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

77 03publicação oficial do conselho brasileiro de oftalmologia

maio/Junho 2014

issn 0004-2749versão impressa

Autofluorescence in blunt trauma

Cataract surgery in Paraguay

Lutein-based dye for capsulorhexis

Conjunctival melanoma in Mexico

Pediatric cataracts

indexada nas bases de dados

medline | embase | isi | scielO

NADA MELHOR QUE O NOVOMUITAS COISAS NA VIDA SÃO MELHORES QUANDO NOVAS, NÃO PODERIA SER DIFERENTE COM AS LENTES DE CONTATO.

DESCARTE DIÁRIO

© Johnson & Johnson do Brasil Indústria E Comércio de Produtos Para Saúde Ltda - MAIO/20141. Morgan PB et al. Ocular physiology and comfort in neophyte subjects fi tted with daily disposable silicone hydrogel contact lenses. Cont. Lens Anterior Eye. 2013 Jun;36(3):118-25. 2. MEYLER, J.; VEYSAND , J. Do new daily disposable lenses improve patient comfort? Optician. 2006; 6046(231): 34-6 3. RUSTON , D.; MOODY, K. A daily disposable designed for healthy contact lens wear. Optician. 01.10.09: 34-37CLMTruEye.Narafi lcon A - 111-DAY ACUVUE® TRUEYE® com HYDRACLEAR® 1: Reg.ANVISA 80148620065. VENDA SOB PRESCRIÇÃO MÉDICA REFRACIONAL. Johnson & Johnson Industrial Ltda. Rod. Pres. Dutra, Km 154 - S. J. dos Campos, SP. CNPJ: 59.748.988/0001-14. Resp. Téc.: Evelise S. Godoy – CRQ nº 04345341. Mais informações sobre cuidados de manutenção, advertências e indicação de uso do produto verifi que o Guia de Instruções ao Usuário, acesse www.acuvue.com.br ou ligue para Central de Relacionamento com o Consumidor 0800 7274040.

As lentes de contato de descarte diário 1-DAY ACUVUE® TRUEYE® oferecem a saúde ocular com a conveniência e a praticidade da modalidade de uso único.

SAÚDE COM CONFORTOSENSAÇÃO DE ESTAR SEM LENTES.1

SAÚDE COM PRATICIDADEDISPENSA SOLUÇÃO DE LIMPEZA E ESTOJO.2

SAÚDE VISUALOLHOS BRANCOS E SAUDÁVEIS.3

SAÚDE PREVENTIVAPROTEÇÃO UV CLASSE I.3

ATENDIMENTO PERSONALIZADO ATRAVÉS DE NOSSO SAC: 0800 728 8281

Portanto, ao recomendar lentes de contato aos seus pacientes, lembre-se de que quanto mais frequente o descarte, melhor.Considere 1-DAY ACUVUE® TRUEYE® como a primeira opção.

Barreira microporosa1

Evita o uso de conservantesmemBrana filtrante de 0,2µ1

tuBo flexível e ergonômico1

gotas caliBradas (30µl)1

Doses precisas

Até 2 mesesde utilização após aberto2

Referências Bibliográficas: 1) Patente de Laboratoires Théa. 2) Bula do produto: Hyabak. Registro MS nº 8042140002.HYABAK®. Solução sem conservantes para hidratação e lubrificação dos olhos e lentes de contacto. Frasco ABAK®. COMPOSIÇÃO: Hialuronato de sódio 0,15g. Cloreto de sódio, trometamol, ácido clorídrico, água para preparações injetáveis q.b.p. 100 mL. NOME E MORADA DO FABRICANTE: Laboratoires Théa, 12 rue Louis Blériot, 63017 CLERMONT-FERRAND CEDEX 2 - França. QUANDO SE DEVE UTILIZAR ESTE DISPOSITIVO: HYABAK® contém uma solução destinada a ser administrada nos olhos ou nas lentes de contato. Foi concebido: • Para humedecimento e lubrificação dos olhos, em caso de sensações de secura ou de fadiga ocular induzidas por fatores exteriores, tais como, o vento, o fumo, a poluição, as poeiras, o calor seco, o ar condicionado, uma viagem de avião ou o trabalho prolongado à frente de um ecrã de computador. • Nos utilizadores de lentes de contato, permite a lubrificação e a hidratação da lente, com vista a facilitar a colocação e a retirada, e proporcionando um conforto imediato na utilização ao longo de todo o dia. Graças ao dispositivo ABAK®, HYABAK® permite fornecer gotas de solução sem conservantes. Pode, assim, ser utilizado com qualquer tipo de lente de contato. A ausência de conservantes permite igualmente respeitar os tecidos oculares. ADVERTÊNCIAS E PRECAUÇÕES ESPECIAIS DE UTILIZAÇÃO: • Evitar tocar nos olhos com a ponta do frasco. • Não injetar, não engolir. Não utilize o produto caso o invólucro de inviolabilidade esteja danificado. MANTER FORA DO ALCANCE DAS CRIANÇAS. INTERAÇÕES: É conveniente aguardar 10 minutos entre a administração de dois produtos oculares. COMO UTILIZAR ESTE DISPOSITIVO: POSOLOGIA: 1 gota em cada olho durante o dia, sempre que necessário. Nos utilizadores de lentes: uma gota em cada lente ao colocar e retirar as lentes e também sempre que necessário ao longo do dia. MODO E VIA DE ADMINISTRAÇÃO: INSTILAÇÃO OCULAR. STERILE A - Para uma utilização correta do produto é necessário ter em conta determinadas precauções: • Lavar cuidadosamente as mãos antes de proceder à aplicação. • Evitar o contato da extremidade do frasco com os olhos ou as pálpebras. Instilar 1 gota de produto no canto do saco lacrimal inferior, puxando ligeiramente a pálpebra inferior para baixo e dirigindo o olhar para cima. O tempo de aparição de uma gota é mais longo do que com um frasco clássico. Tapar o frasco após a utilização. Ao colocar as lentes de contato: instilar uma gota de HYABAK® na concavidade da lente. FREQUÊNCIA E MOMENTO EM QUE O PRODUTO DEVE SER ADMINISTRADO: Distribuir as instilações ao longo do dia, conforme necessário. EFEITOS NÃO PRETENDIDOS E INCÔMODOS (EFEITOS INDESEJÁVEIS): Rara possibilidade de ligeiras irritações oculares. CONSERVAÇÃO DE DISPOSITIVO: NÃO EXCEDER O PRAZO LIMITE DE UTILIZAÇÃO, INDICADO NA EMBALAGEM EXTERIOR. PRECAUÇÕES ESPECIAIS DE CONSERVAÇÃO: Conservar a uma temperatura inferior a 25ºC. Depois de aberto, o frasco não deve ser conservado mais de 8 semanas. DATA DE REVISÃO DESTE FOLHETO INFORMATIVO: 04/2009. Registro MS nº 80424140002.

Material dirigido exclusivamente a profissionais habilitados a prescrever e/ou dispensar medicamentos.

uso compátivel com lentes de contato2

facilita a colocaçãoe a retirada, e proporciona

conforto imediatoP

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4

Frequency of publication: Bimonthly Arq Bras Oftalmol. São Paulo, v. 77, issue 3, pages 139-208, May/Jun. 2014

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Contents

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

iSSN 1678-2925(Electronic version)

Frequency of publication: Bimonthly Arq Bras Oftalmol. São Paulo, v. 77, issue 3, pages 139-208, May/Jun. 2014

PUBLICAÇÃO OFICIAL DOCONSELHO BRASILEIRO

DE OFTALMOLOGIA

EditorialV Open-angle glaucoma surgery: the current standing Cirurgia do glaucoma de ângulo aberto: estado atual Ivan Maynart Tavares

Original Articles139 Fundus autofluorescence in blunt ocular trauma Autofluorescência do fundo de olho no trauma ocular contuso Ricardo Luz Leitão Guerra, Igor Sandes Pessoa da Silva, Eduardo Ferrari Marback, Otacílio de Oliveira Maia Jr., Roberto Lorens Marback

143 Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features Catarata pediátrica: aspectos clínicos, frequência de estrabismo e características cronológicas, etiológicas e morfológicas Márcia Beatriz Tartarella, Gloria Fátima Britez-Colombi, Suanne Milhomem, Márcia Cordeiro Emery Lopes, João Borges Fortes Filho

148 Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomography Medição da espessura da coroide em gestantes utilizando tomografia de coerência óptica com profundidade de imagem aprimorada Sertan Goktas, Ahmet Basaran, Yasar Sakarya, Muammer Ozcimen, Zehra Kucukaydin, Rabia Sakarya, Mustafa Basaran, Erkan Erdogan, Ismail Alpfidan

152 Ocular biometry and central corneal thickness in children: a hospital-based study Biometria ocular e espessura corneana central em crianças: um estudo de base hospitalar Adem Gul, Cagatay Caglar, Adnan Cınal, Tekin Yasar, Adil Kılıc

155 Conjunctival melanoma: survival analysis in twenty-two Mexican patients Melanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos Rosa Angélica Salcedo-Hernández, Kuauhyama Luna-Ortiz, Leonardo Saúl Lino-Silva, Ángel Herrera-Gómez, Verónica Villavicencio-Valencia,

Miriam Tejeda-Rojas, José F. Carrillo

159 Static cyclotorsion measurements using the Schwind Amaris laser Medições da ciclotorção estática usando o laser Schwind Amaris Daoud C. Fahd, Elyse Jabbour, Charbel D. Fahed

164 is the cost the primary barrier for cataract surgery in Paraguay? A taxa para a cirurgia é a principal barreira para a adesão à cirurgia de catarata no Paraguai? Harumi G. Burga, Celeste N. Hinds, Van C. Lansingh, Margarita Samudio, Susan Lewallen, Paul Courtright, Rainald Duerksen, Pablo Cibils, Manuel Zegarra

168 Expression of TNF-α and il-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits Expressão das citocinas TNF-α and IL-6 na coroide e esclera de coelhos hipercolesterolêmicos Rogil José de Almeida Torres, Andrea Luchini, Lucas Younes Barberini, Leonardo Precoma,Caroline Luzia de Almeida Torres, Robson Antonio de Almeida Torres,

Lucia de Noronha, Bruna Olandoski Erbano, Antonio Marcelo Barbante Casella, Dalton Bertolim Precoma

173 Efficacy of a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsification

Eficácia de corante à base de luteína (PhacodyneTM) para observação da capsulorrexis anterior em cirurgia de facoemulsificação Lucas Monferrari Monteiro Vianna, Marcos J. Cohen, Cristina Muccioli, Acácio Lima, Diogo Sousa-Martins, Maurício Maia, Rubens Belfort Jr.

178 Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirin Achados oftalmológicos nos pacientes portadores de hepatite C em tratamento com

interferon peguilado α-2b e ribavirina Fernando José de Novelli, André Przysiezny, Evandro Luis Rosa, Raquel Francine Liermann Garcia, Mário Junqueira Nóbrega

Case Reports182 Severe scleral dellen as an early complication of pterygium excision with simple conjunctival closure

and review of the literature “Dellen” escleral grave como complicação precoce de excisão de pterígio com fechamento conjuntival simples e revisão da literatura Jose Javier Garcia-Medina, Mónica del-Rio-Vellosillo, Vicente Zanon-Moreno, Amanda Ortiz-Gomariz, Manuela Morcillo-Guardiola, Maria Dolores Pinazo-Duran

185 Transient spectral domain optical coherence tomography findings in classic meWDS: a case report Alterações transitórias evidenciadas na tomografia de coerência óptica de domíno espectral em quadro clássico de MEWDS: relato de caso Luciana Castro Lavigne, David Leonardo Cruvinel Isaac, José Osório Duarte Júnior, Marcos Pereira de Ávila

188 Susac syndrome: diverse clinical findings and treatment Síndrome de Susac: achados clínicos diversos e tratamento Ricardo Canto Bardal, Emmerson Badaro, Jayme Arana, Fabio Alves, Eduardo Cunha de Souza, Pedro Paulo Bonomo, Ezequiel Portella, Mauricio Maia

191 intrastromal crosslinking in post-laSiK ectasia “Crosslinking” intraestromal em ectasia pós-LASIK Bernardo Kaplan Moscovici, Mauro Campos

Review Articles193 is dry eye an environmental disease? O olho seco é uma doença relacionada a exposição ambiental? Monica Alves, Priscila Novaes, Monica de Andrade Morraye, Peter Sol Reinach, Eduardo Melani Rocha

Letters to the Editor201 Bilateral acute depigmentation of the iris (BADi): first reported case in Brazil Saban Gonul, Banu Bozkurt

201 Reply Heloisa Andrade Maestrini

203 Refractive error in school children in Campinas, Brazil Erros refrativos em escolares de Campinas, Brasil Rodrigo Pessoa Cavalcanti Lira, Italo Fernandes do Espírito Santo, Gustavo Lima do Valle Astur, Diana Maziero, Thais Helena Moreira Passos, Carlos Eduardo Leite Arieta

205 Instructions to Authors

V

Editorial

http://dx.doi.org/10.5935/0004-2749.20140035

Open-angle glaucoma surgery: the current standingCirurgia do glaucoma de ângulo aberto: estado atual

Ivan Maynart tavares

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

Glaucoma Service, Department of Ophthalmology and Visual Sciences, Universidade Federal de São Paulo - Escola Paulista de Medicina - UNIFESP - São Paulo (SP) - Brazil.

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

Disclosure of potential conflicts of interest: The author has any potential conflicts of interest to disclose.

Corresponding author: Ivan Maynart Tavares. Rua Botucatu, 821 - São Paulo, SP - 04023-062 - Brazil E-mail: im.tavares@unifesp.br

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells(1). It is the main cause of irreversible blindness in the world, and affects more than 70 million people worldwide, being 10% bilaterally blind(2). Glaucoma can remain asymptomatic until it is severe, leading glaucoma filtration surgery to be performed in advanced cases, often by general ophthalmologists, which may be, in part, responsible for the wrong impression of its low success-rates and high incidence of complications. Therefore, glaucoma surgery is feared by patients and even by some ophthalmologists. Nevertheless, recently published studies on glaucoma surgery safety and efficacy have reported a different reality.

First, due to recent diagnostic and therapeutic advancements, including improvements in surgery techni-ques, the 20-year probability of glaucoma-related blindness in at least one eye was reduced to half during the period from 1965 to 2009(3). One of these enhancements was the advent of the safe trabeculectomy technique, proposed by Peng Khaw from the Moorfields Eye Hospital(4). Moreover, a multicenter analysis showed that good trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive postoperative care is required. These authors showed an intraocular pressure (IOP) equal or less than 18 mmHg in 86% of the patients after a two-year follow-up period, when included hypotensive medication use(5). They also reported antifibrotics use in 93% of the cases, what corroborated the current practice pattern among glauco-ma specialists. The use of mitomycin-C (MMC) during trabeculectomy has not only enhanced its IOP-lowering effect, but also made the postoperative period more challenging. Suture manipulation (including massage, laser suture lysis, etc.), bleb needling and subconjunctival 5-fluorouracil injections are directly related to success, and demand both time and expertise. In the same report, 31 patients (7%) had late-onset hypotony (three of them with visual acuity decreased by >2 Snellen lines), and two patients developed bleb-related endophthalmitis(5). Incidentally, another recent paper reported that visual loss after surgery, the “wipe-out” phenomenon, is rare, even in patients with advanced glaucomatous visual field loss and split fixation(6).

The Ex-Press® implantation during glaucoma filtration surgery should be considered as a modification in trabeculectomy, and not as an entirely new procedure. A recent meta-analysis of randomized clinical trials com-paring both procedures reported similar efficacy in IOP-lowering, medication reduction, vision recovery, quali-fied operative success-rates, and a greater incidence of most complications, with the exception of hyphema(7). Controversy over its application in daily practice exists, as its efficacy and safety are similar to trabeculectomy, however it makes the procedure more costly.

Non-penetrating surgical procedures, including deep sclerectomy (DS), are more difficult to perform and require a longer learning curve. The addition of MMC to DS not only decreased the difference in the reduction in IOP (from -2.65 to -0.83 mmHg), but also increased the incidence of complications, when compared to trabe-culectomy with MMC. Even though, the absolute risk of complications is higher in the trabeculectomy group(8). Hence, good result reports with this technique have been limited to a select group of skilled surgeons.

With regard to glaucoma drainage devices (GDD), the Tube versus Trabeculectomy Study (TVT), a multicen-ter, randomized clinical trial, demonstrated that IOP in the low-teens could be achieved with GDD (350 mm2 Baerveldt implant; Abbot Medical Optics Inc., USA), in patients with previous cataract extraction or trabeculec-tomy(9). Although the TVT study has expanded the use of tube shunts beyond refractory glaucoma, a major shift in glaucoma surgical practice patterns has not been seen, and GDD continue to be often used either after two failed filtration surgeries or in cases in which these procedures are not indicated.

Cyclodestructive procedures, both trans-scleral and endoscopic, have been reserved for cases in which other surgical techniques have failed. Though they are effective, potential for serious complications exists(10); therefore they are seldom indicated before filtration procedures or GDD.

Open-angle glaucoma surgery: the current standing

VI

Finally, the advent of new devices and innovative techniques led on to new procedures, the minimally invasive glaucoma surgeries (MIGS). MIGS are ab interno and ab externo procedures, with limited manipulation of the sclera, little or no manipulation of the conjunctiva, and no bleb formation. Trabectome (NeoMedix, USA), Hydrus (Ivantis, USA), iStent (Glaukos, USA) and canaloplasty are some examples of MIGS approved in the USA or Europe. They are indicated for mild to moderate glaucoma, whereas IOP is reduced to mid-to-high teens, preferably combined with cataract extraction. Furthermore, most MIGS are fast to perform, have a more rapid visual recovery, and have a lower complication rate than filtration surgery(11,12). Nonetheless, there is limited data on costs, as well as on how they could negatively affect a future trabeculectomy. Unfortunately, none of the MIGS devices is approved in Brazil, in part due to regulatory authorities costly and bureaucratic procedures and requirements for registration of medical devices, what have limited our armamentarium for glaucoma treatment and hampered science development.

REFERENCES 1. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma:

a review. JAMA. 2014;311(18):1901-11. 2. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010

and 2020. Br J Ophthalmol. 2006;90(3):262-7. 3. Malihi M, Moura Filho ER, Hodge DO, Sit AJ. Long-term trends in glaucoma-related

blindness in Olmsted Country, Minnesota. Ophthalmology. 2014;121(1):134-41. 4. Khaw PT, Chiang M, Shah P, Sii F, Lockwood A, Khalil A. Enhanced trabeculectomy:

the Moorfields Safer Surgery System. Dev Ophthalmol. 2012;50:1-28. 5. Kirwan JF, Lockwood AJ, Shah P, Macleod A, Broadway DC, King AJ, et al. Trabeculec-

tomy in the 21st century: a multicenter analysis. Ophthalmology. 2013;120(12):2532-9. 6. Balekudaru S, George R, Panday M, Singh M, Neog A, Lingam V. Prospective evaluation

of early visual loss following glaucoma-filtering surgery in eyes with split fixation. J Glaucoma. 2014;23(4):211-8.

7. Wang W, Zhang X. Meta-Analysis of Randomized Controlled Trials Comparing EX-PRESS implantation with trabeculectomy for open-angle glaucoma. PLoS One. 2014;9(6):e100578.

8. Rulli E, Biagioli E, Riva I, et al. Efficacy and safety of trabeculectomy vs nonpenetra-ting surgical procedures: a systematic review and meta-analysis. JAMA Ophthalmol. 2013;131(12):1573-82.

9. Gedde SJ, Singh K, Schiffman JC, Feuer WJ. The Tube Versus Trabeculectomy Study: interpretation of results and application to clinical practice. Curr Opin Ophthalmol. 2012;23(2):118-26.

10. Huang G, Lin SC. When should we give up filtration surgery: indications, te chniques and results of cyclodestruction. Dev Ophthalmol. 2012;50:173-83.

11. Brandao LM, Grieshaber MC. Update on minimally invasive glaucoma surgery (MIGS) and new implants. J Ophthalmol. 2013;2013:705915.

12. Au L. Are newer surgical interventions for glaucoma making a difference? Br J Ophthal-mol. 2014;98(1):1-2.

Original Article

139Arq Bras Oftalmol. 2014;77(3):139-42http://dx.doi.org/10.5935/0004-2749.20140036

Fundus autofluorescence in blunt ocular traumaAutofluorescência do fundo de olho no trauma ocular contuso

rIcardo Luz LeItão Guerra1, IGor sandes Pessoa da sILva2, eduardo FerrarI Marback3, otacíLIo de oLIveIra MaIa Jr.2, roberto Lorens Marback3

Submitted for publication: December 19, 2013 Accepted for publication: April 2, 2014

Study conducted at Retina and Vitreous Service, Hospital São Rafael, Fundação Monte Tabor, Salvador, BA, Brazil.

1 Clínica de Olhos Leitão Guerra, Salvador, BA, Brazil.2 Hospital São Rafael, Fundação Monte Tabor, Salvador, BA, Brazil.3 Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil.

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: Ricardo Leitão Guerra. Rua Catarina Paraguaçu, 8 - Salvador (BA) - 40150-200 - Brazil - E-mail: ricardo@leitaoguerra.com.br

INtRoduCtIoNBlunt ocular trauma is an injury that does not compromise the

in tegrity of the eye wall(1). It manifests in various ways in the posterior segment of the eye and causes serious sequelae(1). Vitreous hemor-rhage, retinal edema (commotio retinae), choroidal rupture, macular holes, retinitis sclopetaria, retinal rupture, and retinal dialysis are com-plications involving the posterior segment in blunt ocular trauma(1).

Fundus autofluorescence (FAF) imaging is a method that uses a non-invasive imaging technique to evaluate the integrity of the retinal pigment epithelium (RPE)(2). A homogeneous pattern on FAF images indicates normal metabolic activity of the PER cells, whereas decreased fluorescence (hypoautofluorescence) suggests impairment of photoreceptors or PER cells(3).

ABStRACtPurpose: To describe the findings of fundus autofluorescence (FAF) imaging in patients with blunt ocular trauma. Methods: In this non-interventional retrospective study, we reviewed medical records and imaging examination results. The data analyzed included gender, age, laterality, trauma etiology, time between trauma and imaging, visual acuity, changes in the retinal periphery, fundus examination results, and FAF imaging findings. FAF imaging was performed using a Topcon TRC-50DX Retinal Camera (Tokyo, Japan). Results: Eight eyes from 8 patients were studied. The mean age was 27.6 years (range, 19-43 years). Men (n=7) were more frequently affected by blunt ocular trauma than women (n=1). Physical aggression was the most common trauma etiology (n=3), followed by accidents with fireworks (n=2). Other causes were car accidents (n=1), occupational trauma caused by a grinder (n=1), or being hit by a stone (n=1). Visual acuity ranged from 20/80 to light perception. Traumatic pigment epitheliopathy (TPE) was identified in 5 cases, choroidal rupture in 3 cases, subretinal hemorrhage in 3 cases, and Purtscher’s retinopathy in 1 case. Hypoautofluores-cence was observed in cases of choroidal rupture, recent subretinal hemorrhage, and intraretinal hemorrhage, and in two cases of TPE. Hyperautofluorescence was observed in cases of old subretinal hemorrhage and at the edge of the lesion in two cases of choroidal rupture. Mild hyperautofluorescence was observed in the posterior pole in Purtscher’s retinopathy. Three cases of TPE exhibited hypoauto-fluorescence with diffuse hyperautofluorescent areas.Conclusion: FAF imaging is a non-invasive method for assessing changes in the posterior segment of the eye resulting from blunt ocular trauma. Furthermore, this technique provides valuable information. We described the findings of FAF imaging in cases of TPE, choroidal rupture, subretinal hemorrhage, and Purtscher’s retinopathy.

Keywords: Trauma; Retinal pigment epithelium; Retinal diseases; Ocular trauma

RESUMOObjetivo: Descrever os achados do exame de autofluorescência do fundo de olho (AFF) em pacientes vítimas de trauma ocular contuso. Métodos: Estudo retrospectivo, não intervencionista, realizado através da revisão de prontuários e exames de imagem. Os dados analisados foram: sexo, idade, lateralida -de, etiologia do trauma, tempo decorrente entre o trauma e a realização do exame, acuidade visual, alterações na periferia da retina, diagnóstico fundoscópico e achados ao exame de AFF (realizada no aparelho Topcon TRC-50DX Retinal Camera). Resultados: Oito olhos de 8 pacientes foram estudados. A idade média foi de 27,6 anos (de 19 a 43 anos), o sexo masculino (n=7) foi mais acometido do que o femi-nino (n=1), agressão física foi a etiologia mais comum do trauma (n=3), seguido de acidente com fogos de artifício (n=2). Outras causas foram acidente automobilístico (n=1), trauma ocupacional com lixadeira (n=1) e pedrada (n=1). A acuidade visual variou de 20/80 a percepção luminosa. Epiteliopatia pigmentar traumática (EPT ) foi identificada em 5 casos, rotura de coroide em 3, hemorragia sub-retiniana em 3 e retinopatia de Purtscher em 1 caso. Hipoautofluorescência foi observada nos casos de rotura de coroide, hemorragia sub-retiniana recente, hemorragia intrarretiniana e em 2 casos de EPT. Hiperautofluorescência foi visualizada nos casos de hemorra gia sub-retiniana em degradação, na borda de 2 casos de roturas de coroide e discreta-mente no polo posterior na retinopatia de Purtcher. Três casos de EPT apresentaram hipoautofluorescência com pontos hiperautofluorescentes difusos. Conclusão: O exame de AFF permite avaliar as alterações do segmento posterior do olho decorrentes do trauma ocular contuso de forma não invasiva, somando informa-ções valiosas. Foram descritos achados do exame em casos de epiteliopatia pigmentar traumática, rotura de coroide, hemorragia sub-retiniana e retinopatia de Purtscher.

Descritores: Trauma; Epitélio pigmentado da retina; Doenças retinianas; Trauma-tismos oculares

The usefulness of FAF imaging is well described in several eye conditions such as retinal dystrophies(2) and pigmented intraocular tumors(4). This study aimed to describe the findings of FAF imaging in patients with blunt ocular trauma. In the reviewed literature, we only found three articles describing the findings of FAF imaging in patients that showed changes in the posterior segment associated with blunt ocular trauma(5-7).

MEtHodSThis was a non-interventional retrospective study. In this study,

the medical records and imaging results of patients, who were diagnosed with injury caused by blunt ocular trauma involving the posterior segment, were reviewed.

Fundus autofluorescence in blunt ocular trauma

140 Arq Bras Oftalmol. 2014;77(3):139-42

All patients were submitted to an ophthalmologic examination, color fundus photography, and FAF at Hospital São Rafael-Fundação Monte-Tabor in Salvador, Bahia-Brazil from 02/01/2011 to 01/31/2013. Patient selection was based on a diagnosis of ocular blunt trauma collected from the institution’s fundus photography registry book. Patients with incomplete data were excluded from the study. This study was approved by the research ethics committee of the same institution (CAAE - 14929313.4.0000.0048).

The data analyzed included sex, age, laterality, trauma etiology, time between trauma and imaging, visual acuity, changes in the re tinal periphery, fundus examination results, and FAF imaging findings. FAF imaging was performed using a Topcon TRC-50DX Retinal Camera (Tokyo, Japan).

RESuLtSEight eyes in 8 patients were studied. No patient was excluded

from the study. A summary of the cases is shown in table 1; color fun-dus photography and FAF findings are shown in figures 1 and 2. The mean age was 27.6 years (range, 19-43 years), and men (n=7) were more frequently affected by blunt ocular trauma than women (n=1), and the right eye (n=5) was more affected than the left eye (n=3).

Physical aggression was the most common trauma etiology (n=3), followed by accidents with fireworks (n=2). Other causes were car accidents (n=1), occupational trauma caused by a grinder (n=1), and being hit by a stone (n=1).

Visual acuity ranged from 20/80 to light perception, and 2 pa -tients exhibited changes on peripheral retinal examination that included retinal dialysis with peripheral retinal detachment (n=1) and rupture of the retina without retinal detachment (n=1).

Traumatic pigment epitheliopathy (TPE) was the most common finding (n=5), followed by choroidal rupture (n=3), subretinal he-morrhage (n=3), and Purtscher’s retinopathy (n=1). Hypoautofluo-rescence was observed in cases of choroidal rupture, recent sub -retinal hemorrhage, intraretinal hemorrhage, and in 2 cases of TPE. Hyperautofluorescence was observed in cases of old subretinal hemorrhage and at the edge of the lesion in 2 cases of choroidal rupture. Mild hyperautofluorescence was observed in the posterior pole in Purtscher’s retinopathy. Three cases of TPE exhibited hypoau-tofluorescence with diffuse hyperautofluorescent areas. These fin-dings are summarized in table 2.

dISCuSSIoNtPE

TPE usually occurs in cases of severe trauma following resolution of commotio retinae(5,8). When the macular region is involved, TPE is associated with poor visual prognosis(5,8). In these cases, FAF imaging shows a hypoautofluorescent area alternating with punctiform hype-rautofluorescent lesions(5,6).

In this series of cases, 5 of the 8 patients had TPE (cases 4, 5, 6, 7, and 8). Three patients (cases 6, 7, and 8) exhibited the characteristic pattern on FAF images, which is described above. In the other 2 cases (cases 4 and 5), FAF imaging showed a hypoautofluorescent lesion corresponding to the affected region. We observed that FAF imaging was more effective than color fundus photography for the identifica-tion and definition of the areas affected by TPE.

Choroidal rupture

Choroidal rupture can be observed on FAF images as a hypoauto-fluorescent line, and in some cases, FAF imaging provides better visualization and definition of the lesion than color fundus photogra-phy(5,7). In some cases, there is a hyperautofluorescent ring surroun-ding the lesion, which may correspond to hyperplasia of RPE that occurs as the rupture heals(5).

In the 3 patients with choroidal rupture (cases 2, 3, and 4), FAF imaging showed a hypoautofluorescent lesion corresponding to the site of rupture. In 2 cases (cases 3 and 4), a hyperautofluorescent ring was observed at the edge of the lesion. The time elapsed between the trauma and examination was longer for these patients, which confirms the hypothesis of hyperautofluorescence at the edge of the lesion is related to the healing process of a choroidal rupture.

Subretinal hemorrhage

Recent subretinal hemorrhage (when there is no degradation of blood cells) presents itself as a hypoautofluorescent lesion on FAF ima-ges(5). As erythrocytes are degraded and the blood turns yellowish, the appearance on FAF images becomes hyperautofluorescent(5). We note that, in this situation, devitalized blood cells are har mful to photoreceptors and are associated with a poorer visual prognosis(5,9).

Three cases described in this study exhibited signs of subretinal hemorrhage; 1 case of recent hemorrhage (case 2) and 2 cases of old hemorrhage (cases 3 and 4). The results of the FAF imaging examina-tions in these patients agreed with those described in the literature, and they allowed us to better define the extension of a subretinal hemorrhage, both in recent cases and in cases wherein blood cell degradation was observed. The authors believe that this characteris-tic makes FAF imaging a useful tool for identifying and monitoring patients who have subretinal hemorrhage for which there is no indi-cation of surgical treatment.

purtSCher’S retinopathy

One patient (case 1) was diagnosed with Purtscher’s retinopathy, and FAF imaging was performed during the acute phase. We did not find in the literature a description of FAF imaging for similar cases (following trauma). We searched for the terms “Purtscher”, “Retinopa-thy”, and “Autofluorescence” in MEDLINE and SCIELO databases.

Only 1 report of a Purtscher-like retinopathy case (following pan -creatitis) was found in the literature, which described the results of

table 1. Summary of cases studied

Gender Age Eye trauma etiology time VA Periphery diagnosis

Case 1 M 27 LE Car accident 6 days 20/200 Normal Purtscher

Case 2 M 25 LE Grinder 5 days 20/200 Dialysis CR

Case 3 F 19 RE Physical aggression 3 months 20/80 Normal CR

Case 4 M 43 RE Fireworks 8 months 20/200 Normal CR + MH + TPE

Case 5 M 19 LE Stone 3 months CF Normal EPT

Case 6 M 16 RE Fireworks 1 month CF Normal CR + TPE

Case 7 M 32 RE Physical aggression 1 month CF Normal CR + TPE

Case 8 M 40 RE Physical aggression 2 months LP Rupture TPE

M= male; F= female; RE= right eye; LE= left eye; VA= visual acuity; CF= counting fingers; LP= light perception; CR= choroidal rupture; MH= macular hole; TPE= traumatic epitheliopathy.

Guerra RLL, et al.

141Arq Bras Oftalmol. 2014;77(3):139-42

Figure 1. A) Purtscher’s retinopathy. B) FAF exhibits hypoautofluo­rescence in the areas corresponding to intraretinal hemorrhage and mild perimacular hyperautofluorescence. C) Recent subretinal hemorrhage in the macular region, secondary to choroidal rupture temporal to the macula. D) FAF exhibits an extensive hypoauto­fluorescent area in the region affected by the hemorrhage and a hypoautofluorescent line corresponding to choroidal rupture. E) Choroidal rupture with subretinal hemorrhage showing degrada­tion of subretinal blood. F) FAF exhibits hyperautofluorescence corresponding to the degraded blood. Choroidal rupture as a hypoautofluorescent line associated with the hyperautofluo­rescent areas. G) Choroidal rupture, degraded subretinal blood, and macular hole 8 months after blunt trauma. H) FAF exhibits a hypoautofluorescent line corresponding to choroidal rupture, a hyperautofluorescent line caused by degraded blood, and moderate hypoautofluorescence in the posterior pole and in the peripapillary region corresponding to the involvement of RPE.

A

C

E

G

B

d

F

H

Figure 2. A) Hyperchromic lesion in the papillomacular bundle surrounded by hyperchromic and hypochromic pigment changes in the macular region. B) FAF exhibits a large hypoautofluorescent area affecting the macula. C) Choroidal rupture with extensive subretinal fibrosis, mobilization of the pigment in the posterior pole, and retinal architecture anomalies. D) FAF exhibits a hy­poautofluorescent lesion with diffuse hyperautofluorescent areas affecting the posterior pole. E) Subretinal hemorrhage near the area of subretinal fibrosis affecting the temporal macular region. Toward the upper arcade, there is a change in RPR pig­mentation. F) FAF exhibits a hypoautofluorescent area with diff u se hyperautofluorescent areas in the affected region, with a prevalence of hypoautofluorescent lesions. G) Slightly decreased RPE pigmentation in the peripapillary region. H) FAF exhibits a hy poautofluorescent lesion with diffuse hyperautofluorescent areas. In this case, FAF resulted in improved delimitation of the lesion compared with color fundus photography.

A

C

E

G

B

d

F

H

FAF examination(10). In this report, we describe hypoautofluorescence in the areas corresponding to Purtscher’s spots, hyperautofluores-cence in veins affected by ischemia during the acute phase of retino-pathy, and a granular pattern of hyperautofluorescence and hypoau-tofluorescence in the region previously affected by the Purtscher’s spots after the retinopathy had been resolved(10).

Contrary to this finding, FAF imaging of the patient described in the present study showed hypoautofluorescence in the areas corres-ponding to intraretinal hemorrhage and mild hyperautofluorescence surrounding the macular region, corresponding to the sites where Purtscher’s spots were observed.

Despite the similar clinical presentation, the difference between the pathophysiological mechanism of Purtscher’s retinopathy and that of Purtscher-like retinopathy may explain the disparate results among examinations. The lack of experimental studies or other data in the literature precludes a definitive conclusion.

Moreover, we propose that in the case of the patient who sus tained trauma, a different change associated with Purtscher’s retinopathy, such as commotio retinae, contributed to hyperautofluorescence in the posterior pole. This hypothesis is consistent with the results des-cribed by Lavinsky et al(5). Three cases of commotio retinae exhibited

table 2. Correlation between the findings of fundus examination and FAF imaging

Fundus examination n FAF imaging n

Choroidal rupture 3 Hypoautofluorescence at the site of rupture 3

Hyperfluorescence at the edge of the lesion 2

Traumatic pigment epitheliopathy

5 Alternating hypoautofluorescence and hyperautofluorescence 3

Hypoautofluorescence 2

Recent subretinal hemorrhage

1 Hypoautofluorescence 1

Old subretinal hemorrhage

2 Hyperautofluorescence 2

Purtscher’s retinopathy

1 Perimacular hyperautofluorescence and hypoautofluorescence corresponding to hemorrhage 1

n= number of eyes that exhibited the finding.

mild hyperautofluorescence during the acute phases of the disease, which progressed to TPE in a few weeks(5). In the present study, we

Fundus autofluorescence in blunt ocular trauma

142 Arq Bras Oftalmol. 2014;77(3):139-42

were not able to follow this case because the patient did not return for subsequent visits.

CliniCal appliCation

After analyzing the results of this study and comparing them with the reviewed literature, we believe that FAF imaging plays an important role evaluation of patients who sustain blunt ocular trauma. The main advantages of FAF, according to the literature(5,7), are better lesion defi-nition than color and red free fundus photography that improves the quality of patient follow-up. Longitudinal studies are necessary to esta-blish further advantages of FAF imaging in cases of blunt ocular trauma.

CoNCLuSIoNFAF examination is a non-invasive method for assessing changes

in the posterior segment of the eye that result from blunt ocular trau-ma. It provides valuable information. We described the findings of FAF imaging in cases of TPE, choroidal rupture, subretinal hemorrha ge, and Purtscher’s retinopathy.

REFERÊNCIAS 1. Posterior segment manifestations of trauma. In: Basic and Clinical Science Course,

Section 12: Retina and vitreous. American Academy of Ophthalmology. 2011. p.315-33. 2. Coco M, Baba NT, Sallum JM. Avaliação da autofluorescência do fundo de olho nas

distrofias de retina com o aparelho Heidelberg Retina Angiograph2. Arq Bras Oftal-mol. 2007;70(5):739-45.

3. Ishida T, Ohno-Matsui K, Kaneko Y, Tobita H, Hayashi K, Shimada N, Mochizuki M. Autofluorescence of metastatic choroidal tumor. Int Ophthalmol. 2009;29(4):309-13.

4. 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.

5. Lavinsky D, Martins EN, Cardillo JA, Farah ME. Fundus autofluorescence in patients with blunt ocular trauma. Acta Ophthalmol. 2011;89(1):89-94.

6. Mustafa MS, McBain VA, Scott CM. Autofluorescence imaging - a useful adjunct in imaging macular trauma. Clin Ophthalmol. 2010;4:1497-8.

7. Kolomeyer AM, Szirth BC, Nayak NV, Khouri AS. Complimentary imaging technologies in blunt ocular trauma. Oman J Ophthalmol. 2013;6(2):108-11.

8. Sawa M, Ober MD, Spaide RF. Autofluorescence and retinal pigment epithelial atrophy after subretinal hemorrhage. Retina. 2006;26(1):119-20.

9. Yang CS, Chou TF, Liu JH, Hsu WM. Air bag associated posterior segment ocular trauma. J Chin Med Assoc. 2004;67(8):425-31.

10. Giani A, Deiro AP, Sabella P, Eandi CM. Spectral domain-optical coherence tomography and fundus autofluorescence findings in a case of Purtscher-like retinopathy. Retinal Cases & Brief reports. 2011;5(2):167-70.

II Congresso de Estética Periocular da Sociedade Brasileira de Cirurgia Plástica ocular

(SBCPo)

7 e 8 de novembro 2014Rio Othon PalaceRio de Janeiro - RJ

informações: Site: www.ciopcongressos.com.br

Original Article

143Arq Bras Oftalmol. 2014;77(3):143-7http://dx.doi.org/10.5935/0004-2749.20140037

Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological featuresCatarata pediátrica: aspectos clínicos, frequência de estrabismo e características cronológicas, etiológicas e morfológicas

MárcIa beatrIz tartareLLa1, GLorIa FátIMa brItez-coLoMbI1, suanne MILhoMeM1, MárcIa cordeIro eMery LoPes1, João borGes Fortes FILho2

Submitted for publication: August 13, 2013 Accepted for publication: January 29, 2014

Study conducted at Congenital Cataract Section, Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

1 Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.2 Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Federal University of Rio

Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

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: João Borges Fortes Filho. Rua Ramiro Barcelos, 2.350 - Porto Alegre (RS) - 90035-903 - Brazil - E-mail: jbfortes@prorop.com.br

RESUMOObjetivos: Avaliar as frequências do estrabismo e as características cronológica, etiológica e morfológica das cataratas pediátricas. Método: Estudo retrospectivo dos prontuários de crianças atendidas no Ambulatório de Catarata Congênita do Departamento de Oftalmologia da Universidade Federal de São Paulo no período entre 2001 e 2011. Foram incluídos pacientes com diagnóstico de catarata congênita ou de desenvolvimento. Foram excluídos os pacientes com catarata traumática; secundárias a uveíte, radiação ou medicamentos; pacientes operados em outro serviço; pacientes com glaucoma; leucocorias não cristalinianas (retinoblastoma, retinopatia da prematuridade, leucocorias pré-cristalinianas), e com sub-luxação do cristalino. Foram avaliadas: as frequências cronológicas, etiológicas e morfológicas das cataratas; a lateralidade e a ocorrência de estrabismo associado nestes pacientes. Resultados: Foram incluídos 207 pacientes. Cento e dezessete (56,5%) apresentavam catarata congênita e 90 (43,5%) apresentavam catarata de desenvolvimento. Cento e nove (52,6%) pacientes eram portadores de catarata unilateral. Quanto à morfologia, 72 crianças (33,8%) apresentavam catarata zonular e 66 (31,9%) apresentavam cata-rata total. A etiologia idiopática foi a mais frequente (72,5%) afetando 150 pacientes. Foram observados 108 pacientes (52,2%) com estrabismo associado, especialmente endotropias secundárias. Conclusões: A etiologia idiopática foi a mais frequente neste estudo. O tipo morfológico zonular foi o mais frequentemente diagnosticado. Cataratas unilaterais ocorreram mais frequentemente em pacientes com persistência da vasculatura fetal. O estrabismo associado ocorreu em 52% dos pacientes. A análise dos resultados deste estudo pode contribuir para diagnosticar a catarata pediátrica precocemente e de modo mais preciso.

