regarding a correlation between corneal nerves changes and corneal thickness or the duration of corneal edema due to the limited number of cases(7). Our sample constituted of advan-ced cases of BK, considering that the median time of beginning of symptoms was two years in the AMT group and 1.8 years in the ASP group (p=0.624), which is consistent with the elevated values of CCT observed (mean, 832.5 µm; median, 778 µm), with a large variation (463-1725 µm) considering the total number of studied eyes in the preoperative period (n=32). The correlation between CCT and pain

Table 2. Descriptive statistical values for corneal central thickness, epithelial thickness and stromal thickness in AMT- and ASP-treated symptoma-tic eyes with bullous keratopathy preoperatively and at 90 and 180 days follow-up

follow-up Group n Mean SD Minimum Median Maximum IQ

Central corneal thickness (mµ)

Preoperative AMT 17 899.4 290.9 608 809.0 1603 330.0

ASP 15 756.7 294.6 463 718.0 1725 226.0

Total 32 832.5 296.8 463 778.0 1725 254.5

90 days AMT 20 1075.3 314.6 723 950.5 1750 457.3

ASP 14 849.6 158.8 561 839.5 1100 208.3

Total 34 982.3 282.2 561 923.5 1750 292.8

180 days AMT 16 1122.5 323.9 741 969.5 1720 583.5

ASP 13 914.8 274.9 573 862.0 1476 329.5

Total 29 1029.4 315.7 573 943.0 1720 443.5

epithelial thickness (µm)


ASP 15 102.1 29.2 52 105.0 168 43.0

Total 32 130.9 61.8 52 114.5 296 43.3

90 days AMT 20 195.0 108.5 52 179.5 440 129.8

ASP 14 212.9 120.3 84 185.5 568 73.5

Total 34 202.4 112.0 52 185.5 568 107.8

180 days AMT 16 247.8 111.5 92 243.5 425 226.3

ASP 13 245.2 157.6 76 162.0 572 280.5

Total 29 246.6 131.6 76 243.0 572 245.5

Stromal thickness (µm)


ASP 15 654.6 297.9 364 600.0 1610 241.0

Total 32 701.5 285.3 364 619.5 1610 211.5

90 days AMT 20 828.9 269.9 538 692.0 1418 410.3

ASP 14 636.6 119.3 370 630.5 880 128.0

Total 34 749.7 238.2 370 671.5 1418 157.3

180 days AMT 16 826.3 306.0 507 703.0 1410 507.5

ASP 13 681.5 250.9 492 556.0 1343 257.0

Total 29 761.4 287.2 492 637.0 1410 318.0

SD= standard deviation; AMT= amniotic membrane transplantation, ASP= anterior stromal puncture; IQ= interquartile interval. Nonparametric analysis of ordered categorical data in designs with longitudinal observations was performed.

Ultrasound biomicroscopy after palliative surgical procedures for bullous keratopathy: a descriptive comparative study


intensity was not significant in both groups preoperatively and at the 180-day follow-up (Table 3). New studies that correlate CCT with clinical and histological data should elucidate the influence of edema and corneal nerve changes in pain related to BK.

The main UBM characteristics in eyes with BK are epithelial and stromal edema, Descemet‘s membrane folds, and epithelial bullae. In clinical practice, these features are frequently observed when the en-dothelial barrier and the ionic pump functions are impaired, leading to epithelial fragility, neovascularization, and corneal opacification. Also, interface fluid [three eyes (17.6%)] is a particular finding obser-ved postoperatively in the AMT group. When the amnion-epithelial sheet is not fully attached to the corneal stroma after AMT, aqueous

humor from the edematous stroma may lead to fluid accumulation in this interface. Said et al evaluated histological changes of receptor corneas of eyes with painful BK that underwent AMT before PK and observed that cells from the corneal stroma can migrate and proli-ferate on the amniotic stroma only through breaks in the Bowman’s zone. In these sites of migration, the membrane was firmly attached to the corneal surface and, in regions with no breaks, hydration of the cornea and accumulation of fluid continued to occur, but without bullae formation because fluid did not appear to move beyond the transplanted re-epithelialized amnion. At slit-lamp examination, this was evidenced by the observation of a fluid cleft between the epi-thelialized amniotic membrane and the Bowman’s zone(28). Clinically, interface fluid does not appear to have an impact on pain intensity because none of these three patients reported pain in the 180-day follow-up.

We recognize that an anterior segment optical coherence tomo-graphy (OCT) would visualize the digital sectioning of the cornea with high resolution, superior to UBM resolution. Both methods can provide the quantitative and qualitative information needed for the study; however, in contrast to OCT, UBM enables the measurement of corneal thickness >1,000 µm, independently of the degree of opa-city. At the preoperative measurement, we noted that some patients had CCT >1,000 µm. Thus, UBM represents a potential alternative to measure corneal thickness and to evaluate details of densely opaque corneas in the entire sample. OCT would provide additional corneal pachymetric map with a non-contact technology. Although UBM requires immersion and could be a factor leading to an epithelial

Table 3. Spearman’s correlation coefficient of central corneal thickness (CCT) and pain intensity in preoperative and at 90 and 180 days pos-toperatively

Group

AMT ASP

follow-up r p n r p n

Preoperative -0.32 0.209 17 -0.38 0.157 15

90 days -0.21 0.366 20 -0.18 0.543 14

180 days -0.33 0.209 16 -0.25 0.426 12

AMT= amniotic membrane transplantation; ASP= anterior stromal puncture. The statistical test used was Spearman’s correlation coefficient.

A

C

B

AMT= amniotic membrane transplantation; ASP= anterior stromal puncture. Nonparametric analysis of ordered categorical data in designs with longitudinal observations was performed.

figure 2. Box-plots of corneal central thickness (A), epithelial thickness (B), and stromal thickness (C) in AMT and ASP-treated symptomatic bullous keratopathy eyes, preoperatively and at 90 and 180 days follow-up.

Paris FS, et al.


defect in fragile epithelium such as that observed in eyes with BK, the rapeutic contact lenses after UBM examination was not routine.

COnCLUSIOnAt the 180-day follow up, CCT was increased (p<0.001) in both

groups (AMT and ASP). The magnitude of CCT did not correlate with pain intensity in the sample studied. Interface fluid was a qualitative feature specifically found in some patients submitted to AMT.

RefeRenCeS 1. Joyce NC. Cell cycle status in human corneal endothelium. Exp Eye Res. 2005;81(6):

629-38. 2. Pires RT, Tseng SC, Prabhasawat P, Puangsricharern V, Maskin SL, Kim JC, et al. Amniotic

membrane transplantation for symptomatic bullous keratopathy. Arch Ophthalmol. 1999;117(10):1291-7.

3. Paris Fdos S, Goncalves ED, Campos MS, Sato EH, Dua HS, Gomes JA. Amniotic mem-brane transplantation versus anterior stromal puncture in bullous keratopathy: a com parative study. Br J Ophthalmol. 2013;97(8):980-4.

4. Fischbarg J, Maurice DM. An update on corneal hydration control. Exp Eye Res. 2004; 78(3):537-41.

5. Dighiero P, Guigou S, Mercie M, Briat B, Ellies P, Gicquel JJ. Penetrating keratoplasty com bined with posterior Artisan iris-fixated intraocular lens implantation. Acta Oph-thalmol. Scand. 2006;84(2):197-200.

6. Bourne WM, McLaren JW. Clinical responses of the corneal endothelium. Exp Eye Res. 2004;78(3):561-72.

7. Al-Aqaba M, Alomar T, Lowe J, Dua HS. Corneal nerve aberrations in bullous kerato-pathy. Am J Ophthalmol. 2011;151(5):840-9 e1.

8. Gomes JA, Haraguchi DK, Zambrano DU, Izquierdo Junior L, Cunha MC, de Freitas D. Anterior stromal puncture in the treatment of bullous keratopathy: six-month follow-up. Cornea. 2001;20(6):570-2.

9. Tsai TC, Su CY, Lin CP. Anterior stromal puncture for bullous keratopathy. Ophthalmic Surg Lasers Imaging. 2003;34(5):371-4.

10. Cormier G, Brunette I, Boisjoly HM, LeFrancois M, Shi ZH, Guertin MC. Anterior stromal punctures for bullous keratopathy. Arch Ophthalmol. 1996;114(6):654-8.

11. Thomann U, Niesen U, Schipper I. Successful phototherapeutic keratectomy for recurrent erosions in bullous keratopathy. J Refract Surg. 1996;12(2):S290-2.

12. Koenig SB. Annular keratotomy for the treatment of painful bullous keratopathy. Am J Ophthalmol. 1996;121(1):93-4.

13. Pavlin CJ, Harasiewicz K, Sherar MD, Foster FS. Clinical use of ultrasound biomicros-copy. Ophthalmology. 1991;98(3):287-95.

14. Madhavan C, Basti S, Naduvilath TJ, Sangwan VS. Use of ultrasound biomicroscopic eva-luation in preoperative planning of penetrating keratoplasty. Cornea. 2000;19(1):17-21.

15. Avitabile T, Russo V, Ghirlanda R, Castiglione F, Marino A, Reibaldi A. Corneal oedemas: diagnosis and surgical planning with ultrasound biomicroscopy. Ophthalmologica. 1998;212 Suppl 1:13-6.

16. Allemann N, Chamon W, Silverman RH, Azar DT, Reinstein DZ, Stark WJ, et al. High-fre-quency ultrasound quantitative analyses of corneal scarring following excimer laser keratectomy. Arch Ophthalmol. 1993;111(7):968-73.

17. Paris Fdos S, Goncalves ED, Barros Jde N, Campos MS, Sato EH, Gomes JA. Impression cytology findings in bullous keratopathy. Br J Ophthalmol. 2010;94(6):773-6.

18. Johnson RA, Wichern DW. Applied Multivariate Statistical Analysis. 6th ed. New Jersey; 2007.

19. Brunner E, Langer F. Nonparametric analysis of ordered categorical data in designs with longitudinal observations and small sample sizes. Biom J. 2000;42(6):663-75.

20. Fisher LD, van Belle G. Biostatistics. New York: John Wiley & Sons; 1993. 21. Ghosheh FR, Cremona FA, Rapuano CJ, Cohen EJ, Ayres BD, Hammersmith KM, et al.

Trends in penetrating keratoplasty in the United States 1980-2005. Int Ophthalmol. 2008;28(3):147-53.

22. Tan DT, Janardhanan P, Zhou H, Chan YH, Htoon HM, Ang LP, et al. Penetrating ke-ra toplasty in Asian eyes: the Singapore Corneal Transplant Study. Ophthalmology. 2008;115(6):975-82 e1.

23. Goncalves ED, Campos M, Paris F, Gomes JA, Farias CC. [Bullous keratopathy: etiopa-thogenesis and treatment]. Arq Bras Oftalmol. 2008;71(6 Suppl):61-4. Portuguese.

24. Al-Yousuf N, Mavrikakis I, Mavrikakis E, Daya SM. Penetrating keratoplasty: indications over a 10 year period. Br J Ophthalmol. 2004;88(8):998-1001.

25. Sano FT, Dantas PE, Silvino WR, Sanchez JZ, Sano RY, Adams F, et al. [Trends in the indi-cations for penetrating keratoplasty]. Arq Bras Oftalmol. 2008;71(3):400-4. Portuguese.

26. Fabris C, Corrêa ZMS, Marcon AS, Castro TN, Marcon ÍM, Pawlowski C. Estudo retros-pectivo dos transplantes penetrantes de córnea da Santa Casa de Porto Alegre. Arq Bras Oftalmol. 2001;64(5):449-53.

27. Sridhar MS, Vemuganti GK, Bansal AK, Rao GN. Impression cytology-proven corneal stem cell deficiency in patients after surgeries involving the limbus. Cornea. 2001;20(2): 145-8.

28. Said DG, Nubile M, Alomar T, Hopkinson A, Gray T, Lowe J, et al. Histologic features of transplanted amniotic membrane: implications for corneal wound healing. Ophthal-mology. 2009;116(7):1287-95.

A C e

B D f

figure 3. Ultrasound biomicroscopy in bullous keratopathy. Preoperative measures (3A, 3C, and 3E) demonstrating stromal hyper-reflectivity and thickening, epithelial thickening, and posterior surface irregularity (Descemet’s membrane folds). Total corneal thickness was found to be 1,725 (3A), 689 (3C), and 880 µm (3E). Examples of each group of treatment: 3B. Anterior stromal puncture with reduction in thickness (1,476 µm); 3D. Amniotic membrane transplantation (membrane positioned at the corneal surface, interface detected); 3F. Amniotic membrane transplantation with a complication: presence of fluid in the interface between the membrane and corneal surface.

Original Article


InTRODUCTIOn Trypan blue (TB) is used to facilitate the creation of a continuous

curvilinear capsulorhexis during cataract surgery(1,2). Several methods have been used to assess the toxic effects of TB on corneal cells: the concentration-related effect of TB on corneal cell viability; the effects of duration of exposure to TB on cell survival; the effect of the vehicle on the degree of TB toxicity; and the damage caused by (experimen-tal) manipulation of cells or endothelia(3).

Several experimental and clinical studies have tested the cyto-toxicity of TB on various ocular anterior segment structures during cataract surgery, and all have demonstrated good biocompatibility

for conventional intracameral application of TB 0.1%. However, in vitro studies have demonstrated toxicity of TB to corneal endothelium and corneal fibroblasts at higher concentrations and longer exposure times(4-7). Briefly, at commonly used concentrations, both during ca-taract surgery and in corneal tissue banks, TB is harmless to corneal cells. However, at higher concentrations or longer exposures, extre-me caution is warranted.

Oxidative stress is believed to be a central mechanism of the cellular damage affecting all organs and tissues. Oxygen-derived free radicals appear to be responsible for injury to various organs, and apoptosis mediated by oxidative stress is well established(8-11). Considering the

Evaluation of the safety of intracameral trypan blue injection on corneal tissue using oxidative stress parameters and apoptotic activity: an experimental study Avaliação da segurança de injeção de azul de tripan intracameral no tecido da córnea utilizando parâmetros de estresse oxidativo e atividade apoptótica: um estudo experimental

ali akal1, turgay ulaS2, tugba goncu1, MehMet Fatih adibelli1, Sezen kocarSlan3, MuhaMMet eMin guldur3, MuSluM guler4, uFuk ozkan5, MehMet duSunur1, tuncer deMir6

Submitted for publication: July 31, 2014 Accepted for publication: October 12, 2014

Study conducted at Harran University School of Medicine, Department of Ophthalmology.1 Department of Ophthalmology, Faculty of Medicine, Harran University, Sanliurfa, Turkey.2 Department of Internal Medicine, Faculty of Medicine, Harran University, Sanliurfa, Turkey.3 Department of Pathology, Faculty of Medicine, Harran University, Sanliurfa, Turkey.4 Department of Ophthalmology, Balikligol Training and Research Hospital, Sanliurfa, Turkey.5 Department of Biochemistry, Harran University, Faculty of Medicine, Sanliurfa, Turkey.6 Department of Physiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.



Corresponding author: Ali Akal. Harran University School of Medicine. Department of Ophthalmo-logy - Yenisehir Campus - Sanliurfa - 63000 - Turkey - E mail: [email protected]

ABSTRACT Purpose: The present experimental study aimed to investigate the effects of intracameral trypan blue (TB) on oxidative stress parameters and apoptosis in cor neal tissue. Methods: Thirty rats were randomly assigned to three groups of 10 rats each: the sham group (Group 1); control group (Group 2); and treatment group (Group 3). The control group was administered 0.01 cc of balanced salt solution. The treatment group was administered 0.006 mg/0.01 cc of TB. The total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood were measured and the oxidative stress index (OSI) was calculated. Finally, corneal tissue histopathology was evaluated using staining for caspase-3 and -8, and apoptotic activity was examined. Results: The TAS, TOS and OSI levels in the blood samples were not significantly different (p>0.05 for all). Compared with the sham and control groups, the TOS and OSI levels in corneal tissue were significantly different in the treatment group (p<0.05 for all). No significant difference was observed between the sham group and the control group (p>0.05). Immunohistochemical staining for caspase-3 and caspase-8 demonstrated higher apoptotic activity in the TB group than in the sham and control groups. Conclusion: The present study showed that intracameral TB injection is safe systematically but may be toxic to corneal tissue, as demonstrated using oxidative stress parameters and histopathological evaluation.

Keywords: Trypan blue/administration & dosage; Injections; Intraocular; Cornea; Oxidative stress; Apoptosis; Animals; Rats

RESUMO Objetivo: Este estudo experimental tem como objetivo investigar os efeitos do azul de tripan intracameral (TB) sobre parâmetros de estresse oxidativo e apoptose no tecido da córnea. Métodos: Trinta ratos foram divididos aleatoriamente em três grupos de 10 ani mais cada: grupo simulação (Grupo 1); grupo controle (Grupo 2); e grupo tratamento (Grupo 3). No grupo controle foi administrado 0,01 cc de solução salina balanceada (BSS). No grupo tratamento foi administrado 0,006 mg/0,01 cm de TB. O estado antioxidante total ( TAS) e estado oxidante total ( TOS) no tecido da córnea e sangue foram medidos e o índice de estresse oxidativo (OSI) foi calculado. Finalmente, histopatologia do tecido da córnea foi avaliada por meio da coloração para caspase-3 e -8; atividade apoptótica também foi examinada. Resultados: Os níveis de TAS, TOS e OSI das amostras de sangue não foram significa-tivamente diferentes (p>0,05 para todos). Em comparação com os grupos simulação e controle, os níveis de TOS e OSI no tecido da córnea foram significativamente diferentes no grupo tratamento (p<0,05 para todos). Não houve diferença significativa entre o grupo simulção e o grupo controle (p>0,05). A coloração imuno-histoquímica com a caspase-3 e caspase-8 demonstrou maior atividade apoptótica no grupo tratamento do que nos grupos controle e simulação. Conclusão: Este estudo mostrou que a injeção intracameral TB é segura sistemati-camente, mas pode ser tóxica ao tecido da córnea, como demonstrado através de parâmetros de estresse oxidativo e avaliação histopatológica.

Descritores: Azul tripano/administração & dosagem; Injeções intraoculares; Córnea; Estresse oxidativo; Apoptose; Animais; Ratos

Akal A, et al.


controversial safety results of TB on corneal tissue mentioned above, the current study aimed to further investigate the possible toxic effects of TB using oxidative stress parameters and the degree of apoptosis in corneal tissue.

MeTHODSaNImalS aND experImeNtal GrOUpS

Thirty adult male Wistar Albino rats, aged 4-8 weeks and weighing 180-200 g each, were used. Animals were housed under continuous observation in appropriate cages under ambient temperature (21 ± 2°C) and humidity (60% ± 5%) with a 12-h light:dark cycle. The animals were housed five per cage and fed a commercial standard diet with water ad libitum. All experiments in the present study were perfor-med in accordance with the “Principles of Laboratory Animal Care” and were approved by the Ethical Committee on Human and Animal Research at Harran University, Sanliurfa, Turkey.

Rats were randomly assigned to three groups of 10 rats each as follows: the sham group (Group 1) (n=10); the control group (Group 2) (n=10), which was administered 0.01 cc balanced sterile salt solution (BSS); and the treatment group (Group 3) (n=10), which was adminis-tered 0.006 mg/0.01 cc TB.

The total antioxidant status (TAS) and total oxidant status (TOS) were measured in corneal tissue and blood, and the oxidative stress index (OSI) was calculated. Corneal tissue histopathology was evalua-ted using caspase-3 and caspase-8 staining, and apoptotic activity was assessed.

SUrGICal prOCeDUreS aND tISSUe preparatION

Intracameral injection technique

Before the intracameral injection, the rats were aseptically anes-thetized with an intramuscular injection of 50 mg/kg ketamine (Ke-talar; Parke Davis, Eczacibasi, Istanbul, Turkey) and 10 mg/kg xylazine (Rompun; Bayer AG, Leverkusen, Germany). Topical anesthetic drops (0.5% proparacaine) were applied to the rats’ eyes 10 min before injection. The globe was then detached from the edge of the limb using horizontal angled conjunctival forceps with teeth; anterior chamber injections, tangential to the limbus, were then administered at 3 o’clock using an insulin syringe [0.30 x 8 mm (30-G x 5/16’’) (Ayset Medical Products Industry Co., Adana, Turkey)] under guidance using a YZ20T9 microscope (Nanjing, Redsun Optical Co., Ltd. Jiangsu, Chi-na). Group 1 received no injection; Group 2 received intracameral BSS (0.01 cc) [Industrıa Farmaceutica Galenica Senese Materino d’Arbia (SI), Italy]; and Group 3 received intracameral TB (0.006 mg/0.01 cc) (Bio-Blue, Biotech Ophthalmics Pvt. Ltd, Gujarat, India). After 7 days, two rats in Group 2 and one rat in Group 3 had died.

