Ocular rosacea Crotoxin for paralysis of extraocular muscles ...

issn 0004-2749 

versão impressa 

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

publicação oficial do conselho brasileiro de oftalmologia 

SETEMBRO/OUTUBRO 2012 

75 05 

Ocular rosacea 

Crotoxin for paralysis of 

extraocular muscles 

Pseudomonas endophthalmitis 

after phaco 

Radiation therapy for Graves 

Prevalence of blindness in 

Paraguay 

indexada nas bases de dados 

medline | embase | isi | SciELO

Arquivos Brasileiros de Oftalmologia | set-out 2012 | v.75 n.5 p.301-376

2013 

10 

AGOSTO 

92013 

82013 

AGOSTO 

72013 

AGOSTO 

AGOSTO 

www. 

cbo2013 

.com.br

Chegou! 

® 

(alcaftadina solução oftálmica 0,25%) 

Uso pediátrico: A partir de 2 anos. 1 

Rapidez de ação comprovada: 

Eficácia demonstrada em 3 minutos 2 

Comprovada ação durante todo o dia: 

Previne a coceira ocular durante 

16 horas 2 

Referências Bibliográficas: 1. LASTACAFT Informações na bula. 2. Torkildsen G, Shedden A. The safety and effi cacy of alcaftadine 0.25% ophthalmic solution for the prevention of itching associated 

with allergic conjunctivitis. Curr Med Res Opin. 2011;27(3):623-631. 

INDICAÇÕES: LASTACAFT ® é indicado para profi laxia/prevenção do prurido associado com conjuntivites alérgicas. REAÇÕES ADVERSAS: Reação comum (> 1/100 e < 1/10): irritação ocular, ardor e/ou 

sensação de pontadas nos olhos à instilação, vermelhidão ocular, prurido ocular, rinofaringite, cefaleia e infl uenza. ADVERTÊNCIAS E PRECAUÇÕES: Para não contaminar o colírio evite o contato do conta 

gotas com qualquer superfície. Não permita que a ponta do frasco entre em contato direto com os olhos. Mantenha o frasco bem fechado enquanto não estiver sendo utilizado. Gestação e Lactação: 

Categoria de risco na gravidez: B. Este medicamento não deve ser utilizado por mulheres grávidas sem orientação médica ou do cirurgião-dentista. Estudos sobre reprodução realizados em ratos 

e coelhos não revelaram evidências de alteração na reprodução feminina ou perigos para o feto devidos à alcaftadina. Doses orais em ratos e coelhos de 20 e 80 mg/kg/dia, respectivamente, produziram 

níveis de exposição plasmática de aproximadamente 200 e 9000 vezes maior do que a exposição com a dose recomendada para uso ocular em humanos. Entretanto, não foram realizados estudos 

controlados em mulheres grávidas. Considerando que os estudos em animais nem sempre podem prever a resposta em humanos, este medicamento deve ser utilizado durante a gestação apenas se 

for claramente necessário. Não se sabe se esta substância é excretada no leite humano. Recomenda-se cautela quando LASTACAFT ® for administrado a mulheres durante a amamentação. Pacientes 

pediátricos: A efi cácia e segurança de LASTACAFT ® não foram estabelecidas em crianças com menos de 2 anos de idade. Pacientes idosos: Não foram observadas diferenças na segurança e efi cácia 

entre pacientes idosos e adultos mais jovens. Pacientes que utilizam lentes de contato: LASTACAFT ® não deve ser aplicado durante o uso de lentes de contato gelatinosas ou hidrofílicas. Os pacientes 

devem ser instruídos a retirar as lentes antes da aplicação do colírio e aguardar pelo menos 10 minutos para recolocá-las após a aplicação de LASTACAFT ® . Os pacientes devem ser advertidos a não utilizar 

lentes de contato se seus olhos estiverem avermelhados. LASTACAFT ® não deve ser utilizado para o tratamento de irritação ocular relacionada ao uso de lentes de contato. Pacientes que utilizam mais 

de um medicamento oftálmico: Quando mais de um medicamento tópico oftálmico estiver sendo utilizando pelo paciente, deve ser respeitado o intervalo de pelo menos 5 minutos entre a administração 

dos medicamentos. POSOLOGIA: A dose usual é de 1 gota aplicada no(s) olho(s) afetado(s), uma vez ao dia. Para informações completas para prescrição, consultar a bula do produto ou a Allergan 

Produtos Farmacêuticos Ltda. VENDA SOB PRESCRIÇÃO MÉDICA. Reg. ANVISA/MS - 1.0147.0179. 

CONTRAINDICAÇÕES: LASTACAFT ® é contraindicado para pacientes que apresentam alergia a qualquer um dos componentes da sua fórmula. 

INTERAÇÕES MEDICAMENTOSAS: Não são conhecidas interações entre a alcaftadina e outras substâncias de uso tópico ocular. 