Descritores: Catarata/congênito; Catara/diagnóstico; Estrabismo; Síndrome da per -sistência do padrão de circulação fetal; Humanos; Criança

ABStRACtPurpose: This study aimed to evaluate the frequency of strabismus and chronolo-gical, etiological, and morphological features in patients with pediatric cataracts. Methods: Medical records of pediatric patients were evaluated at the Congenital Cataract Section, Department of Ophthalmology, Federal University of São Paulo, from 2001 to 2011. Patients with congenital cataract or developmental cataract were included. The patients with traumatic cataract, cataract secondary to uveitis, radiation or drugs, aphakic or pseudophakic patients who underwent surgery in another hospital, patients with glaucoma, non-lenticular leukocorias (retinoblas-toma, retinopathy of prematurity, prelenticular leukocorias), and lens subluxation were excluded from the study. The following outcomes were evaluated: frequency of chronological, etiological, and morphological features, laterality, and occurrence of associated strabismus.Results: A total of 207 patients were included. One hundred and seventeen pa-tients (56.5%) had congenital cataract and 90 patients (43.5%) had developmental cataract. One hundred and nine patients (52.6%) had unilateral cataract. In terms of morphology, 72 children (33.8%) had zonular cataract and 66 (31.9%) had total cataract. Idiopathic cataract affected 150 patients (72.5%). There were 108 patients (52.2%) with strabismus, mainly secondary esotropia.Conclusion: Idiopathic etiology was the most frequent cause in this group of pa tients. Zonular cataract was the main morphological type of cataract in the study. Unilateral cataract occurred more frequently in patients with persistent fetal vasculature (PFV). Strabismus presented in 52% of the patients. The current analysis may help establish an earlier and more accurate diagnosis of pediatric cataracts.

Keywords: Cataract; Congenital; Diagnosis; Strabismus; Persistent fetal circulation syndrome; Humans; Pediatric

INtRoduCtIoNCataract is a major cause of visual impairment during childhood.

Pediatric cataract often leads to amblyopia and secondary strabis-mus(1-4). Early diagnosis and treatment to prevent lateral geniculate body atrophy during the critical period of visual development is important for the visual prognosis of children affected by cataract(5-7).

Pediatric cataracts are classified according to their time of onset (chronological), etiology, and morphology. The chronological classifi-cation is based on the time of onset of the opacity in the lens(8). When lens opacity is detected within the first 3 months of life after birth, the disease is classified as congenital cataract. When the diagnosis or the

onset of opacity occurs after 3 months of life, the disease is classified as developmental cataract or infantile cataract. Early developmental cataract occurs within the first 12 months of life and late develop-mental cataract occurs after the first year of life(8-10). The chronological classification helps establish the visual prognosis in patients.

Pediatric cataracts have different etiologies including hereditary, secondary to congenital infections associated with systemic syndro-mes and ocular abnormalities [aniridia, persistent fetal vasculature (PFV), Peters anomaly, anterior segment dysgenesis, prior ocular sur-gery and uveitis], secondary to external agents, such as drugs (e.g., corticosteroids), radiotherapy, or environmental factors, and ocular

Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features

144 Arq Bras Oftalmol. 2014;77(3):143-7

trauma(10-14). Cataracts with undetermined causes are classified as idiopathic(15).

Morphologically, pediatric cataracts are classified into total cata-ract, zonular cataract (lamellar, pulverulent, nuclear, sutural), capsular cataract (anterior subcapsular, posterior subcapsular, lenticonus), and membranous cataract(16). When associated with syndromes, metabolic diseases, or inherited cataracts, the morphological features of the cataract may provide clues to the possible etiology(14).

The objective of the present study was to evaluate the frequency of strabismus as well as the chronological, etiological, and morpholo-gical features of the disease in pediatric cataract patients.

METHODSThis retrospective and descriptive study was conducted at the

Congenital Cataract Section, Department of Ophthalmology, Univer-sidade Federal de São Paulo (UNIFESP), Brazil, from February 2001 to January 2011. Patients diagnosed with congenital or developmental cataract were included in the study. Exclusion criteria were the following: traumatic cataract, cataract secondary to uveitis, radiation, or drugs, aphakic or pseudophakic patients who underwent surgery at an un-re lated service, patients with glaucoma, non-lenticular leukocorias (re tinoblastoma, retinopathy of prematurity, prelenticular leukocorias), and patients with lens subluxation.

Data collected from the patient files at the first presentation in -cluded gestational, familial, and personal health information. Eye examination included analysis of the cataract morphology at biomi-croscopy. Patients underwent ocular ultrasound when the opacity of the lens prevented the examination of the ocular fundus by binocular indirect ophthalmoscopy. For the outcomes evaluated, we collected the following data: time of onset of the cataract, laterality, etiology, morphology, and evaluated the ocular alignment by Hirschberg test. We also performed strabismus detection with the help of cover test. The visual acuity was assessed by the age-paired tests, Teller cards acuity test, Lea Hyvarigen test, or Snellen visual acuity test.

Cataract was classified chronologically according to the time when the disease was detected. Cases showing lens opacity within the first 3 months of life following birth were classified as congenital cataracts. Cases in which diagnosis or the onset of opacity occurred after the first 3 months of life were classified as developmental cata-ract. To establish the etiology of the disease, children were referred to a pediatrician for clinical evaluation and routine tests. Children up to 18 months of age were requested to undergo routine sero-logic tests for the detection of any possible toxoplasmosis, rubella, syphilis, and cytomegalovirus. The following laboratory tests were performed routinely: complete blood count test, blood glucose test, neonatal heel prick test (Guthrie test), and total serum calcium test. Patients with cataracts of suspected genetic etiology were referred to the Section of Genetics of the Pediatric Department at the UNIFESP. After the required tests were performed at the institute, the patients with no identifiable cause for cataracts were included in the group of idiopathic etiology.

Cataract was classified according to the morphology as total (Fi gure 1), zonular, polar, capsular, and membranous. Zonular cata-racts, which effect the fetal nucleus of the lens, were further classified as lamellar (Figure 2), pulverulent (Figure 3), nuclear (Figure 4), and sutu-ral. According to the site of lens opacity, polar cataracts were classi fied as anterior, posterior, or pyramidal (Figure 5). Capsular cataracts were further classified as anterior, posterior, and lenticonus. When multiple morphological types of cataract co-exist in the same child or in the same eye, they are considered as mixed cataract.

RESuLtSWe analyzed a total of 428 medical files. However, only 207 of these

files contained complete medical history, time of onset of the disease,

etiology, and morphology of the cataract. Therefore, only these 207 cases were included in our study. Age of the patients ranged from 19 days to 12 years.

Of the 207 patients included in the study, 117 had congenital ca -taract (56.5%), and 90 patients (43.5%) had developmental cataract. At the time of diagnosis, 109 patients (52.6%) had unilateral cataract. Of these patients, 51.3% had congenital cataract and 54.4% had deve-lopmental cataract. The frequencies of congenital and develop mental cataracts, according to their laterality, are shown in table 1.

Figure 1. Total cataract.

Figure 2. Lamellar cataract.

Figure 3. Pulverulent cataract.

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145Arq Bras Oftalmol. 2014;77(3):143-7

Of the 207 patients, 150 (72.5%) had idiopathic cataract. Among these 150 cases, 74 (49.3%) had bilateral cataract. Infectious etiology was present in 18 patients (8.7%). Congenital rubella occurred in 14 patients (6.8%) and accounted for 77.8% of the cases in which infection was identified as the etiology. PFV was diagnosed in 17 patients (8.2%), of which 16 had unilateral cataract (94.1%). Familial history of pediatric cataracts was confirmed in 14 cases (6.8%). Hereditary patterns detected were either autosomal dominant or autosomal recessive. The etiology established in the present study is shown in table 2.

Serum calcium test was performed to detect parathyroid disorders. Total serum calcium was within the normal range in all the patients (between 6.7 and 10.7 mg/dL).

Total cataract was diagnosed in 66 patients (31.9%), whereas 72 cases (33.8%) had zonular cataract. Among the different types of zonular cataract, lamellar cataract was the most frequent and was

detected in 46 cases. As shown in table 3, mixed cataracts were pre-sent in 33 patients (15.9%).

The association between the etiology of detected cataract and the morphological types is shown in table 4. Zonular (60 cases) and total (43 cases) cataracts were more frequent in the idiopathic etio-logy group. PFV had more cases of posterior capsular cataracts (10 cases) than the entire group.

Strabismus was diagnosed in 108 (52.2%) patients, of which 65 (55.55%) were children with congenital cataracts and 43 were chil-dren (47.77%) with developmental cataracts.

Esotropia and exotropia were diagnosed in 60 (55.6%) and 48 (44.4%) patients, respectively. Esotropia was present in 40 (34.2%) pa-tients with congenital cataracts and 20 (22.22%) patients with deve-lopmental cataracts. Vertical deviations were found in three patients. However, all three cases were associated with horizontal deviation. The distribution of the cases of strabismus among the patients with cataract is shown in table 5.

Visual acuity ranged from light perception in total cataract cases to 20/20 in lamellar cataracts. Only children with visual acuities worse than 20/70 were selected for surgery.

dISCuSSIoNThe present study demonstrated a similar frequency of occur-

rence of congenital and developmental cataracts (56.5% vs. 43.5%,

Figure 4. Nuclear cataract.

Figure 5. Polar cataract.

table 1. distribution of laterality in congenital and developmental cataracts

unilateral Bilateral total

Congenital cataract 060 (51.3%) 57 (48.7%) 117 (56.5%)

Developmental cataract 049 (54.4%) 41 (45.6%) 090 (43.5%)

Total 109 (52.6%) 98 (47.4%) 207 (100%)

P=0.976.

table 2. Etiology of laterality

Etiology unilateral Bilateral total

Idiopathic 076 74 150 (72.5%)

Infectious 015 03 018 (08.7%)

Congenital rubella 0013 01 14 (77.8% in the group)

Toxoplasmosis 002 02 4 (22.2% in the group)

Secondary to PFV 016 01 17 (08.2%)

Hereditary 001 13 14 (06.8%)

Syndromes 001 07 08 (03.9%)

Down syndrome 000 06 6 (75% in the group)

Other 001 01 2 (25% in the group)

Total of patients 109 98 207 (100%)

PFV= persistent fetal vasculature.

table 3. Morphology of pediatric cataracts and laterality

Morphological characteristics unilateral Bilateral total

Total cataract 043 23 66 (31.9%)

Zonular 026 46 72 (33.8%)

Lamellar 012 36 48

Pulverulent 000 02 02

Nuclear 008 06 14

Sutural 006 02 08

Capsular 013 03 16 (07.7%)

Anterior subcapsular 000 00 00

Posterior subcapsular 013 03 16

Polar 016 04 20 (09.7%)

Anterior 001 04 05

Posterior 015 00 15

Mixed 011 22 33 (15.9%)

Total of patients 109 98 207 (100%)

Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features

146 Arq Bras Oftalmol. 2014;77(3):143-7

respectively), as well as similar rates of cataract laterality (47.3% of bi -lateral cataract vs. 52.7% unilateral cataract). Laterality may indicate the etiology. In this study, we found that bilateral cataracts were usually associated with syndromes or a familial history (hereditary) of the di-sease. Unilateral cataracts occurred more frequently in cases of PFV and congenital rubella. A previous study of unilateral congenital cataracts found that almost all unilateral cases were due to PFV(17).

Analysis of the etiology revealed that idiopathic cataracts occur-red most frequently (72.5%) followed by cataracts caused by conge-nital infections (8.7%) such as rubella. In agreement with the results of an earlier study, we found that 17 patients (8.2%) had cataracts associated with PFV and majority of these cases (16 patients, 94.1%) had unilateral cataracts(18). Among 8 patients with genetic disorders, 7 had bilateral cataract (87.5%) and all 8 cases had Down’s syndrome. Hereditary cataracts accounted for only 6.8% of the cases. This rate is substantially lower than an earlier reported study, which noted that nearly one-third of the cases were inherited(19). Further, a study of 85 patients conducted in Tunisia found that 32.5% of the patients had idiopathic cataract, 42.3% had hereditary cataract, and 4.7% had cataract caused by infection(20).

To establish the etiology of pediatric cataracts the routine work up protocol should include tests for metabolic disease markers, urine reducing substance test, and eye examination of relatives (patient’s parents, grandparents, and siblings). In the recent years, DNA analysis has been widely used to identify the affected genes. Accordingly, mutations in crystallins and connexins have been identified to play important role in the development of cataracts. To date, more than 30 independent loci have been mapped and identified as playing key roles in inherited cataracts(21-25).

Other measures that could improve the identification of the etio-logy of pediatric cataracts include a questionnaire regarding exposure to environmental risk factors or chemicals and implementation of polymerase chain reaction (PCR)-based tests to detect viral infection of the lens. We performed serum calcium test to detect parathyroid disorders and found that total serum calcium was normal in all the patients.

Accurate diagnosis of the etiology of pediatric cataract is impor-tant for epidemiological studies and future preventive actions.

Pediatric cataracts exhibit substantial heterogeneity. The opacity of the lens may affect the lens nucleus or alternatively the nucleus could remain transparent while the cortex or the lamellae surroun-ding the nucleus become opaque. The morphological diversity makes the morphological classification a challenging task. Additionally, there exists the possibility for overlapping morphologies. We found that

table 4. Analysis of the etiology and morphology of pediatric cataracts

total Cataract Zonular Capsular Polar Mixed total

Infectious 11 03 00 02 02 018

Syndromes 04 03 00 00 01 008

Hereditary 03 06 00 01 04 014

PFV 05 00 10 00 02 017

Idiopathic 43 60 06 17 24 150

Total of patients 66 72 16 20 33 207

PFV= persistent fetal vasculature.

table 5. Association between pediatric cataract and the occurrence of strabismus

Cataract orthophoria Esotropia Exotropia total

Congenital 52 (44.4%) 40 (34.2%) 25 (21.3%) 117

Developmental 47 (52.2%) 20 (22.2%) 23 (25.5%) 090

Total of patients 99 60 48 207

zonular cataracts occurred with the highest frequency, in 72 (33.8%) patients. Among these cases, the lamellar subtype (Figure 2) was the most common (66.7%). Total cataract occurred in 66 (31.9%) patients (Figure 1).

Morphology or laterality of pediatric cataract may be indicative of its etiology. Hereditary cataracts display a variety of phenotypes, more frequently display a zonular morphology (Figure 3), and are usually bilateral. In most cases, the opacity of the lens caused by PFV are unilateral posterior subcapsular, which progress into complete opacity of the lens. We found that among the PFV patients, 52.94% had posterior subcapsular cataract (Table 4). Nuclear cataract (Figure 4) is usually detected at birth, whereas lamellar cataract (Figure 2) de-velops at a later stage and can be progressive. Visual prognosis may depend on the morphological type, with less favorable outcomes in cases of total cataracts(26).

As described earlier, strabismus was diagnosed in 108 (52.2%) pa tients. A total of 65 (55.55%) children with congenital cataracts and 43 children (47.77%) with developmental cataracts had strabismus; this suggested that the earlier the onset of the visual deprivation, the greater the involvement of the visual pathways. Esotropia was more frequent in patients with congenital cataracts (34.2%) (Table 5).

In a previous study of children with congenital cataract who un-derwent lensectomy, strabismus was present in 54.8% of the patients and esotropia accounted for 64.7% of the cases(27).

A study of ocular alignment after surgery conducted in 41 children with dense cataracts, among which 27 (66%) developed strabismus, demonstrated that congenital cataract was associated with a greater risk for the occurrence of strabismus than developmental cataract. The study concluded that laterality and the time of onset of the cataract were not significant risk factors for the development of stra-bismus. Further, the study showed that there is a significant risk for the occurrence of strabismus in cases where the visual deprivation lasted longer than 6 weeks(28). A separate study that analyzed 113 patients who underwent surgery for developmental cataract found strabismus in 39 patients (34%), a higher incidence rate than that of the general population. The authors concluded that strabismus might have an impact on visual acuity in cases of unilateral and total cataracts. The occurrence of strabismus in children with cataract can be related to four factors that could affect the visual perception: reduced vision in one eye with the presence of amblyopia, asymmetry in visual acuity in bilateral cataract cases, loss of stereopsis, and ani-sometropia. Parents must be made aware that these patients may have difficulty in viewing three-dimensional (3D) images in movies and computers(29).

Programs implementing the red reflex test to detect leukocoria in newborn and the administration of visual acuity screening tests in pre-school children are of importance. These tests will enable the early diagnosis of pediatric cataract, particularly since approximately 50% of pediatric cataract patients do not present with strabismus and might not be referred on time for appropriate treatment(30).

CoNCLuSIoNSIdiopathic etiology was the most frequent cause of cataract in the

group of patients studied. Zonular cataracts were the main morpho-logical type of cataract. Unilateral cataracts occurred more frequently in cases of PFV. Strabismus was present in 52% of the patients. The results of our study may help establish a program for earlier and more accurate diagnosis of pediatric cataracts.

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Original Article

148 Arq Bras Oftalmol. 2014;77(3):148-51 http://dx.doi.org/10.5935/0004-2749.20140038

Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomographyMedição da espessura da coroide em gestantes utilizando tomografia de coerência óptica com profundidade de imagem aprimorada

sertan Goktas1, ahMet basaran2, yasar sakarya1, MuaMMer ozcIMen1, zehra kucukaydIn2, rabIa sakarya1, MustaFa basaran2, erkan erdoGan1, IsMaIL aLPFIdan1

Submitted for publication: February 12, 2014 Accepted for publication: March 24, 2014

Study conducted at Konya Training and Research Hospital, Konya, Turkey.1 Department of Opthalmology, Konya Training and Research Hospital, Konya, Turkey.2 Department of Obstetrics and Gynecology, Konya Training and Research Hospital, Konya, Turkey.

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: Sertan Goktas. Department of Opthalmology. Konya Research and Training Hospital, 42090 Meram - Konya, Turkey - E-mail:drsertandr@gmail.com

INtRoduCtIoNPregnancy is associated with metabolic, hormonal, and hemody-

namic changes. The renin-angiotensin system regulates salt and water hemostasis in the body, and both renin and angiotensin levels increase during pregnancy. These changes lead to increasing blood volume beginning in the first trimester(1,2). Systemic vascular resis-tance decreases during pregnancy(3,4), and hemodynamic changes affect blood pressure. In normal pregnancy, blood pressure initially decreases until the eighteenth to twentieth gestation week, but then increases until delivery(5,6). One study reported that total macular vo-lume and foveal retinal thickness increase during pregnancy in the

ABStRACtPurpose: To investigate choroidal thickness in healthy pregnant women during different trimesters using enhanced depth imaging optical coherence tomogra-phy (EDI-OCT). Methods: This prospective study included 90 healthy pregnant women in their first, second, or third trimester (groups 1, 2, and 3, respectively) and 30 non-pregnant healthy women (group 4). The age range for all groups was 18-40 years. Spectral domain optical coherence tomography scans were obtained to estimate the average choroidal thickness. Using EDI-OCT, we measured choroidal thickness manually from the outer border of the retinal pigment epithelium to the inner scleral border at the subfovea, 3 mm temporal, and 3 mm nasal to the fovea. Differences among groups were analyzed by one-way ANOVA. Results: We found a statistically significant difference between groups 2 and group 4 for subfoveal, temporal, and nasal mean choroidal thickness (p=0.007, p<0.001, p=0.026, respectively). The mean choroidal thickness for group 2 was 395 ± 80 µm, 338 ± 74 µm, and 233 ± 61 µm at the regions subfoveal, temporal, and nasal to the fovea, respectively. In comparison, the mean choroidal thickness for group 4 was 335 ± 86 µm, 274 ± 54 µm, and 200 ± 53 μm at the regions subfoveal, tem-poral, and nasal to the fovea, respectively. No statistically significant differences were found for choroidal thickness among groups 1-4 (p=0.214, p=0.177, p=0.094, respectively) and between groups 3-4 (p=0.105, p=0.261, p=0.695, respectively) for all measured points. Conclusion: Our results suggest that choroidal thickening can occur at the regions subfoveal, temporal, and nasal to the fovea in the second trimester.

Keywords: Choroid/anatomy & pathology; Choroid/pathology; Enhanced depth imaging; Tomography, optical coherence; Diagnostic techniques, ophthalmolo-gical; Pregnancy

RESUMOObjetivo: Investigar a espessura da coroide em gestantes saudáveis durante os di-ferentes trimestres utilizando tomografia de coerência óptica com profundidade de imagem aprimorada (EDI-OCT ).Métodos: Este estudo prospectivo incluiu 90 gestantes saudáveis nos primeiro, segundo e terceiro trimestres da gravidez (grupos 1, 2 e 3, respectivamente) e 30 mu-lheres saudáveis não-gestantes (grupo 4) com faixa etária de 18-40 anos de idade. Foi realizada tomografia de coerência óptica espectral para estimar a espessura média da coroide. A espessura da coroide foi medida manualmente da borda externa do epitélio pigmentar da retina até o limite interno da esclera nas regiões subfoveal, 3 mm temporal e 3 mm nasal à fóvea utilizando EDI-OCT. As diferenças entre os grupos foram analisadas com o teste ANOVA unicaudal.Resultados: Houve diferença estatística significativa na espessura média da coroide entre os grupos 2 e 4 nas regiões subfoveal, temporal e nasal à fóvea (p=0,007; p<0,001; p=0,026, respectivamente). A espessura média da coroide no grupo 2 foi: 395 ± 80 µm, 338 ± 77 µm e 233 ± 61 µm nas regiões subfoveal, temporal e nasal à fóvea, respecti-vamente. Em comparação, a espessura média da coroide no grupo 4 foi de: 335 ± 86 µm, 275 ± 54 µm e 200 ± 53 µm, nas regiões subfoveal, temporal e nasal à fóvea, respectivamente. Não foi encontrada diferença estatística significativa entre os grupos 1-4 (p=0,214, p=0,177, p=0,094, respectivamente) e os grupos 3-4 (p=0,105, p=0,261, p=0,695 respectivamente), para todas as medidas.Conclusão: Nossos resultados sugerem que há espessamento da coroide nas regiões subfoveal, temporal e nasal à fóvea no segundo trimestre gestacional.

Descritores: Coroide/anatomia & histologia; Coroide/patologia; Tomografia de coe-rência óptica; Técnicas de diagnóstico oftalmológico; Gravidez

second and third trimesters because of fluid accumulation(7). During pregnancy, hemodynamic changes affect other parts of the body, including choroidal flow.

The choroid is the vascular layer between the retina and the sclera that provides the blood supply to the eye and plays an important role in ocular nutrition. Histopathological examination showed that it is 0.22 mm thick posteriorly(8). The choroid is composed of a vascular ne-twork that contributes to ocular nutrition through volume regulation and is extremely sensitive to blood pressure changes. The choroidal thickness is affected by blood flow and perfusion pressure(9). Therefore, hemodynamic alterations can affect choroidal thickness.

Goktas S, et al.

149Arq Bras Oftalmol. 2014;77(3):148-51

Optical coherence tomography (OCT) provides high-resolution, cross-sectional digital images of live biological tissues in vivo. With the use of enhanced depth imaging optical coherence tomography (EDI-OCT), choroid images can be obtained and the choroidal thick-ness can be measured. Using OCT, one study reported the choroid thickness as 287 μm, 261 μm, and 145 μm at subfoveal regions, 3 mm temporal to the fovea, and 3 mm nasal to the fovea, respectively, in healthy individuals(10). The change in the choroid thickness may play a role in the pathophysiology of various ocular conditions.

In the present study, we used EDI-OCT to examine choroidal thi-ckness at each trimester in healthy pregnant women, and then com-pared these measures with those for non-pregnant healthy women.

MEtHodSWe examined 4 groups in the present study. Group 1 consisted of

30 eyes in 30 healthy women in the first trimester, group 2 consisted of 30 eyes in 30 healthy women in the second trimester, and group 3 consisted of 30 eyes of 30 healthy women in the third trimester. Group 4 was the control group and consisted of 30 eyes in 30 healthy non-pregnant women. Only the right eye was assessed in each study participant. This study followed the tenets of the Declaration of Helsinki. All participants provided informed consent. The inclusion criteria for groups 1, 2, and 3 were healthy pregnant women in their first, second, or third trimester Inclusion criteria for the control group (group 4) included an age of 18-40 years old, non-pregnant healthy regularly menstruating women. High myopic and hyperopic refrac-tive errors greater than -1.0 or +1.0 diopters, or intraocular surgical intervention were excluded from the study. Subjects with systemic diseases or conditions that might affect retinal or choroidal thickness were excluded. For example, patients with diabetes mellitus were excluded. Pregnant with high blood pressure was excluded. In addition, patients with any retinal or choroidal abnormalities detected in spectral-domain OCT scans were excluded.

All subjects underwent a thorough ocular examination, including an auto-refractometer, best-corrected visual acuity measurement, slit-lam p examination, intraocular pressure measurement, and dila ted funduscopy. Choroidal thickness was measured using a spectral-do main OCT device (Spectralis: wavelength, 870 nm; Heidelberg Engineering, Germany) with an enhanced depth-imaging mode after pupil dilation. All measurements were performed in the mor-ning. The horizontal section running through the center of the fovea was selected for further analysis. The OCT images were assessed independently by 2 ophthalmologists.

The choroidal thickness was measured from the outer portion of the hyperreflective line, corresponding to the retinal pigment epi-

thelium, to the inner surface of the sclera. Choroidal thickness was measured at the fovea and at positions 3 mm temporal, and nasal to the fovea. The values of the measurements were compared for each observer and then averaged for analysis.

Diastolic blood pressure, systolic blood pressure, and ocular per-fusion pressure were measured for each subject. Ocular perfusion pressure was calculated according to the following formula(11): Ocular perfusion pressure = mean blood pressure - intraocular pressure.

Statistical calculations were performed using SPSS (Statistical Package for Social Sciences version 15.0; SPSS, Inc., Chicago, IL). Cho-roidal thickness is presented as the mean ± standard deviation. The Kolmogorov-Smirnov test was used to assess correlations for data with a normal distribution. Groups were compared with an analysis of variance (ANOVA) and post hoc tests. The differences in choroidal thickness detected by ANOVA and post hoc tests between healthy (control group) and pregnant individuals were also analyzed by the t-test. P values less than 0.05 were considered significant.

RESuLtSNinety eyes in 90 healthy pregnant women and 30 eyes of 30

age-matched healthy non-pregnant women were included. The mean gestational age was 7.4 ± 2.6, 19.2 ± 2.9, and 33.1 ± 2.8 weeks in groups 1, 2, and 3, respectively. Mean age was 28.5 ± 6.4, 26.6 ± 4.2, 26.9 ± 6.2, and 29.4 ± .2 years, in groups 1, 2, 3, and 4, respecti-vely. There were no statistically significant differences in age among the groups (p=0.183). Representative EDI-OCT scans for a pregnant women and the control group is presented in figure 1. Table 1 shows the mean choroidal thickness values for the groups that were mea-sured at subfoveal regions, and those 3 mm nasal to fovea, and 3 mm temporal to fovea. There were statistically significant differences in subfoveal, temporal, and nasal choroidal thickness among the groups (p<0.05). The mean subfoveal, temporal, and nasal choroidal thickness was significantly greater in group 2 compared with the control group (p=0.007, p<0.001, p=0.026, respectively). There was no difference in mean subfoveal, nasal, and temporal choroidal thickness between group 1 and the control group (p=0.214, p=0.177, p=0.094, respectively). There was also no statistical significance among the 3 groups and control group for the mean subfoveal, temporal, and nasal choroidal thickness (p=0.105, p=0.261, p=0.695, respectively). Figure 2 shows the distribution of choroidal thickness according to group.

The ocular perfusion pressure was 36.3 ± 3.5 mmHg in pregnant women and 37.3 ± 2.8 mmHg in the control group. No significant correlations were found between the choroidal thickness and ocular perfusion pressure, gestational week.

Figure 1. A) Optical coherence tomography image from the control group demonstrating enhanced depth imaging on Spectralis (Heidelberg Engineering). The choroidal thickness was measured from the outer portion of the hyperreflective line, corresponding to the retinal pigment epithelium to the inner surface of the sclera at the subfovea, 3 mm temporal, and 3 mm nasal to the fovea. Calipers were positioned manually using computer software provided by the manufacturer. B) Optical coherence tomography image from second trimester, which depicts the increased the choroidal thickness.

A

B

Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomography

150 Arq Bras Oftalmol. 2014;77(3):148-51

dISCuSSIoNPregnancy can affect the eyes. Non-pathological events occurring

during pregnancy includes reduced corneal sensitivity and increased corneal thickness related to the water retention. Choroidal thickness changes can be expected because of this water retention. There are some additional pathologic conditions reported to develop during pregnancy such as central serous chorioretinopathy(12). However, few studies have investigated choroid thickness in pregnant women(13-15). Takahashi et al. have demonstrated that there was no significant difference in choroidal thickness between healthy pregnant and non-pregnant women at the subfoveal and other measurement points(13). However, only the pregnant women in the third trimester were included in that study. Similarly, we did not find any difference in choroidal thickness measurement between pregnant women in the third trimester and the control group. Kara et al. investigated pregnant women in 15-38 weeks of gestational age(14). They reported that subfoveal choroidal thickness increased in pregnant women but no significant correlation between the choroidal thickness and gestational age was found. Sayin et al. investigated pregnant women in 17-37 weeks of gestational age(15). They reported that subfoveal choroidal thickness increased in pregnant women and found that ne-gative correlation between the choroidal thickness and gestational age. As distinct from these studies, we examined the mean choroidal thickness in pregnant subjects in each trimester via EDI-OCT. To our knowledge, the current study is the first to investigate the choroidal thickness in three trimesters compared with non-pregnant healthy women. It can be considered as an important finding that the cho-roidal thickness significantly increased in the second trimester but it did not change in the first and third trimesters.

While blood volume progressively increases, a rapid increase is ty-pically noted until mid-pregnancy, with a slower increase thereafter.

Additionally, during pregnancy, vascular resistance decreases from the fifth week of the gestation due to hormonal change(3,4). As vascular resistance decreases, vascular compliance increases(16). The decrease of the vascular resistance results in reduced blood pressure particu-larly in the mid-pregnancy. Thereafter, systemic pressure begins to increase again and ultimately reaches or exceeds the pre-pregnancy level(17). The reduction of blood pressure and systemic vascular resis-tance, which is observed particularly in the middle of preg nancy, may explain the increase in choroidal thickness in the second trimester.

During pregnancy blood flow increases in many organs, including the kidneys, extremities, and skin(18-20). One study reported increa sed ocular blood flow during pregnancy caused by vasodilation due to estrogen change(21). We suggest that increased choroidal thickness may be secondary to increased blood flow.

Choroidal changes during pregnancy may play a vital role in the pathophysiology of ocular diseases such as central serous choriore-tinopathy. Choroidal vasodilation and choroidal vascular hyperper-meability causes subsequent vascular leakage resulting in increased hydrostatic pressure in the choroid. Recent studies demonstrated a significantly increased choroidal thickness in patients with acute cen-tral serous chorioretinopathy(22,23). Central serous chorioretinopathy may be caused by an increased hydrostatic pressure in the choroid. Pregnancy is one of the several known risk factors for central serous chorioretinopathy, which commonly develops in the third trimester(24). We speculate the increased choroidal thickness observed in the se-cond trimester may be the causative factor underlying development of central serous chorioretinopathy in the third trimester. This may explain why central serous chorioretinopathy is more commonly observed in the third trimester.

The current study has several limitations. First, we did not measu-re ocular blood flow. Color Doppler imaging can measure the velocity of blood and vascular resistance within each vessel(25). Although this technique is useful for determining choroidal blood flow, it does not provide three-dimensional anatomical information about the cho-roidal layers. In our study, ocular blood flow was not examined; the-refore, our study cannot determine the relationship between cho roidal thickness and ocular blood flow. We can speculate that the thicker choroid may indicate an overall increase in choroidal blood flow in pregnant women, as was previously demonstrated with a pulsatile ocular blood flow pneumotonometer(21). Therefore, it is likely that the increased choroidal thickness may be related to increased ocular blood flow. Another limitation of our study was the small number of participants.

High refraction and age affect the thickness of the choroid(10,26). Consequently, in our study we included similar groups with respect to meaningful characteristics, such as age and refraction, for both the pregnant and control groups.

In conclusion, our study showed a significant increase in choroi-dal thickness in the second trimester whereas there was no increase in the choroidal thickness during the first and third trimesters. These data favor the idea that in pregnant women, increased choroidal thi ckness may lead to increased vascular permeability, which can explain the relationship between pregnancy and central serous cho-rioretinopathy. Further studies with a larger number of subjects should be performed in a pregnant population to correlate choroidal blood flow with choroidal thickness.

REFERENCES 1. August P, Lenz T, Ales KL, Druzin ML, Edersheim TG, Hutson JM, et al. Longitudinal

study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia. Am J Obstet Gynecol. 1990;163(5):1612-21.

2. Pritchard JA, Rowland RC. Blood volume changes in pregnancy and the puerperium. III. Whole body and large vessel hematocrits in pregnant and nonpregnant women. Am J Obstet Gynecol. 1964;88:391-5.

3. Duvekot JJ, Peeters LL. Maternal cardiovascular hemodynamic adaptation to pregnancy. Obstet Gynecol Surv. 1994;49(12):1-14.

table 1. Mean choroidal thickness values (µm) for each group

Location

Group 1 (n=30)

Group 2 (n=30)

Group 3 (n=30)

Group 4 (n=30) P* control

first trimester

second trimester

third trimester

Subfoveal 362 ± 81 395 ± 80 368 ± 70 335 ± 86 0.037

Temporal 297 ± 73 338 ± 74 293 ± 72 274 ± 54 0.004

Nasal 225 ± 60 233 ± 61 205 ± 46 200 ± 53 0.044

Values are presented as the mean ± SD.*= ANOVA test.

Figure 2. Graph showing subfoveal, temporal, and nasal choroidal thickness distribu­tion according to groups.

Goktas S, et al.

151Arq Bras Oftalmol. 2014;77(3):148-51

4. Gaillard R, Bakker R, Willemsen SP, Hofman A, Steegers EA, Jaddoe VW. Blood pressure tracking during pregnancy and the risk of gestational hypertensive disorders: the Generation R Study. Eur Heart J. 2011;32(24):3088-97.

5. Moutquin JM, Rainville C, Giroux L, Raynauld P, Amyot G, Bilodeau R, et al. A prospecti-ve study of blood pressure in pregnancy: prediction of preeclampsia. Am J Obstet Gynecol. 1985;151(2):191-6.

6. Macdonald-Wallis C, Tilling K, Fraser A, Nelson SM, Lawlor DA. Established pre-eclam psia risk factors are related to patterns of blood pressure change in normal term pregnan-cy: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). J Hypertens. 2011;29(9):1703-11.

7. Cankaya C, Bozkurt M, Ulutas O. Total macular volume and foveal retinal thickness alterations in healthy pregnant women. Semin Ophthalmol. 2013;28(2):103-11.

8. Ryan SJ. Retina. 4th ed. Philadelphia, PA: Elsevier Mosby; 2006. p.33-4. 9. Cioffi GA, Granstam E, Alm A. Ocular circulation. In: Kaufman PL, Alm A, editors. Ader’s

physiology of the eye: clinical application. 10th ed. St. Louis: Mosby; 2003. p.747-84. 10. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence

tomography of the choroid in normal eyes. Am J Ophthalmol. 2009;147(5):811-5. 11. Maul EA, Friedman DS, Chang DS, Boland MV, Ramulu PY, Jampel HD, et al. Choroidal

thickness measured by spectral domain optical coherence tomography: factors affecting thickness in glaucoma patients. Ophthalmology. 2011;118:1571-9.

12. Sunness JS. The pregnant woman’s eye. Surv Ophthalmol. 1988;32(4):219-38. 13. Takahashi J, Kado M, Mizumoto K, Igarashi S, Kojo T. Choroidal thickness in pregnant

women measured by enhanced depth imaging optical coherence tomography. Jpn J Ophthalmol. 2013;57(5):435-9.

14. Kara N, Sayin N, Pirhan D, Vural AD, Araz-Ersan HB, Tekirdag AI, et al. Evaluation of sub foveal choroidal thickness in pregnant women using enhanced depth imaging optical coherence tomography. Curr Eye Res. 2014:39(6):642-7.

15. Sayin N, Kara N, Pirhan D, Vural A, Araz Ersan HB, Tekirdag AI, et al. Subfoveal choroi-dal thickness in preeclampsia: comparison with normal pregnant and nonpregnant women. Semin Ophthalmol. 2014;29:11-7.

16. Spaanderman ME1, Willekes C, Hoeks AP, Ekhart TH, Peeters LL. The effect of pregnancy on the compliance of large arteries and veins in healthy parous control subjects and women with a history of preeclampsia. Am J Obstet Gynecol. 2000;183(5):1278-86.

17. Duvekot JJ, Cheriex EC, Pieters FA, Menheere PP, Peeters LH. Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone. Am J Obstet Gynecol. 1993;169(6):1382-92.

18. Dunlop W. Serial changes in renal hemodynamics during normal human pregnancy. Br J Obstet Gynaecol. 1981;88(1):1-9.

19. Katz M, Sokal MM. Skin perfusion in pregnancy. Am J Obstet Gynecol. 1980;137(1):30-3. 20. Ginsburg J, Duncan SL. Peripheral blood flow in normal pregnancy. Cardiovasc Res.

1967;1(2):132-7. 21. Centofanti M, Migliardi R, Bonini S, Manni G, Bucci MG, Pesavento CB, et al. Pulsatile

ocular blood flow during pregnancy. Eur J Ophthalmol. 2002;12(4):276-80. 22. Tan CS, Cheong KX, Sadda SR. Change in subfoveal choroidal thickness in central

serous chorioretinopathy. Eye (Lond). 2013;27(10):1221-2. 23. Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical cohe-

rence tomography of the choroid in central serous chorioretinopathy. Retina. 2009; 29(10):1469-73.

24. Gass JDM. Central serous chorioretinopathy and white subretinal exudation during pregnancy. Arch Ophthalmol. 1991;109(5):677-88.

25. Belden CJ, Abbitt PL, Beadles KA. Color Doppler US of the orbit. Radiographics. 1995; 15(3):589-608.

26. Ikuno Y, Tano Y. Retinal and choroidal biometry in highly myopic eyes with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2009;50(8):3876-80.

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Original Article

152 Arq Bras Oftalmol. 2014;77(3):152-4 http://dx.doi.org/10.5935/0004-2749.20140039

Ocular biometry and central corneal thickness in children: a hospital-based studyBiometria ocular e espessura corneana central em crianças: um estudo de base hospitalar

adeM GuL1, caGatay caGLar2, adnan cInaL3, tekIn yasar4, adIL kILIc5

Submitted for publication: November 22, 2013 Accepted for publication: March 20, 2014

Study conducted at Yuzuncu Yil University, Van, Turkey.1 Ophthalmology Department, Ondokuz Mayis University, Samsun, Turkey.2 Ophthalmology Department, Hitit University, Corum, Turkey.3 Beyoglu Eye Research and Training Hospital, Istanbul, Turkey.4 Ophthalmology Department, Yuzuncu Yil University, Van, Turkey.5 Ophthalmology Department, Balikesir University, Balikesir, Turkey.

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: Adem Gul. Korfez Mah. Mehmet Akif Ersoy Bulvari, 84/15 - Atakum, Samsun - Turkey - E-mail: karsadem@yahoo.com

INtRoduCtIoNOcular biometry, the refractive status of developing human eyes

and how they change with age, is essential for understanding the ocular growth and development of other ocular pathologies.

Many published studies have examined ocular biometry in older populations and have provided significant data. However, there are few population-based age norms for ocular biometry in children due to the technical difficulties in measuring biometric parameters, particularly in small children(1). When we searched for pediatric ocular biometric studies in the ophthalmology literature, we noted some restrictions in the design of previous studies, particularly those with school-age children. There was a paucity of data regarding biometry and central corneal thickness in preschool children. We decided to search for both preschool and school age children to investigate the normal distribution of axial length and central corneal thickness among children in different age groups.

Ocular biometric status varies in different ethnicities. Therefore, data from different areas and ethnicities should be studied. In this

ABStRACtPurpose: To investigate the distribution of axial length, anterior chamber depth, lens thickness, vitreous chamber depth, and central corneal thickness in children at different age groups.Methods: We studied 364 eyes in 182 children with ages between 1 and 12 years. Axial length, anterior chamber depth, lens thickness, and vitreous chamber depth were measured by ultrasound biometry. Central corneal thickness was measured by ultrasound pachymetry in all children.Results: The mean age was 6.54 ± 3.42 years. The axial length was 20.95 mm in 1-2 years old and 22.95 mm in 11-12 years old. The central corneal thickness was 556 µm in 1-2 years old and 555 µm in 11-12 years old. The mean anterior chamber depth and vitreous chamber depth increased with age (3.06 mm to 3.44 mm in anterior chamber depth, 13.75 mm to 15.99 mm in vitreous chamber depth), and the lens thickness decreased as age increased (3.67-3.51 mm).Conclusion: The axial length increased with age and reached adult levels by the age of 9-10 years. The lens thickness gradually decreased until 12 years. The central corneal thickness measurements did not yield a linear algorithm.