After 7 days, rats were again anesthetized before enucleation. To reach the back of the globe, pressure was applied to the edge of the limb using conjunctival forceps and enucleation was performed using corneoscleral scissors. Following enucleation, the bulbus oculi was removed, after which all animals were euthanized by exsangui-nation. Round corneal specimens were removed via a limbal incision using a 15° corneal blade; the histopathological specimens were placed in 10% formaldehyde and the biochemical specimens were placed into dry boxes. Last, a 3-cm midline abdominal incision was made and 1.5 cc of blood was drawn from the inferior vena cava. The tissue and blood samples were stored at -70°C until measurement of TAS and TOS activity.

Repeatability of the experimental results: With regard to the re-peatability of this experimental result (i.e., whether it is sufficiently re peatable in different trials), the experimental protocol does not in-volve any different techniques compared with previously published studies, which will help to improve the stability and repeatability of the experimental results.

CaSpaSe-3 aND -8 StaINING

The samples were fixed with 10% formaldehyde and 4 µm thick spe-cimens obtained from paraffin blocks were stained using a standard streptavidin-biotin immunoperoxidase method with anti-caspase-3 (cleaved) (Clone: N/A, Catalog No: PP 229 AA, Biocare Medical) and -caspase-8 antibodies (Clone: C502S, Catalog No: GTX59555, Gene Tex). Tonsillar tissue was used as a positive control, and all specimens were evaluated using light microscopy (Olympus BX51TF, Olympus Corporation, Tokyo, Japan). Also, immunohistochemical staining was evaluated semi-quantitatively using a scale from 0 to 3, on which ne gative staining was rated 0, weak staining was rated 1, moderate staining was rated 2 and intense staining was rated 3.

taSThe TAS of supernatant fractions was determined using a novel

automated measurement method developed by Erel(12). This method produces the hydroxyl radical, the most potent biological radical. In the assay, ferrous ion solution, present in Reagent 1, is mixed with hydrogen peroxide, present in Reagent 2. The resulting radicals, such as a brown-colored dianisidinyl radical cation produced by the hydro-xyl radical, are very potent. Using this method, the anti-oxidative effect of the sample against the potent free radical reactions, which are initiated by the produced hydroxyl radical, is measured. The assay yields precision values <3%. The results are expressed as nmol Trolox equivalents/mg protein.

tOSThe TOS of supernatant fractions was determined using a novel

automated measurement method developed by Erel(13). The oxi-dants in the sample oxidize the ferrous ion-o-dianisidine complex to a ferric ion. The oxidation reaction is enhanced by glycerol in the reaction medium. The ferric ion creates a colored complex with xylenol orange in an acidic medium. The color intensity can be mea-sured spectrophotometrically and is related to the total amount of oxidant molecules present in the sample. The assay is calibrated using hydrogen peroxide, and the results are expressed in terms of nmol H

2O

2 equivalents/mg protein.

OSIThe OSI was defined as the ratio of TOS to TAS levels. For calcula-

tions, TAS units were converted to mmol/L, and the OSI was calcu-lated according to the following formula: OSI (arbitrary units) = TOS (μmol H

2O

2 equivalents/L)/TAS (mmol Trolox equivalents/L)(12,13).

StatIStICal aNalySIS

All statistical analyses were performed using SPSS for Windows software, version 17.0 (SPSS, Chicago, IL, USA), and non-parametric in -dependent group comparisons were performed. Data were expressed as medians, minimums and maximums. The Kruskal-Wallis was used for multiple comparisons between groups and the Mann-Whitney test was used if statistical significance was found. A two-sided p value <0.05 was considered to indicate statistical significance.

ReSULTSThe TAS, TOS and OSI levels of the blood samples and corneal tissues

are presented in tables 1 and 2. The TAS, TOS and OSI levels in the blood samples were not significantly different among the groups (p>0.05 for all). The OSI levels in corneal tissue were significantly diffe-rent in the TB group compared with the sham and control groups (p<0.05 for all); however, no significant difference was found between the control and sham groups (p>0.05 for all). Additionally, immuno-histochemical staining for caspase-3 and -8 showed higher apoptotic activity in the TB group than in the sham and control groups (Tables 3 and 4; Figures 1 and 2).

Evaluation of the safety of intracameral trypan blue injection on corneal tissue using oxidative stress parameters and apoptotic activity: an experimental study


viscosurgical device, before washout(14). Most studies investigating potential TB toxicity have examined the effects of TB on corneal cells in vitro(1,3,4,15,16). Panda et al. included 205 eyes of 205 patients that had undergone phacoemulisification of cataracts or corneal opacities(17). The authors revealed that TB (0.06%) dye-assisted capsulorhexis was successfully completed in all eyes and the patients were followed up at day 1, day 7, and one and three months postoperatively. Also, some studies found good biocompatibility at incubation times of up to 15 min and concentrations up to 0.40%, indicating that TB is safe for corneal endothelial cells(3,4,15,18-21). Chung et al. also evaluated the sa-fety of TB 1% for assisting visualization of the anterior capsule during phacoemulsification of a mature cataract, and found it to be safe(22). Moreover, Norn reported the perioperative use of this dye (at 0.1%) for the staining of corneal endothelium in anterior segment surgery. No ocular complications were found during eight years of follow-up. Additionally, Melles et al. advocated the use of TB (0.1 mL of a 0.06% solution) to visualize the anterior capsule in cataract surgery(1,15).

Although the safety of TB is well established, it is not without re ports of toxicity. Several animal studies have indicated that TB has teratogenic and carcinogenic potential(16,23,24). In animal studies, in-crea sing the concentration from that used clinically (0.006 mg) to 0.017% resulted in a 38% reduction in endothelial cell viability using generic TB and 15% using the proprietary TB. When the concentration was increased to 0.05%, viability decreased by 55% with generic TB, and by 30% with the proprietary TB. A study performed using corneal fibroblasts and endothelial cells in human donor eyes demonstrated a TB-induced dose-dependent cytotoxic effect after incubation times of up to 24 h. High TB concentrations and long incubation times have also been shown to exhibit significant cytotoxicity in human cultured corneal endothelial cells(14,25).

Given these findings, controversy exists over whether TB is safe for corneal tissue. In our study, we detected no systemic effects using oxidative stress parameters from blood samples; however, caspase-3 and -8 staining demonstrated increased apoptotic activity in the corneal tissue samples, and levels of oxidative stress markers were also increased.

COnCLUSIOnSOur evaluation showed that intracameral TB is safe systemically

but may be toxic to corneal tissue, as confirmed by histopathological evaluation. However, the present study was performed in animals and future clinical studies are needed to support these findings in hu -mans.

Table 1. Biochemical oxidative stress parameters

Sham group (n=10) Control group (n=8) Trypan blue group (n=9) p-value

TAS (mmol Trolox equivalents/L) 01.00 (00.90, 01.13) 01.00 (00.90, 01.48) 01.00 (00.91, 01.18) 0.890

TOS (μmol H2O

2 equivalents/L) 28.65 (16.20, 53.12) 39.15 (15.21, 69.42) 22.13 (15.21, 70.34) 0.112

OSI (arbitrary units) 02.85 (01.79, 06.10) 04.29 (03.00, 06.10) 03.24 (02.11, 05.96) 0.109

The variables expressed as median (minimum, maximum). The Kruskal-Wallis test was used; TAS= total antioxidant status; TOS= total oxidant status; OSI= oxidative stress index.

Table 2. Corneal tissue oxidative stress parameters

Sham group (n=10) Control group (n=8) Trypan blue group (n=9) p-value

TAS (mmol Trolox equivalents/L) 0.28 (0.14, 0.44) 0.52 (0.17, 0.97) 0.25 (0.16, 0.29)¥, £ 0.068

TOS (μmol H2O

2 equivalents/L) 5.13 (2.67, 9.51) 4.18 (1.38, 8.25) 4.01 (1.98, 4.73)¥, £ 0.125

OSI (arbitrary units) 1.27 (1.01, 1.71) 1.35 (1.02, 1.96) 1.82 (1.48, 2.04)¥, £ 0.002

The variables expressed as median (minimum, maximum). Kruskal-Wallis and Mann-Whitney U tests were used; TAS= total antioxidant status; TOS= total oxidant status; OSI= oxidative stress index; Trypan blue vs sham¥= p=0.001; Trypan blue vs control£= p=0.012.

Table 3. Immunohistochemical staining for caspase-3

0 + ++ +++ Total

Sham group 9 1 - - 10

Control group 7 1 - - 08

Trypan blue group 4 4 1 - 09

Table 4. Immunohistochemical staining for caspase-8

0 + ++ +++ Total

Sham group 9 1 - - 10

Control group 6 2 - - 08

Trypan blue group 3 4 2 - 09

figure 1. Immunohistochemical staining of the endothelial cells for caspase-3. Negative (A), weak (B), and moderate (C) (caspase-3 × 400).

A B C

A B C

figure 2. Immunohistochemical staining of the endothelial cells for caspase 8. Negative (A), weak (B), and moderate (C) (caspase-8 × 400).

DISCUSSIOnThe present study yielded intriguing results and, to our knowled-

ge, is the first report of the safety of intracameral TB in corneal tissue using oxidative stress parameters and apoptotic activity. The present study showed that although intracameral TB does not exert a syste-mic effect, it might be locally toxic to corneal tissue.

Clinically, TB is commonly used at 0.06% or 0.10%, and is instilled into the anterior chamber for 1 min, with or without air or an ophthalmic

Akal A, et al.


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11. Tanaka Y, Komatsu T, Shigemi H, Yamauchi T, Fujii Y. BIM(EL) is a key effector molecule in oxidative stress-mediated apoptosis in acute myeloid leukemia cells when combi-ned with arsenic trioxide and buthionine sulfoximine. BMC Cancer. 2014;14:27.

12. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11.

13. Erel O. A novel automated method to measure total antioxidant response against po tent free radical reactions. Clin Biochem. 2004;37(2):112-9.

14. Thaler S, Hofmann J, Bartz-Schmidt KU, Schuettauf F, Haritoglou C, Yoeruek E. Methyl blue and aniline blue versus patent blue and trypan blue as vital dyes in cataract surgery: capsule staining properties and cytotoxicity to human cultured corneal endothelial cells. J Cataract Refract Surg. 2011;37(6):1147-53.

15. Norn MS. Per operative trypan blue vital staining of corneal endothelium. Eight years’ follow up. Acta Ophthalmol (Copenh). 1980;58(4):550-5.

16. Veckeneer M, van Overdam K, Monzer J, Kobuch K, van Marle W, Spekreijse H, van Meurs J. Ocular toxicity study of trypan blue injected into the vitreous cavity of rabbit eyes. Graefes Arch Clin Exp Ophthalmol. 2001;239(9):698-704.

17. Panda A, Krishna SN, Dada T. Outcome of phacoemulsification in eyes with cataract and cornea opacity partially obscuring the pupillary area. Nepal J Ophthalmol. 2012; 4(2):217-23.

18. Sperling S. Evaluation of the endothelium of human donor corneas by induced di-lation of intercellular spaces and trypan blue. Graefes Arch Clin Exp Ophthalmol. 1986; 224(5):428-34.

19. Chang YS, Tseng SY, Tseng SH, Chen YT, Hsiao JH. Comparison of dyes for cataract surgery. Part 1: cytotoxicity to corneal endothelial cells in a rabbit model. J Cataract Refract Surg. 2005;31(4):792-8.

20. Kothari K, Jain SS, Shah NJ. Anterior capsular staining with trypan blue for capsulorhe-xis in mature and hypermature cataracts; a preliminary study. Indian J Ophthalmol. 2001;49(3):177-80.

21. Yoeruek E, Spitzer MS, Tatar O, Aisenbrey S, Bartz-Schmidt KU, Szurman P. Safety profile of bevacizumab on cultured human corneal cells. Cornea. 2007;26(8):977-82.

22. Chung CF, Liang CC, Lai JS, Lo ES, Lam DS. Safety of trypan blue 1% and indocyanine green 0.5% in assisting visualization of anterior capsule during phacoemulsification in mature cataract. J Cataract Refract Surg. 2005;31(5):938-42.

23. Chung KT. The significance of azo-reduction in the mutagenesis and carcinogenesis of azo dyes. Mutat Res. 1983;114(3):269-81.

24. Ema M, Kanoh S. [Studies on the pharmacological bases of fetal toxicity of drugs. (II). Effect of trypan blue on the pregnant rats and their offspring]. Nihon Yakurigaku Zasshi. 1982;79(5):369-81.

25. Buzard K, Zhang JR, Thumann G, Stripecke R, Sunalp M. Two cases of toxic anterior seg-ment syndrome from generic trypan blue. J Cataract Refract Surg. 2010;36(12):2195-9.

Case Report


InTRODUCTIOnCorneal laceration is one of the leading causes of ocular morbi-

dity(1). Preoperative evaluation of these cases requires meticulous assessment of the etiological agent and extent of the injury. Surgical management of corneal lacerations requires understanding of the wound architecture in order to use appropriate suturing technique to minimize corneal scarring and restore anatomical integrity of the globe. Postoperatively, corneal penetrating injuries have the risk of developing wound leakage, epithelial ingrowth, and excessive corneal astigmatism(2). Wound overriding is a rare but serious complication of the surgical management of ocular penetrating injuries; it is caused by unequal suturing of both sides of oblique corneal wounds.

Ultrasound biomicroscopy (UBM) is a valuable diagnostic tool and is preferred in the detailed evaluation of the anterior segment. UBM has the ability to evaluate anterior segment structures, including the structures posterior to the iris plane. The ability of UBM to completely analyze all structures of the anterior segment makes it a valuable tool in the preoperative evaluation of traumatic cases(3).

In this paper, we present the clinical properties of a case of cor -neal overriding that developed after surgical management of a case with corneal laceration. We used UBM in the diagnosis of corneal overriding as slit lamp examination did not demonstrate the exact

structure of the corneal wound due to severe irregularity and loca-lized corneal edema. To the best of our knowledge, our paper is the first study to demonstrate the use of UBM in the management of abnormal wound architecture of a corneal laceration.

CASe RePORTA 28-year-old male soldier with a history of penetrating ocular

injury caused by a bayonet was referred to our institution. The prima-ry suturation was performed at another institution 2 months ago. Ocular examination of the patient’s left eye was unremarkable with a visual acuity of 20/20. Visual acuity in the right eye was light per-ception. Slit lamp examination demonstrated a horizontal limbus to limbus laceration between the 3 and 9 o’clock positions in the cornea (Figure 1 A). The corneal wound was sutured with multiple, single, interrupted sutures. There was a 2.5-mm difference between hori-zontal and vertical white-to-white measurements. There was vitreous hemorrhage and the retina was attached in B-scan ultrasonography.

Slit lamp findings were inconclusive; we used UBM to define the wound architecture in detail. UBM was performed with the patient in the supine position after receiving topical anesthesia. A 50-MHz probe was used with an immersion technique (OTI Scan, Ophthalmic Technologies, Inc.). UBM images demonstrated significant overriding

Ultrasound biomicroscopy confirmation of corneal overriding due to improper suturing of full-thickness corneal laceration Confirmação por biomicroscopia ultrassônica de encavalamento corneano devido à sutura inadequada de laceração de espessura total da córnea

Murat kucukevcilioglu1,2, volkan hurMeric3

Submitted for publication: January 6, 2914 Accepted for publication: February 17, 2014

Study conducted at Gulhane Military Medical School, Department of Ophthalmology and World Eye Hospital, Ankara.

1 University of Iowa, Department of Ophthalmology, Iowa City, Iowa, USA.2 Gulhane Military Medical School, Department of Ophthalmology, Ankara, Turkey.3 World Eye Hospital, Ankara, Turkey.



Corresponding author: Murat Kucukevcilioglu. GATA Goz Klinigi - Etlik, Ankara - Turkey E-mail: [email protected]

ABSTRACTWe herein present a case with corneal overriding due to improper suturing of a full-thickness corneal laceration. There was a 2.5-mm difference between ho-rizontal and vertical white-to-white measurements in the cornea. However, slit lamp examination failed to demonstrate the exact architecture of the laceration. Ultrasound biomicroscopy defined the wound edges thoroughly and confirmed the presence of corneal overriding. Six weeks after suture enhancement, the abnor mal oval appearance of the cornea was absent and correct apposition of the corneal edges was seen on ultrasound biomicroscopy. Ultrasound biomicroscopy can be used in preoperative surgical planning of cases with complicated corneal lacerations. It can be used to adjust and enhance wound architecture in eyes with penetrating injury.

Keywords: Cornea/injuries; Lacerations; Eye injuries, penetrating/ultrasonography; Suture techniques; Humans; Male; Adult; Case reports

RESUMO Apresentamos um caso com encavalamento corneano devido à sutura inadequa da de uma laceração da córnea de espessura total. Houve uma diferença 2,5 mm entre as medidas do branco ao branco horizontais e verticais na córnea. No entanto, o exame da lâmpada de fenda não conseguiu demonstrar a arquitetura exata da laceração. A biomicroscopia ultrassônica definiu as bordas da ferida completamente e confirmou a presença de encavalamento da córnea. Seis semanas após a melhora da sutura, a aparência oval anormal da córnea havia desaparecido, e a correta aposição das bordas da córnea foi identificada na biomicroscopia ultrassônica. A biomicroscopia ultrassônica pode ser usada no planejamento cirúrgico pré-operatório de casos com lacerações corneanas complicadas. Ela pode ser utilizada para ajustar e melhorar a arquitetura da ferida em olhos com lesão penetrante.

Descritores: Córnea/lesões; Lacerações; Ferimentos oculares penetrantes/ultrasso-nografia; Técnicas de sutura; Humanos; Masculino; Adulto; Relatos de casos

Kucukevcilioglu M, Hurmeric V


of the corneal wound edges in the central part of the cornea (Figure 2 A). We discussed surgical alternatives with the patient and sugges-ted adjustment of the corneal sutures before starting management of the vitreous hemorrhage.

Surgery was performed under general anesthesia. All of the corneal sutures were cut and re-sutured according to the oblique architecture of the wound. The postoperative 6-week visit demons-trated proper alignment of the cornea (Figure 1 B). The structure of the wound edges was analyzed with UBM, demonstrating correct apposition of the corneal wound edges (Figure 2 B). The patient was managed with pars plano vitrectomy, and visual acuity was 20/200 at his last visit at 4 months after the corneal laceration.

DISCUSSIOnIn our case, we used UBM to demonstrate the exact architecture

of the corneal wound. Our patient had a history of ocular penetrating injury with a sharp object; however, slit lamp examination demons-

trated a significant difference in white-to-white measurements in the horizontal and vertical planes of the cornea. UBM images helped us exclude corneal tissue loss and changed our surgical approach. After the confirmation of inappropriate suturing of the corneal wound with UBM, we preferred to treat the patient with suture enhancement instead of penetrating keratoplasty.

Anterior segment imaging techniques have limited applications in the management of anterior segment trauma. UBM has been used in several corneal pathologies, including edema, keratoconus, dystrophies, corneal scars, and trauma(4). Anterior segment optical coherence tomography (AS-OCT) and Scheimpflug imaging are al-ternative imaging techniques that could have been used in our case. AS-OCT is a no-touch technique that could also have been used on our patient(5). With its higher lateral and axial resolution, AS-OCT can provide a more detailed image of the cornea. However, our facility does not have this imaging tool at present, and UBM was found to be quite satisfactory in imaging the corneal wound. Scheimpflug imaging has been used in penetrating injuries to analyze the localiza-

A B

figure 1. Slit lamp image demonstrating the horizontal laceration with an irregular wound architecture, edema and a significant difference in white-to-white measurements in the horizontal and vertical planes of the cornea (A). Slit lamp image demonstrating favorable wound architecture and substantial recovery in the shape of the cornea after suture enhancement surgery (B).

figure 2. Preoperative ultrasound biomicroscopy of the cornea showing over-ri ding of the wound edges (white arrow demonstrates the upper flap, white arrow head demonstrates the lower flap and asterisks demonstrate the anterior synechia) (A). Postoperative ultrasound biomicroscopy of the cornea showing correct apposition of the wound edges (white arrow indicates the start point of the oblique laceration on the anterior surface of the cornea) (B).

Ultrasound biomicroscopy confirmation of corneal overriding due to improper suturing of full-thickness corneal laceration


tion and dimensions of anterior segment foreign bodies(6). However, Scheimpflug imaging has limited imaging quality in corneal opacities and edema, which rendered it unsuitable in our presented case.

The most significant disadvantages of UBM are the need for immersion, the necessity of the supine position, and the need for pa-tient cooperation during image acquisition. UBM is a user-dependent technique and requires an experienced imaging technician. We used the classic “shell and gel technique” in our patient, which requires insertion of a hard plastic shell inside the eye(7). Furthermore, recently introduced disposable ultrasound probe covers eliminate the need for the supine position and insertion of a plastic shell during image acquisition with UBM. In open-globe injuries and uncooperative pa-tients, UBM can be used with disposable probe covers.

Corneal lacerations must be addressed according to the pattern of the wound(8). In oblique corneal lacerations, the length of passage of the suture in the stroma should be equal to the posterior aspect of the corneal laceration. The distance between the needle entry site and the posterior edge of the oblique incision must be gauged from the posterior aspect of the cornea(9).