Keywords: Biometry; Cornea/anatomy & histology; Axial length eye; Child

RESUMOObjetivo: Investigar a distribuição do comprimento axial, profundidade da câmara anterior, espessura do cristalino, profundidade da câmara vítrea e espessura corneal central em crianças em diferentes faixas etárias. Métodos: Foram estudados 364 olhos de 182 crianças entre 1 e 12 anos de idade. O comprimento axial, a profundidade da câmara anterior , a espessura do cristalino e a profundidade da câmara vítrea foram medidos por biometria ultrassônica. A espessu ra corneal central foi medida por paquimetria ultrassônica em todas as crianças. Resultados: A idade média foi de 6,54 ± 3,42 anos. O comprimento axial foi 20,95 mm no grupo de 1-2 anos de idade e 22,95 mm no grupo de 11-12 anos de idade. A espessura corneal central foi 556 µm no grupo de 1-2 anos de idade e 555 µm no grupo de 11-12 anos de idade. A profundidade da câmara anterior média e profundidade da câmara vítrea aumentou com a idade (3,06 mm a 3,44 mm de profundidade da câmara anterior, 13,75 mm a 15,99 mm de profundidade da câmara vítrea) e da espessura do cristalino diminuiu com o aumento da idade (3,67 mm a 3,51 mm). Conclusões: Em nosso estudo, os valores do comprimento axial aumentou com a idade e atingiu os níveis adultos aos 9-10 anos de idade. A espessura do cristalino diminuiu gradualmente até os 12 anos de idade. As medições de espessura corneal central não seguiu um algoritmo linear.

Descritores: Biometria; Córnea/anatomia & histologia; Comprimento axial do olho; Criança

article, we present data for ocular biometry and central corneal thick-ness in a pediatric population. This data contributes to the literature by studying the Caucasian population in the eastern region of Turkey.

MEtHodSThis study was carried out in Yuzuncu Yil University, Faculty of Me-

dicine, Ophthalmology Department. It was approved by the Human Ethics Committee at Yuzuncu Yil University. The research adhered to the tenets of the Declaration of Helsinki.

The study was performed prospectively. Subjects were children between the ages of 1 and 12 years. The subjects were divided accor-ding to age into six groups: 1-2 years, 3-4 years, 5-6 years, 7-8 years, 9-10 years, and 11-12 years. The exclusion criteria were an ocular trau-ma, ocular surgery, uveitis, glaucoma, cataract, corneal pathologies, vitreous pathologies, retinal pathologies, or premature retinopathy. We did not include children younger than 12 months.

Gul A, et al.

153Arq Bras Oftalmol. 2014;77(3):152-4

We measured axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and central corneal thickness (CCT). AL and CCT measurements were performed with the US-1800 Echoscan (Nidek, Japan) using of A-scan biometry and pachymetry probes via the contact method. The measurements were taken after instilling anesthetic drops (proparacaine) on the cornea. On average, 5 measurements were taken with the pachymetry pro-be and 10 measurements were taken with the biometry probe to obtain better results. All measurements were taken between 08:30 and 11:30 a.m.

In this study, 364 eyes in 182 individuals were examined. Bilateral evaluation was performed for all patients. The measurements were taken under general anesthesia for 67 patients who had an interven-tion (probing) for naso-lacrimal dacryostenosis. The measurements were taken during the pre-intervention period in patients who had probing. All measurements were taken by the same ophthalmologist.

Statistical analyses were completed with independently paired t-tests, ANOVAs, and correlation tests.

RESuLtSThe mean age was 6.54 ± 3.42 years. For girls, the mean age was

6.61 ± 3.50 years in girls and 6.41 ± 3.30 years in boys. There was no signi-ficant age difference between boys and girls. Among all subjects, 63% were boys and 37% were girls; the ratio was 1.70 (n: boys/girls: 115/67).

The mean CCT was 556 ± 34 µm. There was a significant diff erence between the age groups in terms of CCT. The mean AL, ACD, LT, and VCD were 22.02 ± 1.19, 3.22 ± 0.36, 3.58 ± 0.23, and 15.17 ± 1.11 mm, respectively. Details for the age groups are given in table 1. Significant differences in the age groups were observed in the AL, ACD, LT, and VCD results.

Increasing age was significantly correlated with increasing AL, ACD, and VCD (p=0.000, p=0.000, p=0.000, respectively). Although there was a significant positive correlation between AL, ACD, and VCD, there was also a significant negative association between all of the above measurements and the LT (p=0.054, p=0.000, p=0.000, respectively). An important finding was that LT decreased as the age increased (p=0.000).

When we compared girls and the boys, there were significant differences in AL, ACD, and VCD (p=0.000, p=0.001, p=0.000, respec-tively), but there was no correlation in terms of CCT and LT (p=0.128, p=0.147, respectively). The AL was 0.74 mm longer in boys than in girls (Graphic 1).

dISCuSSIoN The most striking aspect of our study was that it was not perfor-

med with postmortem subjects or with congenital cataract patients, as could be observed in some studies(2,3).

oCular biometry

Most of the studies with A-scans were conducted with adoles-cent and adult subjects. In this study, children were studied and

the distributions of ocular biometry and CCT were documented in a hospital-based sample of children between 1 and 12 years of age. When we reviewed the literature on ocular biometry with focusing on children, most data was from older children between 5 and 16 years of age(4-7).

In the literature, AL in newborns ranged from 17 to 17.3 mm, and rapid increase was found in the postnatal period. The AL reached 20.6 mm after the first year of life. This rapid increase continued until the third year of life. After this rapid phase, increases in AL slowed until the seventh year and reached adult size at 10 years old(8-10). Our study found similar results showing that AL reached 20.49 mm after the first year of life and reached adult levels between 9 and 10 years of age.

Gordon et al. performed a study with age groups that reported eye growth increased approximately 1 mm/year during the first 2 years of life, 0.4 mm/year between 2 and 5 years, and 0.1 mm/year between 5 and 15 years(9). In our study, similar findings showed that eye growth increased about 1 mm/year in the first 2 years of life and increased 0.3 to 0.4 mm/year after 2 years. The average annual growth rate in our study was 0.26 mm, and we did not observe a linear in-crease in AL.

Our study also examined whether there were differences between girls and boys. Girls tended to have shorter eyes compared to boys. The males are typically have a deeper anterior chamber and a larger vitreous chamber. In the present study, the AL was 0.74 mm longer in boys than in girls. This finding is consistent with Zadnik et al., who repor-ted that AL was longer in boys(10). Twelker et al. and Ojaimi et al. stu-died AL in school-age children and reported the same findings(11,12).

In our study, lens thickness was 3.67 mm in the first 2 years of life and 3.51 mm in 11-12 years (Graphic 2). Zadnik et al. studied 869 children between 6 and 14 years of age and reported that there was a decrease in lens thickness between 6 and 10 years(13). Saw et al. studied myopic children who were between 7 and 9 years of age and reported a decrease of about 0.01 mm in lens thickness over 3 years(14). The same finding was also present in Shih et al.’s study, which

Graphic 1. Axial length in boys and girls.

Graphic 2. Lens thickness in age groups.

table 1. Results by age group

1-2 years

3-4 years

5-6 years

7-8 years

9-10 years

11-12 years

n 30 29 30 33 32 28

CCT 556 547 565 563 550 555

AL 020.49 021.81 021.97 022.25 022.66 022.95

ACD 003.06 003.20 003.02 003.30 003.31 003.44

LT 003.67 003.63 003.59 003.56 003.54 003.51

VCD 013.75 014.94 015.30 015.34 015.76 015.99

n= number; CCT= central corneal thickness (µm); AL= axial length (mm); ACD= anterior chamber depth (mm); LT= lens thickness (mm); VCD= vitreous chamber depth (mm).

Ocular biometry and central corneal thickness in children: a hospital-based study

154 Arq Bras Oftalmol. 2014;77(3):152-4

showed that a decrease was present in children between the ages of 7 and 11 years(15). Our study found that lens thickness continuously decreased until 12 years of age. Therefore, we can say that there was a decrease in lens thickness during the first 12 years of life.

Central Corneal thiCkneSS

The literature included different results about CCT in children, ranging from 529 to 564 µm(16-21). The average CCT in our study was 556 µm, and the range was between 448 and 678 µm.

Portellinha et al. reported that CCT is 573 µm in the newborn and decreases after birth(22). However, they did not find differences between boys and girls. In our study, there was only a 6-µm difference between boys and girls, which was not statistically significant.

Prost et al. studied 360 children between 0 and 14 years old(23). In newborns, the average CCT was 537 µm, and at 14 years of age, the average was 567 µm. Parentin et al. hypothesized that this decrease took place during the first and second years of life. They claimed that rearrangements in collagen bundles and remodeling occurred in the early years of life(24).

Hussein et al. studied children between the ages of 7 months and 14 years and reported that CCT was 538 µm in children under 2 years old, 546 µm in children between 2 and 4 years, 565 µm between 5 and 9 years, and 555 µm between 10 and 14 years old. The mean CCT for all age groups was 549 µm(16). Our present results are similar to that study. As table 1 indicates, CCT was 556 µm in the first 2 years, 547 µm between 3 and 4 years, 564 µm between 5 and 8 years, and 553 µm between 9 and 12 years. We did not identify a gradual decrease or increase, unlike that reported in other studies(16,22,23) in terms of CCT during the first 12 years of life. The limitations of our study for CCT are an insufficient number of subjects and the extreme measurement results in age groups that make it difficult to obtain a linear algorithm.

In conclusion, axial length was 20.49 mm in first 2 years. It was increasingly reached adult levels of approximately 22.66 mm during years 9-10. Lens thickness was 3.67 mm in first 2 years and conti-nuously decreased to 3.51 mm up to 11-12 years old. Central corneal thickness was 556 µm in the first 2 years, and 555 µm in years 11-12. There was no linear increase/decrease in central corneal thickness measurements, which may be due to an insufficient subject number and extreme values in age groups.

The results of this study may contribute to the literature, parti-cularly in the aspect of understanding pediatric eye growth and trea ting the most common surgical entity (congenital cataract) in early childhood period.

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biometry. Exp Eye Res. 2012;102(3):70-5.

3. Capozzi P, Morini C, Piga S, Cuttini M, Vadalà P. Corneal curvature and axial length values in children with congenital/infantile cataract in the first 42 months of life. Invest Ophthalmol Vis Sci. 2008;49(11):4774-8.

4. Lam DS, Fan DS, Lam RF, Rao SK, Chong KS, Lau JT et al. The Effect of Parental History of Myopia on Children’s Eye Size and Growth: Results of a Longitudinal Study. Invest Ophthalmol Vis Sci. 2008;49(3):873-6.

5. Tong L, Wong EH, Chan YH, Balakrishnan V. A multiple regression approach to study optical components of myopia in Singapore school children. Ophthalmic Physiol Opt. 2002;22(1):32-7.

6. Saw SM, Carkeet A, Chia KS, Stone RA, Tan DT. Component dependent risk factors for ocular parameters in Singapore Chinese children. Ophthalmology. 2002;109(11): 2065-71.

7. Jones LA, Mitchell GL, Mutti DO, et al. Comparison of ocular component growth curves among refractive error groups in children. Invest Ophthalmol Vis Sci. 2005; 46(7):2317-27.

8. Isenberg SJ. Physical and refractive characteristics of the eye at birth and during infancy. In: Isenberg SJ, editor. The eye in infancy. 2nd edition. St. Louis: Mosby; 1994; p.36-51.

9. Gordon RA, Donzis PB. Refractive development of the human eye. Arch Ophthalmol. 1985;103(6):785-9.

10. Zadnik K, Manny RE, Yu JA, et al. Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group. Ocular component data in schoolchildren as a function of age and gender. Optom Vis Sci. 2003;80(3):226-36.

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15. Shih YF, Chiang TH, Lin LL. Lens thickness changes among schoolchildren in Taiwan. Invest Ophthalmol Vis Sci. 2009;50(6):2637-44.

16. Hussein MA, Paysse EA, Bell NP, et al. Corneal thickness in children. Am J Ophthalmol. 2004;138(5):744-8.

17. Shimmyo M, Ross AJ, Moy A, et al. Intraocular pressure, Goldmann applanation tension, corneal thickness, and corneal curvature in Caucasians, Asians, Hispanics and African Americans. Am J Ophthalmol. 2003;136(4):603-13.

18. Muir KW, Jin J, Freedman SF. Central corneal thickness and its relationship to intraocu-lar pressure in children. Ophthalmology. 2004;111(12):2220-3.

19. Yildirim N, Sahin A, Basmak H, Bal C. Effect of central corneal thickness and radius of the corneal curvature on intraocular pressure measured with the Tono-Pen and noncontact tonometer in healthy schoolchildren. J Pediatr Ophthalmol Strabismus. 2007;44(4): 216-22.

20. Sahin A, Basmak H, Yildirim N. The influence of central corneal thickness and corneal curvature on intraocular pressure measured by tono-pen and rebound tonometer in children. J Glaucoma. 2008;17(1):57-61.

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22. Portellinha W. Belfort R Jr. Central and peripheral corneal thickness in newborns. Acta Ophthalmol. 1991;69(2):247-50.

23. Prost ME, Oleszczyńska-Prost E. Central corneal thickness measurements in children. Klin Oczna. 2005;107(7-9):442-4.

24. Parentin F, Pensiero S. Central corneal thickness in children with growth hormone de ficiency. Acta Ophthalmol. 2010;88(6):692-4.

Original Article

155Arq Bras Oftalmol. 2014;77(3):155-8http://dx.doi.org/10.5935/0004-2749.20140040

Conjunctival melanoma: survival analysis in twenty-two Mexican patientsMelanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos

rosa anGéLIca saLcedo-hernández1, kuauhyaMa Luna-ortIz1,2, Leonardo saúL LIno-sILva3, ánGeL herrera-GóMez1, verónIca vILLavIcencIo-vaLencIa1, MIrIaM teJeda-roJas1, José F. carrILLo1

Submitted for publication: February 25, 2014 Accepted for publication: April 22, 2014

Study conducted at Instituto Nacional de Cancerología, México, D.F., México.1 Department of Head and Neck Surgery, Instituto Nacional de Cancerología, México, D.F., México.2 División de Estudios de Posgrado, Universidad Nacional Autónoma de México (UNAM), México,

D.F., México.3 Departament of Anatomic Pathology, Instituto Nacional de Cancerología, México, D.F., México.

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.

Correspondence address: Leonardo Saúl Lino-Silva. Instituto Nacional de Cancerología, Anatomic Pathology. Av. San Fernando #22, Col. Sección XVI, Tlalpan, México, D.F., 14080

E-mail: saul.lino.sil@gmail.com

Approval of the Institutional Review Board (IRB): This work was approved for The Comité de Ética del Instituto Nacional de Cancerología de México, although evaluation of the project by the Committee was not necessary.

INtRoduCtIoNOcular melanomas may arise from the eyelids, conjunctiva, and

intraocular and orbital structures. Conjunctival melanoma and pri-mary acquired melanosis (PAM) are pigmented lesions of the ocular surface. The incidence of conjunctival melanoma is low, estimated to occur in 0.2 to 0.5 cases/million of the Caucasian population. In a study of 4,836 patients with melanomas, 5.2% occurred in ocular structures, from which 85% occurred in the uvea and 4.8% in the conjunctiva(1,2). However, in recent years there has been a significant increase in the number of cases of conjunctival melanoma in males, whereas the incidence of conjunctival melanoma has remained un-changed in females(1,3). Conjunctival melanomas constitute 1% of the ocular melanomas and can originate from a PAM in 75% of cases or develop de novo. Generally, it presents as a pigmented lesion although 30% are amelanic(4). Twenty-six percent of cases with metastasis have been reported without nodular involvement. Other authors have reported lymph node disease in 41% of patients, with the most affected lymph nodes being pre-auricular(5). The most significant factors

ABStRACtPurpose: To describe the cases of conjunctival melanoma (CM) and report the disease-free interval (DFI) and overall survival (OS). Methods: The charts of 22 patients who were admitted to two hospitals between 1985 and 2006 were reviewed for pertinent data, including demographics, site of involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant treatment.Results: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was 52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7 (31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treatment. Disease-free survival at 5 years was 51% and the overall survival at 5 and 10 years was 50% and 37%, respectively. Conclusion: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive, and the optimal treatment is surgery with adjuvant therapy.

Keywords: Conjunctival neoplasms/surgery; Melanoma; Disease-free survival; Sur -vival analysis

RESUMOObjetivo: Descrever o intervalo livre de doença (DFI) e sobrevida global (OS) de pa-cientes com melanoma conjuntival (CM).Método: Prontuários de 22 pacientes que foram internados em dois hospitais entre 1985 e 2006 foram revisados para dados pertinentes, incluindo dados demográficos, local de envolvimento na conjuntiva e outros locais de acometimento, tratamento cirúrgico e tratamento adjuvante.Resultados: Dez (45,45%) homens e 12 (54,55%) mulheres foram selecionados. A mé dia de idade foi de 52,3 anos. Em 15 pacientes (68,1%) CM envolveu a conjuntiva bulbar, e em 7 (31,9%) envolveu a conjuntiva palpebral. Dos 22 pacientes, 72,72% tinham história de melanose conjuntival. O tamanho médio do tumor foi de 20,4 mm. Oito (36,36%) pacientes foram submetidos à exenteração orbital, 2 (9,06% ) à enu clea ção, 5 (22,72%) à ampla excisão da lesão seguida de radioterapia, 2 (9,06%) à exenteração orbital com esvaziamento cervical e os restantes 5 pacientes (22,72%) foram conside-rados adequadamente tratados apenas com excisão ampla. Oito (36,36%) pacientes receberam tratamento adjuvante. Sobrevida livre de doença em 5 anos foi de 51% e sobrevida global em 5 e 10 anos foi de 50% e 37%, respectivamente. Conclusão: Melanoma conjuntival é uma entidade rara. Comportamento do tumor é agressivo, e o melhor tratamento é a cirurgia com terapia adjuvante.

Descritores: Neoplasias da conjuntiva/cirurgia; melanoma; Sobrevida livre de doença; Análise de sobrevivência

reported for recurrence and metastatic disease are the presence of multi-focal tumors, myxoid cells, depth >4 mm, unfavorable locations (such as palpebral, caruncle, and cornea), scleral extension, advan-ced tumor node metastasis staging (TNM) and incomplete surgical excision(4,5). Treatment options for conjunctival melanoma include surgical excision, excision combined with cryotherapy, radiotherapy, and topical chemotherapy(6,7). Mortality at 10 years related to the tu-mor is between 10 and 30%(3). The purpose of this study is to report the natural history and results of treatment and follow-up of a series of cases with conjunctival melanoma recorded in a single Mexican oncology center.

MEtHodS

This is a retrospective study from 1985 to 2006. Thirty clinical charts of patients diagnosed with conjunctival melanoma were reviewed. Eight patients were excluded because they refused treatment. The cases analyzed had been subjected to biopsy in one center spe cia-

Conjunctival melanoma: survival analysis in twenty-two Mexican patients

156 Arq Bras Oftalmol. 2014;77(3):155-8

lizing in oncology (Instituto Nacional de Cancerología). They were subsequently surgically resected in our institution or arrived with a pre-vious surgery for evaluation at our centers for a possible subsequent treatment. All patients had a diagnosis of conjunctival melanoma confirmed by histology, and all underwent liver function tests, chest x-ray, and liver ultrasound to rule out distant metastases. Computed tomography (CT) was performed when the exam results showed suspicious findings of local infiltration. The 2010 American Joint Com mittee on Cancer (AJCC) staging system was applied to patients in this series. Treatment with chemotherapy or radiotherapy was provided to selected patients (refer to the Results section). Overall, survival (OS) and disease free interval (DFI) curves were constructed using the Kaplan-Meier method and significant differences were analyzed with log-rank test.

RESuLtSThe clinical-pathological data of the patients are summarized in

table 1. We analyzed 22 patients; 10 (45.45%) were men and twelve (54.55%) were women. The average age of all patients at the time of diagnosis was 52.3 years (range: 16-82 years). The mean follow-up time was 43.5 months (range: 2-218 months). All lesions were unila-teral and had caused extensive damage (extension to ocular globe). Of the 22 patients, 72.72% had a previous history of melanosis. Fifteen lesions (68.1%) involved the bulbar conjunctiva, and seven lesions (31.9%) the palpebral conjunctiva. The limbus, fornix, and caruncle were involved in 9 (40.9%), 8 (36.36%), and 5 (22.72%) cases, respec-tively. The mean tumor size was 20.4 mm (range: 3-70 mm). Alkaline phosphatase levels were elevated in 10 (45.45%) cases.

All patients had a diagnosis of melanoma confirmed by histology. One patient (4.54%) had bone infiltration. At clinical presentation, 6 patients (27.27%) were staged as T1, 12 patients (54.55%) as T3, and 4 patients (18.18%) as T4. One patient (4.54%) had metastatic disease at the time of diagnosis. The overall survival curves regarding T clas-sification are shown in figure 1. One case (4.54%) had positive lymph nodes at presentation. The OS curve corresponding to the N factor is depicted in figure 2 (p=0.004).

Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion follo-wed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision.

Eight (36.36%) patients received adjuvant treatment. Four pa-tients (18.18%) received chemo-radiotherapy, 2 patients (9.09%) received chemotherapy alone, and 2 patients (9.09%) received only radiotherapy. Disease-free survival at 5 years was 50% and overall survival rates at 5 and 10 years were 51 and 37%, respectively (Fi-gures 3 and 4). The chemotherapy treatment supplied was based on carmustine, dacarbazine, and cisplatin, in the case of metastatic melanoma (two patients). The radiotherapy regimen consisted on hypo-fractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days.

dISCuSSIoN

The incidence of conjunctival melanoma is low, with an esti-mated rate of 0.2 to 0.5 per million in the Caucasian population(8). However, in recent years a significant increase in the number of cases of conjunctival melanoma has been reported in males with the inci-

table 1. Clinical characteristics of twenty-two melanomas of the conjunctiva

Case Sex Age Follow up Survival (months) treatment Metastasis outcome

01 Female 16 002 002 OE + ND Yes, nodal DOD

02 Male 53 030 258 E + CT No DOD

03 Female 42 036 060 WE + CTRT No DOD

04 Male 65 020 152 WE + CT No DFD

05 Male 47 032 060 WE + ND No DOD

06 Female 73 050 001 OE No AWD

07 Male 27 258 032 OE No DOD

08 Female 85 020 005 OE + ND No DOD

09 Male 55 066 017 OE + RT No AFD

10 Female 85 010 015 WE* No DOD

11 Male 53 040 007 WE* No AFD

12 Female 29 005 030 E No DOD

13 Male 70 020 012 WE* No DFD

14 Female 50 032 007 OE + RT No AWD

15 Male 65 050 010 WE* No DOD

16 Female 42 045 008 WE* Yes, bone DOD

17 Female 56 030 009 OE No DOD

18 Male 57 068 008 WE + CTRT No DOD

19 Male 60 061 030 OE No AFD

20 Female 52 024 024 OE + CTRT No AWD

21 Female 40 034 058 OE No AFD

22 Female 30 025 063 WE + CTRT No AFD

CC= cribriform carcinoma; TNM= tumor, node metastasis staging; AWD= alive with disease; DOD= dead of disease; AFD= alive free of disease; OE= orbital exenteration; E= enucleation; WE= wide excision; ND= neck dissection; CTRT= chemoradiotherapy. CT= chemotherapy. RT= radiotherapy.(*) Performed out of our institution.

Salcedo-Hernández RA, et al.

157Arq Bras Oftalmol. 2014;77(3):155-8

Figure 1. Disease free survival according to Kaplan­Meier. The mean follow up time was 122 months. The 5­years disease free survival was 51%.

Figure 2. Overall survival according to Kaplan­Meier. The 5­years overall survival was 50% and the 10­years overall survival was 37%. The mean follow up time was 107 months.

Figure 3. Survival by T stage, according to Kaplan­Meier. Tumors in advanced T stage show the worse prognosis. For T3 tumors, the 5­years survival is 40% and 0% for T4 tumors.

Figure 4. Survival by the N stage, according to Kaplan­Meier. Tumors without nodal metastasis showed a 5­year survival of 53%, but tumors with nodal metastasis.

dence of conjunctival melanoma remaining unchanged in females(8). In the present study, we report a male to female ratio of 1:1.2 (45.8% males and 54.17% females). The age of presentation of conjunctival melanoma is usually in the fifth decade and it is only exceptionally observed in patients under 20 years of age, data which are in agree-ment with our results, with only one patient presented being under 20 years old(9,10).

These tumors may arise de novo or from a pre-existing nevus, or more frequently from a PAM with proportions highly variable among different studies. Approximately 50% to 75% originate from areas of PAM, 4% to 26% from conjunctival nevi and 18% to 39% arise de novo(8-11). We found that 18 patients (75%) had a previous history of melanosis. The most common presentation of conjunctival melano-ma is a raised, irregular, unilateral pigmented area, brownish-black in color and most often without other associated symptoms. The presence of prominent and complex blood vessels is frequent(10). In our study, all lesions were unilateral, and unlike the most common symptoms, they included a foreign body sensation and pain in the affected eye. Fifteen lesions (68.18%) involved the bulbar conjunctiva and seven lesions (31.81%) involved the palpebral conjunctiva. These data are in agreement with previous reports(8-10).

The standard management of conjunctival melanomas is wide sur gical excision, after which cryotherapy is applied to the normal residual margins of resection(11). Patients treated initially with tumor excision alone had a statistically higher recurrence rate than those treated initially with excision and supplemental cryotherapy(12,13). Surgical treatment of conjunctival melanoma has evolved to more conservative procedures. In the past, conjunctival melanoma implied an orbital exenteration(13).

Prognosis of conjunctival melanoma depends on several factors previously reported in the literature: thickness >4 mm is associated with a mortality rate 3.8 times higher than tumors measuring <1 mm thick(8,10). Lesions located on the palpebral or fornix conjunctiva have a poorer prognosis with a mortality rate 2.2 times higher than those located in the bulbar conjunctiva or in the limbus. Conjunctival me-lanoma of mixed cellular type has three times higher mortality than melanoma of fusiform cells(14). Lymphatic invasion is associated with four times higher mortality rate. Amelanotic lesions demonstrate the most aggressive course and neither age nor gender is significant to the prognosis(10). According to our results, the prognosis was unfavo-rable because of the characteristics of the tumor, which showed an average tumor size of 20.4 mm (range: 3-70 mm), with 68.1% of them located in the extra-bulbar conjunctiva.

Conjunctival melanoma: survival analysis in twenty-two Mexican patients

158 Arq Bras Oftalmol. 2014;77(3):155-8

As well as other treatment modalities such as cryotherapy, surgi-cal techniques for management of this tumor have evolved slowly, being performed mainly at oncology centers(9). In conjunctival me-lanoma, relatively narrow margins are obtained to preserve visual func tion. Orbital exenteration (removal of eyelids, eye, membranes, mucous membranes and orbital content) is reserved for patients with massive invasive melanomas and for tumors that originate in unfavo-rable sites (palpebral or fornix conjunctiva). This is mostly because the palpebral conjunctiva is closely attached to the tarsus by numerous septal connections and a minor surgical procedure would not give adequate margins. However, this procedure has not been shown to increase overall survival of these patients(14). In our study, 8 (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the re maining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treat ment. Treatment with exenteration was indicated by the size and extent of the melanoma because these tumors were larger than those reported in the literature.

Our results show that 6 patients had a T1 tumor. All of them were treated with wide excision with no adjuvant treatment, and showed no recurrence after a long term survival. In figure 1, as well, the prog-nostic significance of the T classification of the tumor is demonstra-ted, which has been pointed out previously(15). These findings raise the case against the indiscriminate use of orbital exenteration, which could be reserved for T4 and selected T3 cases, since no real improve-ment in survival is obtained with this procedure. However, recently, other studies have found greater significance for multi-focality and status of surgical margins, which may require surgery that is more extensive and/or radiotherapy to achieve local control(16). Therefore, our results show that the use of chemotherapy alone or combined with radiotherapy appears to give a survival benefit to our patients (not extensively analyzed because of the small number of patients of our series) and it helps to plan the surgical treatment with a less invasive approach.

It is estimated that ~50% of patients present recurrence at 10 years(14). A recent review set a survival rate at 5 and 10 years of ~85% and 70%, respectively(17). Overall mortality reported in different studies is ~25%(10). In this study, 18% of patients developed late cervical metas-tases, pre-auricular and sub-mandibular lymph nodes involvement in descending order. This is due mainly to the fact that lymphatic channels exist in all parts of the stroma of the conjunctiva and these nodes mainly drain these sites(18). Of the total patient pool, 18.18% died because of melanoma metastases.

In this study, the disease-free survival at 5 years was 51% and overall survival at 5 and 10 years was 50% and 37%, respectively. This is lower than reported in the literature because the tumor characteris-tics in our study had an unfavorable prognosis. While the primary treatment of eyelid and conjunctival tumors is frequently surgical, se veral forms of ophthalmic radiation therapy have also been used to treat these malignancies. The goal of radiation therapy is to eradicate the tumor burden in a manner that maintains visual function and preserves surrounding sensitive ocular tissues. Ophthalmic radiation may be used as a curative therapy, as adjuvant treatment following surgical excision, or as palliative therapy for advanced cases of eye-lid and conjunctival tumors(18). Some reports have mentioned that radiation therapy has not proved useful and generally results in the loss of the eye as a complication(17-19). However, in our experience and in the experience of others(18-20), the use of adjuvant therapy is being increased due the greater prevalence of limited (organ preservative) resections, with little, but useful, increase in survival and local control.

CoNCLuSIoNConjunctival melanomas are rare lesions showing an aggressive

local behavior. They most frequently originate from a primary acquired melanosis. Any pigmented lesion in the conjunctiva in adults should be evaluated properly in a way as to rule out melanoma. The most common location is the bulbar conjunctiva. Surgery remains the cor -nerstone of treatment, and in our study, we found some benefit from adjuvant therapy, and its usage could determine a less aggressive surgery. Five- and 10-year survival is reported as 85% and 70%, res-pectively in tumors staged as T1-T2. This figure decreases to 30% in tumors classified in higher stages.

REFERENCES 1. Yu G. Hu D, McCormick S, Finger PT. Conjunctival melanoma: is it increasing in the

United States? Am J Ophthalmol. 2003;135(6):800-6. Comment in: Am J Ophthalmol. 2003;136(6):1189-90; author reply 1190; Am J Ophthalmol. 2003;136(6):1190; author reply 1190-1.

2. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83(8):1664-78.

3. Burgués-Ceballos A, Saornil MA, García-Alvarez C, Lagarto EG. Pigmented conjuncti-val growing lesion in a teenager: nevus or melanoma? Can J Ophthalmol. 2013;48(6): e154-6.

4. Anastassiou G, Heiligenhaus A, Bechrakis N, Bader E, Bornfeld N, Steuhl KP. Prognostic value of clinical and histopathological parameters in conjunctival melanomas: a retros-pective study. Br J Ophthalmol. 2002;86(2):163-7. Comment in: Br J Ophthalmol. 2002; 86(2):127.

5. Werschnik C, Lommatzsch PK. Long-term follow-up of patients with conjunctival me lanoma. Am J Clin Oncol. 2002;25:248-55.

6. Salazar Méndez R, Baamonde Arbaiza B, de la Roz Martín P, Parra Rodríguez T. [Treatment of conjunctival melanoma]. Arch Soc Esp Oftalmol. 2012;89(2):82-4. Spanish.

7. Aronow ME, Singh AD. Radiation therapy: conjunctival and eyelid tumors. Dev Ophthal-mol. 2013;52:85-93.

8. Kurli M, Chin K, Finger PT. Whole-body 18 FDG PET/CT imaging for lymph node and metastasic staging of conjunctival melanoma. Br J Ophthalmol. 2008;92(4):479-82. Comment in: Br J Ophthalmol. 2008;92(4):443-5.

9. Grin JM, Grant-Kels JM, Grin CM, Berke A, Kels BD. Ocular melanomas and melanocytic lesions of the eye. J Am Acad Dermatol. 1998;38(5 Pt 1):716-30. Comment in: J Am Acad Dermatol. 2000;42(1 Pt 1):145.

10. Shields CL, Shields JA, Gündüz K, Cater J, Mercado GV, Gross N, et al. Conjunctival mela-noma. Risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol. 2000:118(11):1497-507. Comment in: Arch Ophthalmol. 2000; 118(11):1525-33.

11. Jakobiec FA, Rini FJ, Fraunfelder FT, Brownstein S. Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases. Ophthalmo-logy. 1988;95(8):1058-70.

12. De Potter P, Shields CL, Shields JA, Menduke H. Clinical predictive factors for develo-pment of recurrence and metastasis in conjunctival melanoma: A review of 68 cases. Br J Ophthalmol. 1993;77(10):624-30.

13. Fang ZJ, He WM. A fast growing conjunctival malignant melanoma. Chin Med J. 2013; 126(18):3593.

14. Farber M, Schutzer P, Mihm MC. Pigmented lesions of the conjunctiva. J Am Acad Dermatol. 1998;38(6 Pt 1):971-8. Comment in: J Am Acad Dermatol. 2000;42(1 Pt 1):145.

15. Char DH. Ocular melanoma. Surg Clin North Am. 2003;83(2):253-74. 16. Shildkrot Y, Wilson MW. Conjunctival melanoma: pitfalls and dilemmas in manage-

ment. Curr Opin Ophthalmol. 2010;21(5):380-6. 17. Kivelä T, Kujala E. Prognostication in eye cancer: the latest tumor, node, metastasis

clas sification and beyond. Eye (Lond). 2013;27(2):243-52. 18. Missotten GS, Keijser S, De Keizer RJ, De Wolff-Rouendaal D. Conjunctival melanoma

in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci. 2005;46(1):75-82. 19. Demirci H, Shields CL, Shields JA, Eagle RC Jr. Malignant melanoma arising from

unusual conjunctival blue nevus. Arch Ophthalmol. 2000;118(11):1581-4. 20. Damato B. Heimann H. Personalized treatment of uveal melanoma. Eye (Lond). 2013;

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Original Article

159Arq Bras Oftalmol. 2014;77(3):159-63http://dx.doi.org/10.5935/0004-2749.20140041

Static cyclotorsion measurements using the Schwind Amaris laserMedições da ciclotorção estática usando o laser Schwind Amaris

daoud c. Fahd1, eLyse Jabbour1, charbeL d. Fahed1

Submitted for publication: January 10, 2014 Accepted for publication: March 31, 2014

Study conducted at Ophthalmic Consultants of Beirut, Jal El Dib, Lebanon.1 Ophthalmic Consultants of Beirut, Jal El Dib, Lebanon.

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: Charbel D. Fahed. Chairman Department of Ophthalmology, Lebanese American University - Ophthalmic Consultants of Beirut - 20/20 Bldg, 1st floor - Jal-El-Dib, Metn, Lebanon - E-mail: fahd@ocbleb.com

INtRoduCtIoNExcimer laser ablation is an effective method for correcting errors

of refraction either by surface treatment or by applying laser under a corneal flap. Postoperative results depend on proper centration of the ablation profile on the cornea. Customized excimer laser correc-tion may enable individualized higher-order aberration correction(1). However, centration and compensation for cyclotorsion are crucial in these cases. Many patients were noted to have a cyclotorsion of their eyes when shifting from erect to supine position, with one study reporting as much as 96% of eyes having cyclotorsion(2) and a different study reporting an amount as high as 9.5°(3). Compensation for the cyclotorsion is particularly important in irregular corneas undergoing topography-guided ablation, in eyes with a significant

ABStRACt Purpose: To assess the reliability and reproducibility of static cyclotorsion correction (SCC) measurements made using the Schwind Amaris Excimer laser in patients undergoing LASIK or PRK, and compare the outcomes of treating astigmatism with and without SCC. Methods: Eighty eyes of 40 patients were included in this study. All eyes un-derwent 2 or 3 sets of five measurements: before and after speculum placement, and after flap-lift (in LASIK cases). We assessed the reproducibility, accuracy, and the percentage of “no catch” measurements. The astigmatism was calculated pre-and 3-months-postoperatively by vector analysis. Results: The mean age of the patients was 23.67 ± 4.19 years. Preoperative spherical equivalent and astigmatism were -2.56 ± 2.86 D and +1.36 ± 0.98 D, respectively. The mean measurement time was 15.1 seconds per measurement. The percentages of “no catch” were: 63.8%, 14.9%, and 26.9%; pre-speculum, post-speculum, and post flap-lift, respectively. Cyclotorsion of ≥±2° was seen in 41.25% and 66% of the cases before and after the flap-lift, respectively. Significant cyclotorsion (≥±5°) was seen in 12.50% and 18% of the eyes pre and post flap-lift. The mean as tigma-tism dropped from +1.53 D@1° to +0.34D@3° when SCC was used and from +1.86D@1° to +0.23D@7° when SCC was not used. No statistical difference was noticed between the groups (p>0.05) in the postoperative residual astigmatism. A postoperative astigmatism of ≥1 D was seen in 10% and 20% of eyes with and without SCC, respectively (p<0.01).Conclusion: Although not always feasible, the SCC measurement is a simple and useful tool. Postoperative astigmatism showed less variability when SCC was used.

Keywords: Astigmatism/physiopathology; Astigmatism/surgery; Torsion abnor-mality; Keratomileusis, laser in situ; Posture; Photorefractive keratectomy/methods; Visual acuity

RESUMOObjetivo: Avaliar a confiabilidade e reprodutibilidade da correção da medida de ciclotorção estática (SCC), realizada com o excimer laser Schwind Amaris em pacientes submetidos a LASIK ou PRK, e comparar os resultados do tratamento de astigmatismo com e sem SCC.Método: Oitenta olhos (40 pacientes). Todos os olhos foram submetidos a 2 ou 3 séries de 5 medições: antes e após a colocação do espéculo, e depois do levantamento do flap (nos casos de LASIK). Foram avaliadas a reprodutibilidade, a precisão e a porcentagem de medições “não obtidas”. O astigmatismo foi avaliado no pré-operatório e aos 3 meses de pós-operatório, por meio de análise vetorial.Resultados: A idade foi 23,67 ± 4,19 anos. O equivalente esférico e o astigmatismo pré-operatórios foram -2,56 ± 2,86 D, e 1,36 ± 0,98 D, respectivamente. O tempo de medição médio foi 15,1 segundos por medição; as porcentagens de medidas “não obtidas” foram: 63,8%, 14,9% e 26,9%; pré, pós-espéculo, e pós-levantamento do flap, respectivamente. Ciclotorção ≥±2° foi observada em 41,25% e 66 % dos casos pré e pós-levantamento do flap. Ciclotorção significativa (≥±5°) foi observada em 12,50% e 18% pré e pós-levantamento do flap. A média do astigmatismo diminuiu de 1,53D @ 1° para 0,34D @ 3° quando SCC foi usado e de 1,86D @ 1° a 0,23D @7° quando SCC não foi usado. O astigmatismo residual pós-operatório não foi estatisticamente diferente entre os grupos (p>0,05). O astigmatismo pós-operatório ≥1D foi observado em 10% e 20 % dos olhos com e sem SCC, respectivamente (p<0,01). Conclusão: A medição do SCC é fácil e útil, apesar de nem sempre ser possível nem viável. O astigmatismo pós-operatório apresentou menor variabilidade quando a SCC foi usada.

Descritores: Astigmatismo/fisiopatologia; Astigmatismo/cirurgia; Anormalidade torcional; Ceratomileuse assistida por excimer laser in situ; Postura; Ceratectomia fo torrefrativa/métodos; Acuidade visual

cy lindrical component, or when a wavefront-guided treatment is de sired. Not all laser platforms are able to automatically correct for the cyclotorsion(4,5). The Schwind Excimer Laser Platform takes eye movements into account and compensates before and during the excimer treatment.

Previous reports have described the effect of centration and cyclotorsion correction on postoperative cylinder and uncorrected visual acuity (UDVA) in eyes with spherocylindrical errors of refrac-tion(1,2,6,7). Here we report the efficacy, reliability, and reproducibility of Static Cyclotorsion Correction (SCC) measurement using the Schwind Amaris excimer laser in eyes undergoing LASIK or t-PRK refractive surgery. We also report the time taken for cyclotorsion measurements and compare the results of treating astigmatism with and without SCC.

Static cyclotorsion measurements using the Schwind Amaris laser

160 Arq Bras Oftalmol. 2014;77(3):159-63

MEtHodSThis is a prospective study conducted on 80 eyes of 40 patients

operated in the Ophthalmic Consultants of Beirut, Jal el Dib, Lebanon between the months of May and July of the year 2012. The study was approved by the institutional review board and the ethics committee of the Ophthalmic Consultants of Beirut. This study adhered to the Declarations of Helsinki.

preoperative teSting

Patients wearing soft contact lens were asked to remove their lenses for at least two weeks prior to performing the topography. Pa-tients wearing hard contact lens were not included in this study. The preoperative screening consisted of a complete ophthalmic workup, including UDVA, corrected distance visual acuity (CDVA), manifest re fraction, ocular motility, and a full slit lamp examination, which in c luded a dilated fundus examination. Patients also underwent a cor neal wavefront analysis using the Keratron Scout Optikon 2000 Cor neal Wavefront Analyzer (Optikon 2000 S.p.A., Rome, Italy), an ocular wavefront measurement using the Ocular Wavefront Analyzer (Schwind Eye-Tech Solutions, GmbH, Kleinostheim, Germany), and a Placido-Scheimpflug topography using the Orbscan IIZ (Bausch and Lomb, Rochester, NY). Images used for comparisons of SCC were obtained using the Keratron analyzer. For imaging, the patient was asked to sit erect and the head was adjusted to be straight. The head was positioned such that the vertical axis of the nose was perpendi-cular to the chin rest. The patient was also asked to look at the fixation light positioned at the center of the machine with their eyes open. No speculum or digital lid opening was performed. An experienced optometrist made all measurements. At least 3 measurements were made, which were used for assessing the reproducibility using a re-producibility curve. Only the best measurements were used in later analyses. Pupil centroid shift was recorded and the laser system was compensated for only when the shift was >0.2 mm in magnitude.

All the details of the study including the surgical procedures were explained to the patients in detail. An oral informed consent for measurements and surgery was obtained prior to making the mea-surements.

SurgiCal teChnique and meaSurementS

All procedures were performed by one surgeon (SF) at the same surgical center using a single excimer laser (Schwind Amaris 500 Ex cimer laser, Schwind Eye-Tech Solutions, GmbH, Kleinostheim, Ger many). Both eyes were operated using the same settings. Patients were given 5 mg of diazepam (Valium®) orally 30-40 minutes before the start of the surgery. One drop of propacaine (Novocain®) and one drop of ofloxacin (Oflox®, Allergan) were applied to both eyes on three occasions, each separated by 2 minute-intervals. The patients were asked to lay flat on the laser table and measurements were first made on the right eye. The fellow eye was occluded. Before each measurement, the patient was asked to look at the blinking fixation light and the head was adjusted to eliminate any possible head tilt, with the vertical axis of the nose aligning with the sagittal plane of the body. Care was taken to ensure that the shoulders were lying equally flat on the table. The centration lights of the laser were used on the glabella to ensure that the head was properly positioned (Figure 1, additional video showing the effect of head rotation on the centra-tion lights can be seen online). The eyes were scrubbed and draped. A closed-loop speculum with suction was used. The amount of SCC and the number of “no-catch” trials were recorded before the speculum was placed, after the speculum was placed, and after the flap was lifted (in LASIK eyes). When performing t-PRK (30 eyes, 37.5%), a third set of measurements was not taken and the laser was directly applied to the virgin cornea.

The cornea of the eyes that were to undergo LASIK (50 eyes, 62.5%) was marked and washed with BSS. The suction ring was applied and maintained until the pressure on the console reached

a value between 600 and 630 mmHg. The flap was done using the Schwind pendular microkeratome with hinges placed superiorly. The flap was reflected superiorly along its hinge. Patient position was examined and adjusted as described earlier, and a third set of 5-SCC measurements was recorded. Following this, laser ablation was applied. Intraoperative Dynamic Cyclotorsion Control (DCC) was used in all cases.

All patients received the routine postoperative treatment regi-men and follow-up, including steroid, artificial tears, and antibiotic drops for the first week, a steroid taper for one month, and artificial tears for at least 3 months(8). Astigmatism (manifest and cycloplegic cy linder) was measured preoperatively and at 3 months postopera-tively. We assessed the postoperative astigmatism and the effect of SCC compensation in the eyes that underwent LASIK.

variableS aSSeSSed and StatiStiCal analySiS

We noted the number of times when SCC could not be measured (percentage “no catch”). The percentage of registration was calcula-ted as, (Eyes in which measurements were successful/Total number of eyes) x 100%. We recorded the amount of cyclotorsion and subcatego-rized SCC into those with a negative value (counter-clockwise) and those with a positive value (clockwise). Time taken for completing the measurement was also recorded from the moment the “measure” button was pressed on the screen to the time the result was displayed on the screen.

Reproducibility, as indicated by the standard deviation and the accuracy of the measurements were compared. Astigmatism analy-sis was performed using the polar method of vector analysis(9) with cycloplegic cylinder values compared. The paired Student t-test was used for statistical analysis. A p-value less than 0.05 was considered statistically significant.

RESuLtSdemographiCS

This study included 80 eyes of 40 patients with mild to moderate errors of refraction. Thirty eyes (37.5%) underwent t-PRK, and 50 eyes

Figure 1. Adjustment of head positioning using the centration lights of the excimer laser on the glabella. A) Patient position on the excimer laser table: shoulders lying flat on the bed and head facing straight at the fixation light. The axis of the nose is aligned with the sagittal axis of the body. Three line­lights are brought into focus and proper superposition as in C). When the chin is tilted excessively down or up, the lights shows pattern B) or D), respectively.

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(62.5%) underwent LASIK. The mean age of patients was 23.67 ± 4.19 years. Of the 40 patients, 21 were males (52.5%). The mean preopera-tive sphere was -3.06 ± 2.82 D (-7.25 D to +4.25 D) with a preoperative cylinder of +1.36 ± 0.98 D (+0.25 D to +3.00 D). The mean preope-rative spherical equivalent (SE) was -2.56 ± 2.86 D. All eyes had a preoperative CDVA equal to or better than 20/20.

ability to meaSure SCCWe were unable to measure SCC in 30 eyes (37.5%) before the

spe culum was placed, in 7 eyes (8.8%) after the speculum was in-serted, and in 6 eyes (12.0% eyes that underwent LASIK) after the flap was lifted. In 2 eyes (4.0%) that were to undergo LASIK, the SCC measurement was not successful after lifting the flap (no-catch in 5 con secutive measurements). However, the measurement could be made before and after the speculum placement.

The percentage of registration was 62.5% pre-speculum, 91.2% after placing the speculum, and 88.0% after lifting the flap. The per -centage of “no catch” in the total number of measurements was 63.8%, 14.9%, and 26.9% pre-and post-speculum placement, and post-flap lift, respectively.

The mean time taken per SCC measurement was 15.1 ± 2.7 se-conds (range was 9.0 to 25.0 seconds). The mean time taken for 5 consecutive measurements was 3.6 ± 0.7 minutes (range was 2.0 to 5.5 minutes).

The mean standard deviation between the 5 successive measu-rements was 2.33° before speculum placement, 1.83° after speculum placement, and 1.96° after flap lift.

the effeCt of the SpeCulum on SCC meaSurement In the eyes with a counter-clockwise rotation, the mean SCC was

-4.3° and -3.2° pre-, and post-speculum, respectively (p=0.304), whereas in the eyes with a clockwise rotation, the mean SCC was +4.3° and +4.9° pre-, and post-speculum, respectively (p=0.706).

Before placing the speculum, 11 measurements showed an SCC of 0° (3.3%), 79 measurements (23.6%) showed an SCC of >±2°, and 36 measurements (10.8%) had an SCC of >±5°. After averaging the 5 measurements for each eye, 6 eyes (15.0%) were found to have no cyclotorsion, 35 eyes (43.8%) had a cyclotorsion of >±2°, and 14 eyes (17.5%) had a cyclotorsion of >±5°.

After placing the speculum, 34 measurements showed an SCC of 0° (10.3%), 151 measurements (45.8%) showed an SCC of >±2°, and 88 measurements (26.7%) showed >±5° SCC. After averaging the 5 measurements for each eye, 4 eyes (5.0%) had no cyclotorsion, 33 eyes (41.2%) had a cyclotorsion of >±2°, and 10 eyes (12.5%) had a cyclotorsion >±5°. Table 1 shows the distribution of SCC measure-ments based on the amount of cyclotorsion. Figure 2 shows the effect of the speculum on the SCC measurements. The Bland-Altman plot shows the difference between measurements made before and after inserting the speculum. The difference was statistically significant and was more pronounced when SCC was >2°.

the effeCt of the flap lift on SCC meaSurement In the eyes that had a counterclockwise rotation, the mean SCC was

-3.2° before lifting the flap and -2.8° after lifting the flap (p=0.138), whereas in the eyes that had a clockwise rotation, the mean SCC was +4.9° before the flap was lifted and +2.0° after lifting the flap (p=0.203).

Before lifting the flap, 34 measurements (10.3%) showed an SCC of 0°, 151 measurements (45.8%) showed >±2° SCC, and 88 mea -surements (26.7%) had an SCC of >±5°. After averaging the 5 mea-surements for each eye, 4 eyes (5.0%) showed no cyclotorsion, 33 eyes (41.2%) had a cyclotorsion of >±2°, and 10 eyes (12.5%) had a cyclotorsion of >±5°.

After the flap was lifted, 15 measurements (9.4%) showed an SCC of 0°, 71 measurements (44.4%) showed >±2° SCC, and 25 mea -su rements (15.6%) showed an SCC of >±5°. After averaging the 5 measurements for each eye, 3 eyes (6.0%) showed no cyclotorsion, 33 eyes (66.0%) had a cyclotorsion of >±2°, and 9 eyes (18.0%) had a cyclotorsion of >±5°. Figure 3 shows the Bland-Altman plot of the difference between the measurements made before and after lifting the flap. The difference was statistically significant and was more pro-nounced when SCC was >2°. Figure 4 shows the Bland-Altman plot of the difference in the measurements made before the speculum

table 1. distribution of static cyclotorsion correction (SCC) measurements based on the amount measured, at each time-point

Amount time-point %

0 ➡ |2|° Pre-speculum 33.87%

Post-speculum 46.15%

Post-flap lift 38.30%

|2.01| ➡ |5|° Pre-Speculum 37.30%

Post-Speculum 22.12%

Post-Flap Lift 38.40%

>±5.01° Pre-Speculum 29.00%

Post-Speculum 31.73%

Post-Flap Lift 22.30%

Figure 2. Bland­Altman plot of mean static cyclotorsion correction (SCC) measurements pre­speculum placement versus the difference in the mean SCC measurements pre­ and post­speculum placement.

Figure 3. Bland­Altman plot of mean static cyclotorsion correction (SCC) measurements pre­flap lift versus the difference in the mean SCC measurements pre­and post­flap lift.

Static cyclotorsion measurements using the Schwind Amaris laser

162 Arq Bras Oftalmol. 2014;77(3):159-63

placement and after lifting the flap in the eyes that underwent LASIK surgery. There was no statistical significance between the first and the last set of measurements.

Study of aStigmatiSm CorreCtion

Among the eyes that had a cylinder between +1.00 D and +2.00 D (40 eyes), those in which SCC measurement was successful (20 eyes) were compared to 20 matched eyes that underwent LASIK in which SCC measurement was not possible. The eyes in which SCC measu-rement was successful had a preoperative cylinder of +1.53 D@1° as com pared to a value of +1.86 D@-1° when SCC was not used (p=0.865). After 3 months of surgery, the mean cylinder became +0.34 D@3° in the eyes where SCC was used and +0.23 D@7° in the eyes where SCC was not used (p=0.611). Both preoperative and postoperative cylin-ders did not show any statistically significant differences between the groups (p>0.05). Postoperatively, 10% of the eyes had a cylinder ≥1D when SCC was used and 20% when SCC was not used (p<0.001).

dISCuSSIoNThe SCC measurement on the Schwind Custom Ablation Mana-

ger (CAM) platform is based on an algorithm that registers landmarks and patterns on the iris and limbus. These landmarks taken from the topography image are recognized by the cameras of the laser system. The resultant angular difference between the images is recor-ded as the SCC. In the Schwind Amaris Excimer laser platform, the measurement starts from the center of the iris and rotates spirally, recognizing and registering points on the iris as it rotates. To the best of our knowledge, this is the first study that assessed the accuracy and reliability of SCC measurements made using the Schwind CAM platform. The ablation profile is adjusted to compensate the measu-red cyclotorsion.

Cyclotorsion can be due to many causes: i) positional (the eyes cyclorotate when the patient assumes a supine position), ii) secondary to head tilt (thus assuring a correct position on the laser bed is crucial), iii) unmasking of a cyclophoria (patients had a motility assessment preo peratively) following monocular occlusion(6,7), or iv) secondary to distortion of the globe by the speculum. Compensating for the in -duced cyclotorsion as a result of assuming a supine position leads to better results of astigmatism correction(10-12). Although cylinder values of >1 D were not common, we found that this difference was neither sta tistically nor clinically significant in postoperative cylinder.

It has been reported that the percentage of eyes with “no catch” varies between 5 to 10%(10,13,14). We found that the percentage of “no catch” dropped when the speculum was placed. This was expected

since more of the limbus will be exposed when a lid-speculum is placed and blinking is abolished. SCC registration after lifting the flap diminished because the image of the iris is less recognizable due to the stromal dryness.

The mean standard deviation between the 5 successive measu-rements was 2.3° before speculum placement, 1.8° after speculum placement, and 2.0° after the flap was lifted. Many practitioners opt to measure SCC only once before deciding whether or not to compensate for the SCC while operating. The Schwind Excimer laser software does not store repeated measurements and only allows re-measurements if the surgeon suspects the SCC value. Therefore, it is not possible to have an average of multiple consecutive measu-rements or to revert to a previously determined value. Additionally, although we rehydrated all corneas initially and after the second set of measurements, the measurement time was long, leading to increa-sed corneal desiccation. The time taken for the SCC measurement could be shortened by the use of a Sirius Schwind (Schwind Eye-Tech Solutions, GmbH, Kleinostheim, Germany) instrument (discussion with company representative).

The variation between the measurements likely originated from various factors-the ocular surface dries out easily when the eye is left open by the speculum (since blinking is suppressed) and the time taken for repeated measurements is relatively long. Additionally, many of the eyes were found to “wiggle and jiggle” before stabilizing.

If the laser system stored data from successive measurements, the surgeon will be able to verify the reproducibility and calculate a weighted average that can be used for customization. Additionally, faster measurements would lead to less corneal dryness and increase the yield of measurements. For custom treatments this becomes a necessity, particularly since rotational malposition can be high(15).

One limitation of this study is that the follow-up was done at 3 months postoperatively. A second limitation is that the precise assessment of the “wiggle and jiggle” that some patients experience during the course of the procedure was not possible since the laser system was not equipped for the continuous video-monitoring of the eye movement.

CoNCLuSIoNAlthough the SCC measurement is a simple and straightforward

ma neuver, the measurement is not always possible. There was no statistically significant difference between the measurements made pre-and post-speculum placement, and post-flap lift. When the cylinder was significant, the residual astigmatism correction was better when SCC was used.

REFERENCES 1. Netto MV, Dupps W, Jr., Wilson SE. Wavefront-guided ablation: evidence for efficacy

compared to traditional ablation. Am J Ophthalmol. 2006;141(2):360-68. 2. Ciccio AE, Durrie DS, Stahl JE, Schwendeman F. Ocular cyclotorsion during customi-

zed laser ablation. J Refract Surg. 2005;21(6):S772-4. 3. Chernyak DA. Cyclotorsional eye motion occurring between wavefront measure-

ment and refractive surgery. J Cataract Refract Surg.2004;30(3):633-8. 4. Chen X, Stojanovic A, Stojanovic F, Eidet JR, Raeder S, Oritsland H, et al. Effect of limbal

marking prior to laser ablation on the magnitude of cyclotorsional error. J Refract Surg. 2012;28(5):358-62. Erratum in: J Refract Surg. 2012;28(7):449.

5. Shen EP, Chen WL, Hu FR. Manual limbal markings versus iris-registration software for correction of myopic astigmatism by laser in situ keratomileusis. J Cataract Refract Surg. 2010;36(3):431-6.

6. Chang J. Cyclotorsion during laser in situ keratomileusis. J Cataract Refract Surg. 2008; 34(10):1720-6.

7. Tjon-Fo-Sang MJ, de Faber JT, Kingma C, Beekhuis WH. Cyclotorsion: a possible cause of residual astigmatism in refractive surgery. J Cataract Refract Surg. 2002;28(4):599-602.

8. Fadlallah A, Fahed D, Khalil K, Dunia I, Menassa J, El Rami H, et al. Transepithelial pho-torefractive keratectomy: clinical results. J Cataract Refract Surg. 2011;37(10):1852-7.

9. Alpins N. Astigmatism analysis by the Alpins method. J Cataract Refract Surg. 2001; 27(1):31-49.

10. Febbraro JL, Koch DD, Khan HN, Saad A, Gatinel D. Detection of static cyclotorsion and compensation for dynamic cyclotorsion in laser in situ keratomileusis. J Cataract Refract Surg. 2010;36(10):1718-23.

Figure 4. Bland­Altman plot of mean static cyclotorsion correction (SCC) measurements pre­speculum placement versus the difference in the mean SCC measurements pre­specu­lum placement and post­flap lift.

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I Simpósio de Atualização em oftalmologia do CERoF/uFG

21 e 22 de novembro de 2014Sede do Conselho Regional de Medicina de Goiás

Goiânia - GO

informações: Tels.: (62) 3928-1416 / 9614-7922

E-mail: congressos@brturbo.com.br

11. Prakash G, Agarwal A, Ashok Kumar D, Jacob S, Agarwal A. Comparison of laser in situ keratomileusis for myopic astigmatism without iris registration, with iris registration, and with iris registration-assisted dynamic rotational eye tracking. J Cataract Refract Surg. 2011;37(3):574-81.

12. Prakash G, Agarwal A, Kumar DA, Jacob S, Agarwal A, Maity A. Surface ablation with iris recognition and dynamic rotational eye tracking-based tissue saving treatment with the Technolas 217z excimer laser. J Refract Surg. 2011;27(3):223-31.

13. Arba-Mosquera S, Arbelaez MC. Three-month clinical outcomes with static and dyna-mic cyclotorsion correction using the SCHWIND AMARIS. Cornea. 2011;30(9):951-7.

14. Aslanides IM, Toliou G, Padroni S, Arba Mosquera S, Kolli S. The effect of static cyclo torsion compensation on refractive and visual outcomes using the Schwind Amaris laser platform for the correction of high astigmatism. Cont Lens Anterior Eye. 2011;34(3):114-20.

15. Swami AU, Steinert RF, Osborne WE, White AA. Rotational malposition during laser in situ keratomileusis. Am J Ophthalmol. 2002;133(4):561-2.

Original Article

164 Arq Bras Oftalmol. 2014;77(3):164-7 http://dx.doi.org/10.5935/0004-2749.20140042

INtRoduCtIoNThe World Health Organization (WHO) recently estimated that over

280 million of the global population is visually impaired and 39 million of them are blind. Eighty-two percent of the blind and 65% of the visually impaired are aged 50 and above(1). In Americas, approximately 3.2 million people are blind and 26.6 million people are visually im-paired(2).

Cataract is responsible for 33% of the visual impairment worldwi-de and is the single most important cause of blindness affecting 51% of the global population. Surveys in Latin America and the Caribbean show that cataract is the leading cause of blindness and visual impair-ment, with 47%-87% of individuals bilaterally blinded(3,4).

The cataract surgical rate (CSR), the number of cataract operations performed per year per million population, though is often associated

with the socio-economic development of the country, this is not always true, especially in countries such as India and China(5-7). Across Latin America, the CSR ranges from approximately 900-6,000, with an average of 2,672(8).

Despite significant developments in the region, unless the regio-nal CSR increases considerably, the VISION 2020 goal of eliminating avoidable vision loss by cataract will not be met. In developed coun-tries in the region,the visual impairment due to cataract is not a major issue; however, for developing countries in the region increasing CSRs remains a challenge due to several factors such as affordability, place of residence, and difficult-to-reach communities with poor access to information and services(5). Surgical fees are often reported as barrier to undergo cataract surgery(9). However, some studies have suggested that fear of surgery and a low perceived need for better

Is the cost the primary barrier for cataract surgery in Paraguay?A taxa para a cirurgia é a principal barreira para a adesão à cirurgia de catarata no Paraguai?

haruMI G. burGa1, ceLeste n. hInds1, van c. LansInGh1,2, MarGarIta saMudIo3, susan LewaLLen4,5, PauL courtrIGht4,5, raInaLd duerksen1, PabLo cIbILs1, ManueL zeGarra1

Submitted for publication: January 20, 2014 Accepted for publication: May 1, 2014

Study conducted at Rapid Assessment of Avoidable Blindness (RAAB).1 Fundación Visión, Asunción, Paraguay.2 IAPB/VISION 2020 Latina America Regional Office.3 National University of Asunción, Asunción, Paraguay.4 Kilimanjaro Centre for Community Ophthalmology, Moshi, Tanzania.5 Kilimanjaro Centre for Community Ophthalmology, Division of Ophthalmology, University of Cape

Town, Cape Town, South Africa.

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: Harumi G Burga. Quartier Las Marías 5-108. San Lorenzo - Paraguay - E-mail: harumibk@hotmail.com

ABStRACtPurpose: To determine if the cost was the main barrier to undergo cataract sur-gery in Paraguay. Methods: We conducted a cohort study with patients screened in the 2011 Rapid Assessment of Avoidable Blindness (RAAB) who had reported that the cost was the main barrier to undergo cataract surgery in Paraguay. All patients with ope-rable cataract from the RAAB study and with registered telephone numbers were interviewed by telephone and were offered free surgery services. The patients who did not come for surgery were re-interviewed by telephone to analyze the reasons for not undergoing the operation.Results: Out of 122 patients identified in the RAAB study with barriers for cataract surgery, 69 (56.6%) reported that the surgical fee was the main barrier; 52 (75.4%) of them had their telephone numbers registered. Thirty-six (69.2%) patients did not reside in the metropolitan area of Asunción. Six patients (12%), all from Asunción, agreed to undergo free surgery. Forty-six patients did not agree the free surgery mainly due to the costs associated with their transportation (n=31, 67%) and the travel costs of their companion (n=6, 13%).Conclusion: Surgery fee alone was not the major contributing factor for not un-dergoing cataract surgery. Place of residence and other indirect out-of-pocket expenses, such as transportation and companion-related costs appear to be more relevant. While further investigation is needed to assess if reducing the cost of transport will improve the uptake, the findings in this study suggest that a surgical package with all costs should be offered to patients of cataract surgical programs to increase cataract surgical coverage in Paraguay.

Keywords: Cataract extraction/statistics and numerical data; Costs and cost analysis; Health services accessibility; Paraguay

RESUMOObjetivo: Determinar se a taxa de cirurgia é a principal barreira para a adesão à cirurgia de catarata no Paraguai. Métodos: Foi realizado um estudo de coorte com pacientes identificados na Avaliação Rápida da Cegueira Evitável (RAAB) de 2011, que haviam informado ser a taxa para a cirurgia a principal barreira para se submeter à cirurgia de catarata no Paraguai. Todos os pacientes com catarata operável a partir do estudo RAAB, cujos números de telefone foram registrados, foram entrevistados por telefone e foi oferecida a cirurgia gratuitamente. Aqueles pacientes que não compareceram para a cirurgia foram então re-entrevistados por telefone para confirmar as suas razões para não fazer a cirurgia. Resultados: Das 122 pessoas identificadas no estudo RAAB com barreiras para a cirur-gia de catarata, 69 (56,6%) relataram a taxa cirúrgica como a principal barreira para a cirurgia; 52 (75,4%) destes indivíduos tiveram seus números de telefone registrados. Trinta e seis (69,2%) pacientes não residiam na área metropolitana de Assunção. Seis pacientes (12%) aceitaram se submeter à cirurgia gratuita, todos eles de Assunção. Dos 46 pacientes que não aceitaram a cirurgia gratuita, as duas principais razões para o não comparecimento foi o custo de transporte (n=31, 67%) e os custos de viagem de seu companheiro (n=6, 13%). Conclusão: A taxa de cirurgia de catarata per se não foi a barreira principal. Local de residência e outras despesas pessoais indiretas, como transporte e custos relacionados à companhia parecem ser mais relevantes. Embora mais estudos sejam necessários para avaliar se a redução do custo do transporte vai melhorar a adesão, os resultados sugerem que um pacote cirúrgico que inclua todos os custos deve ser oferecido aos pacientes dos programas de cirurgia de catarata a fim de aumentar a cobertura da cirurgia de catarata no Paraguai.

Descritores: Extração de catarata/estatística & dados numéricos; Custos e análise de custos; Acesso aos serviços de saúde; Paraguai

Burga HG, et al.

165Arq Bras Oftalmol. 2014;77(3):164-7

sight contribute more significantly. Even when free surgical services are offered, there can be a lack of demand and low utilization(9-11).

In 2011, a Rapid Assessment of Avoidable Blindness (RAAB) survey was conducted in Paraguay to follow up the RAACS (Rapid Assessment of Cataract Surgical Services) survey conducted in 2000. The RAAB survey showed that cataract was the main cause of blindness (43.8%) and severe visual impairment (40.5%). The results of the study indica-ted an impressive reduction in the prevalence of blindness from 3.0% to 1.1% among the people of age 50 years and above; cataract surgi-cal coverage (at<6/60) increased from 36% to 78% and good quality outcomes of cataract surgeries increased from 64% to 90%(12,13). These results suggest that cataract is now better managed in Paraguay.

We sought to determine if the fee is the main barrier to undertake cataract surgery in Paraguay.

MEtHodSIn October and November, 2011, a Rapid Assessment of Avoidable

Blindness (RAAB) national survey was undertaken in Paraguay(12). The RAAB study was conducted by five third year ophthalmology resi-dents, supervised by a senior ophthalmologist. All patients identified in the RAAB with a visual acuity (VA) <6/18 attributed to cataract in one or both eyes and judged to have an operable cataract. The pa tients, who reported that surgical fee was the main barrier to undergo cataract surgery, were selected for the study. Patients with incomplete forms, (n=13) and those who refused to respond to the questionnaire (n=4) were excluded from the study.

All patients were contacted by phone by a trained social worker. The questionnaire was designed to investigate if the fee for cataract surgery was a barrier to undergo the surgery. Questions were asked to reconfirm demographic data, the indication of cataract surgery, and the issues regarding fees. As part of the study protocol, the social worker then offered the patient cataract surgery free of charge. The free surgeries were to be conducted during the cataract surgical cam-paign in Fundación Vision’s central clinic located in Asunción, Paraguay and were scheduled to take place within the next two weeks following the interview. Transportation costs to and from their residence and accommodation were not provided with the free cataract surgery.

One week after the end of the surgical campaign the patients who did not attend the free surgery were contacted and re-inter-viewed by telephone to establish the reasons for failure to attend. An open ended quasi-structured questionnaire was used to solicit the responses.

We first analyzed the differences between the people with and without phone numbers. We next determined the proportion of tho se who took advantage of the free surgery service (and factors

associated with acceptance). Finally, we assessed the reasons to opt out of the free surgery service. Comparisons were made based on sex, age, province, and pre-operative VA. Data were entered in an Excel 6.0 spreadsheet and subsequently analyzed by SPSS 11.5 (Chicago, IL) for Windows. Descriptive statistics for socio-demographic characteristics and causes of nonattendance to cataract surgery nominal variables were expressed as percentage.

The study was approved by the Investigation and the Medical Ethics Committee of Fundación Vision, and was performed in accor-dance with the ethical standards laid down in the 1964 Declaration of Helsinki. All patients signed a consent form prior to their inclusion in the RAAB.

RESuLtSFrom the RAAB survey, among the 2,862 persons studied, 54 pe-

ople had a bilateral cataract surgery and 75 people had undergone unilateral cataract surgery. For this study, 122 people had operable cataract with presenting vision of <6/18 in one or both eyes and qua-lified the study parameters. The study population included 4 people who underwent a cataract surgery in one eye and visually impairing cataract in the other eye. Among the 122 people, 69 (56.6%) reported that the fee for surgery was the main barrier to undergo cataract surgery. Other reasons included, fear (n=22), lack of desire to have surgery (n=9), difficulty accessing surgical facilities (n=7), and other reasons (n=15). Of the 69 people, 52 (75.4%) had a valid registered telephone number. Of these, 37 (63.45) had unilateral cataract with normal vision or vision loss due to other conditions such as refractive error in the other eye. People with registered phone numbers were slightly younger than those without phone numbers (Table 1).

After the phone interviews surgical campaign was conducted for two weeks and offered free cataract surgery to the patients; only 6 out of the 52 people enrolled in the study (12%) attended the clinic in Asunción for surgery and all were from the metropolitan area of Asunción (Table 2).

The people who did not take advantage of the free cataract sur-gery were contacted by telephone after one week after the surgical campaign. While 31 people (67%) had reported that the cost of trans-portation was the reason for not coming for the surgery, 6 people (13%) reported that the cost of transportation of their companion was the reason. Nine people (20%) mentioned other causes such as difficulty traveling, other medical conditions, or poor weather condi-tions. Although the numbers are small, uptake was highest among those who underwent a previous cataract surgery (50% uptake), followed by those who had bilateral cataracts, (3/19) and finally those with unilateral cataract (1/28).

Patient characteristicstelephone number registered (n=52)

N (%)No telephone number (n=17)

N (%)odds ratio (95% CI)

p value

Average age (SD) 71.6 ± 11.0 78.8 ± 8.9 p=0.02

Sex

Males 22 (42.3) 09 (52.9) 0.65 (0.22-1.96)

Females 30 (57.7) 08 (47.1) p=0.62

Residence

Metropolitan 16 (30.8) 05 (29.4) 1.07 (0.32-3.53)

Outside metro 36 (69.2) 12 (70.6) p=0.84

Visual acuity of eye to be operated

6/18 32 (61.5) 10 (58.8) 1.0 (reference)

<6/18 to 6/60 13 (25.0) 04 (23.5) 1.02 (0.27-3.83)

<6/60 to 3/60 04 (07.7) 01 (05.9) 0.73 (0.07-3.21)

<3/60 03 (05.7) 02 (11.7)

*= odds ratio includes <6/60 to 3/60 and <3/60.

Is the cost the primary barrier for cataract surgery in Paraguay?

166 Arq Bras Oftalmol. 2014;77(3):164-7

dISCuSSIoNIn most cases one can infer that free surgery would provide increa-

se access to patients who would not otherwise consider it; however, there are always other complex factors involved in the decision to undergo cataract surgery(14,15).

Lack of awareness, poor quality service, cost of surgery and cultu-ral beliefs, distance to service, lack of escort, and fear are some of ma-jor barriers between cataract patients and service providers resulting in a low uptake in the presence of adequate service availability(15,16).

There were slightly more women in our study compared to men; however, this reflects the underlying prevalence of cataract in the population. The average age of people accepting the surgery was slightly younger than those not accepting the surgery, consistent with studies in other settings(17).

The most important factor toward acceptance was residence; while one in three cataract patients living in Asunción accepted sur-gery, none of those living outside of Asunción traveled to the capital for surgery.

Some studies reported that the surgical fee is the single most im-portant barrier to cataract surgery uptake(18, 19). If surgical fee is above the affordable limits of the individual or family, this can be a significant barrier. However, it should be recognized that families make financial decisions regarding surgery based upon the total anticipated costs

associated with the surgery. Besides the surgical fee, these costs include additional medications, transport to and from the surgical facility, food at the surgical facility, transport and accommodation expenses of the escort, and loss of income during the surgery and recovery(6,19-21).

In our setting the offer to waive the fee for the surgery (approxima-tely PGY1, 500,000 /US$334) (not including transportation, accommo-dation or medication) resulted in a low uptake (12%), only comprising those living in the same metropolitan area as the surgical facility. Further only one-third of the population living in the city accepted the surgery.

Our results are consistent with findings from Kenya, Bangladesh, and the Philippines(22), where free cataract surgery was offered and only 30% of cases attended. In Nepal, where both transportation and free surgery were offered, the utilization rate was still below 60%(23). Similarly, in Tanzania when surgery and transportation services were offered to those reporting the surgical fee as the primary barrier to surgery, only a small proportion had accepted(14). In the Tanzanian setting it was recognized that reporting “too poor to pay” was a conve-nient response that did not actually reflect reality. While our findings are similar to the Tanzanian study, since free transport was not offered in Paraguay it cannot be claimed that offer of free transport would increase the uptake of surgery. The average cost of transportation

table 2. Characteristics of people with cataract who attended the free cataract program

CharacteristicAttended free cataract surgery n=6

N (%)did not attend free cataract surgery n=46

N (%)odds ratio (95% CI)

p value

Sex

Females 4 (13.8) 25 (086.2) 1.68 (0.28-10.10)

Males 2 (09.0) 21 (091.0) p=0.89

Age*

50-59 years 0 (00.0) 09 (100.0) 1.0 (reference)

60-69 years 1 (11.1) 08 (088.9) 2.22 (0.17-28.86)

70-79 years 3 (12.0) 22 (088.0) 1.74 (0.17-17.59)

80-89 years 2 (40.0) 03 (060.0) 7.50 (0.59-95.38)

≥90 years 0 (00.0) 04 (100.0) 2.00 (0.10-39.08)

Average age (SD) 69.8 (±11.1) 72.0 (±11.0) p=0.22

Residence*

Metropolitan 6 (37.5) 10 (062.5) 23.55 (2.61-212.67)

Outside metro 0 (00.0) 36 (100.0) p=0.001

Visual acuity of eye to be operated

6/18+ 2 (33.3) 30 (065.2) 1.0 (reference)

<6/18 to 6/60 3 (50.0) 10 (021.7) 4.50 (0.66-30.91)

<6/60 to 3/60 1 (16.6) 03 (006.5) 2.50 (0.19-32.20)**

<3/60 0 (00.0) 03 (006.5)

Visual acuity in the better eye*

6/18+ 4 (66.6) 11 (023.9) 1.0 (reference)

<6/18 to 6/60 2 (33.3) 21 (045.6) 0.26 (0.04-1.66)

<6/60 to 3/60 0 (00.0) 08 (017.3) 0.16 (0.02-1.56)**

<3/60 0 (00.0) 06 (013.0)

Previous cataract surgery

No cataract surgery received (unilateral cataract)

1 (16.6) 28 (060.8) (reference)

Cataract surgery in one eye (cataract causing vision loss in the second eye)

2 (33.3) 02 (004.3) 28.0 (1.71-458.8) p=0.04

No cataract surgery received (bilateral cataract)

3 (50.0) 16 (034.7) 5.25 (0.50-54.78) p=0.33

*= note in cases with 0 is one or more cells, 1 has been added to each cell to calculate an estimated odds ratio and 95% CI; **= odds ratio includes <6/60 to 3/60 and <3/60.

Burga HG, et al.

167Arq Bras Oftalmol. 2014;77(3):164-7

from the most rural areas of Paraguay to Asunción and back via public transport (bus) is approximately PGY 80,000/US$20, while accom-modation per night per person in moderate lodgings costs about PGY100,000/US$25. Fundación Vision offers lodging at its central at a cost of PGY 50,000 for both the patient and the companion. Free transport offer to many of these patients may not result in a signifi-cant uptake of cataract surgery.

Some studies have highlighted the link between acceptance and lack of information or awareness of the disease and its treatment(6,22). However, it should be noted that in our setting, all the people with ca-taract enrolled in the study were provided information twice: during the RAAB survey and during the phone interviews. Thus, it is unlikely that lack of information is a contributing factor in the decision to not to seek surgery.

While visual needs differ from person to person it may be surmi-sed that people with the most reduced vision would more likely opt for surgery. Evidence in other settings suggests just the opposite. In the Tanzanian setting people with better pre-operative vision were more likely to come for surgery. The more elderly and visually disa-bled did not seek surgery or were not supported by the family to seek surgery(24). None of the 14 people, 3 from the metropolitan area, with a best eye vision of <20/200 accepted surgery, similar to the Tanzanian setting. People with unilateral cataract may not seek care if only one eye is affected; however, once having had the surgery, it appears that patients are keen to have the second eye operated. Perceptions of vision needs can change with a successful operation(14,25). Studies have noted that patients who had undergone a cataract surgery in one eye with a good post-operative vision were more inclined to accept surgery for the second eye as compared with those with poor outcomes, highlighting the impact of postoperative visual acuity on decision making(6,25).

There are several aspects of this study which limit interpretations of findings. Although the study was nationwide, the number of study participants was limited, making it difficult to assess factors associa-ted with uptake. Few of our patients were blind per WHO definition from cataract. Further, while participants who did not have a tele-phone number did not differ significantly with regard to age, sex, and visual acuity of those with a telephone number. It is likely that those without a telephone are poorer. The two weeks of free surgery cam-paign time may be too short for people to adequately prepare and travel for the surgery. As noted above, we cannot infer with certainty from our findings that transport is the primary barrier to accept the surgery among this group. By offering free transport and assessing the uptake we can further understand the contribution of transport to undertake the surgery.

In Latin America there is a large gap between the target CSRs to ope-rate on all eyes with VA<6/18 with the regional CSR being 1,425(15,26,27). Resent analysis in 2012 show that the current CSR in the Latin Ameri-can region at 2,672 per million with Paraguay at 1,539 indicating that lot needs to be done to address the multiple factors influencing the uptake of cataract surgery(5,8).

Our findings suggest that the direct fee for surgery is not the im-portant contributing factor in cataract surgery services in Paraguay. Similar to Ethiopia, indirect costs such as transportation, accommo-dation for both the patient and his/her companion, and medication may play a more significant role in service uptake even if surgery fee is completely waived(28).

Future work in Paraguay may need to focus on assisting ophthal-mologists to work in rural areas of the country as well as conducting more outreach in which surgeries are done in distant surgical facili-ties. Programmes should consider “packaging” transportation to and from the clinics, accommodation, and medicines to reduce indirect costs. The use of low cost mobile clinical and surgical services may also be an additional approach to improve access to cataract surgical

services. That being said, further investigation is needed to clarify if free transportation improves the uptake.

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22. Eusebio C, Foster A. Kuper H, Mamunur AK, et al. Predictors of attendance and barriers to cataract surgery in Kenya, Bangladesh and the Philippines. Disabil Rehabil. 2013; 35(19):1660-7.

23. Snellingen T, Shrestha BR, Gharti MP, Shrestha JK, Upadhyay MP, Pokhrel RP. Socioe-conomic barriers to cataract surgery in Nepal: the South Asian cataract management study. Br J Ophthalmol. 1998;82:1424-8.

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Original Article

168 Arq Bras Oftalmol. 2014;77(3):168-72 http://dx.doi.org/10.5935/0004-2749.20140043

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbitsExpressão das citocinas TNF-α and IL-6 na coroide e esclera de coelhos hipercolesterolêmicos

roGIL José de aLMeIda torres1, andrea LuchInI2, Lucas younes barberInI1, Leonardo PrecoMa3,caroLIne LuzIa de aLMeIda torres4, robson antonIo de aLMeIda torres4, LucIa de noronha1, bruna oLandoskI erbano5, antonIo MarceLo barbante caseLLa6, daLton bertoLIM PrecoMa1

Submitted for publication: November 19, 2013 Accepted for publication: March 20, 2014

Study conducted at Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.1 Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.2 Centro Oftalmológico de Curitiba, Curitiba, Paraná, Brazil.3 Medical Clinicat the Hospital Angelina Caron, Campina Grande do Sul, Paraná, Brazil.4 Universidade Positivo, Curitiba, Paraná, Brazil.5 Universidade Evangélica, Curitiba, Paraná, Brazil.6 Universidade Estadual de Londrina, Londrina, Paraná, Brazil.

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: Rogil Jose de Almeida Torres. Rua Emiliano Perneta, 390 - Conj. 1.407 - Curitiba (PR) - 80420-080 - Brazil - E-mail: rjat@terra.com.br

Project Number 240/080. CEUA - Pontifícia Universidade Católica do Paraná. CEUA Authorization Registration: 678- 2nd version. Authorization Date: 08/24/2012.

INtRoduCtIoNThe inflammation, as an inducer of diseases, is no longer exclu-

sively associated with autoimmune and infectious diseases. Convin-cing experimental evidence and many histopathological findings support the current view of inflammation as a critical regulator in Age-Related Macular Degeneration (AMD)(1,2). Macrophages, retinal pigment epithelial (RPE) cells, and endothelial cells (EC) play an im -portant role in the pathogenesis of ocular inflammation and the co nsequent formation of subretinal neovascular membrane (CNV). These cells secrete various inflammatory, growth, and angiogenic factors as well as pro-inflammatory cytokines, which contribute to the development of wet AMD(3-5). The role of growth factors, such as vascular endothelial growth factor (VEGF), on the formation of CNV has been identified. However, the influence and the mechanism of action of the inflammatory cytokines on the development of exuda-tive AMD are poorly understood. It has been reported that signaling

ABStRACtPurpose: This study aimed to evaluate the expression of the inflammatory cy-tokines TNF-α and IL-6 in the sclera and choroid of hypercholesterolemic rabbits. Method: Twenty-one New Zealand male albino rabbits were divided into two groups: NG and HG. The NG group was fed a standard rabbit diet and the HG group was fed a cholesterol-enriched diet (1%). The serum total cholesterol, triglyceride, HDL cholesterol, and fasting blood glucose levels were determined at the beginning of the experiment and on the day of euthanasia. Euthanasia of animals in the NG and HG groups was performed at the end of the 4th and 8th week, respectively. The eyes were analyzed immunohistochemically using TNF-α and IL-6 antibodies. Results: At the time of euthanasia, the HG group showed a significant increase in total cholesterol and triglyceride when compared with the NG group (p<0.001). When compared with the NG group, there was a significant increase in the expression of TNF-α (p<0.001) and IL-6 (p=0.002) in the choroid and sclera of animals in the HG group. Conclusion: This study demonstrates that the hypercholesterolemic diet induces expression of TNF-α and IL-6 in the choroid and sclera of rabbits.

Keywords: Cholesterol; Macrophages; Cytokines; Tumor necrosis factor; Inter-leukin-6; Choroid; Sclera; Macular degeneration

RESUMOObjetivo: Avaliar a expressão das citocinas inflamatórias TNF-α e IL-6 na esclera e coroide de coelhos hipercolesterolêmicos. Método: Coelhos New Zealand foram organizados em dois grupos: GN recebeu ração padrão para coelhos; GH recebeu dieta rica em colesterol a 1%. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 4a semana para o GN e 8a semana para o GH foi realizada a eutanásia dos animais. Os olhos foram submetidos à análise imuno-histoquímica com os anticorpos TNF-α e IL-6. Resultados: O GH manifestou significativo aumento do colesterol total e triglicerídeos em relação ao GN (p<0,001). Houve significativo aumento da expressão da TNF-α (p<0,001) e da IL-6 (p=0,002) na coroide e esclera dos animais do GH em relação ao GN. Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento da expressão das citocinas TNF-α e IL-6 na coroide e esclera de coelhos.

Descritores: Colesterol; Macrófagos; Citocinas; Fator de necrose tumoral; Interleuci-na-6; Coroide; Esclera; Degeneração macular

events initiated by cytokines trigger the inflammatory reaction and contribute to the development of CNV(6).

The tumor necrosis factor alpha (TNF-α) is a low-molecular weight protein, primarily produced by activated macrophages. TNF-α pro -motes VEGF signaling by promoting its production(7) and by mo-dulating the expression of its receptors(8). It has been reported that TNF-α regulates cell survival and cell death through Tnfrsf1a and Tnfrsf1b receptor. Activation of Tnfrsf1a receptors induces inflammation, inhibits endothelial cell migration and apoptosis(9), which may inhibit CNV. The Tnfrsf1b receptors regulate lymphocyte proliferation(10) and promote endothelial cell activation, migration, and survival(11). It has been reported that Tnfrsf1b promotes CNV(12). Studies have de monstrated that therapeutic targeting of TNF-α may provide benefits from CNV(12-15). TNF-α stimulates the production of Interleukin 6 (IL-6)(16), a multifunctio-nal cytokine that acts on a number of tissues and cell types(17). IL-6 is an important mediator of the inflammatory and immune respon-ses(18), and regulates VEGF expression(19).