In conclusion, UBM can be used in preoperative surgical planning of cases with complicated corneal lacerations. It can be used to adjust and enhance wound architecture in eyes with penetrating injuries. UBM with the soft-shell technique has the potential to be used as a

pre-surgical diagnostic tool to better understand wound architecture in anterior segment injuries.

RefeRenCeS 1. Thakker MM, Ray S. Vision-limiting complications in open-globe injuries. Can J Ophthal-

mol. 2006;41(1):86-92. 2. Barr CC. Prognostic factors in corneoscleral lacerations. Arch Ophthalmol. 1983;101(6):

919-24. 3. Kucukevcilioglu M, Hurmeric V, Ceylan OM. Preoperative detection of posterior

capsule tear with ultrasound biomicroscopy in traumatic cataract. J Cataract Refract Surg. 2013;39(2):289-91.

4. Silverman RH. High-resolution ultrasound imaging of the eye - a review. Clin Experiment Ophthalmol. 2009;37(1):54-67.

5. Wylegala E, Dobrowolski D, Nowinska A, Tarnawska D. Anterior segment optical co-herence tomography in eye injuries. Graefes Arch Clin Exp Ophthalmol. 2009;247(4): 451-5.

6. Arora R, Mehta S, Goyal JL, Pahuja S, Gupta D, Gupta R. Pattern of Scheimpflug imaging in anterior segment foreign bodies. Eye (Lond). 2010;24(7):1304-6.

7. Bell NP, Anand A, Wanger A, Prager TC. Microbial contamination of ultrasound biomi-croscopy probes: evaluation of cross-infection risk. J Cataract Refract Surg. 2012;38(1): 174-5.

8. Akkin C, Kayikcioglu O, Erakgun T. A novel suture technique in stellate corneal lacera-tions. Ophthalmic Surg Lasers. 2001;32(5):436-7.

9. Macsai MS. The management of corneal trauma: advances in the past twenty-five years. Cornea. 2000;19(5):617-24.

Case Report


InTRODUCTIOnPupil abnormalities are common in patients with leprosy(1-4). Cha-

racteristically, the pupils show persistent miosis, sluggish reaction to light, and poor dilation in response to anticholinergic mydriatics. They are usually associated with chronic iritis and iris atrophy, loss of iris stroma and development of synechiae as well as corneal and lenticular changes that cause visual loss. These changes have been ascribed to postganglionic sympathetic denervation of the dilator muscle cells(1).

We report two patients with leprosy who presented unexpected pupillary features of tonic pupil, such as mydriasis, abolished reaction to light, exaggerated miosis during accommodation, and a hyper-sensitive reaction to weak cholinergic solutions(5,6). To the best of our knowledge, tonic pupils had not been previously described in leprosy.

CASe RePORTSCaSe 1

A 33-year-old white woman with lepromatous leprosy for 10 years was referred for neuro-ophthalmological evaluation due to a 1-year history of intermittent anisocoria. She stated that on awakening in the mornings, she frequently noticed that her left pupil was dilated but decreased in size during the course of the day, usually reaching sym-metry with the right pupil in the late afternoon. She had completed the WHO-recommended antileprosy multidrug therapy (MDT).

Ophthalmic examination revealed a corrected visual acuity at a distance of 20/20 OU. Slit-lamp biomicroscopy was unremarka-

ble and the intraocular pressure was 10 mmHg OU. In dim light, the right pupil measured 3 mm and the left pupil 5 mm. The left pupil showed neither direct nor consensual reaction to light and did not constrict on immediate attempted accommodation. The right pupil constricted to near vision and to light. After instillation of a drop of dilute 0.1% pilocarpine OU, the right pupil showed no constriction, whereas the left pupil constricted to 1 mm in diameter. The rest of the examination was negative.

CaSe 2A 42-year-old black woman with lepromatous leprosy for 22 years

was examined because of anisocoria associated with diffuse episcle-ritis in both eyes. She had experienced recurring anterior uveitis in both eyes and had been treated with MDT for five years associated with intermittent courses of oral prednisone.

On examination the visual acuity was 20/20 OD and 20/20 OS. Slit-lamp biomicroscopy disclosed evidence of diffuse scleritis OU. Ophthalmoscopy was unrevealing. The right pupil measured 6 mm in diameter and did not react to light or accommodation. The left pupil was 3 mm in diameter and showed normal constriction to light and near vision. Thirty minutes after instillation of pilocarpine 0.1%, the right pupil constricted to 1 mm whereas the left pupil remained unchanged. One month later the patient noticed that her left pupil was also dilated. The right pupil measured 7 mm in diameter and the left pupil 6 mm. Neither pupil constricted to light or attempted accommo dation. Instillation of pilocarpine 0.1% provoked a remarka-ble miosis bilaterally (Figures 1-4). The patient was again put on ste-roids and anti-leprosy drugs.

Tonic pupil in leprosyPupila tônica em doença de Hansen

Marco aurélio lana-Peixoto1, WeSley ribeiro caMPoS1, Pedro auguSto coSta reiS1, chriStian MarcelluS caMargo caMPoS1, carloS alberto rodrigueS2

Submitted for publication: September 30, 2013 Accepted for publication: May 1, 2014

Study conducted at Department of Ophthalmology, Universidade Federal de Minas Gerais Belo Horizonte (UFMG), MG, Brazil.

1 Department of Ophthalmology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

2 In Memoriam.



Corresponding author: Wesley Ribeiro Campos. Rua Lavras, 599 - Passos, MG - 37902-314 - Brazil - E-mail: [email protected]

ABSTRACTPupil abnormalities in leprosy usually result from chronic iritis with loss of stroma, iris miosis, a sluggish reaction to light, and poor dilation in response to anticholinergic mydriatics. We report two patients with long-standing leproma-tous leprosy who developed tonic pupils characterized by mydriasis, absence of reaction to light and hypersensitivity to weak cholinergic solution. Examination revealed iritis and iris atrophy. In both cases, instillation of dilute 0.1% pilocarpine caused miosis in the affected eyes. Tonic pupil occurs in many conditions, but its association with leprosy had not been previously reported.

Keywords: Tonic pupil; Mydriasis; Leprosy; Iritis; Iris/injuries; Atrophy; Case reports

RESUMOAnormalidades da pupila em pacientes com doença de Hansen, ocorrem mais co-mumente devido a irite crônica com perda do estroma iriano, miose, diminuição da reação à luz, e dificuldade de dilatação em resposta a colírios anticolinérgicos. Relatamos dois pacientes com doença de Hansen na forma lepromatosa que de-senvolveram pupilas tônicas, caracterizadas por midríase, ausência de reação a luz e para perto e hipersensibilidade a fraca concentração de solução colinérgica. O exame revelou irite e atrofia iriana. Em ambos os casos a instilação de pilocarpina 0,1% causou miose nos olhos afetados. A pupila tônica tem sido relatada em muitas condições, mas sua associação com doença de Hansen ainda não havia sido descrita.

Descritores: Pupila tônica; Midríase; Hanseníase; Irite; Iris/lesões; Atrofia; Relato de casos

Tonic pupil in leprosy


figure 1. Right eye before instillation of dilute 0.1% pilocarpine (Case 2).

figure 2. Right eye after instillation of dilute 0.1% pilocarpine (Case 2).

figure 4. Left eye after instillation of dilute 0.1% pilocarpine (Case 2).

figure 3. Left eye before instillation of dilute 0.1% pilocarpine (Case 2).

DISCUSSIOnLeprosy (Hansen’s disease) is a chronic granulomatous condition

that is still highly prevalent in very poor populations in Asia, Africa and Latin America(7). Iris changes in leprosy are common and may occur either as a hypersensitivity reaction or as a result of direct bacterial invasion of the iris and its innervation. In lepromatous leprosy, direct bacillary invasion of the tissues takes place insidiously and chronic iritis results from direct involvement of the iris and ciliary body. In later stages of the disease, changes in the iris stroma with ensuing atrophy and synechiae in association with miosis develop(1,2,8,9).

In lepromatous leprosy, chronic iritis with progressive iris atrophy is considered not as a true inflammation, but rather as a neuropa-ralytic condition that results from autonomic denervation of the iris(8). It is well-known that the iris contains, in addition to sensory nerve fibers, small nonmyelinated sympathetic and parasympathetic nerve fibers intimately related to cells of the dilator and sphincter pupillae muscles(10). Deprivation of the autonomic supply of the iris muscles is responsible for the increasingly sluggish and miotic pupils and the poor reaction to non-sympathomimetic mydriatics as well as the premature presbyopia observed in apparently normal patients(9,10).

Evidence supporting the role of sympathetic postganglionic de nervation has been pharmacologically demonstrated by the hy -persensitivity response following the instillation of very weak con-centrations of epinephrine(4). The frequent observation of the presen-ce of lepromatous infiltrates within the iris and the absence of nerve lesions in areas of higher temperature suggest that involvement of the sympathetic fibers occurs within the iris rather than in the long ciliary nerves, carotid plexus or superior cervical ganglion(4).

The reason for the preferential involvement of the sympathetic autonomic function of the iris is not fully understood. Some au-thors(4,9) have ascribed it to differences in size and distribution of the dilator and sphincter muscles, as the dilator muscle is more thinly spread throughout the iris. However, dilator muscle is not fully dener-vated as suggested by the preservation of the ciliospinal reflexes in these patients(5,6).

In contrast, damage to the ciliary ganglion or postganglionic parasympathetic innervation of the intraocular muscles causes a well-established set of clinical signs, including slight to moderate my driasis, poor or absent pupillary reaction to light, segmental con-tractions of the iris sphincter, slow and long-lasting contractions to near vision, and cholinergic hypersensitivity of the denervated muscles(5,6). The tonicity and slowness of the pupillary movements are caused by aberrant reinnervation of the sphincter muscle. Pupils with these features are known as tonic pupils, and have been observed in otherwise healthy individuals as well as in association with local or widespread involvement of the autonomic nervous system(9).

The present report demonstrates for the first time in the literature that tonic pupil may also result from leprosy. The reason for the pre-ferential involvement of the short ciliary nerve fibers within the iris in our patients rather than denervation of the dilator muscle, as usually seen in lepromatous patients, remains to be clarified.

RefeRenCeS 1. Ffytche TJ. The eye and leprosy. Lepr Rev. 1981;52(2):111-9. 2. Choyce DP. The diagnosis and management of ocular leprosy. Br J Ophthalmol 1969;

53(4):217-23. 3. Wood DJ. Ocular leprosy. Br J Ophthalmol. 1925;9(1):1-4. 4. Swift TR, Bauschard FD. Pupillary reactions in lepromatous leprosy. Int J Lepr Other

Mycobact Dis. 1972;40(2):142-8. 5. Thompson HS. Adie’s syndrome: Some new observations. Trans Am Opthalmol Soc.

1977;75:587-626. 6. Loewenfeld IE, Thompson HS. The tonic pupil: a re-evaluation. Am J Ophthalmol. 1967;

63(1):46-87. 7. WHO Expert Committee on Leprosy: WHO Health Organ Tech Rep Ser. 1988;(768):1-51. 8. Slem G. Clinical studies in ocular leprosy. Am J Ophthalmol. 1971;71(1 Pt 2):431-4. 9. Ffytche TJ. Role of iris changes as a cause of blindness in lepromatous lepra. Br J

Oph thalmol. 1981;65(4):231-9. 10. Last RJ. Wolff’s Anatomy of the eye and orbit. 6th ed. London: Lewis;1968.

Case Report


InTRODUCTIOnFirst described in 1955 by Conrad von Gasser(1), hemolytic uremic

syndrome (HUS) is the most common cause of acute renal failure in children, with an incidence of 0.2-3.4 per 100,000 patients per year(2). It is a complex, multisystemic disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure (ARF). The main differential diagnosis is thrombotic thrombocytopenic purpura (TTP) accompanied by the classic triad of HUS, fever, and neurological disorders(3). HUS is divided into two presentation forms determined by different clinical and pathophysio-logical conditions. The classical or typical HUS is the most frequent, accounting for 90% of cases. Its incidence increases in summer due to a correlation with intestinal infection caused by Escherichia coli (O157: H7) and production of verotoxin(4). The atypical form is a heterogeneous group associated with genetic predisposition, systemic inflammatory disease, pregnancy, organ transplantation, use of medications, and other infections, either viral or bacterial, outside the gastrointestinal tract(2,5). In most cases, HUS is preceded by gastroenteritis, sudden abdominal pain, watery or bloody diar-rhea, nausea, vomiting, and mild fever, with onset typically occurring within three days of exposure to the toxin. Other signs upon physical examination include pallor, oliguria, dehydration, edema, petechiae, hepatosplenomegaly, and neurological signs. To establish the diag-

nosis, necessary tests should include complete blood count (CBC), stool culture, biochemistry (including renal function, bilirubin, lactate dehydrogenase and plasma electrolytes), urinalysis, and serology for detection of antilipopolysaccharide (LPS) serotypes of E. coli that produce verotoxin. The classic HUS is a self-limiting disease with high rates of full recovery mainly when early and adequate treatments of symptoms are provided(6).

Ocular involvement in pediatric patients with HUS has rarely been reported and includes retinal, choroid and vitreous hemorrhages as well as ischemic signs such as cotton wool spots, retinal whitening and non-perfusion zones which leads to retinal neovascularization and optic atrophy(7). Some of these characteristics are found in Purtscher-like retinopathy. Purtscher’s retinopathy was first descri-bed in 1910 by Otmar Purtscher as whitish lesions with hemorrhagic retinopathy associated with low visual acuity secondary to a fall(8). From 1975 Inkles introduced the term Purtscher-like retinopathy to describe the same clinical feature in a case of pancreatitis with no his-tory of previous trauma(8). Ever since these terms are used to describe the fundus changes as peripapillary cotton wool spots, intraretinal hemorrhages and Purtscher fleckens.

In this report, we describe a rare association between classic he-molytic uremic syndrome and hemorrhagic retinopathy in a 23-mon-th-old infant, as well as the follow-up after retinal photocoagulation.

Hemorrhagic retinopathy in an infant with hemolytic-uremic syndrome Retinopatia hemorrágica em lactente com síndrome hemolítico-urêmica

João caetano ávila geraiSSate1,2, raFael eidi yaMaMoto2, david leonardo cruvinel iSaac1,2, MarcoS Pereira de ávila1,2

Submitted for publication: September 30, 2013 Accepted for publication: May 1, 2014

Study conducted at Ophthalmology Department of Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.

1 Ophthalmology Department, Centro de Referência em Oftalmologia (CEROF), Goiânia, GO, Brazil.2 Ophthalmology Department, Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.



Corresponding author: Rafael Eidi Yamamoto. Rua 222, 467/502. Setor Leste Universitário - Goiânia, GO 74603-160 - Brazil - E-mail: [email protected]

ABSTRACTWe describe the case of a 23-month-old female infant with a diagnosis of he-molytic uremic syndrome (HUS) and hemorrhagic retinopathy. The patient had a past history of abdominal pain, bloody diarrhea, and acute renal failure. On ophthalmologic examination, indirect ophthalmoscopy revealed extensive areas of flame-shaped hemorrhage, cotton wool spots, macular edema and optic nerve head neovascularization in both eyes. Fluorescein angiography showed severe bilateral retinal ischemia and neovascularization leakage in disk. The patient, who had the visual acuity of 20/1000 in the right eye (OD) and 20/540 in the left eye (OS) at the first examination, was treated with panretinal photocoagulation (PRP) and presented at the end of the 6th month of follow-up improvement to 20/540 in OD and 20/270 in OS. There was also a regression of disc neovascularization, hemorrhages and macular edema. Despite intense retinal ischemia, there were no complications related to angiogenesis such as vitreous hemorrhage and/or neovascular glaucoma. We describe, in this report, the association between hemorrhagic retinopathy with features of Purtscher-like disease and HUS.

Keywords: Hemolytic uremic syndrome; Retinal hemorrhage/etiology; Fluorescein angiography; Light coagulation; Infant; Case reports

RESUMODescrevemos o caso de um lactente do sexo feminino de 23 meses com diagnóstico de síndrome hemolítico-urêmica (SHU) e retinopatia hemorrágica. A paciente apresentou história clínica prévia de dor abdominal, diarréia sanguinolenta e insuficiência renal aguda. Ao exame oftalmológico, a oftalmoscopia indireta evidenciou, em ambos os olhos, extensas áreas de hemorragia em chama de vela, exsudatos algodonosos, edema macular e neovasos na cabeça do nervo óptico. A angiofluoresceinografia mostrou intensa isquemia retiniana bilateral e vazamento na neovascularização de disco. A paciente, a qual apresentava acuidade visual de 20/1000 no olho direito (OD) e 20/540 no olho esquerdo (OE) no primeiro exame, foi tratada com panfotocoagulação retiniana e apresentou no final do 6o mês de acompanhamento a acuidade visual de 20/540 no OD e 20/270 no OE. Observou-se ainda a regressão dos neovasos, das hemorragias retininanas e do edema. Apesar da intensa isquemia retiniana não houve complicações relacionadas à angiogênese como hemorragia vítrea e/ou glaucoma neovascular. Descreve-se, neste relato, a associação entre retinopatia hemorrágicas com características de Purtscher-like e síndrome hemolítico-urêmica.

Descritores: Síndrome hemolítico-urêmica; Hemorragia retiniana/etiologia; Angio-fluoresceinografia; Fotocoagulação; Lactente; Relato de casos

Hemorrhagic retinopathy in an infant with hemolytic-uremic syndrome


CASe RePORTMSBO, female, 23 months old, was admitted to a primary care

unit in the city of Goiás with abdominal pain, bloody diarrhea and dehydration. The case progressed with worsening of renal failure and she was referred to the Department of Nephrology of Hospital das Clínicas of Universidade Federal de Goiás (UFG), where she was diagnosed with hemolytic uremic syndrome and hemodialysis was started. On day 21 of her hospitalization, ophthalmologic evaluation was requested due to decreased vision.

On ophthalmologic examination, a preferential looking test (Teller) showed visual acuity of 20/1000 in the right eye (OD) and 20/540 in the left eye (OS) at 38 cm. Direct pupillary reflexes and ocular motility were normal. Fundus examination showed bilateral retinal hemorrhages in the four retinal quadrants, cotton wool spots, macular edema and neovascularization in the optic nerve head (Fi-gure 1). Fluorescein angiography showed hypofluorescent areas by blocking (hemorrhages) and filling defects (retinal ischemia), mild vascular tortuosity and late hyperfluorescence due to leakage around the optic nerve neovascularization in both eyes (Figures 2 and 3).

The proposed treatment was panretinal photocoagulation (PRP) with a binocular indirect ophthalmoscope (BIO) in both eyes using an 810 nm diode laser. After 6 months there was regression of neo-vascularization, cotton wool spots, hemorrhages and macular edema with remaining mild epiretinal fibrosis, optic disc pallor, vascular narro wing and macular retinal pigment epithelium (RPE) atrophy (Figure 4). Final visual acuity (VA) was 20/540 in OD and 20/270 in OS on Teller acuity cards at 38 cm.

DISCUSSIOnTTP and HUS, two physiologically indistinguishable entities, are

the main representatives of thrombotic microangiopathy. Clinically, the presence of ARF and the absence of fever and neurological signs led to the diagnosis of HUS, which is important because the mor-tality of untreated TTP with plasmapheresis and plasma infusion is up to 90%(3).

The pathophysiological process of typical HUS comprises throm-bosis and non-inflammatory necrosis by Shiga-like toxin, also called verotoxin, which is produced mainly by the strain O157:H7 of E. coli(4). This toxin has a strong affinity to the kidneys due to its receptor to globotriaosylceramide (Gb3), a glycopeptide located mainly in the endothelium of renal vessels. This phenomenon releases vasoactive substances and platelets that activate the coagulation cascade, leading to the formation of edema and microthrombosis in arteries, arterioles and glomerular capillaries, in turn causing reduction of glomerular filtration and resulting ARF, thrombocytopenia by con-sumption of platelets and anemia by hemolysis of microangiopathic erythrocytes(9). Treatment of HUS is based on the control of ARF; with blood disorders and the need for dialysis occurring in 75%-100% of cases because there is no treatment specific to HUS(10).

The first ocular diagnostic impression was bilateral occlusion of the central retinal vein due to extensive areas of hemorrhage and macular edema, but knowing the pathophysiology of the under-lying disease and its relationship to endothelial injury of the arteries, arterioles and capillaries, the diagnosis of Purtscher-like retinopathy was suggested because it would explain the presence of capillary

figure 1. Fundus photograph demonstrating flame-shaped hemorrhages, neovascularization and optic disc swelling.

figure 2. Fluorescein angiography demonstrating contrast leakage through the new vessels and nonperfused retinal areas.