Torres RJA, et al.

169Arq Bras Oftalmol. 2014;77(3):168-72

These cytokines play direct and/or indirect roles in the develop-ment of AMD. However, few reliable experimental models exist that simulate the development of macular degenerative diseases.

The objective of this study was to evaluate the expression of the inflammatory cytokines TNF-α and IL-6 in the choroid and sclera of hypercholesterolemic rabbits.

MEtHodSThe protocol for this study was approved by the Animal Experi-

mentation Ethics Committee of the Pontifícia Universidade Católica do Paraná (PUC-PR) and complies with the guidelines established by the Declaration of Helsinki and the Association for Research in Vision and Ophthalmology (ARVO).

experiment environment

The procedures described in this study were performed at the Surgical Technique Laboratory at PUC-PR and at the Study Center of the Angelina Caron Hospital (HAC). The animals were housed in the bioterium (macro environment) under 12h:12h light-dark cycles with air changes and between 19 and 23ºC room temperature. Animals were fed water ad libitum and were allowed free access to species standard diet Nuvital® (Nuvital, Colombo, Brazil).

animalS and experimental methodS

Twenty-one New Zealand male albino rabbits (Oryctolaguscuni-cullus) of an average age of 110 days and an average weight of 2.770 g were selected from the Central Bioterium of the Pontifícia Universi-dade Católica do Paraná. The animals were divided into 2 groups: group 1, the normal diet group (NG) with 8 rabbits, and group 2, the hypercholesterolemic group (HG) with 13 rabbits. The NG was fed the rabbit standard diet from Nuvital® Lab (Nuvital, Colombo, Brazil) and was euthanized after 4 weeks. The HG group was fed with the standard rabbit diet from Nuvital® Lab (Nuvital, Colombo, Brazil), supplemented with 1% cholesterol. The daily amount of diet per animal was 600 g. The animals in the HG group were euthanized at the end of the eighth week.

Each rabbit underwent measurements of serum total cholesterol, triglycerides, HDL cholesterol, and fasting glucose at the start of the experiment and at the time of euthanasia. Animals were euthanized by intravenous administration of 5 mL pentobarbital. The eyes were removed and immediately placed in 4% paraformaldehyde (Merck, Darmstadt, Germany) in 0.1 M phosphate buffer (pH 7.4) for 4h for immunohistochemical analyses.

tiSSue preparation and immunohiStoChemiCal analySiS

After fixation, the samples were evaluated under a microscope. A coronal section at the level of the optic nerve was performed and the ocular globe was divided into two equal halves. The lower half was stored for future studies. The upper half underwent dehydra-tion, diaphanization, and was embedded in paraffin using a Leica® TP 1020 Automatic Tissue Processor (Leica, Wetzlar, Germany). A Leica® EG1160 paraffin embedding device was used for paraffin embedding. A Leica® RM2145 Microtome was used to prepare 5-micron-thick sections for histology. The sections were placed on glass slides smea-red with albumin, stained with hematoxylin-eosin, and mounted on 24x900-mm coverslips using the Entellan Mounting Media (Merck, Darmstadt, Germany).

The sections were deparaffinized, rehydrated, and the endoge-nous peroxidases were blocked. The sections were then washed with deionized water and incubated in a moist chamber at 95ºC for 20 min for antigen retrieval. Following this, the endogenous peroxidases were blocked again. The slices were stained with rabbit primary mo-noclonal antibody against TNF-α (Imuny Biotechnology, Campinas, Brazil) at a dilution of 1:200 and with rabbit primary monoclonal

antibody against IL-6 (Imuny Biotechnology, Campinas, Brazil) at a dilution of 1:50. The slices were incubated with a secondary antibody, Envision® System labeled polymer-HRP anti-mouse (DakoCytoma-tion, Carpinteria, CA, USA), at room temperature for 30 min. The sections were incubated for 3 to 5 min with freshly prepared DAB substrate (DakoCytomation, Carpinteria, CA, USA). The slides were then counterstained with Mayer hematoxylin and mounted.

Positive and negative controls were used in all evaluations, and the slides were initially analyzed by a masked observer. Positive and negative staining detected for TNF-α and IL-6 were recorded. The immunopositive areas showed a brownish color and were studied using color morphometry. For this purpose, images of 3 consecutive fields close to the optic nerve head were captured with the help of a Bx50 Olympus microscope fitted with a 40x objective and equipped with a Sony Model DXC-107A camera. The program Image Pro Plus was used to select and color the immunopositive areas and measure the immunoreactive areas. The data obtained were compiled in a Mi-crosoft Excel spreadsheet (Redmond, WA) for statistical analysis. The sum total of all immunopositive areas in each of the 3 fields studied represented the variable immunoreactive area.

StatiStiCal analySiS

The t-test was used for the comparison of quantitative variables between the groups. The Mann-Whitney nonparametric test was also used when appropriate. The normality was evaluated with the Shapiro-Wilk test. p<0.05 indicated statistical significance. Statistica v. 8.0 was used for data processing.

RESuLtSCompariSon of variableS between ng and hg groupS: faSting gluCoSe, total CholeSterol, hdl, and triglyCerideS

The total cholesterol, triglycerides, HDL cholesterol, and the fas -ting glucose in the NG group at the time of euthanasia were si milar to those at the start of the experiment. However, in the HG group, the total cholesterol at the time of euthanasia was significantly higher than that of at the start of the experiment. At the start of the experiment, the mean of the total cholesterol in both the groups was approximately 41.3 mg/dL. However, by the end of the experi-ment, the total serum cholesterol in the HG group had increased by 2146.8 mg/dL (p<0.001). HG group also showed significant variation in serum triglyceride levels. At the start of the experiment, the serum triglyceride concentration was approximately 46.5 mg/dL in both the groups, whereas at the time of euthanasia, the serum triglyceride concentration was 168.5 mg/dL (p=0.001) in HG group. Fasting glucose and HDL cholesterol levels did not vary significantly in NG or HG group during the experiment.

CompariSon of tnf-α immunoreaCtivitieS of the ng and hg groupS

The animals in the HG group showed a significant increase in TNF-α expression in the sclera and choroid when compared to the animals in the NG group (p<0.001) (Table 1). This was characterized by the predominance of a brownish hue of these structures (Figure 1B). The sclera and the choroid in the NG group showed a bluish color and a thinner structure compared with the HG group, revealing low immunoreactivity of these structures in NG group to the TNF-α an-tibody (Figure 1A).

CompariSon of il-6 immunoreaCtivitieS of the ng and hg group

Compared with the NG group, the sclera and choroid of the HG group showed a significant increase in IL-6 expression (p=0.002) (Table 2), characterized by the predominance of the brownish hue of these structures (Figure 2B). The sclera and choroid of the animals

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits

170 Arq Bras Oftalmol. 2014;77(3):168-72

in the NG group showed a thinner structure and a predominant bluish color than those of the animals in the HG group, revealing low immunoreactivity of these structures in NG group to IL-6 antibody (Figure 2A).

dISCuSSIoNAngiogenesis, the formation of new blood vessels from pre-existing

endothelium, is an important event during vascular development, wound healing, and organ regeneration. Angiogenesis and neovas-cularization during tumor growth, diabetic retinopathy, rheumatoid arthritis, and AMD produce detrimental effects(20,21).

The critical role of VEGF in angiogenesis is well documented. Ho wever, it has been demonstrated that inflammatory reaction, cha -racterized by the presence of macrophages and inflammatory cyto -kines, also induces the anomalous formation of blood vessels(22). That inflammation mediates neovascularization in AMD is supported by studies that suggested depletion of macrophages can reduce the laser-induced CNV(23).

In the present study, rabbits were fed with cholesterol enriched diet to evaluate the expression of the TNF-α and IL-6 in the choroid-scle ral complex. It has been reported that cholesterol-enriched diet induces hypoxia of the retinal tissue(24), increase in the macrophage concentration in the choroid and sclera(24-25), as well as increase in

table 1. total area of the choroidscleral complex immunoreactive to tNF-α

Variable Group N Mean Median Min MaxStandard deviation p*value

Immunoreactive area HG 13 60317.2 51130.9 24613.5 105314.6 28857.7

NG 08 07134.2 06686.2 01635.9 22214.6 6626.0 <0.001

*= Student’s t-test for independente samples, p<0.05.

NG= normal diet group; HG= cholesterol-enriched diet group.

A B

Figure 1. Immunoreactivity of choroid and sclera to TNF­α antibody. A) Choroid­scleral complex of normal diet group. Predominance of the bluish hue indicates low immu­noreactivity to TNF­α antibody. Thin choroid and sclera. B) Choroid­sclera complex of hypercholesterolemic group. Predominance of a brownish hue indicates high immu­noreactivity to TNF­α antibody. Thick choroid and sclera. reactivity to TNF­α antibody. Thick choroid and sclera.

C= choroid; S= sclera; magnification = 400x.

table 2. total área of the choroidscleral complex immunoreactive to IL-6

Variable Group N Mean Median Min MaxStandard deviation p* value

Immunoreactive area HG 13 5301.0 5138.0 1963.0 9551.0 2590.0

NG 08 2427.0 2427.0 0987.0 3968.0 0893.0 0.002

*= Student’s t-test for independente samples, p<0.05.

NG= normal diet group; HG= cholesterol-enriched diet group.

A B

Figure 2. Immunoreactivity of choroid and sclera to IL­6 antibody. A) Choroid and sclera of normal diet group. Predominance of the bluish hue indicates low immunoreactivity to IL­6 antibody. Thin choroid and sclera. B) Choroid and sclera of hypercholesterolemic group. Predominance of a brownish hue indicates high immunoreactivity to IL­6 antibody. Thick choroid and sclera.

C= choroid; S= sclera; magnification = 400x.

Torres RJA, et al.

171Arq Bras Oftalmol. 2014;77(3):168-72

VEGF expression in these structures(25). Therefore, the significant increase in the TNF-α expression observed in the choroid and sclera of the animals in the HG group was likely due to hypoxia, as well as an increase in the macrophage concentration(26). TNF-α is a mul-tifunctional cytokine. TNF-α receptors are expressed in the retina, including the Muller and the RPE cells, as well as in the choroid(6,13-14). The TNF-α secreted by macrophages(22), observed in a large numbers in this experimental model(24-26), triggers the production of VEGF through Tnfrsf1b receptor by the RPE cells(6). TNF-α also stimulates monocyte adhesion and upregulates the granulocyte-macrophage colony-stimulating factor(27). Additionally, TNF induces EC migration and tube formation in the absence of proangiogenic factors, sugges-ting that TNF can directly activate signaling pathways for epithelial cell migration(27), thereby contributing directly to CNV formation. Indeed, TNF has been considered a therapeutic target in exudative AMD. Although the inhibition of TNF-α leads to the reduction in CNV size and leakage in experimental models(13), clinical research studies have shown inconsistent results(16,28).

It has also been demonstrated that TNF-α stimulates the production of IL-6(16), an important marker of inflammation. RPE and inflamma-tory cells produce IL-6 in response to stimulation(5,16,29). In the present study, a significant increase in the IL-6 expression was observed in the choroid and sclera of the rabbits in the HG group. Besides TNF-α(16), the macrophages and the hypoxia may have contributed to the increased IL-6 expression(19,24). It has been demonstrated that the in duction of IL-6 by hypoxia may induce VEGF expression, leading to angiogenesis. Therefore, IL-6 is regarded as indirect angiogenic factor(19). Further, it has been shown that the inhibition of the IL-6 expression by the pharmacologic blockade of its receptors or by the genetic ablation of this cytokine suppresses laser-induced CNV(29). The IL-6 receptor neutralization led to significant inhibition of the in vivo and in vitro expression of monocyte chemotactic protein, inter-cellular adhesion molecule-1, and vascular endothelial growth factor, and reduced macrophage infiltration into CNV(29). Consistent with these reports, a population study concluded that IL-6 represents a risk factor for CNV due to high levels in the plasma of AMD patients(30). These findings suggest the possibility of using IL-6 receptor blockade as a therapeutic strategy to suppress CNV associated with age-related macular degeneration.

We used rabbits for this research. The advantages of using rabbits over other animals include increased availability, low costs (when compared with transgenic mice lacking receptors for LDL cholesterol or apolipoprotein E), and a better genetic characterization(31). Addi-tionally, the hypercholesterolemic diet rapidly induces endothelial dysfunction and a response similar to atherogenesis, making it a good model for cardiovascular diseases(32). Further, the normal serum cholesterol levels in rabbits range from 25 to 60 mg%, whereas in humans this variation is between 100 and 200 mg%. Therefore, the metabolic system of rabbits may readily be overloaded with a simple daily hypercholesterolemic diet, making the experiments more fea-sible and reproducible(32). Indeed, the total serum cholesterol level in HG group increased from 41.3 mg/dL at the start of the experiment to approximately 2146.8 mg/dL at the time of euthanasia.

Several studies have been performed on rabbits to demonstrate that a cholesterol-enriched diet causes abnormalities in their sclera, choroid, and retina. This include the administration of 0.5% cho -lesterol-enriched diet for at least six months(33,34). In this study, the administered dosage of cholesterol was higher than that used in other studies (1% cholesterol), which enabled the authors to obtain immunohistochemical alterations of the choroid-sclera complex during a period of eight weeks. This demonstrated that alterations in the ocular walls as well as the arteries(32) could be brought about in a shorter period, thus offering opportunities for more experiments and reducing the costs. The NG group underwent euthanasia after 4 weeks. This short period has been proven to be sufficient to demons-trate that the serum total cholesterol, triglycerides, HDL cholesterol,

and fasting glucose level remained stable and did not interfere with the immunohistochemical analysis of the choroid and sclera. The decision to euthanize rabbits of the NG group after 4 weeks was made based on the results of earlier studies(24,35).

We have demonstrated that cholesterol-enriched diet induces an increase in macrophage concentration in the choroid-sclera com plex, causing thickness of these structures(24,25,35). The diet also induced hy-poxia of the retinal tissue, leading to neuronal damage(35). Therefore, the hypercholesterolemic model used in the present study incorpo-rates the increased macrophage concentration and hypoxia, the two conditions that induce TNF-α and IL-6 expression(19,22,24).

CoNCLuSIoNIn this study, we used immunohistochemistry to analyze the ex -

pression of TNF-α and IL-6 in the sclera and choroid of hypercho-lesterolemic rabbits. Although Western blotting is a more sensitive method for the detection of these factors, it requires the use of fresh or frozen tissue. Since the ocular globes were fixed in parafor-maldehyde and embedded in paraffin, we were unable to use the Western blotting technique.

Due to their role in mediating the intraocular inflammatory reaction, VEGF-like functions, and their hypoxia-induced expression, TNF-α and IL-6 have been considered as therapeutic targets in AMD. Our experi-mental model may help understand the development of AMD.

ACKNoWLEGMENtS We thank Dr. Márcia Olandoski for assisting with the statistical

analy sis of data.

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33. Salazar JJ, Ramírez AI, de Hoz R, Rojas B, Ruiz E, Tejerina T, et al. Alterations in the cho-roid in hypercholesterolemic rabbits: reversibility after normalization of cholesterol levels. Exp Eye Res. 2007;84(3):412-22.

34. Triviño A, Ramírez AI, Salazar JJ, de Hoz R, Rojas B, Padilla E, et al. A cholesterol-enriched diet induces ultrastructural changes in retinal and macroglial rabbit cells. Exp Eye Res. 2006;83(2):357-66.

35. Torres RJ, de Noronha L, Casella AM, Grobe SF, Martins Ide C, Torres Rdo R, et al. Effect of olmesartan on leukocyte recruitment in choroid-sclera complex in hypercholeste-rolemia model. J Ocul Pharmacol Ther. 2013;29(8):709-14.

VII Congresso Baiano de oftalmologia

10 e 11 de outubro de 2014Hotel Sheraton

Salvador - BA

informações: Site: www.sofba.com..br

Original Article

173Arq Bras Oftalmol. 2014;77(3):173-7http://dx.doi.org/10.5935/0004-2749.20140044

Efficacy of a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsificationEficácia de corante à base de luteína (PhacodyneTM) para observação da capsulorrexis anterior em cirurgia de facoemulsificação

Lucas MonFerrarI MonteIro vIanna1, Marcos J. cohen1, crIstIna MuccIoLI1, acácIo LIMa1, dIoGo sousa-MartIns1, MaurícIo MaIa1, rubens beLFort Jr.1

Submitted for publication: February 6, 2014 Accepted for publication: March 29, 2014

Study conducted at Departamento de Oftalmologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

1 Departamento de Oftalmologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Funding: This study has been conducted under grants from Kemin Industries Inc.

Disclosure of potential conflicts of interest: Diogo Sousa-Martins is an employee of Kemin Industries Inc. Acacio Lima is the owner of Ophthalmo’s and received personal fees from Kemin Industries Inc. Kemin Industries Inc. has supported the Department of Ophthalmology through Research Grants. Diogo Sousa-Martins, Rubens Belfort Jr., Acácio Lima and Maurício Maia and Kemin Industries Inc. hold patent related to the use of lutein or combinations thereof with synthetic dyes for staining the anterior capsule (patent pending US 20120251458 and Publications WO 2012135432).

Corresponding author: Lucas Monferrari Monteiro Vianna. Rua Botucatu, 821 - São Paulo (SP) - 04023-900 - Brazil - E-mail: lucasmmvianna@yahoo.com.br

Registered at clinicaltrials.org (NCT01627977) and approved by UNIFESP IRB (2146/11)

INtRoduCtIoNThe continuous circular capsulotomy (CCC) of the anterior lens

capsule is a critical step in the modern cataract surgery performed by phacoemulsification, which offers advantage for the implantation of intraocular lens correctly into the capsular bag(1). Good visualization of the anterior capsule flap is needed when performing the CCC, particularly in the absence of a red reflex(2-4). Since the lack of a red reflex results in technical difficulties(2-4), a correct CCC is useful when a more aggressive manipulation of the capsular bag is required(3). In such clinical conditions, the improvement of the anterior capsule

ABStRACtPurpose: To evaluate the efficacy and safety of a novel lutein-based dye for the anterior capsulorhexis during phacoemulsification in cataract surgery in humans. Methods: Twenty-five eyes from 25 patients were operated by 25 different sur geons who performed continuous circular capsulorhexis (CCC) guided by a lutein-based dye (Phacodyne™) during cataract surgery by phacoemulsification. A questionnaire assessed the surgeon’s opinion regarding the efficacy of the dye. Follow-up examinations were performed at 1, 7, and 30 days post-surgery. Eyes were evaluated by full ophthalmic examination, corneal topography/pachymetry, and corneal endothelial cell count. Results: As revealed by the answers to the questionnaire, the dye facilitated the CCC procedure in all eyes. Baseline nuclear cataract classification (according to the Lens Opacities Classification System III; LOCS III) was 3.24 (± 1.12). Preoperative BCVA (logMAR) was 0.89 ± 0.59 and improved to 0.23 ± 0.22 on day 30 after surgery. The intraocular pressure (IOP) remained stable and the inflammatory reaction subsided in all cases within the first 7 days after surgery. The pre-operative values of corneal pachymetry and IOP were similar to those found on follow-up day 30. Loss in endothelial cell number was similar to earlier reports. Conclusion: Phacodyne™ was efficient when used for anterior capsulorhexis du ring cataract surgery by phacoemulsification and showed no signs of toxicity or side effects during the 30-day follow-up period.

Keywords: Cataract extraction; Lutein; Phacoemulsification; Capsulorhexis; Lenses, intraocular

RESUMOObjetivos: Avaliar a eficácia e eficiência de um novo corante à base de luteína para coloração da cápsula anterior durante cirurgia de facoemulsificação em humanos. Métodos: Vinte e cinco olhos de 25 pacientes foram operados por 25 cirurgiões di ferentes que realizaram capsulorrexis circular contínua e facoemulsificação após coloração da cápsula anterior com corante à base de luteína. Um questionário ava liou a opinião dos cirurgiões sobre a eficácia do corante. Exames pós-operatórios foram realizados nos dias 1, 7 e 30 por meio de exame oftalmológico completo, topografia/paquimetria e contagem de células endoteliais. Resultados: De acordo com o questionário aplicado, o corante facilitou a cirurgia em todos os olhos. A classificação da catarata de acordo com o LOCS III foi de 3,24 ± 1,12. A acuidade visual pré-operatória com melhor correção foi de 0,89 ± 0,59 (logMAR), passando a 0,23 ± 0,22 no pós-operatório. A pressão intraocular (PIO) permaneceu estável e houve reação de câmara leve que desapareceu em todos os casos durante os primeiros 7 dias de pós-operatório. Não houve significância estatística comparando a paquimetria e PIO pré e pós-operatórios.Conclusão: O novo corante se mostrou eficiente e sem sinais de toxicidade ou efeitos adversos, após 30 dias, quando usado para auxiliar a cirurgia de facoemulsificação.

Descritores: Extração de catarata/métodos; Luteína; Facoemulsificação; Capsulorrexe; Lentes intraoculares

visualization can also be of great value for surgeons, particularly for those who are learning the surgical technique(4). Additionally, the surgical procedure of staining the anterior capsule during CCC in pediatric cataract extraction is useful since the anterior capsule of these eyes is thin and elastic(5).

Since the first use of fluorescein for improving the visualization during capsulorhexis in 1993(6), alternative techniques and a variety of dyes have been used for anterior capsule staining during cataract surgery(4). Although indocyanine green, trypan blue, sodium fluores-cein, crystal violet, and gentian violet have been shown to be useful

Efficacy of a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsification

174 Arq Bras Oftalmol. 2014;77(3):173-7

for facilitating the CCC maneuver, only the trypan blue 0.06% - Vision blue™ (Dorc, Netherlands) has been approved by the FDA for use in cataract surgery(7,8).

New dyes that enhance the visualization of ocular tissues during surgery have recently emerged(9-11). Lutein and zeaxanthin are two major components of the macular pigment and are the only carote-noids found in the macula and lens of humans. The antioxidant pro-perties of the dyes and the ability to filter blue light facilitated their use during the CCC procedure(12,13).

It has been reported that the green 1% solution of soluble lutein and zeaxanthin-based dye combined with 0.04% trypan blue (Phaco-dyne™, Kemin, USA) is a useful intraocular dye for staining the an terior capsule, enhancing the CCC procedure in human cadaveric eyes(11). Its safety profile has been evaluated by clinical, histological, and electro-retinographic methods after intravitreal injections into rabbit eyes(14).

The objective of this study was to evaluate the feasibility and safety of application of a novel dye comprising 1% soluble lutein-zeaxanthin together with 0.04% trypan blue (Phacodyne™, Kemin, USA) to improve the anterior capsulorhexis during the phacoemulsification surgery in human eyes.

MEtHodS

preparation of the dye

The method of preparation described below is valid for lutein/zeaxanthin regardless of the chemical form, purity, crystallization, or degree of esterification (patent office application #61/468,838).

The initial steps of this study were the development of a wa-ter-soluble solution, characterization of the absorbance of the lutein/zeaxanthin solution using the Aquamate device (Thermo Spectronic, Cambridge, UK), and the identification of the color of the chromo-phoric groups. The physicochemical parameters were tested for the optimum pH, osmolarity/osmolality, and concentration. Solubility in water and polyvinyl alcohol was tested, the ultraviolet spectra were recoded, and the blends showing different colors within the visible spectrum were analyzed.

The method of preparation of the dye included dissolution, agita-tion, sterilization, and filtration. First, the components were dissolved in balanced saline solution (BSS) or any other solution compatible with the components of the formula that provided stability, suitable pH, and osmolarity acceptable for ocular use. Sterilization using wet heat was achieved by autoclaving at 121ºC. The final dye solution contained 1% soluble lutein/zeaxanthin and 0.04% trypan blue (os-molarity, 280 mOsm; density, 1.05; pH, 7.00). Aliquots of 1 mL were prepared, stored at room temperature, and were used within 30 days.

Study deSign

This was a prospective, consecutive, non-randomized, interven-tional study of 25 eyes of 25 patients performed by 25 different sur geons. The study was registered at clinicaltrials.gov under the no NCT01627977. The study was approved by the Ethics Committee of the Federal University of São Paulo and was conducted according to the Research Guidelines of the Association of Research in Vision and Ophthalmology, adhering to the Declaration of Helsinki. All patients were informed of the benefits and risks of the surgical procedure as well as the nature and possible consequences of the new dye tested. This study was conducted after receiving informed consent from all participants.

Eyes were submitted to phacoemulsification at the Ophthalmo-logy Department of Hospital São Paulo, Universidade Federal de São Paulo, Brazil, with PhacodyneTM (Kemin, USA) assisting the CCC technique and the hydrophilic foldable IOL implantation.

inCluSion and exCluSion Criteria

Patients over 50 years of age with indication for cataract surgery in one eye were included in the study. Patients with any previous

ocular surgeries in the eye studied, pregnancy, glaucoma, a past or present intraocular infection, and any other ocular condition detected during the pre-operative examination that could limit or affect the postoperative results were excluded. The minimum follow-up period was 30 days.

phySiCal evaluation and oCular examinationS

All patients underwent a full ophthalmologic examination at the start of the study and postoperatively (days 1, 7, and 30). This inclu-ded evaluation of the best-corrected visual acuity (BCVA) that was measured using the Snellen Charts and converted to logMAR, mea surement of the intraocular pressure (IOP) using the Goldmann tonometer, and slit-lamp evaluation. Complementary exams such as fundoscopy, pachymetry, and specular microscopy (CSO, Firenze, Italy) were also performed at the same time points. Baseline cataracts were graded according to the “Lens Opacities Classification System III” (LOCS III)(15). Anterior chamber reaction was graded according to SUN Working Group(16).

SurgiCal proCedureS

The phacoemulsification was performed by 25 different experien-ced cataract surgeons. The first step consisted of making a 2.75-mm clear corneal incision, filling the anterior chamber with Phacodyne™ (Kemin, USA), washing after 30 seconds with balanced salt solution, and filling the anterior chamber with viscoelastic. The anterior con-tinuous circular capsulorhexis (CCC) (Figure 1) was performed using an Utrata forceps. This was followed by hydrodissection and hydrode-lineation using approximately 0.1 mL BSS. Phacoemulsification was performed using the Infinity Vision System™ (Alcon, USA). Following this, the lens cortex was aspirated and a foldable intraocular lens was inserted through the 2.75-mm corneal incision (Figure 2). At the end of the surgical procedure, the viscoelastic substance was aspirated and no sutures were placed at the corneal incision. Moxifloxacyn and dexamethasone association - Vigadexa™ (Alcon, USA) eye drops were used during the immediate post-operative period.

Figure 1. Dark green color of the dye.

Figure 2. Anterior capsule staining with the solution containing 0.3% lutein/zeaxanthin and 0.04% trypan blue, facilitating the CCC procedure.

Vianna LMM, et al.

175Arq Bras Oftalmol. 2014;77(3):173-7

follow-up

All eyes received 0.5% moxifloxacin eye drops 4 times daily for 7 days and 0.1% dexamethasone as part of a regressive regimen. No hy-potensive eye drops were prescribed. The eyes underwent an ophthal-mologic examination at days 1, 7, and 30 by expert ophthalmologists.

queStionnaireS

Surgeons’ evaluation of the use of PhacodyneTM (Kemin, USA) for the CCC procedure was reported using a questionnaire.

StatiStiCal methodS

All data were presented as the mean and standard deviation for quantitative variables, and absolute (n) and relative (%) values for qua-litative variables. The prevalence of intense staining of the anterior lens capsule was defined. The confidence interval was set at 95%.

RESuLtS

intraoperative findingS

The lutein-based dye produced a green solution (Figure 1) that stained the anterior capsule and facilitated the CCC procedure (Fi-gure 2). The phacoemulsification followed by IOL implantation was performed as traditionally reported by cataract surgeons. No sutures were necessary.

phySiCal evaluation and oCular examinationS at baSeline and follow-up

Nuclear cataract classification (according to LOCS III) was 3.24 ± 1.12 and changed from 2 to 6 in both groups. Preoperative BCVA (logMAR) was 0.89 ± 0.59 and improved to 0.23 ± 0.22 at day 30 after the surgery. The intraocular pressure (IOP) remained stable and similar to the pre-operative measurements during the post-operative visits (p=0.004) (Figure 3). A mild inflammatory reaction (grade 0.5+ accor-ding to SUN Working Group)(16) at the anterior chamber was observed within the first 7 days (Figure 4).

The pre-operative corneal pachymetry average was 538.8 ± 40.0 and that on post-operative follow-up day 30 was 542.5 ± 39.8 (Figure 5). The preoperative endothelial cell count average was 2573.5 ± 235.9 and that on postoperative follow-up day 30 was 2311.36 ± 490.7 (Figure 6).

There were no significant differences between the results of pre- and post-operative fundus biomicroscopy.

queStionnaireS

The questionnaires showed that surgeons considered Phacodyne™ to be efficient for staining the anterior capsule and that the staining facilitated the CCC procedure in all eyes (Table 1).

dISCuSSIoNA previous study showed that a solution containing 1% soluble

lutein-zeaxanthin and 0.04% Brilliant Blue G efficiently stained the anterior capsule and facilitated the CCC in cadaveric eyes(11). Additio-nally, clinical, histological, and electroretinographic evaluations per-formed after the intravitreal injection of the dye in rabbit eyes showed no signs of toxicity,(14) indicating the enhanced safety in case of accidental leak of the dye into the vitreous. Based on these reported we decided to evaluate the application of s the new dye for cataract surgery in humans.

Based on the nuclear cataract classification, LOCS III, the eyes enrolled in this study showed varying grades of cataract from 2 to 6, demonstrating that advanced cases of hypermature cataract were also present(6). The surgeons classified the visualization of the anterior capsule with the dye as “good” and considered it as a useful tool for cataract surgery (Table 1). The green colored dye (Figure 1) stained the anterior capsule of the lens, which facilitated the CCC procedure in all cases, including the hypermature cataracts.

The surgeons observed that in 4 eyes, the cornea, the incision, or iris were stained by the dye. Residual dye was found only in 2 eyes at the end of the surgical procedure (Table 1). The dye was not seen in any eye on the first postoperative day. A mild anterior chamber reaction of grade 0.5+ (according to SUN Working Group)(16) was observed during the first week after surgery (Figure 4). These results were similar to those of earlier clinical studies, where trypan blue was used during phacoemulsification to aid the CCC procedure or when a dye was not used.(3,4,17-19) In agreement with other reports, the IOP remained stable and similar to the pre-operative measurements during the post-operative period (Figure 3)(20).

The pre-operative BCVA (logMAR) was 0.89 ± 0.59 and improved to 0.23 ± 0.22 at day 30 after surgery, clearly showing that there was an improvement in BCVA from 20/160 to approximately 20/32 in

Figure 3. Intraocular pressure (mmHg).

Figure 4. Post­operative anterior chamber reaction (+).

Figure 5. Corneal pachymetry (µm).

Figure 6. Endothelial cell count (/mm2).

Efficacy of a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis during cataract surgery by phacoemulsification

176 Arq Bras Oftalmol. 2014;77(3):173-7

table 1. Questionnaire returned by surgeons showing the effectiveness of the dye

Surgeons questionnaire response % p

How often do the surgeon use dyes in cataract surgery? Never 00 000%

Rarely 08 032%

Frequently 13 052%

Always 04 016%

Which dye does the surgeon use? Trypan blue 25 100%

Indocyanine green 00 000%

Others 00 000%

How was the visualization of the anterior capsule with Phacodyne? Good 25 100% p<0.001

Bad 00 000%

How was the degree of staining of the anterior lens capsule by the dye? Nothing 00 000% p<0.001

Adequate 20 080%

Intense 05 020%

Did it color any other ocular tissues? No 21 084% p<0.001

Yes 04 016%

Conjunctiva 00 000%

Iris 01 004%

Posterior capsule 00 000%

Incision 02 008%

Cornea 01 004%

What is the surgeon’s opinion about the usefulness of the dye? Good 25 100%

Bad 00 000%

Is the color of the dye suitable for dying the anterior lens capsule? Yes 25 100%

No 00 000%

Were there any signs of the dye at the end of the surgery? No 23 092% p<0.001

Yes 02 008%

Incision 02 008%

majority of the eyes. No signs of toxicity were observed during the 30-day follow-up period(21).

Corneal pachymetric changes were observed soon after the sur-gical procedure and peaked at one week during the follow-up. The values returned to the baseline levels on the 30th postoperative day. The pre-operative corneal pachymetry average was 538.8 ± 40.0 and the post-operative value was 542.5 ± 39.8 (Figure 5), demonstrating that anatomical changes of the cornea were temporary and reversi-ble within the first 30 days after the surgery(21,22).

The baseline endothelial cell count average was 2573.5 ± 235.9 and that post-operatively was 2311.36 ± 490.7 (Figure 6), showing an average decrease of 10.18% in the first month after the surgery. Similar endothelial cell loss during phacoemulsification procedures has been reported by others(21,22).

Pre-and post-operative fundus biomicroscopy evaluations showed no significant differences. Pre-and post-operative macular thickness measurements are needed to assess the effect on the retina.

To our knowledge, this is the first study that used a lutein-based dye (PhacodyneTM) for visualizing anterior capsulorhexis during ca-taract surgery by phacoemulsification. However, our study had limi-tations. This include, the small sample size, the absence of a control group, the large number of surgeons (that may affect the outcomes, although it is suitable for analyzing the efficacy), and the limited follow up period of 30 days. The goal of this study using lutein and zea xanthin combined with trypan blue was to evaluate the safety and efficacy of the dye for CCC. Further studies are warranted to eva-luate the effectiveness of the new dye and its advantages over those that are currently being used. We hypothesize that use of lutein and

zeaxanthin in combination with trypan blue may have two favorable effects: 1) The lower concentration of trypan blue (that can also be tested in more reduced concentrations in future studies(23)), and 2) the antioxidant effect of lutein and zeaxanthin molecules that may quench the singlet oxygen generated by the exposure of trypan blue to light. Additionally, since lutein is a natural product, the manufactu-ring costs could be reduced. The use of lutein and zeaxanthin without trypan blue will be investigated in future studies.

CoNCLuSIoNThe newly formulated lutein-based dye facilitated the CCC during

phacoemulsification procedures and showed a good safety profile.

REFERENCES 1. Gimbel HV, Neuhann T. Development, advantages and methods of continuous cir-

cular capsulorhexis technique. J Cataract Refract Surg. 1990;16(1):31-7. Comment in: J Cataract Refract Surg. 2001;27(9):1346-7.

2. Assia EI, Apple DJ, Barden A, Tsai JC, Castaneda VE, Hoggart JS. An experimental study comparing various anterior capsulectomy techniques. Arch Ophthalmol. 1991; 109(5):642-7. Comment in: Arch Ophthalmol. 1992;110(2):170.

3. Marback EF, Freitas LL, Fernandes FP, Branco BC, Belfort Junior R. Anterior capsule staining using 0.025% trypan blue in cataracts without red reflex. Arq Bras Oftalmol. 2001;64(4):333-5.

4. Jacobs DS, Cox TA, Wagoner MD, Ariyasu RG, Karp CL; American Academy of Ophthal mology; Ophthalmic Technology Assessment Committee Anterior Segment Panel. Capsule staining as an adjunct to cataract surgery: a report from the American Academy of Ophthalmology. Ophthalmology. 2006;113(4):707-13. Comment in: Ophthal-mology. 2010;117(7):1462-1462.e1. Ophthalmology. 2007;114(1):197; author reply 197.

Vianna LMM, et al.

177Arq Bras Oftalmol. 2014;77(3):173-7

5. Brown SM, Graham WA, McCartney DL. Trypan blue in pediatric cataract surgery. J Cataract Refract Surg. 2004;30(10):2033. Comment in: J Cataract Refract Surg. 2003; 29(9):1733-7.

6. Hoffer KJ, McFarland JE. Intracameral subcapsular fluorescein staining for improved visualization during capsulorrhexis in mature cataracts. J Cataract Refract Surg. 1993; 19(4):566.

7. Horiguchi M, Miyake K, Ohta I, Ito Y. Staining of the lens capsule for circular continuous capsulorrhexis in eyes with white cataracts. Arch Ophthalmology. 1998;116(4):535-7.

8. Horiguchi M, Nagata S, Yamamoto N, Kojima Y, Shimada Y. Kinetics of indocyanine green dye after intraocular surgeries using indocyanine green staining. Arch Ophthal-mol. 2003;121(3):327-31.

9. 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.

10. Chang YS, Tseng SY, Tseng SH. Comparison of dyes for cataract surgery. Part 2: efficacy of capsule staining in a rabbit model. J Cataract Refract Surg. 2005;31(4):799-804.

11. Sousa-Martins D, Maia M, Moraes M, Lima-Filho AA, Rodrigues EB, Chen J, et al. Use of lutein and zeaxanthin alone or combined with brilliant blue to identify intraocular structures intraoperatively. Retina. 2012;32(7):1328-36.

12. Sato Y, Kobayashi M, Itagaki S, Hirano T, Noda T, Mizuno S, et al. Pharmacokinetic pro-perties of lutein emulsion after oral administration to rats and effect of food intake on plasma concentration of lutein. Biopharm Drug Dispos. 2011;32(3):151-8.

13. Ma L, Lin XM. Effect of lutein and zeaxanthin on aspects of eye health. J Sci Food Agric. 2010;90(1):2-12.

14. Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA, Bailey IL, et al. The Lens Opacities Classification System III. The longitudinal study of cataract study group. Arch Ophthalmol. 1993;111(6):831-6.

15. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005;140(3):509-16. Review.

16. Stock G, Ahlers C, Dunavoelgyi R, Kahraman G, Schauersberger J, Schmidt-Erfurth U, et al. Evaluation of anterior-segment inflammation and retinal thickness change following cataract surgery. Acta Ophthalmol. 2011;89(4):369-75.

17. 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.

18. Jacob S, Agarwal A, Agarwal A, Agarwal S, Chowdhary S, Chowdhary R, et al. Trypan blue as an adjunct for safe phacoemulsification in eyes with white cataract. J Cataract Refract Surg. 2002;28(10):1819-25.

19. Shrivastava A, Singh K. The effect of cataract extraction on intraocular pressure. Curr Opin Ophthalmol. 2010;21(2):118-22. Review.

20. Hengerer FH, Dick HB, Buchwald S, Hütz WW, Conrad-Hengerer I. Evaluation of corneal endothelial cell loss and corneal thickness after cataract removal with light-adjusta-ble intraocular lens implantation: 12-month follow-up. J Cataract Refract Surg. 2011; 37(12):2095-100.

21. Rosado-Adames N, Afshari NA. The changing fate of the corneal endothelium in ca -taract surgery. Curr Opin Ophthalmol. 2012;23(1):3-6.

22. Yetik H, Devranoglu K, Ozkan S. Determining the lowest trypan blue concentration that satisfactorily stains the anterior capsule. J Cataract Refract Surg. 2002;28(6): 988-91.

22. Rosado-Adames N, Afshari NA. The changing fate of the corneal endothelium in cata-ract surgery. Curr Opin Ophthalmol. 2012;23(1):3-6. Review.

23. Yetik H, Devranoglu K, Ozkan S. Determining the lowest trypan blue concentration that satisfactorily stains the anterior capsule. J Cataract Refract Surg. 2002;28(6):988-91.

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Original Article

178 Arq Bras Oftalmol. 2014;77(3):178-81 http://dx.doi.org/10.5935/0004-2749.20140045

INtRoduCtIoNThe hepatitis C virus infection is a severe disease that can beco-

me chronic and progress to hepatic decompensation, cirrhosis, and in 20% of the cases to hepatocellular carcinoma(1). Around 3% of the world’s population (170 million people) is estimated to be the chronic carrier of the hepatitis C virus(2). In Brazil, prevalence of this disease ranges from 0.9% to 1.9%, proportionate to the population of each state(3).

The current FDA approved and recommended treatment for he patitis C is the interpheron-alpha monotherapy, which includes pegylated interferon α-2b or along with ribavirin. Interferon is an immunomodulatory compound with direct antiviral and antiprolife-rative properties; it has been used as a therapeutic for hepatitis C, B, and D, cancer, and multiple sclerosis. In vitro, interferon alpha inhibits viral replication(4). Ribavirin is an immunomodulatory compound that inhibits viral DNA and RNA. When used alone it has no affect on he-patitis C viral replication(5). However, when combined with interferon, viral and biochemical response is sustained, when compared to the stand-alone use of interferon alpha(6). The treatment duration of 24 to 48 weeks has been recommended(6).

ABStRACtPurpose: To identify the effect of pegylated interferon α-2b and ribavirin treatment in the ocular fundus examination, visual acuity, and visual field. Methods: Prospective observational study was performed at the Hepatology Clinic of São José Regional Hospital and at the Vitreoretinal Department at the Sadalla Amin Ghanem Eye Hospital in patients with chronic hepatitis C before and during treatment with pegylated interferon α-2b together with ribavirin. Results: Six (37.5%) of 16 patients developed retinopathy during the treatment, two of which (12.5%) presented retinal hemorrhage, and four patients (6 eyes) presented cotton-wool spots (25%) that regressed during the treatment. One patient (6.25%) presented transient decrease in visual acuity during the treatment and recovered spontaneously without specific therapy. Conclusion: Recommended treatment methods for hepatitis C may cause transient retinopathy, commonly without any damage to visual function in most patients. Although ocular involvement is rare, follow-up with an ophthalmologist is recom-mended during the course of the hepatitis C medication.

Keywords: Antiviral agents/adverse effects; Hepatitis C, chronic/drug therapy; Interferon-alpha/adverse effects; Retinal diseases/chemically induced; Ribavirin/adverse effects

RESUMOObjetivo: Identificar possíveis mudanças no exame de fundo de olho após o início do tratamento, bem como alterações na acuidade visual e campo visual. Métodos: Estudo observacional prospectivo realizado na Clínica de Hepatologia do Hospital Regional de São José e no Departamento de Vítreo e Retina do Hospital de Olhos Sadalla Amin Ghanem, em pacientes com hepatite C crônica antes e durante o tratamento com interferon peguilado α-2b associado à ribavirina. Resultados: Six (37,5%) dos 16 participantes desenvolveram retinopatia durante o tratamento, dois dos quais (12,5%) apresentaram hemorragia retiniana unilateral, e quatro pacientes com exsudatos algodonosos (25%), seis olhos, que regrediu du rante o tratamento. Um participante (6,25%) apresentou diminuição transitória da acuidade visual durante o tratamento com recuperação espontaneamente sem tratamento específico. Conclusão: O tratamento recomendado para a hepatite C pode estar associado com o desenvolvimento de retinopatia transitória, geralmente sem dano à função visual na maioria dos pacientes. Embora o envolvimento ocular seja raro, o acompanhamento com o médico oftalmologista é recomendado durante todo o uso da medicação.

Descritores: Agentes antivirais/efeitos adversos; Hepatite C crônica/quimioterapia; Interferon-alfa/efeitos adversos; Doenças retinianas/quimicamente induzido; Riba-virina/efeitos adversos

The use of interferon as the treatment for hepatitis C in patients might lead to systemic changes, such as myalgia, fever, erythema, weakness, loss of appetite, anemia, and thrombocytopenia(1). Riba-virin has a fewer side effects among which hemolytic anemia being the most frequent one(7). Studies have reported an association of these compounds with optic neuropathy(7), retinopathy(8-14), subcon-junctival hemorrhage(8), cystoid macular edema(15), and retinal and choroidal perfusion deficiency(16).

The objective of this study is to identify possible alterations in ocular fundus examination upon start of the treatment, as well as to analyze the changes in visual acuity and visual field.

MEtHodSThis was a prospective observational study performed at the

Hepatology Clinic of the São José Regional Hospital and at the Vitreo-retinal Department at the Sadalla Amin Ghanem Eye Hospital. The study was conducted in the patients with chronic hepatitis C imme-diately commencing a standard 48-week treatment regimen of pe-gylated interferon α-2b (1.5 mcg/kg/week) subcutaneous injections

Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirinAchados oftalmológicos nos pacientes portadores de hepatite C em tratamento com interferon peguilado α-2b e ribavirina

Fernando José de noveLLI1, andré PrzysIezny1, evandro LuIs rosa1, raqueL FrancIne LIerMann GarcIa2, MárIo JunqueIra nóbreGa1

Submitted for publication: May 29, 2013 Accepted for publication: March 16, 2014

Study conducted at Hepatology Clinic of São José Regional Hospital and at the Vitreoretinal Department at the Sadalla Amin Ghanem Eye Hospital.

1 Sadalla Amin Ghanem Eye Hospital.2 City Program of Viral Hepatitis Control, Joinville, SC, Brazil.

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: Fernando José de Novelli. Joinville - SC - 89216-222 - Brazil E-mail: fernando.novelli@gmail.com

Novelli FJ, et al.

179Arq Bras Oftalmol. 2014;77(3):178-81

and ribavirin twice daily dosage of 800 mg. The study was approved by the Ethics Board under number 196824. All patients signed the informed consent form.

All the patients were interviewed regarding systemic diseases and were evaluated with the following ophthalmologic evaluation items before starting the treatment, after one month and quarterly up to twelve months. Examination consisted of best corrected visual acuity (subjective refraction); biomicroscopy; intraocular pressure (Gold-mann applanation tonometry); retinal mapping with indirect ophthal-moscope (using a 20D lens); direct and consensual pupillary light reflex test; visual field analysis with automated perimetry (Humphrey Field Analyzer II 750i, HFA 750i), with 24-2 SITA-standard strategy (Swedish Interactive Threshold Algorithm). Patients with concomitant diabetes mellitus underwent to fluorescein angiography exam (Topcon, TRC-50IX system, IMAGEnet 2000, intravenous 2.5 ml of 20% sodium fluores-cein solution) before starting the treatment, after one month, and once in three months for up to twelve months. The glycosylated he-moglobin dosage was monitored in the same periods.

Patients with the following characteristics were excluded: age below 18 years; diabetic retinopathy with changes in retinal per fusion at fluorescein angiography exam on initial evaluation or un controlled clinical diabetes upon follow-up (such as glycosylated hemoglobin- HbA1c over 8%) retinopathy; central or brain retinal vein occlu-sion; systemic arterial hypertension with retinopathy upon initial evalua tion, or uncontrolled clinical systemic arterial hypertension upon follow-up during the existence of retinopathy; other type of retinal vas cu lopathy arising due to non-infectious (Behçet’s disease, Wege -ner granu lomatosis, systemic lupus erythematous, polyarthritis no dosa, Crohn’s disease, sarcoidosis, multiple sclerosis), infectious (syphilis, Lyme’s disease, toxoplasmosis, toxocariasis, tuberculosis, herpes, mo -nonucleosis, leptospirosis), and ocular concomitant diseases (Birdshot chorioretinopathy, pars planitis, Eales disease, IRVAN syndrome, mul -tifocal choroiditis).

RESuLtSNineteen patients, 7 females and 12 males of 21 to 65 years of age

were enrolled in the study (mean, 46 years). The duration of follow-up varied from 4 to 48 weeks. Three patients missed the follow up after first examination and were excluded. Out of sixteen patients two were followed up to one month (12.5%), three patients for 3 to 6 months (18.75%), three patients for 6 to 9 months (18.75%), and eight from 9 to 12 months (50%). One patient was followed for 24 months. Average follow-up time was 8.18 months.

Retinopathy developed in six patients (37.5%) and among these two patients (12.5%) showed unilateral retinal hemorrhage presenting with a small and isolated hemorrhage; cotton-wool spots characteri-zed by small, isolated whitish spots, not associated with changes in visual function (Figure 1) were observed in four patients (25%) or six eyes (18.75%).

Out of 16 patients, a group of patients were diagnosed with the following systemic diseases: HIV, 1 (6.25%); diabetes, 3 (18.75%); 3 pa-tients had known treated hypertension (18.75%); and liver failure, 1 (6.25%). After the beginning of treatment, 66.6% of the patients deve-loped diabetic retinopathy and the same occurred with hypertensive patients. Of the total of detected retinopathy, hypertension accounted for 33.3%. The same was true for patients with diabetes.

These patients were instructed to continue systemic treatment with an ophthalmologic evaluation every two months and return if any ophthalmologic signal was detected. All patients adequately completed the treatment without any interruption due to the severi-ty of ophthalmic associated findings.

Upon completion of the treatment and terminating the medication the patients showed no signs of retinopathy or visual damage (Figure 2).

One of the patient, patient number 6 presented bilateral decrease of visual acuity during the treatment (6.25% of patients), associated with cotton wool spots on the right eye. However, this condition

was not connected with that pegylated interferon α-2b and ribavirin treatment as the condition persisted even in absence of the medi-cation. The patient recovered after one year of interruption of the treatment (Table 1). In the initial tests, patient also showed bilateral nonspecific disturbances on peripheral visual field at 30-2 strategy, without disc edema and not compatible with retinal manifestation on the right eye.

No color vision damage was found in any patient throughout the systemic treatment.

dISCuSSIoNPhysiopathology of retinopathy has not been clearly understood.

Guyer et al.(11) suggested that immune-complex deposition and leu-cocyte infiltration in the retinal vasculature would lead to ischemic episodes. Earlier studies(17,18) have shown that the increase in plasma complement levels and plasma aggregation would facilitate capillary infarction, thus explaining the ischemic alterations of retinopathy.

Although treatment with pegylated interferon α-2b associated with ribavirin might lead to ocular side effects, the associated use seems to bring a few side effects(19). Irritability and eye discomfort are most commonly reported due to the drug-induced conjunctivitis as the drug is secreted along with tear(20).

The incidence of retinopathy related to pegylated interferon α-2b has been widely reported in the literature. In a systematic review from Raza et al.(21), the overall incidence of retinopathy during the treatment was around 27%. In a prospective study Vujosevic et al.(22) reported 30% of retinopathy in 97 patients. In another prospective

Figure 1. Color (upper) and red­free retinograph (below) of both eyes of patient 1 at 6­month follow­up treatment for hepatitis C, presenting with multiple cotton­wool spots without associated hemorrhage, smaller in the superior papillomacular bundle area and bigger in the inferior one.

Figure 2. Color retinography of both eyes of patient 1 showing no retinal lesions at one year follow­up.

Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirin

180 Arq Bras Oftalmol. 2014;77(3):178-81

table 1. Profile of patients that underwent follow-up during the treatment for hepatitis C

Age (years) Associated disease ocular changes time of detection of ocular changes

BCVA* before treatment BCVA* last query

Right Left Right Left

01 21 - Bilateral cotton wool spots month 6 1.0 1.0 1.0 1.0

02 62 Hypertension Bilateral cotton wool spots month 3 1.0 1.0 1.0 1.0

03 42 - - - 1.0 1.0 1.0 1.0

04 47 Diabetes Retinal hemorrhage in OS week 3 1.0 1.0 1.0 1.0

05 47 - - - 1.0 1.0 1.0 1.0

06 58 - Cotton wool spots in OD month 5 1.0 1.0 1.0 1.0

07 44 Diabetes and hypertension Retinal hemorrhage in OS month 6 1.0 0.5 1.0 0.5

08 33 - - - 1.0 1.0 1.0 1.0

09 46 - - - 1.0 1.0 1.0 1.0

10 51 Diabetes and hypertension - - 0.9 0.9 1.0 0.9

11 40 - - - 1.0 1.0 1.0 1.0

12 44 HIV** - - 1.0 1.0 1.0 1.0

13 36 - - - 1.0 1.0 1.0 1.0

14 54 - - - 1.0 1.0 1.0 1.0

15 42 - Left eye cotton wool spots month 7 1.0 1.0 1.0 1.0

16 44 Liver failure - - 1.0 1.0 1.0 1.0

*BCVA= best corrected visual acuity; **HIV= human immunodeficiency virus.

study, Kim et al.(23) evaluated 32 patients (64 eyes) and 11 of them developed retinopathy (34.4%). Cotton-wool spots were found in six patients, both eyes (18.7%); retinal hemorrhages in four (12.5%), both eyes. Panetta et al.(24) reported in a retrospective study a very low incidence (3.8%) of retinopathy among 183 patients with chro-nic hepatitis C treated with pegylated interferon α-2b and ribavirin. However, only symptomatic patients were included in this study.

It is likely that the incidence of retinopathy could be under re -presented. The cotton-wool spots were transient, often asymptoma-tic with no visual acuity, so it is possible that they were not always detected, especially when the patients missed or were irregular with the follow-up. Most patients showed full resolution without visual sequelae.

Schulman et al.(25) showed among 42 patients (7%) treated with interferon and ribavirin, three patients had be stopped the treatment due to retinopathy (two) and disc edema (one) with low visual acuity. The patients regressed spontaneously after stopping the treatment, without sequelae.

Nagaoka et al.(26) suggested endothelial dysfunction as a cause of interferon-associated retinopathy, with increased manifestation within 2 weeks of treatment initiation. Schulman et al.(25) reported a 67% chance of development of retinopathy among hypertensive patients. Similar to the findings of Vujosevic et al.(22) that reported a frequency of 68% Kim et al.(23) also claimed hypertension to be a risk factor for retinopathy.

CoNCLuSIoNIn our study, we diagnosed retinopathy in a considerable number

of cases, but most patients showed no changes in visual acuity and quality. Only one patient showed a transient visual loss without loss of term impairing of the visual function. We conclude that according to our study and in agreement with studies published in literature, the treatment for hepatitis C with pegylated interferon α-2b associated with ribavirin although can cause retinal changes, usually do not lead to damages to visual function, and has a transitional character with complete anatomical and functional recovery. Although ocular invol-vement is rare, follow-up with an ophthalmologist is recommended throughout the course of the medication, especially if symptoms are detected.

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9. Kadayifcilar S, Boyacioglu S, Kart H, et al. Ocular complications with high-dose inter-feron alpha in chronic active hepatitis. Eye (Lond). 1999;13(Pt 2):241-6.

10. Hayasaka S, Nagaki Y, Matsumoto M, Sato S. Interferon associated retinopathy. Br J Ophthal mol. 1998;82(3):323-5.

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12. Esmaeli B, Koller C, Papadopoulos N, Romaguera J. Interferon-induced retinopathy in asymptomatic cancer patients. Ophthalmology. 2001;108(5):858-60.

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14. Jain K, Lam WC, Waheeb S, et al. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin. Br J Ophthalmol. 2001;85(10):1171-3.

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16. Hoerauf H, Schmidt-Erfurth U, Asiyo-Vogel M, Laqua H. Combined choroidal and retinal ischemia during interferon therapy: indocyanine green angiographic and microperimetric findings. Arch Ophthalmol. 2000;118(4):580-2.

17. Sugano S, Suzuki T, Watanabe M. Retinal complications and plasma C5a levels during interferon alpha therapy for chronic hepatitis C. Am J Gastroenterol. 1998;93(12):2441-4.

18. Sugano S, Yanagimoto M, Suzuki T. Retinal complications with elevated circulating plasma C5a associated with interferon-alpha therapy for chronic active hepatitis C. Am J Gastroenterol. 1994;89(11):2054-6.

19. Schalm SW, Hansen BE, Chemello L, et al. Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers. J Hepatol. 1997;26(5):961-6.

20. Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical ocular toxicology. Philadelphia, PA: Saunders. 2008;212-4.

21. Raza A, Mittal S, Sood GK. Interferon-Associated Retinopathy During the Treatment of Chronic Hepatitis C. J Viral Hepat. 2013;20(9):593-9.

Novelli FJ, et al.

181Arq Bras Oftalmol. 2014;77(3):178-81

22. Vujosevic S, Tempesta D, Noventa F, Midena E, Sebastiani G. Pegylated interferon-associated retinopathy is frequent in hepatitis C virus patients with hypertension and justifies ophthal mologic screening. Hepatology. 2012;56(2):455-63.

23. Kim ET, Kim LH, Lee JI, Chin HS. Retinopathy in hepatitis C patients due to combina-tion therapy with pegylated interferon and ribavirin. Jpn J Ophthalmol. 2009;53(6): 598-602.

24. Panetta JD, Gilani N. Interferon-induced retinopathy and its risk in patients with dia-

betes and hypertension undergoing treatment for chronic hepatitis C virus infection. Aliment Pharmacol Ther. 2009;30(6):597-602.

25. Schulman JA, Liang C, Kooragayala LM, King J. Posterior segment complication in patients with Hepatitis C treated with interferon and ribavirin. Ophthalmology. 2003;110(2):437-42.

26. Nagaoka T, Sato E, Takahashi A, Yokohama S, Yoshida A. Retinal circulatory changes asso-ciated with interferon-induced retinopathy in patients with hepatitis C. Invest Ophthal mol Vis Sci. 2007;48(1):368-75.

17o Congresso de oftalmologia uSP

16o Congresso de Auxiliar de oftalmologia uSP

28 e 29 de novembro de 2014Centro de Convenções Rebouças

São Paulo - SP

informações: Tels.: (11) 5084-9174 / 5082-3030

E-mail: secretariausp@jdeeventos.com.brSite: www.oftalmologiausp.com.br

182

Case Report

Arq Bras Oftalmol. 2014;77(3):182-4 http://dx.doi.org/10.5935/0004-2749.20140046

Severe scleral dellen as an early complication of pterygium excision with simple conjunctival closure and review of the literature“Dellen” escleral grave como complicação precoce de excisão de pterígio com fechamento conjuntival simples e revisão da literatura

Jose JavIer GarcIa-MedIna1,2,3, MónIca deL-rIo-veLLosILLo4, vIcente zanon-Moreno3,5, aManda ortIz-GoMarIz1, ManueLa MorcILLo-GuardIoLa1, MarIa doLores PInazo-duran3,6

Submitted for publication: August 2, 2013 Accepted for publication: December 17, 2013

Study conducted at Department of Ophthalmology, General University Hospital Reina Sofia, Murcia Spain.

1 Department of Ophthalmology, General University Hospital Reina Sofia, Murcia, Spain.2 Department of Ophthalmology and Optometry, School of Medicine, University of Murcia, Spain.3 Ophthalmology Research Unit “Santiago Grisolia”, Valencia, Spain.4 Department of Anesthesia, University Hospital La Arrixaca, Murcia, Spain.5 Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia,

Valencia, Spain.6 Department of Ophthalmology, School of Medicine, University of Valencia, Valencia, Spain.

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: Jose Javier García-Medina. Department of Ophthalmology. General Uni-versity Hospital Reina Sofia. Avenida Intendente Jorge Palacios, 1 - 30003 Murcia, Spain

E-mail: josegarciam@yahoo.com

INtRoduCtIoNSeveral surgical techniques are available for treating pterygium,

such as bare sclera, simple conjunctival closure, sliding conjunctival flaps, and conjunctival autografts. Adjunctive therapies, such as pos toperative beta radiation or thiotepa drops and intraoperative mitomycin C, can be used to prevent the recurrence of pterygium(1).

Severe scleral dellen (SD) is a rare complication during the early postoperative period following pterygium surgery. The few reports describing this condition are all related to the bare sclera technique without adjunctive therapy(2,3) or with intraoperative mitomycin C(4,5) or beta radiation(6). However, we are unaware of any report of SD asso-ciated with pterygium excision followed by minimal cauterization of episcleral vessels and simple conjunctival closure.

ABStRACtWe describe a patient with acute scleral dellen (SD) after pterygium excision with simple conjunctival closure. In addition, we present a PUBMED review on the medical literature on early SD after pterygium surgery. This case describes a 45-year-old man who presented with severe SD, 7 days after pterygium surgery with minimal cauterization of episcleral vessels and simple conjunctival closure. No other adjunctive therapy was used intraoperatively. The patient refused conjunctival flap coverage of the lesion. Therefore, medical treatment consisted of antibiotic ointment, patching, and daily follow-up. After 7 days, the patching was changed for intensive ocular lubrication. Five weeks later, the surrounding conjunctiva had completely covered the affected sclera. To the best of our knowledge, this is the first report of early SD following pterygium excision and simple conjunctival closure with no other adjunctive therapy. When performing pterygium excision with conjunctival coverage of the sclera, a close follow-up is recommended to rule out wound dehiscence and SD, even when surgical wound closure is considered to prevent SD. If this complication is detected, the treatment can be conservative.

Keywords: Pterygium/surgery; Gentamicins; Scleral diseases/etiology; Case reports

RESUMODescrevemos um paciente com “dellen” escleral agudo (SD) após excisão de pterígio com fechamento conjuntival simples. Uma revisão adicional da literatura médica sobre SD precoce após a cirurgia de pterígio também é realizada. Este caso descreve um homem de 45 anos de idade, que apresentou SD grave, sete dias após a cirurgia de pterígio com cauterização mínima de vasos episclerais e fechamento conjuntival simples. Nenhuma outra terapia adjuvante foi utilizada no intraoperatório. O pa-ciente recusou-se à cobertura de retalho conjuntival da lesão. Portanto, o tratamento médico consistiu em pomada antibiótica, oclusão e acompanhamento diário. Após sete dias, a oclusão foi mudada para a lubrificação ocular intensiva. Cinco semanas após, a conjuntiva cobriu completamente a esclera afetada. Ao melhor de nosso conhecimento, este é o primeiro relato de SD precoce após a excisão do pterígio e fechamento conjuntival simples com nenhuma outra terapia adjuvante. Ao realizar a excisão do pterígio com cobertura conjuntival da esclera, um acompanhamento frequente é recomendado para descartar a deiscência da ferida e SD. Se esta com-plicação for detectada, o tratamento pode ser conservador.

Descritores: Pterígio/cirurgia; Gentamicinas; Doenças da esclera/etiologia; Relatos de casos

CASE REPoRtA 45-year-old bricklayer with a primary pterygium on the nasal

side of his right eye underwent surgical excision with minimal cau-terization of episcleral vessels and simple conjunctival closure with two stitches (7/0 silk). The procedure was carried out under topical and subconjunctival anesthesia (lidocaine 2% and epinephrine 1/200.000). No adjunctive therapy was used intraoperatively. Dexa-methasone (0.5 mg/g) and chloramphenicol (10 mg/g) ointment were applied and the eye was patched. His medical and ocular his-tories were unremarkable. The day following surgery, the outcome looked favorable; there was a nasal corneal epithelial defect and the edges of the conjunctival incision were in close apposition with no signs of infection or excessive inflammation. Topical steroids, antibio-tics, and artificial tears were prescribed.

Garcia-Medina JJ, et al.

183Arq Bras Oftalmol. 2014;77(3):182-4

One week later, the patient arrived at the emergency department complaining of moderate pain and a black dot in his right eye. His best corrected visual acuity was 10/10 and intraocular pressure was 15 mmHg. Slit lamp examination revealed severe scleral thinning reaching the choroid (Figure 1). The conjunctival sutures were no lon-ger in place. The anterior chamber was deep with no Tyndall effect, whereas the pupils were isocoric and normoreactive. The fundus showed transparent media with no other abnormal findings. The patient refused improper eye handling, therapeutic failure, or going back to work in a dusty environment. Reconstructive surgery through a conjunctival flap was offered, but the patient refused; therefore, a conservative medical treatment was prescribed that included gen-tamicin antibiotic ointment (3 mg/g), patching for 7 days, and daily outpatient monitoring, which was followed by intensive ocular lubri-cation (carmellose 10 mg/mL every hour) for 6 weeks. Within a few weeks, the conjunctival defect was replaced by granulation tissue, and later with a flap of adjacent conjunctiva. The photographic series illustrates the patient’s evolution (Figures 2 and 3).

After solving the case, the patient was referred to internal medici-ne to rule out collagen or infectious disease. Medical history, physical examination, and laboratory test (blood count, biochemistry, rheu-matoid factor, autoantibody screening, infectious serology, and Man-toux) revealed no infectious or autoimmune inflammatory disease.

dISCuSSIoNAs seen above, several surgical techniques can be used to treat

pterygium. The bare sclera technique includes excision of the pte -ry gium, which leaves the conjunctival defect to heal by sclera epi-thelization from the surrounding conjunctiva. Exposing the sclera contributes to drying, and therefore is a risk factor for thinning. All severe scleral thinning cases during the early postoperative period seem to be associated with the bare sclera technique. In our case, however, we used the primary excision technique with simple con-junctival closure (Table 1).

The fact that no stitches were found at about 1 week post-surgery suggests improper eye handling by the patient, excessively lax stitches, or a combination of both. The dehiscence of the wound, possibly resulting in exposure of the underlying sclera and edema, and raised conjunctiva edges, may have caused a discontinuity of the tear film leading to exacerbated local dehydration. In their publica-tion, Chen and Noonan(2) attributed SD after pterygium surgery with the bare sclera technique to raised granulation tissue edges, which developed in the conjunctiva margin of exposed sclera.

Whereas the growth of blood vessels in the wound bed is con-sidered to contribute to pterygium recurrence, some authors have recommended cauterization of episcleral vessels, especially at the limbus. However, it appears that coagulation of the episcleral vessels, which do not bleed, neither avoids recurrences nor contributes to accomplishing better esthetic results during pterygium surgery (personal communication of Lawrence W. Hirst). The cauterization applied to our patient was performed carefully and only with the purpose of avoiding bleeding during surgery. Nonetheless, this factor has to be considered in the etiology of scleral perforation as it may Figure 1. Initial appearance of the scleral dellen reaching the choroid.

Figure 2. The sclera dellen on day 3 (top) and on day 7 (bottom) from its onset. Figure 3. The sclera dellen on day 12 (top) and on day 38 (bottom) from its onset.

Severe scleral dellen as an early complication of pterygium excision with simple conjunctival closure and review of the literature

184 Arq Bras Oftalmol. 2014;77(3):182-4

table 1. Summary of published cases of early scleral dellen after pterygium surgery

ReferenceSurgical

technique

Cauterization of episcleral

vessels

Intraoperative adjunctive

therapy

topical corticosteroids

after surgery

onset of signs/symptoms

(from surgery) treatment

Chen and Noonan(2) Bare sclera Minimal None Yes 14 days Conjunctival flap

Mitra et al.(3) Bare sclera Unknown None Yes 7 days Antibiotic and artificial tears

Tsai et al.(4) Bare sclera Unknown Mitomycin C Yes 8 days Artificial tears

Safianik et al.(5) Bare sclera Unknown Mitomycin C Unknown 21 days Conjunctival flap

Hicks et al.(6) Bare sclera Unknown Beta-radiation Unknown 2 days Patching

Garcia-Medina et al. (present case)

Simple conjunctival closure

Minimal None Yes 7 days Patching, antibiotic, and artificial tears

cause local ischemia. In the cases reported in the literature, whether episcleral vessel cauterization was used or its duration is unclear.(2-6) Subconjunctival anesthesia containing a vasoconstrictor agent (epi-nephrine) also may have been a contributory factor for local ischemia in the present case.

Topical corticosteroids enhance collagenases and inhibit colla-gen synthesis, which may have also contributed to SD formation, as pro-posed by Mitra et al.(3). Therefore, they should be removed immediately.

The conjunctival flap graft has been used successfully to manage these complications(2,5). As the patient refused this surgical procedu-re, we had the opportunity to assess the evolution of scleral erosion with medical treatment. We found that eye patching, antibiotic co-verage, and intensive lubrication combined are sufficient for healing this com plication. Conservative treatment has also been proved to be successful in the cases that other authors have presented(3,4,6).

In conclusion, we can state that pterygium excision with primary conjunctival closure and cauterization of episcleral vessels may result

in severe SD, even in patients with no history of risk, as was the case presented here. Conservative treatment may be appropriate to ma-nage this rare complication.

REFERENCES 1. Hirst LW. The treatment of pterygium. Surv Ophthalmol. 2003;48(2):145-80. 2. Chen S, Noonan C. Scleral dellen complicating primary pterygium excision. Eye.

2000;14(Pt 1):100-1. 3. Mitra S, Ganesh A, Shenoy R. Scleral dellen complicating primary pterygium excision.

Eye. 2000;14 (Pt 6):924-5. 4. Tsai YY, Lin JM, Shy JD. Acute scleral thinning after pterygium excision with intraope-

rative mitomycin C: a case report of scleral dellen after bare sclera technique and re view of the literature. Cornea. 2002;21(2):227-9.

5. Safianik B, Ben-Zion I, Garzozi HJ. Serious corneoscleral complications after pterygium excision with mitomycin C. Br J Ophthalmol. 2002;86(3):357-8.

6. Hicks RR, Irvine AR, Spencer WH, Yuhasz Z. Scleral dellen. Arch Ophthalmol. 1975; 93(1):88-9.

Case Report

185Arq Bras Oftalmol. 2014;77(3):185-7http://dx.doi.org/10.5935/0004-2749.20140047

INtRoduCtIoNMultiple evanescent white dot syndrome (MEWDS) is a benign

self-healing disease with an unknown etiology that was first descri-bed in 1984 by Jampol et al. It is a retinal pigment epithelial (RPE) and choroidal inflammatory condition that predominantly affects young to middle-aged women, is unilateral in 80% of cases, and causes visual loss of variable degrees(1-5).

Associated clinical features include flu-like prodrome, blurred disc margins, blind spot enlargement, and temporal scotomata(2,5). Fundos-copy typically reveals multiple, 100-200 µm yellow-white outer retina dots in posterior pole and mid-periphery as well as a unique foveal granularity(1,2,4-7).

Fluorescein angiography (FA) typical aspect comprises early foveal granular hyperfluorescence, early hyperfluorescence, and late staining of the white dots in a wreath-like pattern and disc capillary leakage. Indocyanine green angiography (ICGA) shows numerous hypofluores-cent nummular lesions that are evident in the late phase and predomi-nant in the mid-periphery and around the optic disc(2,4,7).

Here, we report a case of MEWDS notable for its classic retinal appea-rance, foveal granularity, and transient disruption of the macular photoreceptor of the inner segment-outer segment (IS-OS) junction. After six months of follow up, the patient presented full visual reco-very and re-established a normal foveal aspect on Spectral Domain Optical Coherence Tomography (SD-OCT).

ABStRACtThe purpose of this study was to describe a patient with multiple evanescent white dot syndrome (MEWDS) who presented with classic retinal findings and transient changes in outer retinal anatomy. A 20-year-old man presented with mild blurred vision in the left eye, reporting flu-like symptoms 1 week before the visual symptoms started. Fundus examination of the left eye revealed foveal granularity and multiple scattered spots deep to the retina in the posterior pole. Fluorescein angiography and indocyanine green angiography showed typical MEWDS findings. Spectral Domain Optical Coherence Tomography has shown transient changes in outer retinal anatomy with disappearance of inner segment-outer segment junction and mild attenuation of external limiting membrane. Six months later, Spectral Domain Optical Coherence Tomography has shown complete resolution with recovery of normal outer retinal aspect.

Keywords: Retinal diseases/diagnosis; Syndrome/diagnosis; Tomography, optical coherence; Case reports

RESUMOO propósito deste estudo é descrever o caso de um paciente com síndrome dos múltiplos pontos brancos evanescentes (MEWDS), apresentando achados retinianos clássicos e alterações transitórias na anatomia retiniana externa. Paciente do sexo masculino, 20 anos de idade, apresentando embaçamento visual no olho esquerdo, relatando sintomas gripais uma semana antes do início dos sintomas visuais. Fundoscopia do olho esquerdo revelou granularidade foveal, múltiplos pontos brancos retinianos no polo posterior. A angiografia fluoresceínica e a indocianinografia verde evidenciaram achados típicos de MEWDS. A tomografia de coerência óptica de domínio espectral evidenciou alterações transitórias na anatomia retiniana externa como desapareci-mento da junção dos segmentos interno-externo dos fotorreceptores e leve atenuação da membrana limitante externa. Após 6 meses, a tomografia de coerência óptica mostrou completa resolução com recuperação total da anatomia retiniana externa.

Descritores: Doenças retinianas/diagnóstico; Síndrome/diagnóstico; Tomografia de coerência óptica; Relatos de casos

CASE REPoRtA 20-year-old man presented for an ophthalmologic evaluation

with a 2-day history of blurred vision in his left eye and flu-like symptoms that began 1 week before the visual symptoms started. His best-corrected visual acuity was 20/20 (OD) and 20/40 (OS); in -traocular pressure was 15 mmHg in OU. Anterior biomicroscopy was normal in OU. Fundus examination was normal in OD, and OS revea-led multiple 100-500 µm yellow-white dots deep to the retina in the posterior pole and mid-periphery, foveal granularity, and blurred disc margins (Figure 1).

Automated perimetry showed a blind spot enlargement in the affected eye. FA had shown earlier hyperfluorescent lesions in the posterior pole and mid-periphery, with late staining of the white dots in a wreath-like pattern and late staining in the optic nerve (Figure 2). The corresponding ICGA demonstrated numerous hypofluorescent areas predominantly in the mid-periphery and around the optic disc. These hypofluorescent areas were mild and in an early angiographic phase, but became more clearly delineated in the late phase (Figure 2). SD-OCT showed mild attenuation of the external limiting mem-brane, a transient disruption of the macular photoreceptor IS-OS junction, increased RPE reflectivity and enhanced signal penetration into the underlying choroid (Figure 3). The patient was diagnosed with MEWDS and observation without treatment was suggested. The patient was lost at follow-up, but returned 24 weeks later after

Transient spectral domain optical coherence tomography findings in classic MEwdS: a case reportAlterações transitórias evidenciadas na tomografia de coerência óptica de domíno espectral em quadro clássico de mewds: relato de caso

LucIana castro LavIGne1, davId Leonardo cruvIneL Isaac2, José osórIo duarte JúnIor1, Marcos PereIra de ávILa2

Submitted for publication: September 17, 2013 Accepted for publication: January 27, 2014

Study conducted at Universidade Federal de Goiás, GO, Brazil.1 Setor de Retina e Vítreo, Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.2 Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.

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: Luciana Castro Lavigne. Rua S-4, 237 - Qd S19 - Lot 20/24 - Apto. 1.308 - Setor Bela Vista - Goiânia (GO) - 74823-450 - Brazil - E -mail: lucianalavigne@live.com

Transient spectral domain optical coherence tomography findings in classic MEwDS: a case report

186 Arq Bras Oftalmol. 2014;77(3):185-7

contacting the authors. He claimed that he had not attended the visits because he had visual recovery within one month. His BCVA was 20/20 OU. Fundus examination in the OD was normal, and the OS revealed mild foveal granularity and RPE hyperpigmentation surrounding the optic disc. Color and red-free fundus photography showed the retinal white dots disappeared. SD-OCT indicated the IS-OS disruption resolved with reestablishment of outer retina OCT anatomy (Figure 3).

dISCuSSIoNMEWDS is an acute, usually unilateral retinopathy that predomi-

nantly affects macular and mid-periphery regions of young women, causing mild to moderate visual loss. Characteristic symptoms inclu-de photopsia, and a viral prodrome is reported in 50% of the cases. In this case report, the patient was a young male who had unilateral visual loss. He had flu-like symptoms 1 week before the initial evalua-tion, and did not present with photopsia(1,2).

Figure 1. A) Retinography demonstrating normal foveal aspect in the right eye. B) Retinography demonstrating foveal granularity in the left eye.

A B

Figure 2. Multiple evanescent white dot syndrome lesions. A) Fluorescein angiography demonstrating early hyperfluorescent lesions. B) Fluorescein angiography, in late stage, demonstrating staining of the white dots in a wreath­like pattern and disc capillary leakage. C) Indocyanine green angiography, in the early phase, showing discrete hypofluorescent nummular lesions. D) Indocyanine green angiography (late phase) showing numerous clearly delineated hypofluorescent nummular lesions.

A

C d

B

Lavigne LC, et al.

187Arq Bras Oftalmol. 2014;77(3):185-7

In the present case, FA demonstrated typical early hyperfluores-cence with late RPE staining, corresponding to hypofluorescent areas in the late phase of ICGA(1,5). These hypofluorescent areas showed moderately reflective focal lesions in the outer photoreceptor layer, where the macular photoreceptor IS-OS junction was disrupted by SD-OCT, which is associated with foveal granularity. Possibly, the foveal granularity is the most specific characteristic of MEWDS(1,4,8,9).

Considering the clinical and angiographic pattern, and through electrophysiological evidence, previous studies have suggested that the white dot lesions in MEWDS are situated in the RPE and outer re-tina. Electrophysiology analysis has revealed an electro-oculographic reduction in the light-dark ratio, and an electroretinographic altera-tion of the a-wave and early receptor potential(6,8).

Ophthalmologic studies have advocated the hypothesis that injury to the RPE is the early pathologic event in MEWDS. FA showed characteristic early hyperfluorescent lesions that were observed as window defects. It was suggested the primary site of MEWDS is on the RPE(2,6). With the clinical use of ICGA, MEWDS has become known as a choroidopathy, suggesting that the cause of the photoreceptors and RPE dysfunction is associated to decreased perfusion of the choriocapillaris(4-6,10). This supposition is based on their angiographic pattern that demonstrated hypofluorescent lesions on ICGA that may appear even in normal areas on FA and funduscopy(6).

In the case reported here, the FA pattern demonstrated characte-ristic early hyperfluorescence and late staining, which appeared to be due to RPE changes; however, the ICGA showed numerous hypofluo-rescent areas mainly in the mid-periphery. These hypofluorescent areas are mild in initial angiographic phases and become more evi dently delineated in the late phase, which appears to slightly outnumber those observed on FA, suggesting that MEWDS involves both RPE and choriocapillay(2,8).

In this case ICGA was not crucial to diagnosis, because of other classic findings, but it was useful to confirm diagnosis and also in diffe-rential diagnosis with other white dot syndromes. Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) has been con-

sidered an important differential diagnosis. FA patterns in APMPPE show early hypofluorescence, but become hyperfluorescent later in the study. In ICGA, lesions present as early to late hypofluorescence.

MEWDS has been considered the first known disease involving electrophysiological damage of photoreceptor outer segments with complete return to normal conditions(8). We report a case of MEWDS notable for both its classic retinal appearance, confirmed by auto-mated perimetry, FA, ICGA, and SD-OCT exams. SD-OCT has showed disruption of the IS-OS junction. The patient was observed with no medical intervention, and had a favorable recovery of visual function and macular photoreceptor IS-OS junction in SD-OCT. This is consis-tent with previous report and OCT findings about the disease.

REFERENCES 1. Hua R, Chen K, Liu LM, Liu NN, Chen L, Teng WP. Multi-modality imaging on multiple

evanescent white dot syndrome - A Spectralis Study. Int J Ophthalmol. 2012;5(5):644-7. 2. Kuznetcova T, Jeannin B, Herbort CP. A case of overlapping choriocapillaritis syn-

dromes: multimodal imaging appraisal. J Ophthalmic Vis Res. 2012;7(1):67-75. 3. Abu-Yaghi NE, Hartono SP, Hodge DO, Pulido JS, Bakri SJ. White dot syndromes: a

20-year study of incidence, clinical features, and outcomes. Ocul Immunol Inflamm. 2011;19(6):426-30.

4. Nguyen MH, Witkin AJ, Reichel E, Ko TH, Fujimoto JG, Schuman JS, Duker JS. Mi-crostructural abnormalities in MEWDS demonstrated by ultrahigh resolution optical coherence tomography. Retina. 2007;27(4):414-8.

5. Vianna RNG, Socci D, Nehemy MB, Deschênes J, Burnier MN Jr. The white dot syn-dromes. Arq Bras Oftalmol. 2007;70(3):554-62.

6. Penha FM, Navajas EV, Bom Aggio F, Rodrigues EB, Farah ME. Fundus autofluorescence in multiple evanescent white dot syndrome. Case Rep Ophthalmol Med. 2011;807565.

7. Slusher MM, Weaver RG. Multiple Evanescent White Dot Syndrome. Retina. 1988; 8(2):132-5.

8. Silva RA, Albini TA, Flynn HW Jr. Multiple evanescent white dot syndromes. J Ophthal-mic Inflamm Infect. 2012;2(2):109-11.

9. Saito M, Barbazetto IA, Spaide RF. Intravitreal cellular infiltrate imaged as punctate spots by spectral-domain optical coherence tomography in eyes with posterior segment in flammatory disease. Retina. 2013;33(3):559-65.

10. Papadia M, Herbort CP. Idiopathic choroidal neovascularisation as the inaugural sign of mul tiple evanescent white dot syndrome. Middle East Afr J Ophthalmol. 2010;17(3):270-4.

Figure 3. A) Spectral Domain Optical Coherence Tomography (SD­OCT) demonstrating mild attenua­tion of the external limiting membrane, disruption of the macular photoreceptor inner segment­outer segment (IS­OS) junction, and increased RPE reflectivity. B) SD­OCT demonstrating resolution of IS­OS disruption with reestablishment of outer retina OCT anatomy.

A

B

Case Report

188 Arq Bras Oftalmol. 2014;77(3):188-90 http://dx.doi.org/10.5935/0004-2749.20140048

INtRoduCtIoNSusac syndrome (SS), also known as retinal-cerebral-cochlear di -

sea se, although rare, needs to be considered as a differential diagnosis when unexplained visual field or visual acuity loss is detected in a patient. The triad of clinical symptoms that may not all be present at initial stages include diffuse encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss(1).

The etiology and pathogenesis of SS are not clearly understood. Autoimmune processes leading to the damage and inflammation-re-lated occlusion of the microvessels in the brain, retina, and inner ear may play a causal role(2). Electroencephalogram, audiometry, fluores-cein angiography (FA), and magnetic resonance imaging (MRI) of the brain sensitively detects the lesions(3).

Retinal abnormalities may have different clinical features. When arteriolar abnormalities are observed close to the central vision, symptoms of visual loss are more evident and the diagnosis may be faster. However, most cases have peripheral arteriolar micro-occlusive events, resulting in late ophthalmologic evaluation(4).

Multifocal arteriolar wall hyperfluorescence and peripheral branch artery occlusion can occur in normal-appearing fundus. Gass plaques (GP), which are yellow-white deposits seen at the mid segments of the arteriole, are a helpful finding for the diagnosis(5). If an initial FA is normal, it should be repeated at intervals during the early course

of definite or suspected SS. FA abnormalities serve as a valuable bio-marker, and serial FA may be useful in monitoring the effect of the treatment(1).

The natural history and outcomes of SS are not fully understood. The disease may be active for several months and the time to remis-sion can be long(4). After remission it results in various cognitive and functional damages. However, serious loss of vision is not observed in the majority of the patients.

The objectives of this study were to report a case of SS, its clinical manifestations, and to discuss the variability in clinical findings as well as management.

RESuLtS A 19-year-old female was referred by a neurologist because of

visual field loss in the left eye that lasted for 10 days. Three months earlier, the patient was examined for neurological abnormalities associated with bilateral hearing loss and underwent audiometry, impedance testing, brain MRI, and laboratory evaluations. The au-diometry showed severe sensorineural hearing loss in the right ear and moderate sensorineural hearing loss in the left ear. The brain MRI showed multiple small lesions in the white matter in both cerebral hemispheres and at the corpus callosum (Figure 1). The total com-

Susac syndrome: diverse clinical findings and treatmentSíndrome de Susac: achados clínicos diversos e tratamento

rIcardo canto bardaL1, eMMerson badaro2, JayMe arana3, FabIo aLves3, eduardo cunha de souza2, Pedro PauLo bonoMo2, ezequIeL PorteLLa3, MaurIcIo MaIa2

Submitted for publication: December 2, 2013 Accepted for publication: December 6, 2013

Study conducted at Department of Ophthalmology, Hospital Evangélico, Curitiba, PR and Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

1 Department of Ophthalmology, Hospital Evangélico, Curitiba, PR, Brazil.2 Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.3 Paraná Eye Hospital, Curitiba, PR, Brazil.