Geraissate JCA, et al.


figure 3. Fundus photograph.

figure 4. Fundus photograph after treatment with laser photocoagulation demonstrating regression of neovascularization.

microcclusion, cotton wool spots, retinal hemorrhages, ischemia, and macular edema. Furthermore, no important worsening was obser -ved in vascular tortuosity or venous dilatation, which further corro-borates the diagnosis of Purtscher-like retinopathy.

The discussion of the case by the medical team focused on pro -posed treatments for the infant, the rarity of the case, and the severity and possible sequelae of retinal occlusive disease. The case was also discussed with members of the pediatric and nephrology departments of UFG. It was decided that the patient be treated by PRP with BIO in both eyes (Figure 2) to avoid a possible neovascular glaucoma, vitreous hemorrhage or tractional retinal detachment due to severe retinal ischemia. Six months after the laser treatment, the patient had visual sequelae, but with visual acuity better than at the initial evaluation. VA increased from 20/1000 OD and 20/540 OS to 20/540 in OD and 20/270 in OS. Fundus examination showed optic disc pallor and foveal pigmentary changes in both eyes. Optic and macular atrophy might have been the main factors for visual impairment.

HUS is a rare and potentially fatal disease and is unusual in its asso ciation with ocular findings. This case describes a Purtscher-like retinopathy in an infant with HUS, demonstrating the importance

of ophthalmic evaluation, early diagnosis and treatment in patients affected by the disease.

RefeRenCeS 1. Gasser C, Gautier E, Steck A, Siebenmann RE, Oeshslin R. [Hemolytic-uremic syndrome:

bilateral necrosis of the renal cortex in acute acquired hemolytic anemia]. Schweiz Med Wochenschr. 1955;85(38-39):905-9. German.

2. Siegler RL, Pavia AT, Christofferson RD, Milligan MK. A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah. Pediatrics. 1994;94(1):35-40.

3. Elkins SL, Wilson PP Jr, Files JC, Morrison FS. Thrombotic thrombocytopenic purpura: Evolution across 15 years. J Clin Apher. 1996;11(4):173-5.

4. Fitzpatrick MM, Dillon MJ. Current views on aetiology and management of haemoly-tic uraemic syndrome. Postgrad Med J. 1991;67(790):707-9.

5. Neuhaus TJ, Calonder S, Leumann EP. Heterogeneity of atypical haemolytic uraemic syndromes. Arch Dis Child. 1997;76(6):518-21.

6. Amirlak I, Amirlak B. Haemolytic uraemic syndrome: An overview. Nephrology (Carlton). 2006;11(3):213-8.

7. Sturm V, Menke MN, Landau K, Laube GF, Neuhaus TJ. Ocular involvement in paedia-tric haemolytic uraemic syndrome. Acta Ophthalmol. 2010;88(7):804-7.

8. Medeiros HA, Medeiros JE, Caliari LC, Silva JF. Retinopatia de Putscher’s and Putscher-like [revisão]. Rev Bras Oftalmol. 2009;68(2):114-9.

9. Siegler R, Oakes R. Hemolytic uremic syndrome: pathogenesis, treatment, and outco-me. Curr Opin Pediatr. 2005;17(2):200-4.

10. Levin M, Barratt JM. Haemolytic uraemic syndrome. Arch Dis Child. 1984;59(5):397-400.

Case Report


InTRODUCTIOnOptic disk melanocytoma (ODM) is a relatively common and

well-known benign intraocular tumor(1). It can be defined as a mela-nocytic nevus variant located at the optic disk and histopathologi-cally presents as uniform, deeply pigmented cells with melanosomes and after bleaching, small uniform nuclei with inconspicuous nucleo li and abundant cytoplasm(2).

ODM is usually diagnosed by ophthalmoscopic examination due to the characteristic appearance of the tumor(1,3,4). Ancillary procedu-res, such as fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT), can help the diagnosis and are useful for follow-up evaluations(1).

Fundus autofluorescence (FAF) is a non-invasive examination ba-sed on the fluorescent appearance of lipofuscin when illuminated by an external light source(5). Lipofuscin is a mixture of proteins, lipids, and small chromophores that accumulate in retinal pigment epi-thelium (RPE) as a result of incomplete or deficient photoreceptor outer segment degradation(6). Depending on the intensity of the autofluorescence, a lesion may be described as isoautofluorescent, hypoautofluorescent, or hyperautofluorescent(5).

ABSTRACT The authors report fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (OCT) findings of two consecutive patients who presen-ted with optic disk melanocytoma (ODM). A retrospective study was performed by reviewing medical records and ophthalmic imaging examinations. Optical coherence tomography findings were sloped and brightly reflective anterior tumor surface, adjacent retinal desorganization and abrupt posterior optical shadowing. Vitreous seeds were found in one patient. Fundus autofluorescence revealed outstanding hypoautofluorescence at the tumor area and isoautofluo-rescence at the remaining retina. Optical coherence tomography findings of the reported cases are consistent with those reported in the reviewed literature. Fundus autofluorescence has been used in the assessment of choroidal mela-nocytic tumors, but not yet in melanocytomas. We assume that this is the first report of these findings and believe that when its pattern has become clearly defined, fundus autofluorescence will be a useful tool to avoid misdiagnosis in suspicious cases and for follow-up.

Keyword: Melanoma/diagnosis; Optic nerve neoplasms/diagnosis; Tomography, optical coherence; Fluorescein angiography; Humans; Male; Female; Adult; Case reports

RESUMOOs autores descrevem os achados do exame de autofluorescência do fundo de olho (AF) e da tomografia de coerência óptica (TCO) de domínio-espectral em dois pacientes consecutivos apresentando melanocitoma disco óptico (MDO) em um estudo retros-pectivo, por revisão dos prontuários e exames oftalmológicos de imagem. Os achados no exame de tomografia de coerência óptica foram hiperrefletividade e elevação da superfície anterior da lesão, desorganização da retina adjacente, e, sombreamento óptico posterior. Sementes vítreas foram encontrados em um paciente. O exame de autofluorêscencia do fundo de olho revelou hipoautofluorescência marcante na área do tumor e isoautofluorescência nas demais áreas da retina. As características encon-tradas na tomografia de coerência óptica dos pacientes apresentados são consistentes com os achados relatados na literatura atual. A autofluorêscencia do fundo de olho tem sido utilizada na avaliação de tumores melanocíticos da coroide, mas ainda não em melanocitomas. Acreditamos que este seja a primeira descrição dos achados de autofluorêscencia do fundo de olho em pacientes com melanocitoma de disco óptico e que, quando seu padrão de tornar-se claramente definido, a autofluorêscencia do fundo de olho será uma ferramenta útil para evitar erros de diagnóstico em casos suspeitos.

Descritores: Melanoma/diagnóstico; Neoplasias do nervo óptico/diagnóstico; Tomo-grafia de coerência óptica; Angiofluoresceinografia; Humanos; Masculino; Feminino; Adulto; Relato de casos

FAF has been used in the assessment of choroidal melanocytic tumors but not yet in melanocytomas(3). The aim of this paper is to describe the clinical features and FAF and OCT findings of two con-secutive patients who presented with ODM.

MeTHODSA retrospective study was performed by reviewing medical re-

cords of two consecutive patients diagnosed with ODM and referred to an ophthalmic oncology specialist at the Hospital Universitário Professor Edgard Santos, Salvador (BA), Brazil within a three-month period (June-September, 2012). Both patients had undergone an-cillary procedures at the Retina and Vitreous service of the Hospital São Rafael (Fundação Monte-Tabor), Salvador (BA), Brazil.The study protocol was approved by the Institutional Ethics Review Board of the Hospital São Rafael-Fundação Monte-Tabor and conducted by the Retina and Vitreous Service at the same institution (CAAE: 14929313.4.0000.0048).

Ancillary procedures performed were color and red free retino-graphy, FAF, FA and spectral-domain OCT. A Topcon TRC-50DX retinal camera and Optovue-RTVue 100 were used.

Autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytomaAutofluorescência e tomografia de coerência óptica de domínio espectral do melanocitoma do disco óptico

ricardo luz leitão guerra1, eduardo Ferrari Marback2, igor SandeS PeSSoa da Silva3, otacílio de oliveira Maia Jr.3, roberto lorenS Marback3

Submitted for publication: January 6, 2014 Accepted for publication: March 20, 2014

Study conducted at Vitreoretinal Service, Hospital São Rafael - Fundação Monte Tabor - Salvador, BA, Brazil.

1 Clínica de Olhos Leitão Guerra, Salvador, BA, Brazil. 2 Department of Ophthalmology, Universidade Federal da Bahia, (UFBA), Salvador, BA, Brazil.3 Department of Ophthalmology, Hospital São Rafael, Fundação Monte Tabor, Salvador, BA, Brazil.



Corresponding author: Ricardo Leitão Guerra. Rua Catarina Paraguaçu, 8 - Salvador, BA - 40150 - 200 - Brazil - E-mail: [email protected]

Guerra RLL, et al.


Demographics, clinical data, and ophthalmic imaging examina-tion findings were described and compared with the actual relevant literature. The ophthalmological examination, ancillary procedures, and data collection were performed by the same ophthalmologist.

ReSULTSCaSe 1

A 48-year-old female, dark-skinned, without comorbidities, was referred to an ophthalmic oncology specialist due to a pigmented intraocular tumor causing progressive vision loss in the right eye (OD). Best corrected visual acuity was counting fingers (CF) in OD and 20/25 in the left eye (OS). Biomicroscopy and tonometry were normal in both eyes (OU). Ophthalmoscopy presented as a black mass covering the optic disk and adjacent retina, including the fovea, with some vitreous seeding in the OD (Figure 1 A). There were no significant findings in the OS.

FA presented as a hypofluorescent image with regular and well-defined outlines during the whole examination, matching to fluorescence blockage caused by tumor in the OD. There were no significant findings in the OS.

CaSe 2A 53-year-old male, dark-skinned, with systemic arterial hyper-

tension was referred to an ophthalmic oncology specialist due to a pigmented intraocular tumor found in a routine examination. Best corrected visual acuity in OU was 20/20, and biomicroscopy and to-nometry revealed no changes in OU. Ophthalmoscopy showed a black mass covering the optic disk and some adjacent retina, with massive vitreous seeding, preserving the macula in the OD (Figure 1 B). There were no relevant findings in the OS. FA showed the same pattern as that described in case 1.

SpeCtral-DOmaIN OCt aND FaF Both cases presented similar OCT and FAF findings. Spectral-do-

main OCT showed an elevated hi-reflective line corresponding to the tumor surface, followed by a dense shadow pictured as an optically empty mass (Figures 2 A and B). Hi-reflective spots in the vitreous cavity anterior to the tumor and corresponding to vitreous seeding were found in case 2 (Figure 2 C).

FAF revealed an outstanding hypoautofluorescence. The remai-ning retina demonstrated isoautofluorescence (Figures 3 A and B).

DISCUSSIOnDespite the characteristic clinical appearance of melanocytoma,

conditions such as primary or metastatic choroidal melanoma and

combined hamartoma of the retina and RPE must first be ruled out(1,3,4). Other differential diagnoses include choroidal nevus, RPE hy perplasia, and RPE adenoma(1,4). Transformation of melanocytoma into malig-nant melanoma is extremely rare(6).

OCT is a valuable tool for examining the retina and inner choroid architecture(7). OCT patterns and applications are well described in several choroidal and retinal tumors(4,7). OCT findings in ODM include sloped and brightly reflective anterior tumor surface, adjacent retinal disorganization, and abrupt posterior optical shadowing(3). Vitreous seeds can be found(4). Both of the presented cases showed the cha-racteristic features. Vitreous seeds were evident in one patient.

A leading cause of decreased visual acuity in ODM is related to retinal exudation(8). Rarely, excessive tumor growth, involving the fo vea, is the cause of vision loss(1). OCT is useful in providing informa-tion about the adjacent retinal tissue in ODMs(4). In case 1, OCT was va luable in delimitating the tumor extention and excluding other treatable conditions.

FAF has been previously used in the assessment of choroidal me-lanocytic tumors but not yet in melanocytomas(3). In both described cases, FAF showed the same pattern: the tumor appears as an outstanding hypoautofluorescent lesion and the remaining retina was isoautofluorescent.

In an OCT-pathologic correlation, Finger et al. showed a very simi-lar OCT image(9). Histopathologically, they found a thin layer of gliotic and disorganized retina covering the tumor surface(9). We suppose that the absence of RPE over the tumor, and therefore lipofuscin, is associated with the highly pigmented mass blocking the posterior RPE, which can explain the outstanding hypoautofluorescence. Fur-ther studies are necessary to confirm these assumptions due to the great variability of the ODM presentations despite the small sample in this study.

FAF findings in ODM differential diagnoses, such as choroidal me-lanoma and choroidal nevus, have been previously described(5,10,11). FAF is useful in documenting the presence of lipofuscin, a finding that represents an important criterion in differentiating small choroidal melanoma from benign choroidal nevus(5). Choroidal melanomas have mild autofluorescent properties (granular appearance in 92% of cases and nongranular appearance in 8%)(5). Lately, a quantification method of digital autofluorescence was suggested for distinguishing nevi from melanomas with a sensitivity of 0.89 and specificity of 0.93(12). The FAF patterns found in the presented cases can be helpful for diagnosing suspicious melanocytic lesions.

The authors were not able to find any descriptions of ODM FAF in the reviewed literature. Therefore, we assume that this is the first report of these findings and believe that when its pattern has been clearly defined, FAF will be a useful tool to avoid misdiagnosis in suspicious cases and for follow-up.

figure 1. Clinical appearance of optic disk melanocytoma in the described patients. Case 1 (A). Case 2 (B).

A B

Autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytoma


figure 2. Spectral-domain OCT showing an elevated hi-reflective line corresponding to the tumor surface, followed by a dense shadow pictured as an optically empty mass (A and B). Hi-reflective spots in the vitreos cavity, antherior to the tumor, corresponding to vitreos seeding were found in case 2 (C).

A

B

C

RefeRenCeS 1. Shields JA, Demirci H, Mashayekhi A, Eagle RC Jr, Shields CL. Melanocytoma of the

optic disk: a review. Surv Ophthalmol. 2006;51(2):93-104. 2. Rao NA, Spencer WH. Optic nerve. In: Spencer WH. Ophthalmic pathology: an atlas

and textbook. 4th ed. Philadelphia: WB Saunders; 1996. 3. Esmaili DD, Mukai S, Jakobiec FA, Kim IK, Gragoudas ES. Ocular melanocytoma. Int

Ophthalmol Clin. 2009;49(1):165-75. 4. Shields CL, Perez B, Benavides R, Materin MA, Shields JA. Optical coherence tomogra-

phy of optic disk melanocytoma in 15 cases. Retina. 2008;28(3):441-6. 5. Materin MA, Raducu R, Bianciotto C, Shields CL. Fundus autofluorescence and optical

coherence tomography findings in choroidal melanocytic lesions. Middle East Afr J Ophthalmol. 2010;17(3):201-6.

6. Meyer D, Ge J, Blinder KJ, Sinard J, Xu S. Malignant transformation of an optic disk melanocytoma. Am J Ophthalmol. 1999;127(6):710-4.

7. Say EA, Shah SU, Ferenczy S, Shields CL. Optical coherence tomography of retinal and choroidal tumors. J Ophthalmol. 2012;2012:385058.

8. Marback EF, Pereira FF, Galvão C, Maia Jr OO, Marback RL. Melanocitoma associado à membrana neovascular sub-retiniana. Rev Bras Oftalmol. 2009;68(4):237-40.

8. Finger PT, Natesh S, Milman T. Optical coherence tomography: pathology correlation of optic disk melanocytoma. Ophthalmology. 2010;117(1):114-9.

10. Lavinsky D, Belfort RN, Navajas E, Torres V, Martins MC, Belfort R Jr. Fundus autofluo-rescence of choroidal nevus and melanoma. Br J Ophthalmol. 2007;91(10):1299-302.

11. Shields CL, Bianciotto C, Pirondini C, Materin MA, Harmon SA, Shields JA. Autofluo-rescence of orange pigment overlying small choroidal melanoma. Retina. 2007;27(8): 1107-11.

12. Albertus DL, Schachar IH, Zahid S, Elner VM, Demirci H, Jayasundera T. Autofluores-cence quantification of benign and malignant choroidal nevomelanocytic tumors. JAMA Ophthalmol. 2013;131(8):1004-8.

figure 3. Outstanding hypoautofluorescence at the tumor area followed by isoautofluorescence at the remaining re tina (A and B).

A B

Review Article


ABSTRACTPattern electroretinography is used to assess the function of the inner retinal la yers, particularly the retinal ganglion cell layer, using a reversing checkerboard or grating pattern that maintains a constant overall mean luminance over time. A normal transient response comprises a positive component of the wave (P50) followed by a longer negative component of the wave (N95). Glaucomatous optic neu-ropathy causes progressive loss of retinal ganglion cells, potentially detectable as abnormalities on examination, particularly in the N95 component. Therefore, pattern electroretinography may be useful in the diagnosis and evaluation of glaucoma. The present article is an updated review of published data regarding the use of pattern electroretinography for the detection of glaucoma-induced retinal changes.

Keywords: Electroretinography; Glaucoma/diagnosis; Ocular hypertension; In-trao cular pressure; Vision ocular

RESUMOO eletroretinograma de padrão reverso é utilizado para avaliar a função das camadas internas da retina, particularmente a camada de células ganglionares retinianas, utilizando um estímulo em xadrez ou barras alternantes, mantendo constante o nível de contraste total. A resposta transiente normal é constituída por uma onda positiva (P50) seguida de uma onda maior negativa (N95). A neuropatia óptica glaucomatosa causa perda progressiva das células ganglionares da retina, detectável como anor-malidades no exame, especialmente na onda N95. Por isso, o eletroretinograma de padrão reverso pode ser útil no diagnóstico e seguimento de pacientes glaucomatosos. Este artigo é uma revisão atualizada dos dados publicados a respeito da capacidade do eletroretinograma de padrão reverso em detectar alterações retinianas induzidas pelo glaucoma.

Descritores: Eletroretinografia; Glaucoma/diagnóstico; Hipertensão ocular; Pressão intraocular; Visão ocular

InTRODUCTIOnPrimary open-angle glaucoma (POAG) is likely the most common

optic neuropathy and can lead to permanent visual damage if left un-treated(1). Raised intraocular pressure (IOP) is the most significant risk factor for the development and progression of POAG, although not all patients with ocular hypertension (OHT) develop glaucomatous damage(2). Lowering the IOP is currently the only available treatment option(1).

Glaucoma is characterized by chronic retinal ganglion cell (RGC) loss associated with loss of visual function. However, it is widely known that structural abnormalities in RGC and retinal nerve fiber layer (RNFL) may precede the development of visual field (VF) defects in glaucoma. Anatomical studies have documented that VF defects usually develop only after the loss of 30%-50% of ganglion cells(3). To prevent irreversible axonal loss in patients with glaucoma, structural abnormalities should be detected as early as possible; thus, it is im-portant to develop new and more reliable detection methods.

Over the past decade, a number of imaging techniques have been developed to detect early structural damage in glaucoma, including confocal scanning laser ophthalmoscopy (CSLO), scanning laser po-larimetry, and particlularly, optical coherence tomography(4). These techniques can be used to detect and quantify glaucomatous dama-ge in a reproducible manner, and have been shown to be significantly correlated with conventional methods used to assess glaucoma pro-gression, such as standard automated perimetry (SAP) and optic disc stereophotography(5). However, although imaging techniques have become an important tool in the diagnosis of glaucoma, they occa-

sionally fail to identify glaucomatous damage, particularly localized RFNL defects(6) and other structural changes, such as those observed in patients with preperimetric glaucoma. Currently available imaging techniques are more sensitive and specific for advanced glaucoma-tous damage(7).

Electrophysiological methods may also be used to identify early structural and functional damage in glaucoma. Over the past few years, patients with early-stage glaucoma have been evaluated for abnormalities using electrophysiological tests, including different forms of electroretinography (ERG)(8) and visual evoked potential (VEP)(9). On ERG, the amplitude of the photopic negative response, a measure of inner retinal function, may be reduced in early glauco -matous damage(8). Recently, multifocal ERG has been shown to de tect macular dysfunction in POAG(10), suggesting a preganglionic dys function of macular elements in the disease. With regard to VEP, previous studies have shown that a delay in the S-cone response may precede morphological and VF evidence of glaucomatous damage(9). Multifocal VEP has also been used for the objective assessment of glaucomatous VF defects(11). However, despite their ability to detect abnormalities in glaucoma, none of these electrophysiological me-thods directly measure RGC function.

However, RGC function may be estimated using pattern ERG (PERG), a specific form of electroretinography(12). In fact, several stu-dies have shown the ability of PERG to detect structural glaucoma-tous damage (which primarily involves the RGC layer) and have attem pted to correlate these findings with other glaucoma-related functional and morphological abnormalities(13-17). Increasing eviden-

The role of pattern-reversal electroretinography in the diagnosis of glaucomaImportância do eletroretinograma de padrão reverso no diagnóstico do glaucoma

andré carvalho kreuz¹, Maria kiyoko oyaMada1, Marcelo hatanaka1, Mário luiz ribeiro Monteiro1

Submitted for publication: June 30, 2014 Accepted for publication: November 4, 2014

Study conducted at Department of Ophthalmology, Universidade de São Paulo, São Paulo, SP, Brazil.

1 Department of Ophthalmology, Universidade de São Paulo, São Paulo, SP, Brazil.

Corresponding author: André Carvalho Kreuz. Rua da Consolação, 3268/61 - São Paulo, SP - 01416-000 - Brazil - Email: [email protected]



The role of pattern-reversal electroretinography in the diagnosis of glaucoma


ce highlights the importance of PERG amplitude abnormalities for the early diagnosis of glaucoma, especially in patients with pre-perimetric glaucoma(18). The purpose of the present article was to review pre-vious studies evaluating the use of PERG for the detection of glauco-matous damage and its correlation with other methods of structural and functional evaluation.

UnDeRSTAnDInG PeRGOrIGIN OF the reSpONSe

The first PERG model was described in 1964, when Riggs et al. showed that, in a normal patient, a contrast-reversing pattern could be used to generate a small electroretinographic signal, comprising a positive component (P50) followed by a negative component (N95) (i.e., the transient response). This technique is now referred to as PERG(19). In 1985, Berninger and Schuurmans reported that when temporal frequencies of stimulation are higher than 10 reversals per second (rev/s), the successive waveforms overlap and, therefore, the response assumes a sinusoidal configuration referred to as the steady-state response(20).

Although the exact origin of the PERG response has not been clearly established, a number of experimental studies suggest that it originates from the inner retinal layers, particularly the RGC layer. Be cause damage to the optic nerve results in retrograde degene-ration of the RGC, early studies investigating the origin of the PERG response focused on the effects of optic nerve section. The first such model was described in 1980, when PERG and flash ERG were recor-ded at two different time-points in a subject who had experienced optic nerve section due to an accident. On the first examination, a few days after the accident, both tests were normal; however, three months later, PERG was no longer measurable, while flash ERG was normal(21). Several authors have suggested that the PERG response may originate in the inner retina; indeed, experimental studies using animal models have confirmed the extinction of the PERG response after optic nerve section(22-24) and have related the phenomenon to RGC degeneration, as demonstrated by histological examination. Ho wever, using a similar study design, other researchers observed only partial extinction of the PERG response(25). Johnson found that in monkeys with induced intraocular hypertension, a PERG response was still present after almost all optic nerve fibers had been des-troyed, according to the results of histological examination(26). In a human patient with optic nerve glioma, Harrison et al. detected a PERG response 30 months after surgical transection of the optic ner-ve, although it was significantly reduced(27). Berninger and Arden also reported incomplete extinction of the PERG response three months after optic nerve transection: while the negative component of the wave was non-recordable, the positive component was still present, although it was reduced(28). Based on these findings, it has been sug-gested that the PERG response does not depend on RGC alone; part of the response - most likely the positive component of the wave - may originate from other retinal cells.

Experimental studies in humans have also assessed variations in the PERG response amplitudes at different check sizes (spatial fre-quencies). This phenomenon, called spatial tuning, is a property inhe rent to RGCs. In two studies, the spatial response function of the positive component did not show spatial tuning, as opposed to the amplitude of the negative component(20,29). Based on this finding, a non-ganglion cell component of P50 was proposed, which could, at least in part, be generated distally to the ganglion cells. N95, which displayed spatial tuning, was believed to be contrast-related and, consequently, generated by the RGC [42].

Holder conducted a clinical study to investigate the origin of PERG waves and observed that P50 was more affected than N95 in retinal and macular diseases, and that N95 was more affected than P50 in optic nerve dysfunction, supporting the hypothesis that the negative and positive PERG components have different origins(30).

In a recent experimental study, Viswanathan et al. tested the effects of tetrodoxin (TTX), a drug that blocks the spiking activity of amacrine and ganglion cells. They observed that the effects of TTX on PERG were similar to those observed with experimental glaucoma, sugges-ting that glaucoma-related reduction in the PERG response is due to compromised RGC spiking activity(31). The authors also observed that N95 was eliminated by TTX at higher frequencies, while P50 remained less affected than in experimental glaucoma. Because experimental glaucoma compromises the entire RGC layer and its ability to respond while TTX merely blocks spiking activity, the extinction of P50 in experimental glaucoma suggests an origin in local RGC potentials.

Based on the above-mentioned data, it may be inferred that the negative component is a contrast-related component generated by RGC spiking activity, while the positive component is partly RGC-de-rived and partly generated distally to the ganglion cells by a mecha-nism that is currently unclear(32).

Since the 1980s, many researchers have used PERG to study abnor malities associated with optic nerve disorders, although the re cording techniques used in early research varied considerably from study to study(33,34). This, in part, explains the discrepancies among these early studies. The first attempt to standardize the methodolo-gy occurred in 1984(35); subsequently, in 1998, 2007 and 2012, the In ternational Society for Clinical Electrophysiology of Vision (ISCEV) published guidelines standardizing the PERG methodology.

methODOlOGy

The present methodology is described in the 2012 ISCEV stan-dard for clinical PERG(36). The retinal cells are stimulated by a pattern of contrast-reversing black and white squares or bars presented as a checkboard or grating on a monitor, while a constant overall mean lu-minance is maintained. The check size presented on the monitor and the reversal rate can be adjusted at the discretion of the investigator. Retinal evoked potentials are recorded with electrodes that do not interfere with pattern clarity, such as gold foil, Dowson-Trick-Litzkow or Hong Kong loops placed on the corneal limbus, over or under the lower lid. Surface reference electrodes are placed in the outer canthus of each eye, and a ground electrode is attached to the forehead.

Because of its small amplitude, the PERG response is highly sus-ceptible to artifacts. Interference from eye movement and blink is common and should be avoided. Pattern clarity and fixation on the fovea are important for reliability of the response measurement. The presence of cataracts, non-corrected refractive errors or reduced cor-neal transparency can affect image contrast and, consequently, the PERG response(37). Degenerative maculopathy, diabetic retinopathy and other retinal diseases can also compromise the quality of the res ponse(38).

traNSIeNt aND SteaDy-State perG reSpONSe

The PERG response consists of small signals, typically approxima-tely 2-8 µV in normal individuals. Two types of PERG responses (tran-sient and steady-state) can be obtained depending of the reversal rate of the patterned stimulus. The transient PERG response, obtained when the reversal rate is <6 rev/s, is expressed as a single, averaged response. The steady-state PERG response, obtained when the rever-sal rate is >8 rev/s(39), represents an overlap of successive waveforms. Normal transient PERG is represented by a small initial negative com-ponent at 35 ms (N35), which is not always visible, followed by a larger positive component at 45-60 ms (P50) and then by a large negative component at 90-100 ms (N95). A comparison of PERG responses according to reversal rate is presented in figure 1.

The main parameters analyzed in the PERG response are amplitu-de, implicit time and latency. According to ISCEV, the amplitude is the distance between peaks and troughs. The P50 amplitude is measured from the trough of N35 to the peak of P50, while the N95 amplitude is measured from the peak of P50 to the trough of N95. In the case of

Kreuz AC, et al.


the steady-state response, the amplitude of the sinusoidal wave can be analyzed using a fast Fourier transform. The implicit time (time to peak) is the time between the onset of the contrast reversal and the peak of the component of interest, while latency is defined as the time between the onset of the contrast reversal and the response.

mUltIFOCal perG (mFperG)Standard PERG detects the collective response of the ganglion

cells. However, such a global response is rarely useful to detect patho-logical changes in localized areas of the retina. Because some optic nerve diseases, particularly glaucoma, may present with focal RGC defects in the early stages, interest in methods capable of assessing the function of specific retinal areas is increasing(40,41).

mfPERG can detect responses from specific regions, mainly in the macular area, which is densely populated with RGCs and pregan-glionic elements. The ability to measure bioelectrical responses from localized macular areas could be used to establish a relationship between focal RGC dysfunction and focal defects identified by the examination(42). In an experimental and clinical study, Harrison et al. suggested that mfPERG response originates mainly from inner retinal elements (RGCs), with some contribution from outer retinal cells(42).

The earliest studies described different forms of stimulation of specific areas of the retina(41,43). The basic methodological difference compared with standard PERG is the multifocal stimulus: hexagons or squares displayed on a monitor alternating between black and white in a temporal pattern according to a binary m-sequence. The morphology of the retinal response is similar to full-field PERG.

PERGLA Developed by Porciatti et al. in 2004(44) primarily for the diagnosis

and follow-up of glaucoma patients, PERGLA is another method of

obtaining PERG data. It differs from the classic method by the use of skin electrodes placed on the lower eyelids instead of corneal electrodes and by the use of a vertical grating pattern rather than a checkerboard pattern(44). As with the conventional method, a tem-poral frequency of >8 rev/s (steady-state) and Fourier analysis are used. Because the use of a skin electrode reduces the amplitude of the response, spatial-temporal characteristics of the stimulus that maximize the response amplitude are chosen, and the response com-ponent is isolated from unwanted biological activity (noise). While the amplitude response is lower than that of standard PERG, artifacts due to eye movement are less intrusive. The use of skin electrodes avoids some of the problems associated with corneal electrodes: opti-cal de gradation of pattern stimulus, electrode instability, low patient compliance and dependency on a skilled operator. The objective of the method is to make the standard PERG simpler and more patient- and user-friendly.

As in standard PERG, defocus has a negative impact on PERGLA results(45). In addition, significant variability is observed in PERGLA me-asurements when they are obtained by different operators(45). The use of a single operator reduces variability(46), and PERGLA measurements have been shown to be satisfactorily reproducible(47).

PeRG STUDIeS In GLAUCOMASince the first description of PERG abnormalities in glaucoma in

1982(48), several studies describing changes in amplitude and latency have been published, with correlations to RGC dysfunction seconda-ry to primary glaucoma, congenital glaucoma(49) or OHT.

aBNOrmalItIeS IN perG amplItUDe

A large number of studies have demonstrated that glaucomatous damage is associated with a reduction in PERG response amplitude.

figure 1. Example of normal pattern electroretinogram responses. Above: transient response using a reversal rate of 3 Hz, with amplitude values of 3.42 µV (N35-P50) and 6.14 µV (P50-N95) and latency values of 33, 57 and 101 ms (N35, P50 and N95 responses, respectively). Below: Steady-state response with a reversal rate of 10 Hz (amplitude 3.7 µV, phase 57 ms).



In 1983, Wanger and Persson submitted 11 patients with unilateral glaucoma to PERG and observed a significant reduction in amplitude in 10 glaucomatous eyes compared with the fellow eye(14). Howe and Mitchell studied 17 patients with unilateral glaucoma and reported that both P50 and N95 were reduced compared with the contrala-teral eye(28), consistent with the findings of other authors(33,50). When studying the involvement of specific waves in glaucoma, Weinstein et al. and Ohta et al. observed a more pronounced reduction in N95 than in P50(51,52). Few studies have demonstrated reductions in P50(30); in most studies, N95 was the most affected component, supporting the notion that the negative component is more closely associated with RGC function.

In view of the increasing awareness of the relevance of PERG abnormalities to the diagnosis of glaucoma, the role of elevated IOP in PERG response has been extensively investigated. Wanger and Persson submitted seven patients with unilateral OHT to PERG and found reduced amplitudes in four cases(53). In addition, experimental studies have investigated whether elevated IOP can affect PERG res-ponse in the absence of glaucomatous damage. Marx et al. induced OHT in one eye of five primates by applying lasers to the trabecular meshwork, and recorded PERG before and after laser application(54). The authors observed a progressive PERG amplitude reduction throughout the follow-up period, with three monkeys exhibiting compromised PERG amplitudes before developing clinically signifi-cant cupping, supporting the hypothesis that OHT in humans could affect PERG amplitude before the emergence of glaucomatous da-mage. Johnson et al. also observed reduced amplitudes in monkeys with artificially elevated IOP, and correlated this reduction with RGC damage on histological examination(26). In an attempt to explain the reduction in PERG response caused by high IOP, Siliprandi et al. pro-posed that amplitudes decrease in acute intraocular hypertension secondary to reduction in eye perfusion pressure and retinal blood supply(55). The majority of researchers have reported reductions in PERG amplitude associated with elevated IOP, although there are exceptions(26). The mechanism appears to involve the absence of acti vity secondary to RGC loss, reduced activity of viable RGC or a combination of these factors. However, it is important to consider that in such experimental studies, IOP elevation is typically very high and induced in an acute manner, which is considerably different from the situation that is typically observed in glaucoma patients. The fact that reductions in PERG amplitude precede optic disk damage suggests the existence of dysfunction in RGC prior to apoptosis. This has been supported by Banitt et al., who reported abnormalities in PERG amplitude preceding the development of optic nerve RNFL thinning detected by optical coherence tomography (OCT) in glau-coma suspects(56).

Based on the observed correlation between high IOP and redu-ced PERG response, likely as a result of RGC dysfunction, Feghali et al. demonstrated that, in rabbits with low PERG amplitude associated with high IOP, the amplitude was immediately normalized when the IOP was lowered(57). Other studies have evaluated the effect of medically or surgically reduced IOP on PERG response in humans(58-60). After following OHT patients treated with timolol as well as a control group receiving placebo for six years, Nesher et al. observed a signi-ficant correlation between IOP levels and steady-state PERG ampli-tude(58). Spadea et al. observed no recovery of the PERG amplitude trabaculectomy was performed on eyes with advanced glaucoma(59); however, other authors reported that the PERG response could be restored after pharmacologically induced IOP reduction in low- and high-tension glaucomatous eyes, even in the presence of early VF de fects(60), suggesting that PERG reduction is related not only to RGC loss, but also to RGC dysfunction. Elevated IOP has an influence on this dysfunction in patients with OHT and glaucoma; therefore, con-trolling IOP is likely important to the re-establishment of normal RGC function in patients with non-advanced glaucoma.

The response amplitude may be compromised in OHT, but not all eyes with OHT have reduced amplitude(61). Thus, studies have been

conducted to evaluate the risk of OHT eyes developing glaucoma, depending on the presence or absence of a reduced response am-plitude. A longitudinal study showed that one of 15 eyes with OHT with reduced PERG amplitude developed glaucomatous VF defects after three years(62). Pfeiffer followed 29 eyes with OHT for up to three years: five of 12 eyes with abnormal baseline PERG developed glau-comatous field defects, but no defects were observed among eyes with normal PERG (n=18)(63). In a recent study involving 120 eyes of OHT patients followed for 10 years, glaucoma was detected by de-creased PERG amplitudes four years before VF changes occurred(64). These studies suggest that the presence of reduced PERG amplitudes in patients with OHT and in glaucoma suspects may be a predictor of glaucoma.

Another study involving glaucoma suspects examined the pre-dictive value of PERG abnormalities for developing VF defects. The positive and negative predictive values were 69% and 80%, respecti-vely, and N95 had the best predictive value(65). In addition, Bayer and Erb observed that an abnormal N95 amplitude could identify 88% of pre-perimetric glaucomatous eyes before the development of VF loss(66).

Based on the frequently observed association between glaucoma and reduced PERG amplitudes, some researchers have tested diffe-rent check sizes and reversal rates in order to evaluate the sensitivity of the method to detect glaucoma. The response was found to be frequency-dependent in glaucoma (the higher the frequency, the more strongly related)(16,67). The steady-state response at 16 rev/s was relatively more affected than the transient response when comparing responses in the same individual(16); however, rates >18 rev/s could not distinguish normal patients from glaucomatous patients(68). Most studies have demonstrated that steady-state PERG with a reversal rate between 10 and 20 rev/s yields the greatest sensitivity for the detection of glaucomatous damage(16,67,68).

The detection of PERG amplitude reduction also depends on check size(69-71). When large checks (16°) are used, the PERG response is relatively preserved in early glaucoma and reduced in advanced glaucoma(70); however, when small checks (0.8°) are used, the res-ponse is compromised in both early and advanced glaucoma(26,70). This indicates loss of spatial tuning (a characteristic of RGC) with the progression of glaucomatous damage. However, Trick noticed that when very small checks (<0.5°) were used, measurements were no longer meaningful(67). Likewise, in an experimental study, Marx et al. induced OHT in three monkeys and observed that, in the absence of optic nerve cupping, the PERG response obtained with small checks was compromised earlier compared with the response obtained with large checks(71).

Studies have also been performed to investigate the effect of medications on the PERG response in glaucoma. In a recent clinical trial involving patients with glaucoma, the use of antioxidants partly prevented PERG amplitude reduction, suggesting a favorable influen-ce on RGC function(72).

However, the results of these studies may have been influenced by a number of confounding factors. For example, aging is associa-ted with natural RGC loss and, consequently, a natural reduction in amplitude response(73). It is, therefore, important to use age-matched controls in such analyses. Second, the presence of diurnal(74) and in-traindividual variability in IOP during the day may interfere with the PERG response and compromise interpretation(75). Whenever possi-ble, PERG should be measured at the same time of the day to improve comparability. Third, when Jacobi et al. investigated the questions of reproducibility and intraindividual variability, they found a positive correlation between right and left eyes but no correlation between measurements made at seven-day intervals(75). Although this was not suggested by the authors, the difference may be partially explained by variability in IOP. If so, this could interfere with the follow-up analysis of glaucoma patients.

Due to difficulties in the acquisition of PERG data, some authors have used a ratio of the response obtained. The use of a ratio is inte-

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resting because it reduces the problem of populational variability of absolute amplitudes and is not affected by aging(41). Watanabe et al. were among the first to use ratios in a study comparing PERG ampli-tudes of the central and paracentral ring areas(40).

In normal eyes, amplitudes obtained with 0.8° and 16° checks are closely correlated, but this correlation is compromised in early glaucoma: initially, a reduction is observed for amplitudes measured with small checks (0.8°); later, changes become detectable with large checks (16°) as well. Because normal patients are likely to display a high amplitude with both small and large checks (0.8° and 16°), in-terindividual variability(75) may interfere with comparisons between groups. To circumvent this, a PERG ratio was created (steady-state PERG amplitude with 0.8° checks/PERG amplitude with 16° checks) using a frequency of 16 rev/s(74,76). Normalization using the response obtained with large checks may reduce interindividual variability. A longitudinal study following 54 eyes with elevated IOP for 10 years suggested that the PERG ratio was a better biomarker than the PERG amplitude for the detection of glaucoma prior to the emergence of VF defects(76).

It is important to remember that in advanced cases of glaucoma, the denominator may be so small that the PERG ratio becomes unre-liable(76). Interestingly, dioptrical defocus and wide-angle scattering, as observed in patients with cataracts, affect the PERG ratio in the same pattern as glaucoma, compromising the PERG response to 0.8° checks but not to 16° checks(70,77). This may compromise the interpre-tation of PERG results, especially because most glaucoma patients exhibit media opacities, even in the early stages.

Another alternative to overcome some of the above-mentioned difficulties, especially those related to eye movement and blinking during acquisition, is the use of PERGLA. According to Ventura, PERG results were abnormal in at least one of the outcome measures in 69% of patients with early manifest glaucoma(15). This finding is sup-ported by other studies(78,79). Using PERGLA, Sehi et al. evaluated the effect of lowering IOP in glaucoma patients with reduced amplitudes and concluded that amplitudes could be improved by trabeculec-tomy(80), but not by pharmacological treatment(81). The difference may lie in the level of IOP reduction: in the first study, IOP was reduced from 19 mmHg to 10 mmHg, while in the second study, the reduction was only 20%.

aBNOrmalItIeS IN lateNCy

Unlike amplitude, little attention has been devoted to the matter of delay in the time of onset of response. Ringens and Parisi observed a delay in the PERG response in glaucoma patients(50,82) and Komata found a prolonged P50 peak time(83). With regard to OHT, Arai et al. reported an elongated latency of P50(62) and Marx et al. reported a delay in mean PERG latency(84). Similar to amplitude, latency is known to increase with age(85). In a recent study, Jafarzadehpour et al. also reported N95 latency delay in glaucoma suspects and patients with early glaucoma(86). Overall, only a small number of authors have re-ported abnormalities in latency.

aBNOrmalItIeS IN mFperG When introduced, mfPERG was expected to enable the evalua-

tion of the spatial extent of glaucoma-related reduction in PERG amplitude(87,88). The technique has already been shown to correlate well with OCT findings for VF defects and RGC defects, such as in hemianopia due to chiasmal compression(89). However, in three major studies involving glaucoma patients, mfPERG did not reflect localized ganglion cell loss(90-92). Stiefelmeyer et al. observed decreased P50 and N95 values, mainly in the central region, but failed to establish a correlation with VF defects(92). The other two studies reported similar results, suggesting that PERG is diffusely compromised in glaucoma and that current mfPERG technology is of little or no use in the de-tection of localized VF defects in this patient population.