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: Mauricio Maia. Rua Otto Ribeiro, 901 - Assis (SP) - 19840-050 - Brazil - E-mail: maiamauricio@terra.com.br

RESUMORelatamos o caso de uma mulher de 19 anos apresentando perda auditiva neu-rossensorial bilateral, anormalidades mentais e perda de campo visual no olho es querdo. A acuidade visual era 20/20 em OD e 20/25 em OE. Paciente foi sistemati-camente investigada, audiometria mostrou perda auditiva neurossensorial nos dois ouvidos e ressonância magnética nuclear (RNM) cerebral mostrou múltiplas pequenas lesões na substância branca em ambos os hemisférios cerebrais e no corpo caloso. A fundoscopia mostrou disco óptico normal bilateral, e embainhamento das arteríolas na média periferia do olho direito. Edema de retina e exsudatos algodonosos foram vistos. Angiofluoresceinografia mostrou vasculopatia arterial obstrutiva periférica bilateral. A paciente foi diagnosticada com síndrome Susac e tratada com fumarato de quetiapina, flunitrazepam e prednisona resultando em estabilização do quadro. Este caso mostra que um alto índice de suspeita levando ao reconhecimento precoce e tratamento é importante para evitar o diagnóstico tardio.

Descritores: Síndrome de Susac; Oclusão da artéria retiniana; Perda auditiva; Cor po caloso; Angiofluoresceinografia; Humano; Femino; Adulto; Relatos de casos

ABStRACtWe report a case of a 19-year-old woman presenting bilateral neurosensorial hea-ring loss, mental abnormalities, and loss of visual field in the left eye. Visual acuity was 20/20 in OD and 20/25 in OS. Patient was examined systemically. Audiometry showed sensorineural hearing loss in both ears. The magnetic resonance imaging (MRI) of brain revealed multiple small lesions in the white matter in both cerebral hemispheres and at the corpus callosum. Fundoscopy showed bilateral normal optic disc and sheathing of the arterioles in the middle periphery of OD. Retinal edema and cotton-wool spots were observed. Fluorescein angiography showed bilateral peripheral occlusive arterial vasculopathy. The patient was diagnosed with Susac syndrome and treated with quetiapine fumarate, flunitrazepam, and prednisone, which resulted in stabile outcome. This case shows that a high index of suspicion leading to early recognition and treatment is important to avoid irreversible damage.

Keywords: Susac syndrome; Retinal artery occlusion; Hearing loss; Corpus callosum; Fluorescein angiography; Humans; Female; Adult; Case reports

Bardal RC, et al.

189Arq Bras Oftalmol. 2014;77(3):188-90

Figure 2. FA images of both eyes of patient 2 shows microarterial nonperfusion in the peripheral retina. A) Microarterial occlusion in the peripheral retina temporosuperiorly in the left eye. B) A similar image of the peripheral retina temporally in the left eye shows a clearer image of the nonperfused arterioles. C) Unusual leakage pattern of arterial wall hyperfluorescence in the temporal inferior area not located in the arterial occlusion area. D) FA of the right eye shows important nonperfusion of the arterioles in the temporosuperior quadrant of the retina.

A

C

B

d

Figure 1. Brain MRI showing multiple small lesions at the corpus callosum.

plement, complement 3 and 4, antinuclear factor, thyroid-stimulating hormone, and T4 thyroid level were normal.

Ophthalmologic examination showed best corrected visual acuity (BCVA) of 20/20 in OD and 20/25 in OS. Fundoscopy showed bilateral normal optic disc and sheathing of the arterioles in the middle periphery of OD. Retinal edema was seen in the temporal inferior quadrant and at the mid-peripheral temporal superior region associated with cotton-wool spots and sheathing of the arterioles nasally in the left eye.

FA showed bilateral normal choroidal perfusion -arterial nonper-fusion at the peripheral superior and nasal inferior areas in right eye (OD) and in late phase temporal and inferiorly in left eye (OS), suggesting bilateral peripheral occlusive arterial vasculopathy, which was more evident in the left eye. Unusual leakage pattern of arterial wall in the temporal inferior area, but not located in the arterial occlusion area was noted in the right eye (Figure 2).

The clinical findings and the exclusion of other diseases resulted in the diagnosis of SS. Quetiapine fumarate (100 mg/day), flunitra-

Susac syndrome: diverse clinical findings and treatment

190 Arq Bras Oftalmol. 2014;77(3):188-90

zepam (0.5 mg/day), and prednisone (40 mg/day) were prescribed. Photocoagulation was applied to the ischemic areas to prevent re-tinal neovascularization.

dISCuSSIoNSusac syndrome has an unknown etiology and is associated with

varying outcomes(2,4,6). If not suspected of having the syndrome, the diagnosis may be delayed. Once the diagnosis is made, close neuro-logic, otorhinolaryngologic, and ophthalmologic follow-up exami-nations are very important(3) since the damage could be irreversible.

A specific routine for the management of this disease has not been described and approaches can be didactically divided into two strategies, namely the management of complications and the prevention of recurrences. The complications must be evaluated and treated according to the preference of the ophthalmologist to reestablish function. ASA, anticoagulants, steroids, immunosuppressors, and immunoglobulins have been shown to be effective for the pre-vention of recurrence(6-8).

We observed no neovascularization in the peripheral retina and a BCVA of 20/20 in the case.

The current study was limited by the retrospective design, the di versity of the therapeutic approaches, and the difficulties in eva-luating the efficacy of treatment. However, the results of our study, which analyzed the diversity in systemic manifestations from early symptoms are important due to the low disease prevalence.

Susac syndrome is considered as a rare disease. A high index of sus picion, which could lead to early recognition and treatment is im-portant to avoid late diagnosis and to minimize the risk for persistent impairment. Prospective studies analyzing the effectiveness of the proposed treatments are critical for the establishment of therapeutic approaches for each clinical finding.

REFERENCES 1. Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac’s Syndrome-update. J Neurol Sci.

2010;299(1-2):86-91. 2. Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac syndrome: 1975-2005 microan-

giopathy/autoimmune endotheliopathy. J Neurol Sci. 2007;257(1-2):270-2. 3. Dorr J, Jarius S, Wildemann B, Ringelstein EB, Schwindt W, Deppe M, et al. [Susac

syndrome: an interdisciplinary challenge]. Nervenarzt. 2011;82(10):1250-63. Epub 2011/04/12. Susac-Syndrom: Eine interdisziplinare Herausforderung.

4. Milbratz GH, Marquardt FA, Guimaraes Neto HP, Marquardt DA, Souza ES. Retinal vasculitis in Susac syndrome: case report. Arq Bras Oftalmol. 2009;72(3):397-9. Epub 2009/08/12.

5. Egan RA, Ha Nguyen T, Gass JD, Rizzo JF, 3rd, Tivnan J, Susac JO. Retinal arterial wall plaques in Susac syndrome. Am J Ophthalmol. 2003;135(4):483-6. Epub 2003/03/26.

6. Rennebohm RM, Susac JO. Treatment of Susac syndrome. J Neurol Sci. 2007;257(1-2): 215-20.

7. Naacke H, Heron E, Bourcier T, Borderie V, Laroche L. [A new case of Susac syndrome and a review of the literature]. J Fr Ophtalmol. 2003;26(3):284-9. French.

8. Coppeto JR, Currie JN, Monteiro ML, Lessell S. A syndrome of arterial-occlusive reti- nopathy and encephalopathy. Am J Ophthalmol. 1984;98(2):189-202.

XXV Congresso Cearense de oftalmologia

13 a 15 de novembro de 2014Hotel Oásis Atlântico

Fortaleza - CE

informações: Tel.: (85) 3264-9404

E-mail: sco@sco.med.br

Case Report

191Arq Bras Oftalmol. 2014;77(3):191-2http://dx.doi.org/10.5935/0004-2749.20140049

INtRoduCtIoNA 28-year-old female was referred to the Universidade Federal de

São Paulo (UNIFESP), Department of Refractive Surgery in 2010 for refractive surgery. Her refraction was -3.25 D -0.75 D 160° (OD) and -3.25 D -0.75 D 180° (OS). Corneal topography revealed an asymmetry of less than 0.5 diopters in the left eye (Figure 1). Corneal thickness of right eye was 590 µm and the left eye was 591 µm. We performed wavefront-guided laser-assisted in situ keratomileusis (LASIK) surgery in both the eyes using a Moria M2 microkeratome and LADARVision excimer laser with an ablation depth of 63.8 µm in the right eye and 70.5 µm in the left eye. There were no immediate postoperative com -plications and the uncorrected visual acuity was 20/20 bilaterally.

Four months after the procedure, the patient returned with a complaint of decreased visual quality in the right eye. Visual acuity was 20/25 uncorrected and 20/20 with -0.25 D -0.50 D 15° lenses. A comparison of corneal topography findings between postoperative months 1 and 4 (Figure 2) showed inferior corneal steepening (>1 diopter) in the right eye and a diffuse increase in corneal curvature (<1 diopter) in the left eye. Corneal optical coherence tomography (OCT, Figure 3) showed an abnormally thick flap (200-220 µm), whereas aberrometry showed a high RMS (0.84) and an increase in the negative vertical coma. As the patient was scheduled to leave the country within a week for her doctoral studies in Barcelona, we chose to perform under-the-flap intrastromal corneal crosslinking.

operative teChnique

The flap was partially lifted with a corneal spatula so as to enable separation of the stroma above and under the flap, but without lifting the entire flap (Figure 4). A 0.1% riboflavin solution was injected into the stroma at 15-minute intervals for 30 minutes. Crosslinking was

RESUMODescrevemos um caso de ectasia de córnea precoce após cirurgia de LASIK, detectado no primeiro semestre pós-operatório. Nós optamos tratar este paciente com “crosslinking” embaixo do “flap”, sem desepitelização com bons resultados. A paciente permaneceu sem progressão da ectasia até o momento atual, dois anos após o procedimento.

Descritores: Astigmatismo; Procedimentos cirúrgicos refrativos; Ceratomileuse assistida por excimer laser in situ; Aberrações de frente de onda da córnea; Reagentes para ligações cruzadas; Substância própria; Complicações pós-operatórias; Humanos; Feminino; Adulto; Relatos de casos

ABStRACtWe describe a case of early post-LASIK ectasia detected in the first 6 months after surgery. The patient was treated by means of intrastromal corneal crosslinking under the flap, without de-epithelialization, which resulted in a positive outcome. At the time of writing, 2 years after the procedure, the patient remained free of progression.

Keywords: Astigmatism; Refractive surgical procedures; Keratomileusis, laser in situ; Corneal wavefront aberrations; Cross-linking reagent; Corneal stroma; Pos-toperative complications; Humans; Female; Adult; Case reports

performed by standard technique by irradiating with 365 nm UV-A light of intensity 3.0 mW/cm2.

Following surgery, the patient was prescribed with a 3-week course of low-dose corticosteroids (topical fluorometholone), a 1-week course of a fourth-generation quinolone (topical gatifloxa-cin), and artificial tears for every 6 hours. Three days after the procedu-re, the uncorrected visual acuity in the treated eye was 20/25, with the typical corneal haze commonly observed in the early postoperative period of crosslinking in the flap area. The patient traveled as origi-nally scheduled with instructions for eye care and under guidance to seek ophthalmologic evaluation in Barcelona.

RESuLtSThe patient returned to our service for 1-year follow-up and was

asymptomatic. The visual acuity was 20/20 in both eyes (OD: -0.75 D cyl 180°, OS: -0.25 D cyl 140°), and corneal topography showed absence of disease progression bilaterally.

dISCuSSIoNPost-LASIK corneal ectasia is a non-inflammatory process that

results in deformation of the cornea along with thinning and biome-chanical weakening(1-10).

Crosslinking is the gold-standard treatment for progressive corneal ectasia. However, it is often difficult to convince post-LASIK patients with early-stage ectasia to undergo this procedure because of slow and painful recovery periods(1-6).

Some researchers have focused on preventing corneal de-epi-thelialization so as to achieve efficient and recovery from corneal

Intrastromal crosslinking in post-LASIK ectasia“Crosslinking” intraestromal em ectasia pós-LASIK

bernardo kaPLan MoscovIcI1, Mauro caMPos1

Submitted for publication: August 12, 2013 Accepted for publication: December 6, 2013

Study conducted at Department of Ophthalmology, Refractive Surgery Service, Universidade Federal de São Paulo.

1 Department of Ophthalmology, Refractive Surgery Service, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

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: Bernardo Kaplan Moscovici. Rua Apiacás 600/84 - São Paulo - (SP) - 05017-020 - Brazil - E-mail: bernardokaplan@yahoo.com.br

Intrastromal crosslinking in post-LASIK ectasia

192 Arq Bras Oftalmol. 2014;77(3):191-2

Figure 1. Preoperative corneal topography showing an asymmetry of less than 0.5 diopters in the left eye.

Figure 3. Postoperative optical coherence tomography of the cornea measuring the LASIK flap, showing an abnormally thick flap.

Figure 4. Illustration of the new technique: The flap was partially elevated with a corneal spatula to enable separation of the stroma above and under the flap, but without lifting the entire flap. A 0.1% riboflavin solution was injected into the stroma at 15­minute intervals for 30 minutes and after the crosslinking was performed.

crosslinking. In one such study, femtosecond laser was used to create a pocket, and riboflavin was administered for only 2 minutes before UV-A irradiation(6). We propose a new technique in which riboflavin is injected under the flap. As a preexisting flap is used, no decrease in biomechanical power of the cornea should occur. The only disad-vantage of this technique over the usual procedure is the possibility of epithelial ingrowth, which can be easily avoided if the procedure is performed with care.

Double-blind, randomized, case-control studies are required to provide more reliable data, but this procedure appears simple, safe, and effective technique for management of post-LASIK ectasia.

REFERENCES 1. Brenner LF, Alió JL, Vega-Estrada A, Baviera J, Beltrán J, Cobo-Soriano R. Indications

for intrastromal corneal ring segments in ectasia after laser in situ keratomileusis. J Cataract Refract Surg. 2012;38(12):2117-24.

2. Sakhtar S, Kirat O, Alkatan HT, Almubrad T. Stromal alteration in post-lasik ectasia córnea. Acta Ophthalmologica. 2012:90 Suppl.:S249.

3. Peinado TF, Pinero DP, López IA, Alió, JL. Correlation of both corneal surfaces in cor-neal ectasia after myopic LASIK. Optom Vis Sci. 2011;88(4):E539-42.

4. Gaster RN, Cnedo ALC, Rabinowits YS. Corneal collagen cross-linking for keratoconus and Post-LASIK ectasia. Int Ophthalmol Clin. 2013 Winter;53(1):79-90.

5. Kanellopoulos AJ, Collagen Cross-linking in Early Keratoconus with riboflavin in a femtosecond laser-created pocket: initial clinical results. J Refract Surg. 2009;25(11): 1034-7.

6. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia Risk Score System for Preoperative Laser In Situ keratomileusis screening. Am J Ophthalmol. 2008;145(5): 813-8.

7. Spadea L, Cantera E, Cortes M, Conocchia NE, Stewart CW. Corneal ectasia after myo-pic laser in situ keratomileusis: a long-term study. Clin Ophthalmol. 2012;6:1801-13 .

8. Poli M, Cornut PL, Balmitgere T, Aptel F, Janin H, Burillon C. Prospective study of corneal collagen cross-linking efficacy and tolerance in the treatment of keratoconus and corneal ectasia: 3-year results. Cornea. 2013;32(5):583-90.

9. Coskunvensen E, Jankov MR 2nd, Hafezi F, Atun S, Arslan E, Kymionis GD. Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus. J Cataract Refract Surg. 2009;35(12):2084-91.

10. Kiliç A, Kamburoglu G, Akinci A. Riboflavin injection into the corneal channel for combined collagen crosslinking and intrastromal corneal ring segment implantation. J Cataract Refract Surg. 2012;38(5):878-83. Comment in: J Cataract Refract Surg. 2012; 38(10):1878-9; J Cataract Refract Surg. 2012;38(10):1879-80.

Figure 2. Differential corneal topography between first and fourth month postoperative, showing a steepening in both eyes, more evident in the right eye.

Review Article

193Arq Bras Oftalmol. 2014;77(3):193-200http://dx.doi.org/10.5935/0004-2749.20140050

INtRoduCtIoN Epidemiological studies have indicated increasing incidence of

dry eye disease (DED) in the worldwide population(1-3). This com-mon ocular condition has multiple causes, which are not entirely understood. The emerging awareness that environmental factors can contribute to DED is supported by some recent studies and reflects diffe rences in cultural traditions and exposure to unfavora-ble working conditions. In these groups, the impact of environmental factors in DED demands further characterization to develop strategies to reduce its incidence(4,5). Due to the apparent relationship between the aforementioned environmental influences and DED, this disease can be better defined by delineating Environmental Dry Eye Disease (EDED) as a clinical subtype of DED.

We summarize herein our current understanding of environmental causes for DED. However, this review does not deal with some other relevant exogenous factors, such as usage of drugs and alcohol as their effects were recently well addressed(6,7). In addition, we omitted the effect of nutritional factors on DED, which due to its extension and complexity deserves an entire review.

EDED is not only an association between environmental condi-tions and well-defined ocular surface inflammatory conditions, it is considered as a clinical subtype of DED (Table 1). In EDED cases, the inflammatory conditions and ocular discomfort are followed by changes in tear film composition volume and osmolarity, which may persist even after the individuals are no longer exposed to the related environmental factors. In one example of EDED, following an environmental accidence the symptoms persisted for two years(8-10).

EDED is strongly influenced by one or more environmental factor. Additionally, improper diagnosis of toxic keratoconjunctivitis, solar keratitis, allergic keratoconjunctivitis or some other types of ocular surface disease can contribute to EDED. These conditions show simi-lar symptoms and environmental factors on the existing condition further leading to EDED. It is likely that some overlap exists among the mediators of these diseases. This review focuses on some unique environmental factors distinctive of EDED (Figure 1).

EDED gained relevance based on the recognition that environ-mental factors can be deleterious to human health and contributes to DED(11,12). The impact of the environment in the pathophysiology

Is dry eye an environmental disease?O olho seco é uma doença relacionada a exposição ambiental?

MonIca aLves1, PrIscILa novaes2, MonIca de andrade Morraye3, Peter soL reInach1, eduardo MeLanI rocha1

Submitted for publication: April 15, 2014 Accepted for publication: June 4, 2014

Study conducted at Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Universidade de São Paulo - Ribeirão Preto (USP-RP).

1 Universidade de São Paulo, Ribeirão Preto, SP, Brazil2 Universidade de São Paulo, São Paulo, SP, Brazil3 Universidade de Franca, Franca, SP, Brazil

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: Monica Alves. Department of Ophthalmology, Otorhinolaryngology and Head & Neck Surgery. Faculty of Medicine of Ribeirão Preto, University of São Paulo. Av. Bandeirantes, 3.900 - CEP 14049-900 - Ribeirão Preto, SP, Brazil - E-mail: monicalves1@uol.com.br

ABStRACtPrevious studies have revealed that eye contact with either air pollutants or adverse indoor and/or outdoor environmental conditions can affect tear film composition and ocular surface components. These effects are mediated by selective binding of the environmental agents to ocular surface membrane receptors, leading to activation of pro inflammatory signaling pathways. The aim of the current review was to examine the published evidence associated with environmental factors and ocular surface disease and dry eye. Specifically, the reader will appreciate why it is possible to refer to them as mediators of Environmental Dry Eye Disease (EDED), a singular clinical entity inside DED context, directly caused by pollutants and/or adverse climatic conditions. The indicators and clinical findings are described along with EDE differential diagnosis in its acute and the chronic phases. Based on strong existing evidence of clinical reports and epidemiological observations regarding DED and environmental factors we conclude that there is a straight cause-and-effect relationship between ambient stresses and DED. International standards and web-based tools are described for monitoring worldwide envi-ronmental conditions referring localities and populations susceptible to EDED. This information is beneficial to health providers to pinpoint the individuals and predisposed groups afflicted with DED. Such insights may not only improve the understanding and treatment of DED but also help to identify the contributing factors and lower the frequency and progression of EDED.

Keywords: Dry eye syndromes; Lacrimal apparatus diseases; Environmental illness; Environmental pollutants/adverse effects

RESUMODiversos estudos têm demostrado que o contato ocular com poluentes ambientais afeta a composição do filme lacrimal e de estruturas da superfície ocular. Tais efeitos são mediados pela ligação de agentes ambientais com receptores na superfície ocular, levando a ativação de mediadores pró inflamatórios. Esta revisão propõe uma avaliação das evidências publicadas, que associam fatores ambientais as doenças de superfície ocular e ao olho seco. O leitor compreenderá que é possível inferir olho seco ambiental como uma entidade singular dentro do contexto da doença olho seco, diretamente causado pela exposição a poluentes e/ou condições climáticas adversas. Serão descritos os indicadores e achados clínicos, assim como o diagnóstico diferencial das fases aguda e crônica. A avaliação de relatos clínicos e observações epidemiológicas demonstra uma forte associação entre olho seco e fatores ambientais. O conhecimento sobre parâmetros internacionais e ferramentas de monitorização das condições ambientais no mundo, permite identificar localidades e populações mais suceptívies ao olho seco ambiental e pode auxiliar na identificação de indivíduos acometidos e grupos predispostos. E desta forma, melhorar o entendimento e tratamento dessa condição, diminuir os fatores associados, sua frequência e progressão.

Descritores: Síndromes do olho seco; Doenças do aparelho lacrimal; Doença am-biental; Poluentes ambientais/efeitos adversos.

Is dry eye an environmental disease?

194 Arq Bras Oftalmol. 2014;77(3):193-200

of DED has been studied and confirmed in animal models of human DED(13-15).

As indicated, a healthy and pain-free ocular surface depends on identifying and eliminating factors that cause ambient humidity, airflow and purity, and temperature to intolerable levels. Such an undertaking is needed to preserve tear film qualities commensurate with ocular surface health. This is essential to sustain sufficient corneal refractive power, visual acuity, and ocular comfort(5,16,17).

A desiccating environment can lead to increase in tear film eva-poration and/or decline in its turn over and clearance. These initial events lead to exposure of the ocular surface to hazardous environ-mental elements that trigger or exacerbate EDED symptoms. Clinical findings have shown that increased numbers of people are affected by EDED because of exposure to environmental factors (Figure 2).

Our purpose herein is to provide a critical appraisal of the clinical and epidemiological evidence indicating that DED is influenced by environmental factors. Secondly, we delineate EDED as a single clinical entity with a unique set of symptoms and clinical findings different from that of either DED or other diseases, such as Sjögren’s syndrome, diabetes mellitus or drug induced, allergic conjunctivitis, toxic or irritative conjunctivitis, and actinic keratitis. Moreover, we will describe standard tools used to monitor environmental conditions and discuss their relevance in EDED epidemiological studies. This review enables the health care providers and researchers to identify the environmental risk factors associated with the development and progression of EDED. This initiative intends to help future studies to improve our understanding and care for this possibly common and complex disease.

Environmental Dry Eye Disease (EDED) can be considered a cli -nical entity that qualifies the definition of DED(18). The most relevant causal factor is environmental exposure, such as pollutants and/or adver se climate. On the other hand, causative factors related to syste-mic di seases (endocrine, metabolic, nutritional, autoimmune, genetic, viral or neurologic), anti-cholinergic, adrenergic or other drug-related side effects are considered as exclusion factors to maintain EDED as a distinct disease entity within the DED envelope.

EDED differential diagnosis comprises the entities shown in table 1. Possible non-environmental factors or undiagnosed causes of

DED were also considered as differential (for example a suspected Sjögren’s syndrome was not investigated to fulfill the criteria). From this perspective, diseases that were labeled as “pollution keratocon-juncitivitis,” “computer vision syndrome,” and other environmentally related encounters, due to DED clinical presentation would be defi-

table 1. differential diagnosis of Environmental dry Eye disease

disease Causes Clinical features

Solar keratitis (19) UV exposure Keratosis of exposed skin, burning sensation, redness, punctate keratitis

Allergic keratoconjunctivitis(10)(20) Allergy History of allergy, redness, itching, swelling

Floppy eyelid syndrome(21) Rubbery, redundant upper tarsus Lid eversion with minimal pressure. Redness, papillary conjunctivitis

Corneal hiperalgesia(22) Up regulated nocioreception triggered by corneal damage

Disparity between signs and symptoms, corneal sensory deficit and decreased sensory nerve population

Ligneous conjunctivitis(23) Impaired mucosal wound healing and fibrosis due to plasminogen deficiency

Chronic membranous conjunctivitis triggered by local trauma

Mucous fishing syndrome(24) Excess of mucous manipulation Secretion, redness, and foreign body sensation along with signs of epithelial trauma due to discharge of mucus

Pseudopemphigoid(25) History of topical drug exposure. Redness, tearing, itching, and progressive fibrosis of conjunctiva

Chronic blepharitis(26) Dysfunction of lipid production and secretion and epithelial metaplasia

Lid erythema, greasy crusting secretion. Redness and irritation of the eye Seborrhea in other sites of the body

Stevens-Johnsons Syndrome(27) Autoimmune disease triggered by drug or microorganism

Acute: systemic epithelial bullous swelling. Chronic: ocular surface fibrosis, corneal vascularization, and recurrent epithelial defect

Toxic keratoconjunctivitis(28) Toxic agent traumatic, iatrogenic or factitious contact with ocular surface

Variable, depending on agent and time. Commonly, acute epithelial swelling, redness, and tearing

Figure 1. Illustration of conditions whose signs and symptoms may overlap with envi­ronmental dry eye disease clinical presentation.

Figure 2. Environmental factors that influence tear film and ocular surface indoors and outdoors (air borne particles, air flow, temperature, ultraviolet rays).

Alves M, et al.

195Arq Bras Oftalmol. 2014;77(3):193-200

ned as EDED(29-31). Patients can be afflicted with EDED due to expo-sure to a variety of environmental stresses. Conditions that elicit this disease are patient dependent(32,33). To establish a minimal normative classification for research and clinical purposes and therapeutic mea-sures, the following environmental factor categories are included:

Indoors: closed ambient like office settings, such as variations in airflow, humidity, time in front of computer and other video displays, and exposure to toxic elements (for example offices, health care fa-cilities, poorly ventilated confinements such as subway stations and other employment areas).

Outdoors: exposure to open areas with extreme temperatures, gases and/or air suspended particles in the desiccating wind, intense UV exposure, agricultural usage of state of the art technology and mechanization, petrochemical industries, urban traffic, and other polluted environments.

Although the clinical signs of EDED can be similar among indivi-duals exposed to either indoor or outdoor environmental factors, the detection preventive, and therapeutic methods are specific for each of these different settings. Additionally, the combined exposure to indoor and outdoor factors is also plausible.

Since the 1960’s, exposures to environmental factors such as air pollution had been correlated with ocular surface irritation, resulting in symptoms of hyperemia, swelling, tearing, and dry eye sensation(34).

EDED patients present a broad range of symptoms, the most common being sorrow eyes and visual fatigue. The scores obtained from structured questionnaires have been used for the analysis. One of them is the Ocular Symptom Disease Index (OSDI), which evaluates DED severity rather than EDED(35-37). In order to correlate ocular sur-face related DED signs with environmental activities, an interesting activity log for DED was recently developed and tested in patients. However, individual differences in pain perception or exposure to environmental hazards in DED initiation were not evaluated(5).

EDED is distinguishable from aforementioned, because it is chronic and is associated with environmental factors. Such clinical findings are identifiable by the clinician/researcher investigating the disease. EDED identification stems from controlled observations about pollu-tion-induced ocular alterations, such as blinking rate, tear film break up time (TFBUT), and corneal epithelia damage(38,39).

Tear film instability is a consistent finding in studies that showed an association between air pollution and ocular surface damage(37,40-42). Such an effect compromises the corneal epithelial barrier function resulting in corneal and conjunctival epithelial chronic injury and in flammation.

A recent study has described a possible early adaptive response to air pollution in which increased levels of air pollution reduce tear film osmolarity and conjunctival goblet cell density(8,37). This negative cor-relation is indicative of EDED whereby increase in air pollution and/or desiccation are thought to have an early reactive phase followed by a chronic adaptive/metaplastic phase. Clinical findings can help to iden-tify the contributions of exposure time to EDED progression (Table 2).

On the other hand, it is possible that other clinical signs may be asso-ciated with the disease, complicating a definitive diagnosis. For example, larger lid opening, lower mucous production, slower blinking rate, and reduced tear film clearance. Such symptoms may be found in different individuals afflicted with different degrees of EDED severity even if they are exposed to the same adverse environmental factors. Future studies are needed to characterize and weigh the individual contributions of commonly observed environmental factors to EDED progression.

epidemiology of dry eye related to environmental faCtorS Outdoor EDED risk factors include exhaust emissions from automo-

biles and industrial facilities common in densely populated cities(43,44). Furthermore, occupational hazards related to large-scale agriculture and sugar cane processing can lead to exposure to gases, particulate matter, UV exposure, and altered microbiota(45,46).

On the other hand, indoor environmental conditions involving low humidity, excessive use of video display units (VDU), and high levels of CO

2 can be equally threatening to ocular surface health(4,47-49).

Case-control studies confirm the cause-effect relationship between the indoor or outdoor environmental conditions and the irritant symptoms in exposed individuals(49,50). Also, the individual risk factors are similar to those in other populations afflicted with other types of DED(51). They include aging, females, allergic or autoimmune condi-tions, and usage of contact lenses(4,48,52-55).

Part of the confusion that persists about EDED recognition is because individuals exposed to high air pollution levels are often at greater risk of developing allergies and present more symptoms(55). Moreover, there is also an association between increase in air pollu-tion and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematous(56-58). There is also speculation about the existence of an “urban allergy syndrome” (Table 3)(59). Such individuals have a higher incidence of ocular surface inflammation and DED.

Although the acceptable levels of pollutants are established by national and world agencies (see below), the cut-off limits of the most harmful pollutants and environmental risk factors to the ocular sur-face capable to induce EDED are unknown. If more than one factor is involved, depending upon their characteristics they may interact at lower threshold values and induce EDED. Accordingly, the detrimen-tal effects of environmental toxic agents on EDED epidemiology are not entirely understood(43,44,60-62).

The impact of urban pollution and environmental toxins on the ocular surface has been evaluated in a few case-control studies. These studies reported a high incidence of ocular discomfort, tear film ins-tability, and ocular surface changes among individuals lived in highly polluted cities of the world (Table 4).

Two studies in New Delhi compared the groups of individuals living inside and outside the metropolitan area(63). A higher frequency of EDED findings with TFBUT <10 seconds, Schirmer Test (ST) <10 mm, and low lysozyme levels in tears were reported among the individuals living within the metropolitan area. The decline in these values correlate with increase in pollutant levels in the metropolitan area compared with the rural area. Another study on 500 volunteers documented

table 2. Clinical findings in early and chronic phases of Environmental dry Eye disease, compared with non-exposed individuals(8,37,41)

Clinical findings Early reactive phase Chronic adaptive phase

Symptoms Variable Low

Tear film osmolarity Lower Higher

Hyperemia Present Present

MGD Present Present

Schirmer test High Low

TFBUT Lower Lower

Vital staining Normal Altered

Conjunctival Goblet cells Higher number Lower number

table 3. Individual and environmental risk factors for Environmental dry Eye disease (EdEd)

Risk factors for EdEd

Individual Age, female gender, contact lens usage, lengthy exposure to the hazards (video display, air conditioning), allergies, eye make up, blinking frequency

Environmental Humidity, temperature, high levels of pollutants (particulate matter, CO

2, NO

2, elemental carbon), regions with heavy automobile

transport, pollutant industrial activity, subway stations

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196 Arq Bras Oftalmol. 2014;77(3):193-200

a greater frequency of lower ST values and TFBUT values in hospital workers more exposed to traffic derived air pollution(43).

In Italy, patients who presented to an ophthalmological emer-gency unit with “eye discomfort,” reduced ST values and tear film instability were evaluated during the periods of acute rise in air pollu-tion levels, summer and winter. Road traffic, heating system usage, and photochemical smog levels were reported as the main causes of their symptoms. Subjective symptoms were ocular irritation, such as heavy or tired eyes, foreign body sensation, burning, stinging, and photophobia. Also, impression cytology findings in six areas of bulbar and tarsal conjunctiva were altered in 69% of the subjects-49% presented an early loss of goblet cells, 15% showed a total loss of goblet cells without keratinization, and 5% had a total loss of goblet cells with mild keratinization. Women showed higher frequency of symptoms that include ST<10 mm, and higher impression cytology score. In those subjects who lived in more polluted areas (urbanized compared to rural areas), impression cytology documented a greater frequency of keratinization and higher numbers of inflammatory cells (mainly mononuclear cells) in conjunctival scraping scores(44).

Exposure to NO2, traffic derived air pollutant, and ocular surface

changes were studied in volunteers in Sao Paulo, Brazil, the largest city in Latin America, and compared with individuals from a country-side area. The individuals living in Sao Paulo showed high levels of NO

2

exposure and displayed goblet cell hyperplasia as a result of the chro-nic insult(8). The same research group analyzed 55 cases of NO

2 expo-

sure and found that there is a dose-response relationship between incidence of symptoms and higher prevalence of meibomian gland dysfunction. However, there was a weak negative association with TFBUT and no correlation with ST values(41). Recently another study demonstrated that exposure to high levels of air pollutants canlead to eyelid margin alterations(64). The series of studies on the effects of air pollution on EDED in Brazil were innovative. The pollutant levels were individually measured with portable filter paper for a period of time rather than using broad environmental indices. Together, these findings suggest that life in large and polluted cities cause increased exposure of risk factors toward EDED.

Ultraviolet (UV) radiation is a common risk factor to ocular sur-face health for unprotected outdoor workers. For instance, climatic droplet keratopathy has been described and correlated with UV exposure(65). Excess exposure to UV has been considered to result in

acute tear film instability and induce transitory EDED, however, the reports are contradictory. Not enough evidence is currently available to indicate UV is a risk factor for EDED(66-68). On the other hand, it has been well established that UV is one of the major risk factors in ptery-gium, a degenerative condition of the ocular surface resulting tear film instability. However, a cause and effect relationship still needs to be determined(69,70).

A large-scale study in Indonesia had shown that agricultural work is not a risk factor for EDED. Type of agricultural activities, amount, and time of exposures, climatic, chemical, and other environmental con-ditions need to be controlled in future studies to better understand their contributions as possible risk factors. Such an assessment entails delineating involvement of pesticides, fire, and UV irradiation(70).

Indoor environmental contamination also has adverse health effects. The factors are lumped together into a group of signs and symptoms named the “Sick Building Syndrome” (SBS). In the last few decades the symptoms were described in workers in poorly venti-lated office buildings. SBS includes non-specific ocular, nose and throat irritation, headache, and respiratory symptoms. Emission of the volatile organic compounds (VOCs) from the synthetic materials used in homes and offices together with other micro environmental variables such as temperature, humidity, lighting and airborne subs-tances can also contribute to EDED. They can cause ocular symptoms, tear film instability, and alterations in ocular surface characteristics of EDED(40,62,71-74). In 1992, Norn described that “sick building” workers have “pollution keratoconjunctivitis” with decline in BUT values and epithelial alterations detected by lissamine green staining(31).

The broad ranges of environmental factors in office ambience associated with the demanding video display unit disrupt ocular sur-face homeostasis(4,30). In epidemiologic and clinical studies it is impor-tant to consider the weight of confounding or summing factors such as allergic conjunctivitis, certain oral medications, BAK preservative eye drops, eye make up, blinking frequency, and contact lens wear.

The prevalence of indoor EDED can be estimated based on ocu-lar discomfort complaints by office building workers. Based on the studies performed using questionnaires, it ranges from 5%-40%(62,75). This large range may be due to the design of questionnaire, types of reported symptoms, inclusion of confounding variables that include contact lens wear, medications, and differences in recall periods. For instance, in 56 European buildings across 9 countries, 39% of the individuals showed the mean prevalence of dry eye symptoms(76).

table 4. Effects of pollution on ocular surface: summary of epidemiological studies

Author Year Study design Local n Endpoints Conclusions

Versura(44) 1999 Case-control Italy 200 SchirmerFerning

BUTImpression cytology

Inflammation

Abnormal values of BUT 32%, Schirmer 40%, and Ferning 45%. Abnormal impression cytology: odds ratio 2.66 (IC95% 1.42-5.02)

Inflammation: odds ratio 2.27 (IC95% 1.14-2.16)

Gupta(63) 2002 Case- control New Delhi, India 400 BUTSchirmer

Lysozyme activity

BUT (odds ratio: 5.63, IC 95% 2.76-11.46)

Saxena(43) 2003 Case-control New Delhi, India 500 SymptomsLysozyme

Rose bengalBUT

Schirmer

Positive correlation with symptoms BUT and Schirmer were lower in

study groupNo difference in lysozyme

and rose bengal

Novaes(8) 2007 Case-control Sao Paulo, Brazil 029 Impression cytology Increased goblet cells density in individuals exposed to higher levels of NO

2

Novaes(41) 2010 Series of cases Sao Paulo, Brazil 055 SymptomsBUT

Schirmer

Positive correlation with symptomsHigher incidence of MGD, BUT weak

correlation and Schirmer, no correlation with levels of NO

2

Malerbi(64) 2012 Series of cases Sao Paulo, Brazil Meibomian gland evaluation Increased incidence of blepharitis in high levels of NO

2

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197Arq Bras Oftalmol. 2014;77(3):193-200

The anterior ocular surface forms a mucosal interface with large area continuously exposed to the environment. Comfort, proper visual acuity, and cellular maintenance are guaranteed by complex and harmonic interactions of epithelial cells and accessory glands and tear film compounds. Since the anterior ocular surface is the most densely innervated area of the body(77), it is very sensitive to irritants and adverse environmental conditions (Figure 3).

Receptor-induced events that mediate signaling pathway of in-flammatory responses resulting EDED symptoms such as decline in tear volume and altered composition are not completely understood. The following questions are need to be answered: to what extent the ocular surface discriminates different types of hazards? What makes the transition between an early/reactive phase to a chronic/adaptive phase?

Environmental injury might induce increasing expression of cy-to kines, growth factors and other molecules that mediate specific signaling pathways, and corneal inflammatory and allergic response. During acute and chronic phases, specific cell types, inflammatory mediators, and neurotransmitters are involved(78). Such responses vary depending on the nature and intensity of the stimulus and some mediators have been pointed as major contributors in the process of ocular surface damage related to environmental factors. Members of the transient receptor potential (TRP) channel superfamily, which include subfamilies in corneal epithelial and keratocytes, respond to environmental irritants inducing afferent impulses to the central ner-vous system(79). Chemical burns in mice induce a specific TRP vanilloid type 1 (TRPV1) channel deregulated inflammatory responses leading to corneal melt and opacification(80). The injury-induced inflammatory and opacification responses resulting from TRPV1 activation were attributed to the up regulation of pro inflammatory and chemo attractive cytokines. TRPV1-induces downstream events by eliciting time dependent stimulation of the mitogen activated protein ki-nase (MAPK) cascade in epithelial cells and stromal fibroblasts(79,81). Corneal epithelial wound is also accompanied by increased release of mitogens such as, epidermal growth factor (EGF), which induces cell proliferation and migration through activation of a TRP channel in the canonical subfamily identified as TRPC4 and MAPK signaling pathway(82-85).

Flow cytometry analysis of the tear fluid collected from the indi-viduals with atopic keratoconjunctivitis after a conjunctival allergen provocation test presented higher levels of interferon-gamma, IL-6, and a borderline increase in IL-10 after 48 hours. There was a signifi-cant difference between provoked and unprovoked eye for the same cytokines: IL-6, IFNγ, and IL-10(86). We speculate that individuals expo-sed to air pollution or other hazardous stimuli can elicit the similar inflammatory cascade during acute phase and lead to EDED clinical presentation, similar to other ocular surface inflammatory diseases, such as AKC(78).

Goblet cell hyperplasia results from exposure to high levels of air pollution in the urban population(8). This is due to chronic exposure

to air pollution by human nasal and respiratory mucosal surfaces that are considerably similar to conjunctiva(84,87-89). However, studies in mice exposed to a desiccating environment showed the opposite response. The differences between the human and mouse may be explained by species-specific responses, complexity of the trigger (humans are frequently exposed to combined factors, such as pollu-tants and adverse climate), and/or observations collected at different time-points in the disease progression of both the species.

In vitro models are useful to simulate hazardous conditions and assess their effects on the ocular surface at the molecular level. In this re-gard, the observation that particulate pollutants disrupt meibomian gland lipid structure and consequently the tear film organization was reproduced using benzalkonium chloride (BAK) and quartz par-ticles(90). This study suggested that BAK affects the surface activity of meibomian lipids and quartz particles adsorbed to meibomian lipids, by removing them from the air/water interface. The authors propo-sed that a similar mechanism accounts for the effect of particulate pollutants on the tear film lipid layer(90).

The possibility of measuring specific effects of air pollutants and exposure to other environmental hazards on ocular surface integrity and health will identify the individuals with pathologic correlations to EDED. A recently described method is proven to be useful for this purpose. It comprises a filter paper in a small chamber attached to a belt or other piece of clothing (Figure 4). Air pollutants deposited on filters after different times were eluted and measured(41). In this direction, a better understanding of EDED inducing factors and underlying mechanisms can be achieved. Such insights will help the development of more efficient preventive and therapeutic strategies.

environment monitoring toolS The environment is being polluted by industrial waste, automo-

bile and truck exhaust fumes, burning of coal and fossil fuels as well as chemical manufacturing. Air pollution can even come from small- scale every day indoor activities, such as dry cleaning, degrea sing, and painting. These activities accumulate gases and particles that come incontact with our mucosal tissues, especially the anterior ocular surface.

There is an increasing demand for environmental health indi-cators capable of measuring the amount of chemical, climatic, and physical hazards. Since 1987, World Health Organization (WHO) pu-blished guidelines for air quality are reviewed periodically(91,92). Similar guidelines, some with differences in items monitored or cut-off levels are provided by the Environmental Protection Agency (EPA) from the USA and other national or continental agencies (Table 5).

Among outdoor environmental parameters, climatic variables in -cluding temperature, atmospheric precipitation, humidity and UV ra-diation, and air pollutants including particulate matter (PM), CO

2, NO

2, O

3

and SO2 were correlated with ocular and systemic diseases(92-94). As men-

tioned above, the indoor pollutants are same as the more commonly monitored climatic parameters and they include include pollen, tobacco

Figure 3. Illustrative steps of pathophysiological mechanisms in the acute phase of EDED at the cellular level.