CORReLATIOn BeTWeen PeRG AnD OTHeR MeTHODS In THe eVALUATIOn Of STRUCTURAL ABnORMALITIeS In GLAUCOMA

Several articles have investigated the correlation between PERG and other methods in the detection of structural damage of the optic nerve and the RFNL. With regard to fundoscopic abnormalities, Drance et al. was one of the first to correlate PERG and morphological findings of glaucomatous optic nerve damage(93). Marx et al. reported that increasing cupping of the optic disc correlated well with pro-gressive amplitude reduction at IOP levels >40 mmHg(54). Ventura et al. observed that the presence of fundoscopic optic nerve damage (vertical cup/disc ratio >0.5; cup/disc asymmetry ≥0.2; notching or disc hemorrhage) and reduced PERGLA amplitude could predict the later progression of glaucomatous defects(15). With regard to structu-ral analysis based on complementary examinations, a weak but significant correlation has been reported between PERG and CSLO with regard to the shape of the optic disc(94).

PERG amplitudes and RFNL thickness abnormalities assessed by OCT and scanning laser polarimetry (GDx) have also been correlated. Parisi et al. observed that OCT-measured overall and temporal optic nerve RFNL thickness was significantly correlated with P50 implicit time delay and with P50-N95 peak-to-peak(17). However, Ventura et al. observed a weak correlation in patients with early glaucoma: reduc-tions in PERG amplitude were more evident than expected based on the amount of RGC loss estimated by OCT, suggesting that although the RGC population was not greatly reduced, the cells had become severely dysfunctional(15). When comparing the results obtained by OCT and PERG in OHT and early glaucoma patients, Falsini et al. obser-ved a structure-function relationship in the glaucoma group that was absent in the OHT group(95), suggesting that, in the early stage of the disease, loss of RGC function is detectable by PERG before it becomes evident on OCT. Using GDx analysis, Toffoli et al. observed a good correlation between RNFL thickness and PERG amplitude measurements(96). This discrepancy may be explained by the fact that PERG reductions may be associated with either dysfunction or loss of RGC, whereas on OCT RNFL is only affected in the latter case.

CORReLATIOn BeTWeen PeRG AnD OTHeR MeTHODS In THe eVALUATIOn Of fUnCTIOnAL ABnORMALITIeS In GLAUCOMA

PERG can reveal impairment of RGC function before it is detecta-ble by conventional perimetry. A clear central area of a VF with peripheral glaucomatous defect may display reduced amplitude(18). In a study by Ventura et al., 52% of pre-perimetric glaucoma patients (abnormal disc with normal SAP) exhibited PERG abnormalities(15).

A significant correlation between PERG amplitudes and global VF indices (mean deviation [MD] and corrected pattern standard deviation) has been reported(97). With regard to MD, PERG amplitude deteriorates as VF defect advances(18). Whereas Garway-Heath et al. observed a linear correlation between PERG amplitude and differen-tial light sensitivity in the VF (expressed on a logarithmic dB scale)(98), Hood et al. observed no correlation between N95 amplitude and N95:P50 ratio with regard to MD(99) and reported that 25% of patients with abnormal VF had normal PERG responses. The absence of a linear correlation between PERG amplitude values was explained by the wide range of amplitude among normal eyes and the fact that, even in advanced glaucoma, PERG is never reduced to zero due to the presence of noise.

These conflicting results may be due to the fact that PERG and perimetry were designed to test different aspects of visual function. While PERG is an objective test and represents a mass response of the central retina, perimetry is a subjective examination based on focal threshold stimulus of the central and peripheral retina(100). However, it has also been suggested that the PERG response reflects diffuse and non-focal damage to ganglion cells, i.e., pan-retinal ganglion cell damage(101). According to Ventura et al., when a patient with glauco-ma without perimetric defect exhibits changes in the PERG response (Figure 2), the abnormality indicates generalized RGC dysfunction;



figure 2. Representative example of an eye with pre-perimetric glaucoma and reduced pattern electroretinogram (PERG) responses. A) Fundus photograph showing glaucomatous cupping; B) Normal standard automated perimetry (24-2 SITA Standard test); C) Reduced transient PERG responses (P50= 0,95µV; N95= 1,65µV); D) Reduced steady-state PERG amplitude response (1.78 µV).

while the PERG response is normal in a glaucoma patient with VF de -fect, perimetry detects peripheral focal field loss in a patient with near-nor mal RGC function(100).

Although a correlation between glaucomatous VF defects and reduced PERG amplitude in the corresponding hemifield has already been reported(41), it is important to remember that standard PERG is not appropriate for the detection of focal glaucomatous damage(102).

PERG has also been compared with SAP and FDT with regard to diagnostic accuracy in glaucoma patients, and was found to be simi-lar to the former and somewhat inferior to the latter(103).

COnCLUSIOnSBased on our review of current data, pattern electroretinography

appears to be a good option for detecting RGC dysfunction in glauco-ma patients with or without VF loss. However, some methodological aspects may interfere with routine use, such as the technical difficulty in obtaining data, and certain factors and conditions prevalent in glaucoma patients, including advanced age, media opacities and associated retinal diseases. Thus, further studies and technical deve-lopments are necessary to improve the ability of PERG technology to detect glaucoma, especially early-stage disease, in patients with mild or absent VF defects.

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50. Ringens PJ, Vijfvinkel-Bruinenga S, van Lith GH. The pattern-elicited electroretinogram. I. A tool in the early detection of glaucoma? Ophthalmologica. 1986;192(3):171-5.

51. Weinstein GW, Arden GB, Hitchings RA, Ryan S, Calthorpe CM, Odom JV. The pattern electroretinogram (PERG) in ocular hypertension and glaucoma. Arch Ophthalmol. 1988;106(7):923-8.

52. Ohta H, Tamura T, Kawasaki K, Yonemura D. [Negative wave in human pattern ERG and its suppression in glaucoma]. Nihon Ganka Gakkai Zasshi. 1986;90(6):882-7.

53. Wanger P, Persson HE. Pattern-reversal electroretinograms in ocular hypertension. Doc Ophthalmol. 1985;61(1):27-31.

54. Marx MS, Podos SM, Bodis-Wollner I, Howard-Williams JR, Siegel MJ, Teitelbaum CS, et al. Flash and pattern electroretinograms in normal and laser-induced glaucomatous primate eyes. Invest Ophthalmol Vis Sci. 1986;27(3):378-86.

55. Siliprandi R, Bucci MG, Canella R, Carmignoto G. Flash and pattern electroretinograms during and after acute intraocular pressure elevation in cats. Invest Ophthalmol Vis Sci. 1988;29(4):558-65.

56. Banitt MR, Ventura LM, Feuer WJ, Savatovsky E, Luna G, Shif O, et al. Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects. Invest Ophthalmol Vis Sci. 2013;54(3):2346-52.

57. Feghali JG, Jin JC, Odom JV. Effect of short-term intraocular pressure elevation on the rabbit electroretinogram. Invest Ophthalmol Vis Sci. 1991;32(8):2184-9.

58. Nesher R, Trick GL, Kass MA, Gordon MO. Steady-state pattern electroretinogram follo-wing long term unilateral administration of timolol to ocular hypertensive subjects. Doc Ophthalmol. 1990;75(2):101-9.

59. Spadea L, Giuffre I, Bianco G, Balestrazzi E. PERG and P-VEP after surgical trabeculec-tomy in primary open-angle glaucoma. Eur J Ophthalmol. 1995;5(2):92-5.

60. Ventura LM, Porciatti V. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction: a pilot study. Ophthalmology. 2005;112(1):20-7.

61. Trick GL. Pattern reversal retinal potentials in ocular hypertensives at high and low risk of developing glaucoma. Doc Ophthalmol. 1987;65(1):79-85.

62. Arai M, Yoshimura N, Sakaue H, Chihara E, Honda Y. A 3-year follow-up study of ocular hypertension by pattern electroretinogram. Ophthalmologica. 1993;207(4):187-95.

63. Pfeiffer N, Tillmon B, Bach M. Predictive value of the pattern electroretinogram in high-risk ocular hypertension. Invest Ophthalmol Vis Sci. 1993;34(5):1710-5.

64. Bode SF, Jehle T, Bach M. Pattern electroretinogram in glaucoma suspects: new findings from a longitudinal study. Invest Ophthalmol Vis Sci. 2011;52(7):4300-6.

65. Gonzalvo Ibanez FJ, Fernandez Tirado FJ, Almarcegui Lafita C, Polo Llorens V, Sanchez Perez A, Honrubia Lopez FM. [Predictive value of the pattern-electroretinogram in glaucoma]. Arch Soc Esp Oftalmol. 2001;76(8):485-91.

66. Bayer AU, Erb C. Short wavelength automated perimetry, frequency doubling techno logy perimetry, and pattern electroretinography for prediction of progressive glaucomatous standard visual field defects. Ophthalmology. 2002;109(5):1009-17.

67. Trick GL. Retinal potentials in patients with primary open-angle glaucoma: physiolo-gical evidence for temporal frequency tuning deficits. Invest Ophthalmol Vis Sci. 1985; 26(12):1750-8.

68. Hiss P, Fahl G. [Changes in the pattern electroretinogram in glaucoma and ocular hypertension are dependent on stimulus frequency]. Fortschr Ophthalmol. 1991;88(5): 562-5.

69. Porciatti V, Falsini B, Brunori S, Colotto A, Moretti G. Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma. Doc Ophthal-mol. 1987;65(3):349-55.

70. Bach M, Hiss P, Rover J. Check-size specific changes of pattern electroretinogram in patients with early open-angle glaucoma. Doc Ophthalmol. 1988;69(3):315-22.

71. Marx MS, Podos SM, Bodis-Wollner I, Lee PY, Wang RF, Severin C. Signs of early damage in glaucomatous monkey eyes: low spatial frequency losses in the pattern ERG and VEP. Exp Eye Res. 1988;46(2):173-84.

72. Falsini B, Marangoni D, Salgarello T, Stifano G, Montrone L, Di Landro S, et al. Effect of epigallocatechin-gallate on inner retinal function in ocular hypertension and glaucoma: a short-term study by pattern electroretinogram. Graefes Arch Clin Exp Ophthalmol. 2009;247(9):1223-33.

73. Korth M, Horn F, Storck B, Jonas J. The pattern-evoked electroretinogram (PERG): age-related alterations and changes in glaucoma. Graefes Arch Clin Exp Ophthalmol. 1989;227(2):123-30.

74. Otto T, Bach M. Retest variability and diurnal effects in the pattern electroretinogram. Doc Ophthalmol. 1996;92(4):311-23.

75. Jacobi PC, Walter P, Brunner R, Krieglstein GK. Reproducibility and intraindividual variability of the pattern electroretinogram. Ger J Ophthalmol. 1994;3(4-5):216-9.

76. Bach M, Unsoeld AS, Philippin H, Staubach F, Maier P, Walter HS, et al. Pattern ERG as an early glaucoma indicator in ocular hypertension: a long-term, prospective study. Invest Ophthalmol Vis Sci. 2006;47(11):4881-7.

77. Bayer AU, Maag KP, Erb C. Detection of optic neuropathy in glaucomatous eyes with normal standard visual fields using a test battery of short-wavelength automated perimetry and pattern electroretinography. Ophthalmology. 2002;109(7):1350-61.

78. Yang A, Swanson WH. A new pattern electroretinogram paradigm evaluated in terms of user friendliness and agreement with perimetry. Ophthalmology. 2007;114(4):671-9.

79. Bowd C, Vizzeri G, Tafreshi A, Zangwill LM, Sample PA, Weinreb RN. Diagnostic accuracy of pattern electroretinogram optimized for glaucoma detection. Ophthalmology. 2009; 116(3):437-43.

80. Sehi M, Grewal DS, Goodkin ML, Greenfield DS. Reversal of retinal ganglion cell dys function after surgical reduction of intraocular pressure. Ophthalmology. 2010; 117(12):2329-36.

81. Sehi M, Grewal DS, Feuer WJ, Greenfield DS. The impact of intraocular pressure re-duction on retinal ganglion cell function measured using pattern electroretinogram in eyes receiving latanoprost 0.005% versus placebo. Vision Res. 2011;51(2):235-42.

82. Parisi V, Pernini C, Guinetti C, Neuschuler R, Bucci MG. Electrophysiological assess-ment of visual pathways in glaucoma. Eur J Ophthalmol. 1997;7(3):229-35.



83. Komata M, Shirao Y, Watanabe M, Kawasaki K. Delay of pattern electroretinogram peaks and its correlation to contrast threshold for motion perception in glaucoma. Ophthalmic Res. 1995;27(2):110-7.

84. Marx MS, Bodis-Wollner I, Lustgarten JS, Podos SM. Electrophysiological evidence that early glaucoma affects foveal vision. Doc Ophthalmol. 1987;67(3):281-301.

85. Celesia GG, Kaufman D, Cone S. Effects of age and sex on pattern electroretinograms and visual evoked potentials. Electroencephalogr Clin Neurophysiol. 1987;68(3):161-71.

86. Jafarzadehpour E, Radinmehr F, Pakravan M, Mirzajani A, Yazdani S. Pattern electroreti -nography in glaucoma suspects and early primary open angle glaucoma. Journal of ophthalmic & vision research. 2013;8(3):199-206.

87. Hoffmann MB, Flechner JJ. Slow pattern-reversal stimulation facilitates the assessment of retinal function with multifocal recordings. Clin Neurophysiol. 2008;119(2):409-17.

88. Chan HH, Ng YF, Chu PH. Applications of the multifocal electroretinogram in the detection of glaucoma. Clin Exp Optom. 2011;94(3):247-58.

89. Monteiro ML, Hokazono K, Cunha LP, Oyamada MK. Correlation between multifocal pattern electroretinography and Fourier-domain OCT in eyes with temporal hemia-nopia from chiasmal compression. Graefes Arch Clin Exp Ophthalmol. 2013;251(3): 903-15.

90. Klistorner AI, Graham SL, Martins A. Multifocal pattern electroretinogram does not demonstrate localised field defects in glaucoma. Doc Ophthalmol. 2000;100(2-3): 155-65.

91. Lindenberg T, Horn FK, Korth M. [Multifocal steady-state pattern-reversal electroreti-nography in glaucoma patients]. Ophthalmologe. 2003;100(6):453-8.

92. Stiefelmeyer S, Neubauer AS, Berninger T, Arden GB, Rudolph G. The multifocal pattern electroretinogram in glaucoma. Vision Res. 2004;44(1):103-12.

93. Drance SM, Airaksinen PJ, Price M, Schulzer M, Douglas GR, Tansley BW. The corre-lation of functional and structural measurements in glaucoma patients and normal subjects. Am J Ophthalmol. 1986;102(5):612-6.

94. Salgarello T, Colotto A, Falsini B, Buzzonetti L, Cesari L, Iarossi G, et al. Correlation of

pattern electroretinogram with optic disc cup shape in ocular hypertension. Invest Ophthalmol Vis Sci. 1999;40(9):1989-97.

95. Falsini B, Marangoni D, Salgarello T, Stifano G, Montrone L, Campagna F, et al. Struc-ture-function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG. Graefes Arch Clin Exp Ophthalmol. 2008; 246(8):1153-62.

96. Toffoli G, Vattovani O, Cecchini P, Pastori G, Rinaldi G, Ravalico G. Correlation between the retinal nerve fiber layer thickness and the pattern electroretinogram amplitude. Ophthalmologica. 2002;216(3):159-63.

97. Neoh C, Kaye SB, Brown M, Ansons AM, Wishart P. Pattern electroretinogram and auto-mated perimetry in patients with glaucoma and ocular hypertension. Br J Ophthal mol. 1994;78(5):359-62.

98. Garway-Heath DF, Holder GE, Fitzke FW, Hitchings RA. Relationship between electro-physiological, psychophysical, and anatomical measurements in glaucoma. Invest Ophthalmol Vis Sci. 2002;43(7):2213-20.

99. Hood DC, Xu L, Thienprasiddhi P, Greenstein VC, Odel JG, Grippo TM, et al. The pattern electro retinogram in glaucoma patients with confirmed visual field deficits. Invest Ophthalmol Vis Sci. 2005;46(7):2411-8.

100. Ventura LM, Porciatti V. Pattern electroretinogram in glaucoma. Curr Opin Ophthal-mol. 2006;17(2):196-202.

101. Bach M, Birkner-Binder D, Pfeiffer N. [In incipient glaucoma the pattern electroretino-gram displays diffuse, retinal damage]. Ophthalmologe. 1993;90(2):128-31.

102. Neppert B, Breidenbach K, Dannheim F, Hellner KA. [Chronic open angle glaucoma: correlation of pattern electroretinography and visual field indices]. Ophthalmologe. 1996;93(5):539-43.

103. Tafreshi A, Racette L, Weinreb RN, Sample PA, Zangwill LM, Medeiros FA, et al. Pattern electroretinogram and psychophysical tests of visual function for discriminating between healthy and glaucoma eyes. Am J Ophthalmol. 2010;149(3):488-95.

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Letters to the Editor

411Arq Bras Oftalmol. 2014;77(6):411http://dx.doi.org/10.5935/0004-2749.20140102

Metallic corneal foreign bodies: an occupational health hazardCorpos estranhos metálicos na córnea: um problema de saúde ocupacional

Dear Editor:We have read with interest the article titled “Metallic corneal

foreign bodies: an occupational health hazard for anesthetic abuse keratopathy”, by Ozkurt et al.(1). The authors analyze the risk factors, outcomes, demographic characteristics, and attitudes of 100 workers who presented with a metallic corneal foreign body (FB) injury and recommend several prevention measures to lower the incidence of occupational eye injuries. We thank the authors for their study and would like to emphasize another issue associated with metallic corneal FBs: the problem of topical anesthetic abuse keratopathy (TAAK), which is unfortunately often overlooked and diagnosed late in these patients.

Topical anesthetics are mainly abused by young male manual laborers who are exposed to arc welding flash, metallic FB injuries and chemical injuries while working in welding operations and foun-dries(2). Improper use of topical anesthetic agents results in superficial punctate keratitis, persistent corneal epithelial defects, ring-like or dis ciform stromal infiltration, endothelial cell loss, secondary infectious keratitis, and even corneal melting and perforation. This can result in permanent vision loss in severe cases that are not diagnosed or pro-perly treated(2-4). Therefore, TAAK has been a major health problem in these workers, particularly in developing countries. Clinical diagnosis is based on history and slit-lamp biomicroscopy findings. Hospitaliza-tion, along with promptly stopping the use of the topical anesthetic, psychiatric consultation, and close surveillance, are typically necessa-ry because despite the warnings, most of these patients continue to use these agents during their hospitalization.

Because unregistered workers often do not have legal rights in cases of occupational accidents and are ineligible for free health care, they attempt to remove FBs on their own or with the help of their friends rather than seeking care from an ophthalmologist. Therefore, this situation may make a worker more vulnerable to TAAK after self-removal of the corneal FBs because in Turkey, the workers often use a topical anesthetic drop during this procedure. In addition, in most workplaces, particularly in developing countries, the em-ployees can easily obtain topical anesthetic drops from pharmacies because prescriptions are inadequately monitored and the drops are available over the counter. In the study conducted by Ozkurt et al.(1), 55% of the employees were found to be unregistered and 52 patients (52%) attempted corneal FB removal on their own, which can cause further injury. Both FBs and the use of contaminated and potentially

harmful materials to remove them can lead to corneal infections. Furthermore, TAAK can make them more vulnerable to the infections because of changes to the ocular surface, such as insufficiency of the epithelial barrier and instability of the tear film(2,4).

Yagci et al.(2) reported 19 cases with TAAK, most of whom had been referred with a diagnosis of refractory infectious keratitis of unknown etiology after corneal FB and other occupational injuries. Ozkurt et al.(1) also reported that one patient had presented secon-dary infectious keratitis after he had removed the corneal FB on his own. We are unable to exactly diagnose TAAK in this case because the other clinical findings and history of the patient are not available. Ho-wever, we speculate that this patient may have been a TAAK because we consider that he may have used a topical anesthetic drop during corneal FB removal and continued to use the drop. In such cases, for correct diagnosis, it is important to consider TAAK because these patients tend to hide their use of these drugs. Because TAAK had be-come a serious health care problem among male workers in Turkey, the government, in 2012, prohibited both over-the-counter sales of topical proparacaine (Alcaine®, Alcon) and prescription sales by phar-macies in workplaces(4). Ozkurt et al.(1) recommended that workplaces at which there is an increased risk for ocular injuries should take more protective measures, such as the mandatory use of goggles and more educational programs for the workers and occupational physicians about the harm that can result from self-removal of corneal FBs and about repetitive corneal injuries. In addition, information should be provided about the risks associated with uncontrolled use of topical anesthetic agents. Over-the-counter sales of these drugs as well as prescription sales by pharmacies in workplaces should also be pro-hibited.

Saban Gonul, Banu Bozkurt, Suleyman Okudan

Submitted for publication: September 18, 2014 Accepted for publication: September 22, 2014

Department of Ophthalmology, Selcuk University Faculty of Medicine, Konya, Turkey.



Corresponding author: Saban Gonul. Selcuk University Faculty of Medicine, Department of Oph thalmology, Konya, Turkey - E-mail: [email protected]

RefeRenCeS 1. Ozkurt ZG, Yuksel H, Saka G, Guclu H, Evsen S, Balsak S. Metallic corneal foreign bodies:

an occupational health hazard. Arq Bras Oftalmol. 2014;77(2):81-3. 2. Yagci A, Bozkurt B, Egrilmez S, Palamar M, Ozturk BT, Pekel H. Topical anesthetic abuse

keratopathy: a commonly overlooked health care problem. Cornea. 2011;30(5):571-5. 3. Rosenwasser GO, Holland S, Pflugfelder SC, Lugo M, Heidemann DG, Culbertson WW,

et al. Topical anesthetic abuse. Ophthalmology. 1990;97(8):967-72. 4. Burcu A, Dogan E, Yalniz-Akkaya Z, Ornek F. Early amniotic membrane transplantation

for toxic keratopathy secondary to topical proparacaine abuse: a report of seven cases. Cutan Ocul Toxicol. 2013;32(4):241-7.


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BooksBicas HEA. Oftalmologia: fundamentos. São Paulo: Contexto; 1991.

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AnnalsHöfling-Lima AL, Belfort R Jr. Infecção herpética do recém-nascido. In: IV Congresso Brasileiro de Prevenção da Cegueira; 1980 Jul 28-30, Belo Horizonte, Brasil. Anais. Belo Horizonte; 1980. v.2. p. 205-12.

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Arq Bras Oftalmol. 2014;77(6):417-26

Índice por assunto (descritores) | subjeCt index (keywords)

v. 77 - 2014

417

AAberrações de frente de onda da córnea, 191, 267

Abscesso, 293

Acesso aos serviços de saúde, 164

Acidentes de trabalho, 81

Acomodação ocular, 243

Acuidade visual, 8, 34, 50, 71, 103, 159, 222, 297

Adaptação ocular, 250

Adulto, 50, 116, 188, 191, 264, 327, 392, 400

Agentes antivirais efeitos adversos, 178

Ajuste de prótese, 76

Amnio transplante, 382

Análise de elementos finitos, 60

Análise de Fourier, 345

Análise de sobrevivência, 155

Angiofluoresceinografia, 188, 264, 397, 400

Animais, 209, 310, 388

Anormalidade torcional, 159, 364

Anormalidades congênitas, 114 etiologia, 300

Anticorpos monoclonais, 355 uso terapêutico, 4

Apoplexia hipofisaria, 330

Apoptose, 388

Argentina, 25

Astenopia, 21

Astigmatismo, 125, 191 cirurgia, 71, 159 fisiopatologia, 40, 159

Atrofia, 395

Avaliação de eficácia-efetividade de intervenções, 40

Azul tripano administração & dosagem, 388

BBaixa visão reabilitação, 91

Biomecânica métodos, 60

Biometria, 152, 228

Blefaroptose, 377

Bloqueio pupilar, 360

CCabeça, 8

Câmara anterior, 243 patologia, 233

Cápsula posterior do cristalino, 222

Capsulorrexe, 173

Catarata, 12, 373 congênita, 143, 297 diagnóstico, 143 epidemiologia, 25, 222

Células fotorreceptoras retinianas bastonetes, 327

Ceratectomia fotorrefrativa métodos, 159

Ceratocone terapia, 84

Ceratomileuse assistida por excimer laser in situ, 159, 191 efeitos adversos, 119 métodos, 103

Ceratoplastia endotelial com remoção da lâmina limitante posterior, 122

Cetorolaco de trometamina uso terapêutico, 99

Ciclopentolato administração & dosagem, 228

Cirurgia dos olhos, 12

Citocinas, 168

Cloreto de tolônio, 285

Coelhos, 310

Colágeno efeitos de radiação, 84

Colesterol, 168

Complicações, 125

Complicações na gravidez, 300

Complicações pós-operatórias, 191, 222

Comportamento social, 110

Comprimento axial do olho, 152

Conjuntiva, 285, 305, 351

Conjuntivite viral quimioterapia, 99

Consulta remota, 214

Convergência ocular, 21, 275

Córnea, 228, 305, 388 anatomia & histologia, 17, 152, 225, 345 cirurgia, 60 efeito de drogas, 310 fisiologia, 60 lesões, 81, 392 patologia, 17, 119 ultraestrutura, 60 ultrassonografia, 382

Coroide, 168 anatomia & histologia, 148 patologia, 148, 280, 368

Corpo caloso, 188

Corpo ciliar lesões, 50

Corpo vítreo patologia, 256

Corpos estranhos oculares, 81

Córtex visual, 275

Criança, 143, 152, 256

Cuidados intraoperatórios, 355

Cuidados paliativos, 382

Curativos biológicos, 382

Custos e análise de custos, 164

DDacriocistite congênito, 261 ultrassonografia, 261

Dacriocistorinostomia métodos, 261

Degeneração macular, 168, 315

Dengue complicações, 330

Diabetes mellitus, 351

Diagnóstico pré-natal, 261

Diagnóstico tardio, 297

Difusão de inovações, 214

Disco óptico anormalidades, 368

Doença ambiental, 193

Doença de Parkison, 238

Doenças da córnea, 209

Doenças da esclera etiologia, 182

Doenças da íris, 360

Doenças do aparelho lacrimal, 193

Doenças do prematuro, 34

Doenças orbitárias etiologia, 293

Doenças retinianas, 114, 139 diagnóstico, 185 genética, 327 induzido quimicamente, 321 quimicamente induzido, 178

Dominância ocular, 76

Drusas retinianas, 315

eEdema da córnea, 382

Edema macular, 355

Eletrorretinografia, 327, 403

Emergência, 30

Endotélio da córnea, 122

Enucleação ocular, 256

Epitélio pigmentado da retina, 114, 139, 315

Erros de refração cirurgia, 50 diagnóstico, 267

Índice - v. 77 - 2014


Esclera, 168

Escrita manual, 91

Estrabismo, 88, 143, 275 cirurgia, 250, 364 fisiopatologia, 110

Estresse oxidativo, 388

Estudo comparativo, 345

Estudo multicêntrico, 355

Extração de catarata, 12, 297, 355 estatística & dados numéricos, 164 métodos, 173

fFacoemulsificação, 71, 173, 355, 373 métodos, 40

Fator A de crescimento do endotélio vascular, 209

Fator de necrose tumoral, 168

Fechamento angular, 360

Feminino, 57, 188, 191, 256, 261, 264, 400

Fenilefrina, 377

Ferimentos oculares penetrantes, 95 ultrassonografia, 392

Fibras nervosas, 368

Fotocoagulação, 397

Fotografia instrumentação, 17 métodos, 233

GGentamicinas, 182

Glaucoma diagnóstico, 403

Glaucoma de ângulo aberto fisiopatologia, 288

Gonioscopia, 50

Gravidez, 148, 261

HHabilidades, 334

Hamartoma, 114

Hanseníase, 395

Hemoglobina A glicosilada, 351

Hemorragia retiniana, 330 etiologia, 397

Hepatite C crônica quimioterapia, 178

Hipertensão ocular, 403

Hipotensão ocular etiologia, 50

Humanos, 50, 57, 116, 143, 188, 191, 256, 261, 264, 327, 330, 392, 400

IIdade gestacional, 225

Idoso, 57

Implante de lente intraocular, 40, 71, 125, 355

Incontinência pigmentar diagnóstico, 47 terapia, 47

Infecções oculares bacterianas, 324

Inflamação, 1

Inibidores de angiogênese administração & dosagem, 4, 209

Injeções, 4, 209

Injeções intraoculares, 388

Injeções intravítreas, 256

Instabilidade articular, 119

Interferometria, 233

Interferon-alfa efeitos adversos, 178, 321 uso terapêutico, 321

Interleucina-6, 168

Iridectomia, 360

Íris lesões, 395 patologia, 360

Irite, 395

LLacerações, 392

Lactente, 397

Laser, 315

Laser de excimer, 103

Leis de cura em homeopatia, 377

Leitura, 91

Lentes de contato, 76

Lentes intraoculares, 71, 103, 173, 373

Lesão nos olhos complicações, 50 ultrassonografia, 50

Lesões oculares, 81

Limbo da córnea, 305 cirurgia, 40

Linfoma de células do manto diagnóstico, 54

Linfoma de zona marginal tipo células B, 116

Linfoma não Hodgkin, 54

Linguagem, 21, 91

Luteína, 173

Luz, 267

MMacrófagos, 168

Masculino, 50, 116, 327, 392, 400

Mastócitos, 285

Matemática, 267

Medidas, 275

Meia-idade, 116

Melanoma, 155 diagnóstico, 400 patologia, 57 secundário, 321

Melfalan administração & dosagem, 256

Membrana epirretiniana, 264

Metástases neoplásicas, 259

Microbiota, 351 métodos, 50

Midríase, 395

Miopia cirurgia, 103

Miosite orbital, 116

Misoprostol efeitos adversos, 300

Modelos animais de doenças, 209

Modelos biológicos, 60

Modelos de simulação, 334

Músculos oculomotores, 116, 364 fisiopatologia, 250

nNeoplasias da conjuntiva cirurgia, 155

Neoplasias da coroide secundário, 259

Neoplasias da retina cirurgia, 256

Neoplasias da túnica conjuntiva, 57

Neoplasias do nervo óptico diagnóstico, 400

Neoplasias musculares, 116

Neoplasias oculares, 57, 305

Neoplasias orbitárias, 54, 116

Neoplasias pancreáticas, 259

Neovascularização da córnea induzido quimicamente, 209

Nervo troclear, 88

Nistagmo fisiológico, 8

OOclusão da artéria retiniana, 188

Oftalmologia, 214

Oftalmopatias diagnóstico, 214

Oftalmoplegia, 88

Oftalmoscopia direta, 334

Oftalmoscopia indireta, 334

Índice - v. 77 - 2014

Arq Bras Oftalmol. 2014;77(6):417-26 419

Opacificação da cápsula, 222

Óptica e fotônica, 267

PPálpebras inervação, 377

Panuveíte, 324

Paquimetria corneana, 1, 17, 228, 382

Paraguai, 164, 297

Perda auditiva, 188

Perda de células endoteliais da córnea, 382

Peso ao nascer, 225

Pesquisa sobre serviços de saúde estatística & dados numéricos, 25

Pessoas com deficiência visual, 91

Planejamento cirúrgico, 125

Polimetil metacrilato, 71

Polissonografia, 280

Poluentes ambientais efeitos adversos, 193

Posicionamento do paciente, 88

Postura, 8, 159

Potenciais evocados visuais, 238

Pré-escolar, 34

Prematuro, 34, 225

Presbiopia reabilitação, 76

Pressão intraocular, 403 fisiologia, 288

Procedimentos cirúrgicos oftalmológicos métodos, 364

Procedimentos cirúrgicos refrativos, 191

Psicometria, 21

Pterígio, 4, 305 cirurgia, 182 diagnóstico, 285

Pupila, 76, 243 fisiologia, 233

Pupila tônica, 395

QQualidade de vida, 12, 95, 110

Questionário VF-14, 12

Questionários, 21, 95, 110

Quiasma óptico, 330

RRatos, 209, 388

Reagentes para ligações cruzadas, 84, 191, 310

Recém-nascido, 261

Recidiva, 4, 285

Recursos audiovisuais, 91

Refração ocular, 71 fisiologia, 267

Relatos de casos, 47, 50, 54, 57, 114, 116, 119, 122, 182, 185, 188, 191, 256, 261, 264, 321, 324, 327, 330, 392, 395, 397, 400

Remoção, 377

Resultado de tratamento, 360

Retina, 315, 324 citologia, 264

Retinoblastoma cirurgia, 256 quimioterapia, 256

Retinopatia da prematuridade, 34, 225

Retinopatia diabética, 355

Ribavirina efeitos adversos, 178

Riboflavina, 310 uso terapêutico, 84

Ritmo circadiano, 288

Rotação ocular, 250

SSaúde ocupacional, 81

Segmento anterior do olho, 1

Segmento externo das células fotorreceptoras da retina, 219

Segmento interno das células fotorreceptoras da retina, 219

Sensibilidade da córnea, 84

Sensibilidade de contraste, 103, 373

Sífilis, 324

Simulador, 334

Síndrome diagnóstico, 185

Síndrome da persistência do padrão de circulação fetal, 143

Síndrome de Behçet, 219

Síndrome de Möbius fisiopatologia, 300

Síndrome de Susac, 188

Síndrome hemolítico-urêmica, 397

Síndromes da apnéia do sono, 280

Síndromes do olho seco, 193

Sinusite complicações, 293

Sobrevida livre de doença, 155

Soluções oftálmicas, 99, 377

Substância própria, 191

Substâncias viscoelásticas, 250

Superfície ocular, 305

TTécnicas citológicas, 57, 305

Técnicas de diagnóstico oftalmológico, 57, 148, 233, 264

Técnicas de sutura, 392

Técnicas, medidas, equipamentos de medição, 228, 243

Telangiectasia, 264

Telemedicina, 214

Terapia a laser, 47

Terapia a laser de baixa intensidade, 122

Terapia ultravioleta, 84 métodos, 310

Teratogenios, 300

Tomografia de coerência óptica, 1, 114, 122, 148, 185, 219, 280, 324 368, 400 métodos, 50, 238, 345

Tono muscular, 250

Tonometria ocular, 280

Topografia da córnea, 17, 125, 233

Topografia da corneana métodos, 345

Traduções, 21

Transtornos da motilidade ocular, 8

Transtornos da visão etiologia, 330

Trauma, 139

Traumatismos oculares, 139

Triagem, 214

UUveíte, 324 classificação, 30 diagnóstico, 30 epidemiologia, 30 etiologia, 30

Uveíte anterior diagnóstico, 1

Uveíte posterior diagnóstico, 324

VVariações dependentes do observador, 345

Visão ocular, 403

Vitreorretinopatia proliferativa, 327


Subject index (keywords) | ÍndiCe por assunto (desCritores)

v. 77 - 2014

420

AAbscess, 293

Accidents, occupational, 81

Accommodation, ocular, 243

Adaptation, ocular, 250

Adult, 50, 188, 191, 264, 327, 392, 400

Aged, 57

Amnion transplantation, 382

Angiogenesis inhibitors administration & dosage, 4, 209

Angle closure, 360

Animals, 209, 310, 388

Anterior chamber, 243 pathology, 233

Anterior eye segment, 1

Antibodies, monoclonal, 355 therapeutic use, 4

Antiviral agents adverse effects, 178

Apoptosis, 388

Argentina, 25

Asthenopia, 21

Astigmatism, 125, 191 physiopathology, 40, 159 surgery, 71, 159

Atrophy, 395

Audiovisual aids, 91

Axial length eye, 152

BBehçet disease, 219

Biological dressings, 382

Biomechanics methods, 60

Biometry, 152, 228

Birth weight, 225

Blepharoptosis, 377

Body positioning, 88

CCapsule opacification, 222

Capsulorhexis, 173

Case reports, 47, 50, 54, 57, 114, 116, 119, 122, 182, 185, 188, 191, 256, 261, 264, 321, 324, 327, 330, 392, 395, 397, 400

Cataract, 12, 143, 373 congenital, 297 epidemiology, 25, 222

Cataract extraction, 12, 173, 297, 355 statistics and numerical data, 164

Child, 152, 256

Child, preschool, 34

Cholesterol, 168

Choroid, 168 anatomy & pathology, 148 pathology, 148, 280, 368

Choroidal neoplasms secondary, 259

Ciliary body injuries, 50

Circadian rhythm, 288

Clinical competence, 334

Collagen radiation effects, 84

Comparative study, 345

Complications, 125

Congenital, 143

Congenital abnormalities, 114 etiology, 300

Conjunctiva, 285, 305, 351

Conjunctival neoplasms, 57 surgery, 155

Conjunctivitis, viral drug therapy, 99

Contact lenses, 76

Contrast sensitivity, 103, 373

Convergence, ocular, 21, 275

Conjunctiva, 285

Cornea, 228, 305, 388 anatomy & histology, 17, 152, 225, 345 drug effects, 310 injuries, 392 pathology, 17, 119 physiology, 60 surgery, 60 ultrasound, 382 ultrastructure, 60

Corneal diseases, 209 keratomileusis, 119

Corneal edema, 382

Corneal endothelial cell loss, 382

Corneal injuries, 81

Corneal neovascularization chemically induced, 209

Corneal pachymetry, 1, 17, 228, 382

Corneal sensitivity, 84

Corneal stroma, 191

Corneal topography, 17, 125, 233 methods, 345

Corneal wavefront aberration, 191, 267

Corpus callosum, 188

Costs and cost analysis, 164

Cross-linking reagents, 84, 191, 310

Cyclopentolate administration and dosage, 228

Cytokines, 168

Cytological techniques, 57, 305

DDacryocystitis congenital, 261 ultrasonography, 261

Dacryocystorhinostomy methods, 261

Dengue complications, 330

Descemet stripping endothelial keratoplasty, 122

Diabetes mellitus, 351

Diabetic retinopathy, 355

Diagnosis, 143

Diagnostic techniques, ophthalmological, 57, 148, 233, 264

Diffusion of innovation, 214

Disease models, animal, 209

Disease-free survival, 155

Dry eye syndromes, 193

eEducation, medical methods, 334

Electroretinography, 327, 403

Emergencies, 30

Endothelium corneal, 122

Enhanced depth imaging, 148

Environmental illness, 193

Environmental pollutants adverse effects, 193

Epiretinal membrane, 264

Evaluation of the efficacy effectiveness of interventions, 40

Evoked potentials, visual, 238

Eye diseases diagnosis, 214

Eye enucleation, 256

Eye infections, bacterial, 324

Eye injuries, 81 complications, 50 ultrasonography, 50

Eye injuries, penetrating, 95 ultrasonography, 392

Eye neoplasms, 57, 305

Eye surgery, 12

Eyelids innervations, 377

fFemale, 57, 188, 191, 256, 261, 264, 400

Finite element analysis, 60

Fluorescein angiography, 188, 264, 397, 400

Fourier analysis, 345

Índice - v. 77 - 2014


GGentamicins, 182

Gestational age, 225

Glaucoma diagnosis, 403

Glaucoma, open-angle physiopathology, 288

Gonioscopy, 50

HHamartoma pathology, 114

Handwriting, 91

Head, 8

Health services accessibility, 164

Health services research statistics & numerical data, 25

Hearing loss, 188

Hemoglobin A, glycosylated, 351

Hemolytic uremic syndrome, 397

Hepatitis C, chronic drug therapy, 178

Humans, 50, 57, 116, 143, 188, 191, 256, 261, 264, 327, 330, 392, 400

IIncontinentia pigmenti diagnosis, 47 therapy, 47

Infant, 397

Infant, newborn, 261

Infant, premature, 34, 225

Infant, premature, diseases, 34

Inflammation, 1

Injections, 4, 209, 388

Interferometry, 233

Interferon alfa adverse effects, 178, 321 therapeutic use, 321

Interleukin-6, 168

Intraocular, 388

Intraocular pressure, 403 physiology, 288

Intraoperative care, 355

Intravitreal injections, 256

Iridectomy, 360

Iris injuries, 395 pathology, 360

Iris diseases, 360

Iritis, 395

JJoint instability, 119

KKeratoconus therapy, 84

Keratomileusis, laser in situ, 159, 191 methods, 103

Ketorolac tromethamine therapeutic use, 99

LLacerations, 392

Lacrimal apparatus diseases, 193

Language, 21, 91

Laser, 315

Laser in situ adverse effects, 119

Laser therapy, 47

Laser therapy, low-level methods, 122

Lasers, excimer therapeutic use, 103

Late diagnosis, 297

Laws of cure in homeopathy, 377

Lens implantation, intraocular, 40, 71, 355

Lenses, intraocular, 71, 103, 173, 373

Leprosy, 395

Lifting, 377

Light, 267

Light coagulation, 397

Limbus cornea surgery, 40

Limbus corneae, 305

Lutein, 173

Lymphoma, B-Cell, marginal zone, 116

Lymphoma, mantle cell diagnosis, 54

Lymphoma, non-Hodgkin, 54

MMacrophages, 168

Macular degeneration, 168, 315

Macular edema, 355

Male, 50, 116, 327, 392, 400

Mast cells, 285

Mathematics, 267

Measures, 275

Melanoma, 155 diagnosis, 400 pathology, 57 secondary, 321

Melphalan administration & dosage, 256

Microbiota, 351

Microscopy methods, 50

Middle-aged, 116

Misoprostol adverse effects, 300

Möbius syndrome physiopathology, 300

Models, biological, 60

Models, educational, 334

Multicenter study, 355

Muscle neoplasms, 116

Muscle tonus, 250

Mydriasis, 395

Myopia surgery, 103

nNeoplasms metastasis, 259

Nerve fibers, 368

Non-pupillary block mechanisms, 360

Nystagmus, physiologic, 8

OObserver variation, 345

Occupational health, 81

Ocular foreign bodies, 81

Ocular hypertension, 403

Ocular hypotension etiology, 50

Ocular motility disorders, 8

Ocular surface, 305

Ocular trauma, 139

Oculomotor muscles, 364 pathology, 116 physiopathology, 250

Ophthalmic solutions, 99, 377

Ophthalmologic surgical procedures methods, 364

Ophthalmology, 214

Ophthalmoplegia, 88

Ophthalmoscopy methods, 334

Optic chiasm, 330

Optic disc abnormalities, 368

Optic nerve neoplasms diagnosis, 400

Optical rotation, 250

Índice - v. 77 - 2014


Optics and photonics, 267

Orbital diseases etiology, 293

Orbital myositis, 116

Orbital neoplasms, 116 diagnosis, 54

Oxidative stress, 388

PPalliative care, 382

Pancreatic neoplasms, 259

Panuveitis, 324

Paraguay, 164, 297

Parkinson disease, 238

Pediatric, 143

Persistent fetal circulation syndrome, 143

Phacoemulsification, 71, 173, 355, 373 methods, 40

Phenylephrine, 377

Photography instrumentation, 17 methods, 233

Photorefractive keratectomy methods, 159

Pituitary apoplexy, 330

Polymethyl methacrylate, 71

Polysomnography, 280

Posterior capsule of the lens, 222

Postoperative complications, 191, 222

Posture, 8, 159

Pregnancy, 148, 261

Pregnancy complications, 300

Prenatal diagnosis, 261

Presbyopia rehabilitation, 76

Prosthesis fitting dominance, ocular, 76

Psychometrics, 21

Pterygium, 4, 305 diagnostic, 285 surgery, 182

Pupil, 76, 243 physiology, 233

QQuality of life, 12, 95, 110

Questionnaires, 21, 95, 110

RRabbits, 310

Rats, 209, 388

Reading, 91

Recurrence, 4, 285

Refraction ocular, 71 physiology, 267

Refractive errors, 125 diagnosis, 267 surgery, 50

Refractive surgical procedures, 191

Remote consultation, 214

Retina, 315, 324 cytology, 264

Retinal artery occlusion, 188

Retinal diseases, 114, 139 chemically induced, 178, 321 diagnosis, 185 genetics, 327