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198 Arq Bras Oftalmol. 2014;77(3):193-200

smoke elements, mold, pesticides, carbon monoxide, formaldehyde, and lead among others(95).

Those indicators are also monitored by national and international health and/or environmental agencies. They are then applied in health analysis studies to correlate diseases with epidemiology, governmen-tal policy directives, and economic studies(12,96,97).

This approach supports analysis of the health status of individuals or groups exposed to the above-indicated environmental risk factors. The results guide public health policies and preventive care(94,98-100). They also help comparing environmental hazards in different areas or countries to promote actions that may reduce their effects(101).

The information collected by the international or governmen-tal agencies are available for public consulting(102). These agencies work together to adopt similar measurement standards, units, and me thods, and make the data available to the public through web databases and annual publications(91).

Data on air quality or climate could be used to correlate with cli-nical observations of incidences of EDED in different cities or regions. However, the daily range of pollutants, hazardous agents, confoun-ding factors, and individual variable time-exposure to any of the stu-died agents can be too large to precisely identify agents responsible for higher EDED incidence in a certain area. These limitations may make it difficult to draw meaningful conclusions. To avoid that, study designs are required to include homogeneous groups with similar habits and comparable exposure times. One report had described that chil dren living close to three petrochemical companies in Nigeria have te traethyl lead and black carbon tear film(29). Similar studies are necessary to identify the specific pollutants responsible for a cause and effect relationship between an environmental factor and EDED.

CoNCLuSIoNS For several years, environmental factors have been known to be

associated with DED. A more extensive and detailed analysis of the association between environmental factors and DED suggest that EDED as a DED subtype will aid efforts to pinpoint different factors responsible for this disease. To this end, we propose that combined clinical and laboratory studies can help identify different environ-mental factors that induce EDED. At this point, we were able to summarize evidence supporting the association of specific environ-mental hazards such as pollutants and adverse outdoor and indoor environmental factors with EDED.

DED clinical findings and symptoms resulting from environmen-tal factor mediated anterior ocular surface receptor activation induce pro inflammatory cytokines, chemo attractant expression, and elabo-ration of extracellular stromal matrix due to increases in myofibroblast expression. These mechanisms induce tear film instability, stromal immune cell infiltration, and disruption of lacrimal gland mediated tear film volume and composition. Constant exposure to environ-mental factors may allow the clinician to distinguish between acute and a chronic phase of the disease.

Environmental data monitoring and safety limits obtained from in-ternational or governmental agencies may help clinicians to associate DED disease stages with environmental factor exposure. Researchers may be aided in identifying relevant stress to apply to their different model systems to pinpoint the mechanisms mediating responses underlying EDED.

Unfortunately, except for using protective equipment to counter specific hazardous environmental agent stresses, EDED treatment is limited to the same medications and interventions available for other

table 5. Websites of agencies that provide guidelines and databases related to the environmental parameters in different regions of the world

Agency Website Country/area

European Space Agency http://www.earthobservations.org/geoss_cl_ph.shtml Global

United Nation Economic Commission for Europe http://www.unece.org/env/europe/monitoring/iandr_en.html Global

World Health Organization http://www.who.int/ipcs/publications/ehc/ehc_numerical/en/index.html Global

Environmental Protection Agency http://www.epa.gov/oaqps001/montring.html USA

Health Canada http://www.hc-sc.gc.ca/ewh-semt/air/in/res-in/index-eng.php Canada

Instituto Nacional de Metereologia do Brasil http://www.inmet.gov.br/portal/ Brazil

Companhia Ambiental do Estado de São Paulo http://www.cetesb.sp.gov.br/ São Paulo State, Brazil

Ministry of the Environment Government of Japan http://www.env.go.jp/en/ Japan

Ministry of Environmental Protection http://english.mep.gov.cn/ China

Department of Sustainability, Environment, Water, Population and Communities

http://www.environment.gov.au/ Australia

Environment Agency http://www.environment-agency.gov.uk/ United Kingdom

Figure 4. A) Double passive NO2 sampler containing a cellulose filter (Energetica, Rio de Janeiro, Brazil) impregnated with an absorbent solution of 2% triethanolamine, 0.05% o­methoxyphenol, and 0.025% sodium metabisulfite inside a small plastic tube with one of its extremities open to ambient air. The nitrite produced during sampling is determined colorimetrically by reacting the with sulfanilamide and 8­anilino­1­naphthalene­sulfonic acid (ANSA) and monitoring the absorption at 550 nm wavelength; B) Superior view of the NO2 sampler; C) Portable gravimetric impactor with a flow rate of 1.8 L/min. Air is aspirated into the impactor by a pump, PM is retained by a filter, and the particles in suspension in the air are measured gravimetrically; D) Portable sampler carried in a small bag by a research subject.

A B C d

Alves M, et al.

199Arq Bras Oftalmol. 2014;77(3):193-200

types of DED.(103) Given this limitation, it remains important to promote novel investigative interventions to treat or minimize EDED damage.

ACKNoWLEdGEMENt This study was supported by grants from the following Brazilian

governmental agencies: “Fundação de Amparo a Pesquisa do Estado de São Paulo” (FAPESP), “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq), “Fundação de Apoio ao Ensino, Pes-quisa e Assistência do Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo” (FAEPA), and “Núcleo de Apoio a Pesquisa - Fisiopatologia e Terapêutica Ocular (NAP-FTO) da Universidade de São Paulo.”

The authors would like to acknowledge Maria Helena Andrade and Andre Torricelli for their contribution to this study.

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Pathways of corneal and ocular surface inflammation: a perspective from the cullen symposium. Ocul Surf. 2005;3(4 Suppl):S131-8.

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81. Yang Y, Yang H, Wang Z, Mergler S, Wolosin JM, Reinach PS. Functional TRPV1 expres-sion in human corneal fibroblasts. Exp Eye Res. 2013;107:121-9.

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on temperature-related morbidity and mortality in the United States. Environ Health Perspect. 2001;109(Suppl 2):185-9.

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Letters to the Editor

201Arq Bras Oftalmol. 2014;77(3):201-2http://dx.doi.org/10.5935/0004-2749.20140051

Bilateral acute depigmentation of the iris (BAdI): first reported case in Brazil

Dear Editor,We have read with considerable interest the article entitled “Bi-

lateral acute depigmentation of the iris (BADI): first reported case in Brazil”, by Maestrini et al.(1). The authors describe a patient who was diagnosed as having BADI, which has attracted a lot of attention among ophthalmologists in recent years. We would like to thank the authors for reporting on this interesting case, and we want to contri-bute further by making the following three points.

Bilateral acute iris transillumination (BAIT) and BADI are both re -latively new clinical entities and share some important features: an acute onset of severe photophobia and red eyes after a flu-like syn-drome, pigment dispersion into the anterior chamber, and exclusive involvement of the iris. However, in patients who have BAIT the pig-ment discharge is from the iris pigment epithelium, whereas for those with BADI, the pigment discharge comes from the iris stroma. This leads to iris transillumination defects and mydriatic/atonic pupilla in patients with BAIT, but not in those who have BADI.

First, the authors report that there are two clinical sub-types of BADI. The first sub-type has a more benign course, a lower incidence of increased intraocular pressure (IOP), and reversibility of the iris changes without transillumination defects or pupil distortion. The second sub-type, BAIT, has diffuse iris transillumination and mydriatic/atonic pupilla or distorted pupil, occasional posterior synechiae, and in-creased IOP(1). Indeed, the first sub-type mentioned by the authors re-flects the characteristic clinical features of the BADI (2), and the second sub-type, referred to in the study as BAIT, shares some properties with BADI but has differentiating characteristic features(3). In addition, BAIT was first described by Tugal-Tutkun et al. as being a probable distinct entity(3), and several publications have subsequently reported it as being a distinct entity from the BADI(4,5). It is not clear, therefore, whether BAIT is a sub-type of the BADI. It appears to be a different entity or an expanded spectrum of BADI, which makes it incorrect to describe BAIT as a sub-type of BADI.

In addition, Maestrini et al.(1) report that both conditions have a self-limited course and a good prognosis. However, BAIT cases may present with severe IOP rise, which is sometimes resistant to medical treatment and necessitates trabeculectomy surgery as in our case report(5). Therefore, clinicians should be aware of a severe IOP rise in patients with BAIT during their follow-up.

Finally, although the exact etiopathogenesis of BAIT remains un-clear, several publications have reported a relationship between BAIT and systemic use of moxifloxacin(4), upper respiratory tract in fections(3), and a toxic effect following a fumigation therapy(5). Maestrini et al.(1) reported the cause of BADI may be a viral etiology considering em-pirical antiviral therapy has provided some clinical improvement by reducing pigment dispersion into the anterior chamber. However, these authors should have taken an aqueous sample for viral analysis in order to conclude such a relationship. Therefore, further study is needed to include the aqueous tap for local antibody production against the virus, or to demonstrate the viral DNA to clarify the viral etiology in patients with BAIT.

Saban Gonul1, Banu Bozkurt1

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

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: Saban Gonul. Selcuk University Faculty of Medicine, Department of Ophthal-mology, Konya, Turkey - E-mail: drsabangonul@gmail.com

Submitted for publication: April 28, 2014Accepted for publication: May 1, 2014

REFERENCES 1. Maestrini HA, Maestrini AA, Machado Dde O, Santos DV, Almeida HG. Bilateral acute

depigmentation of the iris (BADI): first reported case in Brazil. Arq Bras Oftalmol. 2013; 76(1):42-4.

2. Tugal-Tutkun I, Araz B, Taskapili M, Akova YA, Yalniz-Akkaya Z, Berker N, et al. Bilateral acute depigmentation of the iris: report of 26 new cases and four-year follow-up of two patients. Ophthalmology. 2009;116(8):1552-7.

3. Tugal-Tutkun I, Onal S, Garip A, Taskapili M, Kazokoglu H, Kadayifcilar S, et al. Bilateral acute iris transillumination. Arch Ophthalmol. 2011;129(10):1312-19.

4. Morshedi RG, Bettis DI, Moshirfar M, Vitale AT. Bilateral acute iris transillumination following systemic moxifloxacin for respiratory illness: report of two cases and review of the literature. Ocul Immunol Inflamm. 2012;20(4):266-72.

5. Gonul S, Bozkurt B, Okudan S, Tugal-Tutkun I. Bilateral acute iris transillumination following a fumigation therapy: a village-based traditional method for the treatment of ophthalmomyiasis. Cutan Ocul Toxicol. 2014 Mar 31. [Epub ahead of print]. doi: 10.3109/15569527.2014.886589

Reply

Dear Editor,We were happy to receive the letter from Dr. Saban Gonul, who

resides in Turkey, concerning our article titled ‘‘Bilateral acute de-pigmentation of the iris (BADI): first reported case in Brazil”. The vast majority of BADI and bilateral acute iris transillumination (BAIT) cases have occurred in Turkey; therefore, it is very important to listen to researchers experienced with this fascinating new clinical entity.

Dr. Gonul suggests that it would be incorrect to describe BAIT as a subtype of BADI. However, both are new clinical entities that share many important features, such as an acute onset of severe bilateral photophobia and red eyes, pigment discharge in the anterior cham-ber, heavy pigment deposition in the trabecular meshwork, and a marked symptom relief with topical corticosteroids. In addition, both are more common in women, and in many cases, it occurs after a flu-like illness and many patients have histories of previous antibiotic use, particularly moxifloxacin. It is not yet clear if they are distinct entities or subtypes of the same disease. The fact that both share so many features gives strong support to the idea that they are subtypes of the same disease. Tugal-Tutkun et al. (2011) published the first and most important study on BAIT, with 26 cases(1). In their conclusion, the authors state very clearly that BAIT might be a new entity or might represent an expanded spectrum of BADI. This question has not yet been answered and further research is needed to clarify this point.

Indeed BAIT is more severe than BADI, as we pointed out in our paper. BADI has a more benign course, a shorter duration of pigment discharge, a lower incidence of elevated intraocular pressure (IOP) that is only transient, and sometimes reversible iris changes. BAIT is frequently associated with an early, severely elevated IOP, and the iris changes are usually irreversible. A few cases of BAIT might need a trabeculectomy to control an intractably elevated IOP. In Tugal-Tutkun et al. (2011), 2 of 26 patients needed a bilateral trabeculectomy(1). Although both BADI and BAIT are self-limited, we agree with Dr. Gonul that clinicians should be aware of the possibility of a severe, intractable elevation in IOP and a longer duration of disease in cases of BAIT.

Finally, the exact etiopathogenesis of BADI and BAIT remain un-clear. All previous studies(1-3) have entertained the viral hypothesis. The fact that many cases of BADI and BAIT occur after a flu-like illness or upper respiratory tract infection, with or without the use of antibio-tics, suggests a relationship with some kind of infection, viral or not. In the first paper on BADI, Tugal-Tutkun et al. (2006) suggested that it represents a new entity or an unusual presentation of herpetic eye disease(2). In Tugal-Tutkun et al. (2009)(3), viral serology was performed in 10 of 26 cases of BADI, and all 10 had IgG antibodies against cyto-megalovirus (CMV). Consequently, the authors proposed that BADI be considered part of an expanded spectrum of CMV-related ocular

Cartas ao Editor | Letters to the editor

202 Arq Bras Oftalmol. 2014;77(3):201-2

diseases. Five patients in that series had histories of recurrent fever blisters. In Tugal-Tutkun et al. (2011)(1), 83% of BAIT patients tested were seropositive for IgG antibodies against herpes simplex virus type 1 and 75% were positive for Epstein-Barr virus IgG antibodies. All patients tested for anti-varicella zoster virus and CMV were found to have IgG antibodies. The authors hypothesized that BAIT represents a condition triggered by a viral infection. In Weffers Bettink-Remeijer et al. (2009)(4), the herpetic genome was positive in the aqueous tap of one patient with BAIT. Furthermore, BAIT shares some features of viral herpetic iridocyclitis, in which ischemic necrosis of the iris results in iris atrophy, distortion of the pupil, and transillumination defects. In our study, a herpetic etiology cannot be ruled out because we did not have access to the analysis of intraocular specimens. We decided not to perform an anterior chamber tap to try polymerase chain reaction (PCR) for herpes viruses because PCR of aqueous humor is rather insensitive in the absence of posterior segment involvement(5). A biopsy of the iris or cornea obtained during a trabeculectomy might be more elucidative. We preferred to institute empirical treatment with valacyclovir, which resulted in marked clinical improvement. Obviously, this is not proof of a viral etiology, but it is certainly sugges-tive. In conclusion, the etiopathogenesis of BADI remains to be eluci-

dated, and we still have more questions than answers regarding this interesting and challenging new disease.

Heloisa Andrade Maestrini

Department of Glaucoma, Oculare Centro de Oftalmologia, Belo Horizonte, MG, Brazil.

Corresponding author: Heloisa Andrade Maestrini. Rua Maranhão, 65 - Belo Horizonte (MG) - 30150-330 - Brazil - E-mail: heloisa.maestrini@gmail.com

REFERENCES 1. Tugal-Tutkun I, Onal S, Garip A, Taskapili M, Kazokoglu H, Kadayifcilar S, et al. Bilateral

acute iris transillumination. Arch Ophthalmol. 2011;129(10):1312-9. 2. Tugal-Tutkun I, Urgancioglu M. Bilateral acute depigmentation of the iris. Graefes Arch

Clin Exp Ophthalmol. 2006;244(6):742-6. 3. Tugal-Tutkun I, Araz B, Taskapili M, Akova YA, Yalniz-Akkaya Z, Berker N, et al. Bilateral

acute depigmentation of the iris: report of 26 new cases and four-year follow-up of two patients. Ophthalmology. 2009;116(8):1552-7, 1557 e1.

4. Wefers Bettink-Remeijer M, Brouwers K, van Langenhove L, De Waard PW, Missotten TO, Martinez Ciriano JP, et al. Uveitis-like syndrome and iris transillumination after the use of oral moxifloxacin. Eye (Lond). 2009;23(12):2260-2.

5. Matos K, Muccioli C, Belfort Junior R, Rizzo LV. Correlation between clinical diagnosis and PCR analysis of serum, aqueous, and vitreous samples in patients with inflamma-tory eye disease. Arq Bras Oftalmol. 2007;70(1):109-14.

Letters to the Editor

203Arq Bras Oftalmol. 2014;77(3):203-4http://dx.doi.org/10.5935/0004-2749.20140052

Refractive error in school children in Campinas, BrazilErros refrativos em escolares de Campinas, Brasil

Dear Editor,Refractive errors such as myopia, astigmatism, and hyperopia are

common ocular conditions that have been identified as concerns for public health and economy. The World Health Organization’s “Vision 2020: The Right to Sight” initiative included the correction of refracti-ve errors as one of the target areas to eliminate avoidable causes of visual impairment. Uncorrected refractive error is the most common cause of visual impairment in school-age children in both industria-lised and developing countries(1).

The following report describes the prevalence of refractive error (myopia, hyperopia, and astigmatism) in school children in Campinas, Brazil.

This cross-sectional study was conducted in 2012. According to 2010 census(2), the population of Campinas, Brazil was approximately 1 million. Of these, 180,560 were within the age limits of the study and 126,392 (70%) of them attended public schools. Four groups of children, from the 1st (5-7 years-old), 5th (9-11 years-old), 9th (13-15 years-old), and 12th (16-18 years-old) levels of the Brazilian educational system, a total 1,100, were randomly selected from different public schools. The study has complete approval from the University of Campinas Research Ethics Committee. The research adhered to the prin ciples of the Declaration of Helsinki.

The protocol for data collection included measurement of logMAR monocular distance, best-corrected visual acuity, and cycloplegic autorefraction (1% cyclopentolate hydrochloride) using cycloplegic autorefraction (autorefractor model AR-8900; Topcon Corporation, Tokyo, Japan). The measurements were obtained after adding 1 drop of a topical anesthetic eye drop (proxymetacaine hydrochloride) in both eyes and waiting 2 minutes to achieve ocular surface anes thesia followed by addition of 2 drops of 1% cyclopentolate

hydrochloride 10 minutes apart in each eye. Cycloplegic dilation was performed by an ophthalmic technologist. Five readings were recorded and the representative value, determined by the instru-ment, was used for further analysis. The representative value from the autorefractor was used to calculate spherical equivalent refrac-tion (SER=sphere + cylinder/2). Myopia was defined as SER ≤ -0.50 D, hyperopia as SER ≥ +2.00 D, refractive astigmatism as cylinder ≥ 1.00 D if -0.50 > SER < +2.00, and emetropia as -0.50 > SER < +2.00 with cylinder < 1.00 D(3). All statistical analyses were carried out using PSPP software.

Among the 1,100 students invited to participate in the study, pa rental consent was obtained from 778 (70.7%). 440 (56.5%) were female. Table 1 describes the age and visual acuity of the par ticipants. Table 2 describes the distribution according to the refrac tive errors.

The current paper presents a population-based data descri-bing the prevalence of cycloplegic measures of refractive errors of students in Campinas, Brazil. There was a preponderance of emme-tropes (75.1%), and the prevalence of myopia was only 2.8% among the children of age group 5-7 years. Among the 16-18 years old age group, the prevalence of myopia increased sevenfold (19.3%). Similar findings in young children have been reported by other studies(3). By contrast, the prevalence of myopia in 7-years-old children in Singapo-re is 28%(4). One Brazilian study presented different results, but it was not possible to compare, as the protocols in our study are different from their study(5).

One limitation of this study was the use of SER to classify myopia, which can result in over-estimation of prevalence in populations with significant levels of astigmatism. Despite this aspect, SER has been used to facilitate comparisons with other epidemiological studies of refractive error. Another limitation is that due to the limited data avai-lable for Brazil (a large and multi-ethnic country), it is unclear whether the prevalence of refractive errors in Campinas is representative of the Brazilian population as a whole.

Rodrigo Pessoa Cavalcanti Lira1, Italo Fernandes do Espírito Santo2, Gustavo Lima do Valle Astur2, Diana Maziero2, Thais Helena

Moreira Passos2, Carlos Eduardo Leite Arieta1

table 1. distribution of students according to age and visual acuity

School level Mean Sd Min Max Female Male

Age (years) 01st 06.17 0.67 05 07 06.19 06.15

05th 09.82 0.52 09 11 09.77 09.88

09th 14.03 0.56 13 15 13.99 14.09

12th 17.28 0.58 16 18 17.32 17.22

Total 11.45 4.04 05 18 11.61 11.24

Best-corrected visual acuity 01st 85.08 6.34 P=0.410 38.00 88.00 86.56 86.49

(ETDRS letters) 05th 85.60 6.07 38.00 88.00 86.02 86.22

Right eye 09th 84.72 7.63 38.00 88.00 84.35 85.31

12th 84.91 7.20 38.00 88.00 85.25 85.19

Total 85.47 6.73 38.00 88.00 85.13 85.91

table 2. distribution of students according to refractive errors

School level Myopia Hyperopia Astigmatism Emmetropia total P

1st 05 15 025 136 181 <0.001

5th 17 18 036 195 266

9th 21 08 027 111 167

12th 32 02 036 094 164

Total 75 43 124 536 778

Cartas ao Editor | Letters to the editor

204 Arq Bras Oftalmol. 2014;77(3):203-4

Study conducted at Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brazil.1 Department of Ophthalmologic, Universidade Estadual de Campinas (UNICAMP), Campinas,

SP - Brazil.2 Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brazil.

Funding: This study was supported by FAPESP 2011/21773-2; FAPESP 2011/19835-0; FAPESP 2011/09514-1.

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

Corresponding author: Rodrigo Pessoa Cavalcanti Lira. Rua Irma Maria David, 200/1.302 - Recife - PE - 52061-070 - Brazil - E-mail: rodrigopclira@hotmail.com

Project number and institution responsible for the approval of the Research Ethics Committee: UNICAMP 933/2011 - CAAE 0842.0.146.000-11

Submitted for publication: October 14, 2013 Accepted for publication: June 9, 2014

REFERENCES 1. Resnikoff S, Pararajasegaram R. Blindness prevention programmes: past, present, and

future. Bull World Health Organ. 2001;79(3):222-6. 2. IBGE. São Paulo Campinas Censo Demográfico 2010: Resultados da Amostra -

Educação. [cited 2013 Oct 13]. Available at: http://cidades.ibge.gov.br/xtras/temas.php?lang=&codmun= 350950&idtema=105&search=sao-paulo|campinas|cen so-demografico-2010:-re sultados-da-amostra-educacao

3. Gilbert CE, Ellwein LB. Refractive Error Study in Children Study Group. Prevalence and causes of functional low vision in school-age children: results from standardi-zed population surveys in Asia, Africa, and Latin America. Invest Ophthalmol Vis Sci. 2008;49(3):877-81.

4. Saw SM, Zhang MZ, Hong RZ, Fu ZF, Pang MH, Tan DT. Near-work activity, night-lights, and myopia in the Singapore-China study. Arch Ophthalmol. 2002;120(5):620-7.

5. Garcia CA, Oréfice F, Nobre GF, Souza D de B, Rocha ML, Vianna RN. Prevalence of refractive errors in students in Northeastern Brazil. Arq Bras Oftalmol. 2005;68(3):321-5.

205Arq Bras Oftalmol. 2014;77(3):205-8

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Descriptive studies involving description and theoretical analysis of new hypotheses based on the knowledge available in the literatu-re. Theoretical results must add new information to literature.

tYPES oF MANuSCRIPtSManuscripts submitted to ABO should fit into one of the follo-

wing categories according to their format. The maximum number of words, figures, tables and, references for each type of manuscript are in parentheses at the end of the description for each category. The word count of the manuscript includes the text from the beginning of the introduction up to the end of the discussion; therefore, the following items are not included: title page, abstract, references, acknowledgments, tables and figures, including legends.

editorialS

Editorials are contributed by invitation and should be related to to pics of current interest, preferentially related to articles published in the same issue of ABO (title, maximum of 1,000 words, 2 figures or tables, and 10 references).

original artiCleS

Original articles present complete experiments with results that have never been published before (title, structured abstract, maxi-mum of 3,000 words, 7 figures or tables, and 30 references). The eva-luation of the manuscripts will be based on the following priorities:

1. New and relevant information confirmed in a study using appro-priate methodology.

2. Repetition of information available in the literature, but not previously confirmed locally, based on a study using appropriate methodology.

3. Repetition of information available in the literature and previously confirmed locally, based on a study using appropriate methodology.

* Manuscripts containing speculative conclusions, unsubstantiated by the results or based on a study with inappropriate methodology will not be accepted.

CaSe reportS and CaSe SerieS

Case reports or case series will be considered for publication when describing rare and original findings that have not been internatio-nally confirmed, or when presenting clinical or surgical responses that can contribute to elucidate the pathophysiology of a disease (ti tle, unstructured abstract, maximum of 1,000 words, 4 figures or tables, and 10 references).

letterS to the editor

Letters to the editor are considered for publication if they contain comments related to manuscripts previously published in ABO or, exceptionally, the results of original studies with insufficient content to be submitted as Original Article. These letters should present new information or new interpretation of existing information. When the content of the letter refers to an article previously published in ABO, such article should be mentioned in the first paragraph of the letter and included in its reference list. In these cases, the letters will be linked to the article, and the authors of the article will have their right of reply guaranteed in the same issue. Congratulation letters will not be published (title, maximum of 700 words, 2 figures or tables, and 5 references).

review artiCleS

Review articles follow the editorial line and are accepted only by invitation from the editor. Suggestions of topics for review articles should be sent directly to the editor, but manuscripts cannot be sent without an invitation (title, unstructured abstract, maximum of 4,000 words, 8 figures or tables, and 100 references).

EdItoRIAL PRoCESSManuscripts will only be considered for publication if they meet

all the journal’s requirements. The editorial office will inform the authors if their manuscript fails to meet such requirements. Upon notification, the corresponding author will have 30 days to make the necessary changes in the manuscript. If the deadline is not met, the manuscript will be excluded from the editorial process.

The manuscripts submitted to ABO are initially evaluated by the editors to check for content compliance with the editorial line of the journal. After this assessment, all manuscripts are sent for peer review. The anonymity of reviewers is preserved throughout the whole process. However, the authors of manuscripts do not remain anonymous.

After the initial editorial evaluation, the reviewers’ comments can be sent to the authors to guide the changes to be implemented in the text. After implementing the changes suggested by the revie-wers, the revised manuscript should be resubmitted along with a letter (which is sent as a supplementary document) with specific in dications of all changes made to the manuscript or the reasons why the suggested changes were not made. Manuscripts that are resubmitted without a letter will be withheld until the editorial office receives the letter. The deadline to submit the new version of the ma-

206 Arq Bras Oftalmol. 2014;77(3):205-8

nuscript is 30 days after the authors are informed of the need to make changes in their manuscript. Manuscripts will be excluded from the process if authors fail to meet this deadline. The ultimate publication will be based on the final approval of the editors.

Manuscripts submitted to ABO should not be simultaneously considered for publication by other journals. In addition, total or par-tial publication or translation for publication in another language of the manuscripts submitted to ABO should not be considered without the permission of the editors of ABO.

AutHoRSHIPThe criteria for authorship of manuscripts in medical journals are

well established. Individuals who have contributed in a concrete way during the following three phases of manuscript preparation should be considered authors: I. Conception and design, acquisition of data, or analysis and

interpretation of data. II. Draft or critical revision of the article for important intellectual

content. III. Final approval of the version to be published.

The authors of manuscripts submitted to ABO should make sure that all authors meet the criteria mentioned above and that all per -sons who meet these criteria are listed. Individuals who hold head-ship positions cannot be considered authors of manuscripts based only on their positions. ABO does not accept the participation of honorary authors.

The corresponding author should complete and submit the Au-thor Contribution Statement as a supplementary document.

GuIdELINES FoR EXCELLENt RESEARCHIt is recommended that authors follow the appropriate guideline

bellow before submitting your work: • CONSORT (Controlled and randomized clinical trials) • STARD (Diagnostic instruments or techniques) • PRISMA (Systematic reviews and meta-analyses) • STROBE (Observational studies)

MANuSCRIPt PREPARAtIoNManuscripts should only be submitted online using the appro-

priate interface of ABO. The following guidelines were based on the format suggested by the International Committee of Medical Journal Editors (ICMJE) and published in the document: Uniform Require-ments for Manuscripts Submitted to Biomedical Journals.

Only the manuscripts complying with these guidelines will be considered for analysis.

The text should be sent as a digital file. Only the following formats are accepted: .doc or .rtf. The text should be typed double-spaced, in 12 point font. The pages should be numbered in Arabic numerals, starting each section on a new page.

The sections should be presented according to the following se-quence: Title page (as a separate document); Abstract and Keywords; Introduction; Methods; Results; Discussion; Acknowledgements (if any); References; Tables (optional) and Figures (optional) including legends.

1. title Page. It should contain: a) title (no more than 135 characters with spaces); b) running title to be used as a page heading (no more than 60 characters with spaces); c) authors’ names as they should appear in print; d) each author’s affiliation* (city, state, country and, if applicable, department, school, university); e) corresponding author’s, name, address, phone number, and email; f ) sources of fi-

nancial support (if any); g) project number and institution responsible for the approval of the Research Ethics Committee; h) statement of conflicts of interests of all authors; i) clinical trial registration number on a public trials registry.* Professional or academic degrees, as well as job position will not be published.

Approval of the Institutional Review Board (IRB). All retrospec-tive, cross-sectional, or prospective studies involving primary data collection or clinical and surgical reports should include the project number and name of the institution that provided the approval of the IRB on the title page. Studies involving humans should be compliant with the Declaration of Helsinki, whereas studies involving animals should be in accordance with the principles suggested by the Asso-ciation for Research in Vision and Ophthalmology (ARVO).

As a supplementary document, the corresponding author should send the IRB approval or its report stating that the evaluation of the project by the Committee is not necessary. The author cannot decide on the need for evaluation by the Research Ethics Committee.

Statement of Conflicts of Interest. The title page should contain the statement of conflicts of interest of all authors (even if there is no conflict of interest). For more information about potential conflicts of interest, refer to: World Association of Medical Editors: Conflict of interest in peer-reviewed medical journals.

All authors should send the Form for Disclosure of Potential Con-flicts of Interest as supplementary documents.

Clinical trials. All Clinical Trials shall include on the title page the registration number in an international registry that allows free ac-cess to trial information (examples: U.S. National Institutes of Health, Australian and New Zealand Clinical Trials Registry, International Standard Randomised Controlled Trial Number - ISRCTN, University Hospital Medical Information Network Clinical Trials Registry - UMIN CTR, Nederlands Trial Register).

2. Abstract and Keywords. Structured abstract (Objective, Metho-ds, Results, Conclusions) with no more than 300 words. Unstructured abstract with no more than 150 words. Five keywords in English listed by the National Library of Medicine (MeSH - Medical Subject Headings).

3. Abstract and Keywords in Portuguese. Structured abstract (Objective, Methods, Results, Conclusions) with no more than 300 words. Unstructured abstract with no more than 150 words. Five keywords in Portuguese listed by BIREME (DeCS - Descritores em Ciências da Saúde). Portuguese translation may be provided by ABO at publication.

4. Introduction, Methods, Results, and discussion. Citations in the text should be numbered sequentially in superscript Arabic numerals and in parentheses. The names of the authors should not be cited in the text.

5. Acknowledgements. This section should include the colla-boration of people, groups or institutions that deserve to be ack-nowledged but do not meet the criteria for authorship. Statisticians and medical editors may meet the criteria for authorship and, in this case, should be acknowledged as authors. When they do not meet the criteria for authorship, they should be mentioned in this section. Writers who are not identified in the manuscript cannot be accepted as authors; therefore, professional writers should be acknowledged in this section.

6. References. Citations (references) of authors in the text should be numbered sequentially in the same order as they are cited and identified using superscript Arabic numerals. References should be in accordance with the format suggested by the International

207Arq Bras Oftalmol. 2014;77(3):205-8

Committee of Medical Journal Editors (ICMJE), based on the exam-ples below.

The titles of the journals should be abbreviated according to the style provided by the List of Journal Indexed in Index Medicus of the National Library of Medicine.

The names of all authors should be cited for references with up to six authors. For studies with seven or more authors, cite only the first six authors followed by et al.

Examples of references:

Journal ArticlesCosta VP, Vasconcellos JP, Comegno PEC, José NK. O uso da mitomi cina C em cirurgia combinada. Arq Bras Oftalmol. 1999;62(5):577-80.

BooksBicas HEA. Oftalmologia: fundamentos. São Paulo: Contexto; 1991.

Book ChaptersGómez de Liaño F, Gómez de Liaño P, Gómez de Liaño R. Exploración del niño estrábico. In: Horta-Barbosa P, editor. Estrabismo. Rio de Janeiro: Cultura Médica; 1997. p. 47-72.

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.

DissertationsSchor P. Idealização, desenho, construção e teste de um ceratômetro cirúrgico quantitativo [dissertation]. São Paulo: Universidade Federal de São Paulo; 1997.

Electronic DocumentsMonteiro MLR, Scapolan HB. Constrição campimétrica causada por vigabatrin. Arq Bras Oftalmol. [online journal]. 2000 [cited 2005 Jan 31]; 63(5): [about 4 p.]. Available at:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27492000000500012&lng=pt&nrm=iso

7. tables. Tables should be numbered sequentially using Arabic nu-merals in the order they are mentioned in the text. All tables should have a title and a heading for all columns. Their format should be simple, with no vertical lines or color in the background. All ab-breviations (even if previously defined in the text) and sta tistical tests should be explained below the table. The bibliographical source of the table should also be informed when the table is extracted from another study.Do not include tables in the main document of the manuscript, they should be uploaded as supplementary documents

8. Figures (graphs, photos, illustrations, charts). Figures should be numbered sequentially using Arabic numerals in the order they are mentioned in the text. ABO will publish the figures in black and white at no cost to the authors. Manuscripts with color figures will be published only after the authors pay a publication fee of R$ 500.00 per manuscript.

Graphs should preferably be in shades of gray, on a white background and without three-dimensional or depth effects. Instead of using pie charts, the data should be included in tables or described in the text.Photos and illustrations should have a minimum resolution of 300 DPI for the size of the publication (about 2,500 x 3,300 pixels for a full page). The quality of the images is considered in the evaluation of the manuscript.

The main document should contain all figure legends, typed dou ble-spaced and numbered using Arabic numerals.

Do not include figures in the main document of the manuscript; they should be uploaded as supplementary documents.

Supplemental files can have the following extensions: JPG, BMP, TIF, GIF, EPS, PSD, WMF, EMF or PDF.

9. Abbreviations and Acronyms. Abbreviations and acronyms should be preceded by the spelled-out abbreviation on first mention and in the legends of tables and figures (even if they have been pre-viously mentioned in the text). Titles and abstracts should not contain abbreviations and acronyms.

10. units of Measurement: Values of physical quantities should be used in accordance with the standards of the International System of Units.

11. Language. Texts should be clear to be considered appropriate for publication in a scientific journal. Use short sentences, written in a direct and active voice. Foreign words should be in italics. Thera-peutic agents should be mentioned by their generic names with the following information in parentheses: trade name, manufacturer’s name, city, state and country of origin. All instruments or apparatus should be mentioned including their trade name, manufacturer’s name, city, state and country of origin. The superscript symbol of trademark ® or™ should be used in all names of instruments or trade names of drugs. Whenever there are doubts about style, terminology, units of measurement and related issues, refer to the AMA Manual of Style 10th edition.

12. original documents. Corresponding authors should keep the original documents and the letter of approval from the Research Ethics Committee for studies involving humans or animals, the con-sent form signed by all patients involved, the statement of agreement with the full content of the study signed by all authors and the state-ment of conflict of interest of all authors, as well as the records of the data collected for the study results.

13. Corrections and Retractions. Errors may be noted in published manuscripts that require the publication of a correction. However, some errors pointed out by any reader may invalidate the results or the authorship of a manuscript. If substantial doubt arises about the honesty or integrity of a submitted manuscript, it is the editor’s responsibility to exclude the possibility of fraud. In these situations, the editor will inform the institutions involved and the funding agen-cies about the suspicion and wait for their final decision. If there is confirmation of a fraudulent publication in ABO, the editor will act in compliance with the protocols suggested by the International Com-mittee of Medical Journal Editors (ICMJE) and by the Committee on Publication Ethics (COPE).

CHECKLIStBefore submitting their manuscript, authors should make sure

that all the following items are available: □Manuscript prepared in accordance with the instructions to

authors. □Maximum number of words, tables, figures, and references

according to the type of manuscript. □ Title page including the clinical trial registration number is not

included in the main document □ No figures and tables are included in the main document of

the manuscript. □ All figures and tables were uploaded separately as supple-

mentary documents. □ Author Contribution Statement completed and saved as a

digital file to be sent as a supplementary document. □ Form for Disclosure of Potential Conflicts of Interest of all

authors completed and saved as digital files to be sent as supplementary documents.

□ Digital version of the report provided by the Institutional Re-view Board containing the approval of the project to be sent as a supplementary document.

208 Arq Bras Oftalmol. 2014;77(3):205-8

Chief Executive Officer: Fernando Steven Ullmann;Commercial Director: Helen Suzana Perlmann; Art Director: Elza Rudolf;

Publishing, Printing and CTP: Ipsis Gráfica e Editora S.A.Frequency of publication: Bimonthly; Circulation: 7.500 copies

Edited byiPSiS gRáFiCA E EDiTORA S.A.

Rua Vereador José Nanci, 151 - Parque Jaçatuba 09290-415 - Santo André - SP - Brazil

Phone: (5511) 2172-0511 - Fax (5511) 2273-1557

AdvertisingconSelho BraSileiro De

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R. Casa do Ator, 1.117 - 2nd Floor - São Paulo - SP - Brazil - 04546-004

Contact: Fabrício LacerdaPhone: (5511) 3266-4000 - Fax: (5511) 3171-0953E-mail: assessoria@cbo.com.br

LISt oF WEBSItESAuthorship Principles according to the iCMJEhttp://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors.html

Authors’ Participation Formhttp://www.cbo.com.br/site/files/Formulario Contribuicao dos Autores.pdf

CONSORT (Consolidated Standards of Reporting Trials) http://www.consort-statement.org/consort-statement/

STARD (Standards for the Reporting of Diagnostic accuracy studies) http://www.stard-statement.org/

PRiSMA (Preferred Reporting items for Systematic Reviews and Meta-Analyses) http://www.prisma-statement.org/index.htm

STROBE (Strengthening the Reporting of Observational studies in Epidemiology) http://www.strobe-statement.org/

Online interface for submission of manuscripts to ABOhttp://www.scielo.br/ABO

international Committee of Medical Journal Editors (iCMJE)http://www.icmje.org/

uniform requirements for manuscripts submitted to biomedical journalshttp://www.nlm.nih.gov/bsd/uniform_requirements.html

Declaration of helsinkihttp://www.wma.net/en/30publications/10policies/b3/index.html

Principles of the Association for Research in vision and Ophthal-mology (ARvO)http://www.arvo.org/About_ARVO/Policies/Statement_for_the_Use_of_Animals_in_Ophthalmic_and_Visual_Research/

World association of medical editors: conflict of interest in peer- reviewed medical journalshttp://www.wame.org/about/wame-editorial-on-coi

Form for Disclosure of Potential Conflicts of interesthttp://www.icmje.org/coi_disclosure.pdf

u.S. national institutes of healthhttp://www.clinicaltrials.gov

australian and new zealand clinical trials registryhttp://www.anzctr.org.au

international Standard Randomised Controlled Trial Number - iSRCTNhttp://isrctn.org/

university hospital medical information network clinical trials Registry - uMiN CTRhttp://www.umin.ac.jp/ctr/index.htm

Nederlands Trial Registerhttp://www.trialregister.nl/trialreg/index.asp

meSh - medical Subject headingshttp://www.ncbi.nlm.nih.gov/sites/entrez?db=mesh&term=

DecS - health Sciences Keywords in Portuguesehttp://decs.bvs.br/

Format suggested by the international Committee of Medical Journal Editors (iCMJE)http://www.nlm.nih.gov/bsd/uniform_requirements.html

list of Journal indexed in index Medicushttp://www.ncbi.nlm.nih.gov/journals

AMA Manual of Style 10th editionhttp://www.amamanualofstyle.com/

Protocols of the international Committee of Medical Journal Editors (iCMJE)http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/scientific-misconduct-expressions-of-concern-and-retraction.html

Protocols of the Committee on Publication Ethics (COPE)http://publicationethics.org/resources/flowcharts

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A luz azul-violeta é a luz mais prejudicial para as células da retina.

Ela pode causar danos aos olhos a longo prazo, como a degeneração macular.

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em lentes transparentes*(2).

1 SUA TECNOLOGIA ANTIRREFLEXO SELETIVA PERMITE A PASSAGEM DA LUZ ESSENCIAL, inclusive a azul-turquesa, preservando a percepção das cores e do bem-estar geral, regulando o relógio biológico.

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3

Reflexos Arranhões Manchas Poeira Água

(1) As lentes Crizal Prevencia bloqueiam 20% da luz azul-violeta nociva, reduzindo a morte das células retinianas em 25%. A redução da luz azul-violeta pode variar ligeiramente dependendo do material da lente. Em testes in vitro realizados pela Essilor no Institut de la Vision em Paris, células do epitélio pigmentar da retina (EPR) foram expostas à luz azul-violeta, reproduzindo a exposição fisiológica à luz do sol do olho aos 40 anos.

(2) Índice de referência desenvolvido pelo departamento de Pesquisas e Desenvolvimento da Essilor International certificando a proteção UV global de uma lente. O índice FPS-O de 25 significa que os olhos estão 25 vezes mais bem protegidos com as lentes Crizal do que sem lente alguma. FPS-O de 25 para as lentes Crizal nos materiais Essilor Stylis, Essilor Airwear, Xperio, Transitions e FPS-O de 10 no material Orma transparente. Medições realizadas consideram apenas a performance da lente.

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