Retinal drusen, 315

Retinal hemorrhage, 330 etiology, 397

Retinal neoplasms surgery, 256

Retinal photoreceptor cell inner segment, 219

Retinal photoreceptor cell outer segment, 219

Retinal pigment epithelium, 114, 139, 315

Retinal rod photoreceptor cells, 327

Retinoblastoma drug therapy, 256 surgery, 256

Retinopathy of prematurity, 34, 225

Ribavirin adverse effects, 178

Riboflavin, 310 therapeutic use, 84

SSclera, 168

Scleral diseases etiology, 182

Sinusitis complications, 293

Sleep apnea syndromes, 280

Social behavior, 110

Strabismus, 88, 143, 275, 364 physiopathology, 110 surgery, 250

Survival analysis, 155

Susac syndrome, 188

Suture techniques, 392

Syndrome diagnosis, 185

Syphilis, 324

TTechniques, measures, measurement equipment, 228, 243

Telangiectasia, 264

Telemedicine, 214

Teratogens, 300

Toluidine chloride, 285

Tomography, optical coherence, 1, 114, 122, 148, 185, 219, 280, 324, 368, 400 methods, 50, 238, 345

Tonic pupil, 395

Tonometry, ocular, 280

Toric intraocular lenses, 125

Torsion abnormality, 159, 364

Translations, 21

Trauma, 139

Treatment outcome, 360

Triage, 214

Troclear nerve, 88

Trypan blue administration & dosage, 388

Tumor necrosis factor, 168

UUltraviolet therapy, 84 methods, 310

Uveitis, 324 classification, 30 diagnosis, 30 epidemiology, 30 etiology, 30

Uveitis, anterior diagnosis, 1

Uveitis, posterior diagnosis, 324

VVascular endothelial growth factor A, 209

VF-14 questionnaire, 12

Viscoelastic substances, 250

Vision, low rehabilitation, 91

Vision ocular, 403

Visual acuity, 8, 34, 50, 71, 103, 159, 222, 297

Visual cortex, 275

Visual disorders etiology, 330

Visually impaired individuals, 91

Vitreoretinopathy, proliferative, 327

Vitreous body pathology, 256


Índice por autor | author index

v. 77 - 2014

A

Abreu EB .................................................................................... 238

Abreu Junior L ....................................................................... 261

Abruzzo T .................................................................................. 256

Acar DE ....................................................................................... 225

Acar U.......................................................................................... 225

Adibelli MF ............................................................................... 388

Agra C ...............................................................................................1

Agra L ................................................................................................1

Akal A .......................................................................................... 388

Akay F .......................................................................................... 327

Akdag C ..................................................................................... 209

Akdag M .................................................................................... 293

Albarrán-Diego C ...............................................76, 103, 243

Alezzandrini A ........................................................................ 355

Allemann N ............................................................50, 261, 382

Almeida HC ............................................................................. 110

Alpfidan I ................................................................................... 148

Altintas L.................................................................................... 209

Altintas O .................................................................................. 209

Alves F ......................................................................................... 188

Alves M ....................................................................................... 193

Alves MR ..........................................................................122, 267

Anastásia S ............................................................................... 110

Andrade Neto JL ........................................................................1

Apaydin KC .............................................................................. 259

Arana J ........................................................................................ 188

Arana LA .................................................................................... 114

Arantes TE ....................................................................................99

Araújo RB................................................................................... 330

Arévalo JF ................................................................................. 355

Ari Ş .............................................................................................. 219

Arici C .......................................................................................... 228

Arieta CEL ................................................................................. 203

Arıkan S ...................................................................................... 280

Asouad M.....................................................................................17

Astur GLV................................................................................... 203

Augsburger JJ ........................................................................ 256

Ávila MP ...........................................................................185, 397

Awwad ST ....................................................................................17

Aydin N ...................................................................................... 259

B

Bach AGZ .................................................................................. 110

Badaró E ...........................................................................188, 288

Bakbak B .................................................................................... 345

Balsak S ..........................................................................................81

Barberini LY .............................................................................. 168

Bardal RC ................................................................................... 188

Barros JN ............................................................................ 57, 305

Basaran A .................................................................................. 148

Basaran M ................................................................................. 148

Bastos LC ......................................................................................99

Bekcı TT ...................................................................................... 280

Belfort Jr. R ................................................................................ 173

Berra A ........................................................................................ 119

Berra M ....................................................................................... 119

Berrocal M ................................................................................ 355

Bez Y ................................................................................................95

Bicas HEA ........................................................................250, 275

Bilgin AB .................................................................................... 259

Biteli LG ...................................................................................... 360

Bittar RHG .......................................................................................4

Bonomo PP .............................................................................. 188

Bonotto LB ..................................................................................34

Borrego-Sanz L ...................................................................... 321

Boteon JE .....................................................................................40

Bozkurt B .........................................................................201, 411

Brandt CT .................................................................................. 300

Brink A ......................................................................................... 256

Britez-Colombi GF ............................................................... 143

Burga GH ................................................................................... 297

Burga HG ................................................................................... 164

CCaglar C...................................................................................... 152

Caiado RR .................................................................................. 288

Camilo ENR .................................................................................30

Campos CMC ......................................................................... 395

Campos M ................................................................................ 191

Campos MSQ ......................................................................... 382

Campos WR ............................................................................. 395

Carrillo JF ................................................................................... 155

Carter MJ ......................................................................................25

Carvalho KMM ..........................................................................91

Carvalho MJ................................................................................40

Casella AMB ............................................................................. 168

Celebi ARC ............................................................................... 285

Ceylan OM ............................................................................... 228

Cherfan CG .................................................................................17

Chojniak MM .............................................................................57

Chuffi S ..........................................................................................34

Cibils P ........................................................................................ 164

Cınal A......................................................................................... 152

Çinar Y ................................................................................. 95, 219

Cingü AK ........................................................................... 95, 219

Clara S ......................................................................................... 339

Cohen MJ .................................................................................. 173

Colombo-Barboza G .......................................................... 310

Colombo-Barboza M ......................................................... 310

Conde S ..................................................................................... 339

Correa ZM ................................................................................. 256

Costa ACRV ....................................................................................8

Costa FD .......................................................................................57

Courtright P............................................................................. 164

Cronemberger MF .............................................................. 300

Cunha MC....................................................................................57

Cury SS ....................................................................................... 339

DDantas J ...........................................................................................1

Dantas PEC............................................................................... 310

Del Águila-CarrascoAJ ...................................................... 233

Del-Rio-Vellosillo M ............................................................ 182

Demir T ....................................................................................... 388

Dexter F ..................................................................................... 132

Dias CS ........................................................................................ 300

Dias JSFM .................................................................................. 116

Dias MJM ................................................................................... 300

Díaz-Llopis M .......................................................................... 355

Dittrich MAR ............................................................................ 116

Dittrich MR ..................................................................................54

Dolz-Marco R .......................................................................... 355

Domingues C ......................................................................... 238

Domínguez-Vicent A ...............................................233, 243

Donate-López J ..................................................................... 321

Dorairaj S ................................................................................... 360

Dorantes Y ................................................................................ 297

Duarte E ..................................................................................... 297

Duarte Júnior JO .................................................................. 185

Ducca BL ................................................................................... 364

Duerksen R ............................................................................... 164

Dusunur M ............................................................................... 388

eEckert KA ......................................................................................25

Erbano BO ................................................................................ 168

Erdogan E .......................................................................148, 368

Erol MK ....................................................................................... 225

Índice - v. 77 - 2014


Espíndola RF ........................................................................... 373

Evsen S ..........................................................................................81

fFahd DC ............................................................................. 17, 159

Fahed CD .................................................................................. 159

Faria CM ..................................................................................... 110

Faria e Arantes TE ...............................................................1, 30

Faria e Sousa SJ ...........................................................122, 267

Felberg S ................................................................................... 310

Felix JPF ...................................................................................... 264

Fernandes MBC ..................................................................... 132

Fernández-Tresguerres MF ............................................ 321

Ferraz CA ................................................................................... 334

Ferreira R.................................................................................... 297

Ferrer-Blasco T ................................................................ 76, 103

Figueiredo MNFC .......................................................................4

Forseto AS ................................................................................ 122

Fortes Filho JB ........................................................................ 143

Foster C .........................................................................................60

Freitas GO ....................................................................................40

GGallego-Pinazo R .................................................................. 355

Galperin G ................................................................................ 119

Garcia RFL ................................................................................. 178

García-Lázaro S ....................................................76, 103, 233

Garcia-Medina JJ .................................................................. 182

Gasparetto MERF ....................................................................91

Gedik S ....................................................................................... 345

Geller J ........................................................................................ 256

Gencer B .................................................................................... 280

Geraissate JCA ....................................................................... 397

Ginés JC ..................................................................................... 297

Goktas S ...........................................................................148, 368

Goldchmit M ........................................................88, 300, 364

Gomes FC ................................................................................. 264

Gomes JAP ............................................................................... 382

Gonçalves ED ......................................................................... 382

Goncu T...................................................................................... 388

Gongal D ......................................................................................60

Gonul S ..................................................................201, 345, 411

Gonzalez CH ........................................................................... 300

Grandinetti AA ....................................................................... 114

Guclu H .........................................................................................81

Guerra RLL ......................................................................139, 400

Guerreiro AM .......................................................................... 214

Guimarães AS ............................................................................71

Gul A ............................................................................................ 152

Gul A ............................................................................................ 293

Guldur ME ................................................................................ 388

Guler M....................................................................................... 388

Gundogan FC ......................................................................... 327

HHatanaka M ............................................................................. 403

Herrera-Gómez A ................................................................. 155

Hida WT ........................................................................................71

Hinds CN ................................................................................... 164

Hurmeric V .....................................................................228, 392

Iİhsan Çaça ........................................................................ 95, 219

Ilhan A ......................................................................................... 327

Ilhan HD ..................................................................................... 259

Isaac DLC .........................................................................185, 397

Ivacık IS ....................................................................................... 368

JJabbour E .................................................................................. 159

Jampolsky A ...............................................................................88

Jiménez-Santos M ............................................................... 321

Joob B ......................................................................................... 133

Jorge D ....................................................................................... 222

Jorge EC ..................................................................................... 339

Jorge PA ..................................................................................... 222

Junqueira DLM ...................................................................... 360

KKanecadan LAA..................................................................... 382

Kara S ........................................................................................... 280

Kara-Junior N .....................................................222, 238, 373

Kasahara N ............................................................................... 288

Kılıc A ........................................................................................... 152

Kniggendorf VF ..................................................................... 114

Kocarslan S ............................................................................... 388

Koch DD .................................................................................... 125

Koktekir BE ............................................................................... 345

Kola M ......................................................................................... 228

Kreuz AC .................................................................................... 403

Kucukaydin Z .......................................................................... 148

Kucukevcilioglu M ............................................................... 392

Kuczynski E .............................................................................. 300

LLago AM ..................................................................................4, 84

Lana-Peixoto MA .................................................................. 395

Lansingh V ................................................................................ 297

Lansingh VC .................................................................... 25, 164

Lavigne LC ................................................................................ 185

Lewallen S ................................................................................ 164

Lima A ......................................................................................... 173

Lima RCS ......................................................................................99

Lino-Silva LS ............................................................................ 155

Lira RPC ............................................................................203, 264

Lira W ........................................................................................... 222

Lopes FS .................................................................................... 360

Lopes MCB .....................................................................................8

Lopes MCE ............................................................................... 143

Lowen MS ................................................................................. 305

Luchini A ................................................................................... 168

Lui ACF ....................................................................................... 364

Luna-Ortiz K ............................................................................ 155

Luvizotto RAM ....................................................................... 339

Lyra AFV ........................................................................................99

MMachado MAC ....................................................................... 261

Machado ML .................................................................................4

Maestrini HA ........................................................................... 201

Maia Jr. OO .....................................................................139, 400

Maia M ........................................................................................ 173

Maia M ..............................................................................188, 355

Malafaia O ................................................................................. 315

Manso PG ......................................................................... 54, 116

Maranhão LVL ...........................................................................99

Marback EF ....................................................................139, 400

Marback RL ....................................................................139, 400

Martins MC .............................................................................. 305

Matayoshi S ............................................................................. 377

Matias JEF ................................................................................. 315

Mazeto GMFS ......................................................................... 339

Maziero D ................................................................................. 203

Medrado JSF ..............................................................................54

Mendonça LT .............................................................................12

Mendonça PT ............................................................................12

Índice - v. 77 - 2014


Merıc F ........................................................................................ 293

Milhomem S ........................................................................... 143

Miller MT.................................................................................... 300

Mirza GE ..................................................................................... 285

Mitne S ..........................................................................................50

Monsálvez-Romín D .................................................233, 243

Monteiro MLR ...................................................330, 373, 403

Monteiro MMB .........................................................................91

Monteiro PML ...........................................................................21

Montés-Micó R .........................................76, 103, 233, 243

Montilha RCL .............................................................................91

Moraes FP ....................................................................................88

Moraes-Filho MN .................................................................. 305

Morales MSA ........................................................................... 382

Morcillo-Guardiola M ........................................................ 182

Moreira ATR ............................................................. 34, 47, 315

Moreira Jr. CA ............................................................................47

Moreira Neto CA ......................................................................47

Moreno NP ............................................................................... 351

Moreno RD............................................................................... 351

Morraye MA ............................................................................. 193

Moscovici BK ........................................................................... 191

Motono M ...................................................................................57

Motta AF.......................................................................................71

Moura GL .....................................................................................30

Muccioli C ........................................................................173,324

Murta F ..........................................................................................50

n

Nakanami CR .....................................................................8, 300

Nakano CT...................................................................................71

Nano ME .......................................................................................25

Nascimento HM .................................................................... 324

Nascimento MA .................................................................... 264

Nassaralla BRA ...........................................................................84

Nassaralla Junior JJ ...........................................................4, 84

Nejad TM ......................................................................................60

Nóbrega MJ ............................................................................. 178

Nogueira CR ............................................................................ 339

Noronha L................................................................................. 168

Nosé W ....................................................................................... 122

Novaes P .................................................................................... 193

Novelli FJ.................................................................................... 178

Nunes AAMF ..............................................................................21

Nunes AJS ...................................................................................21

Nunes VS ................................................................................... 339

OOkudan S .................................................................................. 411

Oliveira M .................................................................................. 339

Ortiz-Gomariz A .................................................................... 182

Oyamada MK .......................................................................... 403

Ozbey C ..................................................................................... 285

Ozcimen M .........................................................148, 280, 368

Ozdemir O ......................................................................209, 225

Ozkan B ...................................................................................... 209

Ozkan U ..................................................................................... 388

Ozkurt FE ................................................................................... 293

Özkurt Z ............................................................................. 95, 219

Ozkurt ZG ......................................................................... 81, 293

PParanhos Junior A ...................................................................50

Paris FS ........................................................................................ 382

Passos THM .............................................................................. 203

Pato MV .........................................................................................21

Pereira IC ................................................................................... 377

Pérez-Vives C........................................................................... 103

Petriçli IS .................................................................................... 225

Pinazo-Duran MD ................................................................ 182

Pinto RMC ....................................................................................40

Polati M ...................................................................................... 300

Portella E ................................................................................... 188

Prado VG .................................................................................... 360

Prata TS ....................................................................................... 360

Precoma DB............................................................................. 168

Precoma L ................................................................................. 168

Przysiezny A ............................................................................ 178

QQuagliato EMAB.................................................................... 238

Quagliato LB ........................................................................... 238

RRaad C ............................................................................................17

Radhakrishnan H .....................................................................76

Regatieri CVS .......................................................................... 214

Reinach PS................................................................................ 193

Reis PAC ..................................................................................... 395

Resnikoff S ...................................................................................25

Ribeiro AG ................................................................................ 214

Ribeiro GB ................................................................................. 110

Ricci LH ....................................................................................... 334

Robinson SB ............................................................................ 125

Rocha EM .................................................................................. 193

Rodrigues CA.......................................................................... 395

Rodrigues RAM ...........................................................214, 324

Rosa AAM ....................................................................................12

Rosa EL ....................................................................................... 178

SSáenz-Francés F .................................................................... 321

Şahin A ....................................................................................... 219

Şahin M .............................................................................. 95, 219

Saka G ............................................................................................81

Sakarya R .........................................................................148, 368

Sakarya Y ................................................................................... 148

Sakarya Y .........................................................................280, 368

Salcedo-Hernández RA .................................................... 155

Samudio M ....................................................................164, 297

Sanchis-Jurado V .................................................................. 243

Santhiago MR ......................................................................... 222

Santhiago MR ......................................................................... 373

Santo IFE .................................................................................... 203

Sato EH .............................................................................310, 382

Sckudlarek SMB ........................................................................34

Sengul E ..................................................................................... 293

Serrano M ................................................................................. 355

Shimoda G ..................................................................................71

Shimoda T ...................................................................................71

Síbio MT ..................................................................................... 339

Silva ISP ............................................................................139, 400

Silva JAF ..................................................................................... 261

Silveira LCL ..................................................................................12

Sousa JM ........................................................................... 54, 116

Sousa LB .................................................................................... 351

Sousa-Martins D ................................................................... 173

Souza EC ..........................................................................188, 330

Souza-Dias CR ................................................................ 88, 364

Stival LRS .................................................................................4, 84

Suzuki ACF ............................................................................... 330

TTartarella MB ........................................................................... 143

Tavares C ......................................................................................21

Teixeira LF ......................................................................... 54, 116

Tejeda-Rojas M ...................................................................... 155

Índice - v. 77 - 2014


Thorell MR ................................................................................ 114

Torres CLA ................................................................................ 168

Torres RAA ................................................................................ 168

Torres RJA ................................................................................. 168

Tufan HA .................................................................................... 280

Tunay ZÖ ................................................................................... 225

Turk A .......................................................................................... 228

Türkcü FM ......................................................................... 95, 219

Turkoglu EB.............................................................................. 259

Tzelikis PFM .................................................................................71

U

Ulas T ........................................................................................... 388

Unal M ........................................................................................ 259

V

Ventura BV ......................................................................125, 222

Ventura CV .....................................................................222, 300

Ventura LO ............................................................................... 300

Ventura MC .............................................................................. 222

Vianna LMM ............................................................................ 173

Victor G.............................................................................122, 267

Villavicencio-Valencia V .................................................... 155

W

Wang L ....................................................................................... 125

Weikert MP............................................................................... 125

Wiwanitkit V ............................................................................ 133

Wu L ............................................................................................. 355

yYamamoto RE ......................................................................... 397

Yasar T ......................................................................................... 152

Yener H I .................................................................................... 368

Yılmaz B...................................................................................... 293

Yolcu U ....................................................................................... 327

Yuksel H ...........................................................81, 95, 219, 293

Yüksel N ..................................................................................... 209

ZZago Filho LA ......................................................................... 315

Zanon-Moreno V .................................................................. 182

Zárate N ........................................................................................25

Zegarra M .......................................................................164, 297

Zepeda L ................................................................................... 297

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