VENDA SOB PRESCRIÇÃO MÉDICA. 

www.allergan.com.br 

BR/0236/2012 ABR/2012

Olho Seco 

& Pós-Cirurgia Refrativa1 

Ronda Propaganda 

Alta capacidade de retenção de água 2,3 

- Conforto prolongado 

Visco-elástico 4 

- Impede a visão turva 

Muco-adesivo 2,4 

- Hidratação prolongada 

Melhora as propriedades de adesão intercelular 3,4 

Promove rápida cicatrização pós-cirurgias 

Ph e osmolaridade semelhantes 

às do filme lacrimal normal 2 

Mais conforto ao paciente 

Até 

8semanas de 

tratamento 

após a abertura 

Tratamento sintomático do olho seco 

Lubrificação e hidratação de lentes de contato 1 

Referências Bibliográficas: 1) Bula do produto: Hyabak. Registro MS nº 8042140002. 2) Snibson GR, Greaves JL, Soper ND, Tiffany JM, Wilson CG, Bron AJ. Ocular surface residence times of artificial tear solutions. Cornea. 1992 Jul;11(4):288-93. 3) Nakamura M, Hikida M. Nakano T, Ito S, Hamano T, Kinoshita S. Characterization of water retentive properties of hyaluronan. Cornea. 1993 

Sep;12(5):433-6. 4) Gomes JA, Amankwah R, Powell-Richards A, Dua HS. Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. Br J Ophthalmol. 2004 Jun;88(6);821-5. 

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 uma tela 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. 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. Registro MS nº 8042140002. 

Produzido em Outubro/2012 

UNIÃO QUÍMICA FARMACÊUTICA NACIONAL S/A 

Divisão GENOM 

Unidade Brasília: Trecho 01 Conjunto 11 Lote 6 a 12 

Pólo de Desenvolvimento JK 

Santa Maria - Brasília - DF - CEP: 72549-555

Restaura 

o conforto 

ao piscar 1 

Pode ser usado 

com lentes 

de contato 1 15 mL 10 mL 

Alívio imediato e prolongado do ardor e da secura ocular 1 

Sem riscos de lesões induzidas pelos conservantes 2,3 

Nova 

Apresentação 

Referências Bibliográficas: 1) Bula do Produto: Lacrifilm ® . 2) Noecker R. Ophthalmic preservatives: considerations for long-term use in patients with dry eye or glaucoma. Rev Ophthalmol 2001; June: 1-10. 3) Chalmers RL. Hydrogen peroxide in anterior segment physiology: a literature review. Optom Vis 

Sci 1989;66:796-803.7. 

Lacrifilm ® . (carmelose sódica). Solução Oftálmica Estéril. FORMA FARMACÊUTICA E APRESENTAÇÃO: Solução Oftálmica Estéril 5mg/mL: embalagem contendo frasco de 10 mL ou 15 mL. USO ADULTO. USO OFTÁLMICO. COMPOSIÇÃO: Cada 

mL contém: carmelose sódica-5 mg . Veículo: cloreto de sódio, fosfato de sódio, ácido bórico, perborato de sódio, ácido clorídrico e água para injetáveis. INFORMAÇÕES AO PACIENTE. AÇÃO ESPERADA DO MEDICAMENTO: Lacrifilm ® é uma solução 

que apresenta composição muito semelhante à composição das lágrimas naturais. Este medicamento é indicado para melhorar a irritação, ardor e secura ocular, que podem ser causados pela exposição ao vento, sol, calor, ar seco, e para melhorar o 

desconforto que pode estar associado com a utilização de lentes de contato. REAÇÕES ADVERSAS: Informe seu médico o aparecimento de reações desagradáveis. TODO MEDICAMENTO DEVE SER MANTIDO FORA DO ALCANCE DAS CRIANÇAS. 

CONTRAINDICAÇÕES E PRECAUÇÕES: Lacrifilm ® é contraindicado nos casos de alergia a qualquer componente do medicamento. NÃO USE REMÉDIO SEM O CONHECIMENTO DO SEU MÉDICO, PODE SER PERIGOSO PARA A SAÚDE. 

INDICAÇÕES: Lacrifilm ® é indicado para melhorar a irritação, ardor e secura ocular, que podem ser causados pela exposição ao vento, sol, calor, ar seco, e também como protetor contra irritações oculares. É também indicado como lubrificante e reumidificante 

durante o uso de lentes de contato. CONTRAINDICAÇÕES: O produto está contraindicado nos casos de alergia a qualquer componente do medicamento. PRECAUÇÕES E ADVERTÊNCIAS: Evite o contato do conta-gotas do frasco com 

qualquer superfície para evitar contaminação. Não permitir que a ponta do frasco entre em contato direto com os olhos. Mantenha a tampa do frasco bem fechada após o seu uso. Manter o produto fora do alcance das crianças. Armazenar em temperatura 

ambiente. Em caso de aparecimento de dor, alterações da visão, ou se ocorrer piora ou persistência da vermelhidão, ou da irritação dos olhos, por mais de 72h após início de uso do produto, descontinuar o tratamento e procurar auxílio médico. Não utilizar 

o produto se ocorrer modificação da coloração da solução ou se a solução se tornar turva. Produto de uso exclusivo em adultos. O uso em crianças representa risco à saúde. INTERAÇÕES MEDICAMENTOSAS: Não são conhecidas interações com 

outros medicamentos. REAÇÕES ADVERSAS: Não foram detectadas reações adversas com o uso do Lacrifilm ® . POSOLOGIA: Aplicar 1 a 2 gotas no(s) olhos(s) afetado(s), tantas vezes quantas forem necessárias. SIGA CORRETAMENTE O MODO 

DE USAR, NÃO DESAPARECENDO OS SINTOMAS PROCURE ORIENTAÇÃO MÉDICA. Registro MS - 1.0497.1289. 

CONTRAINDICAÇÕES: o produto está contraindicado em pacientes com história de hipersensibilidade a qualquer 

componente da fórmula. INTERAÇÃO MEDICAMENTOSA: não se conhecem interações medicamentosas. 

“LACRIFILM ® 

É UM MEDICAMENTO. SEU USO PODE TRAZER RISCOS. PROCURE O MÉDICO E O FARMACÊUTICO. LEIA A BULA.” 

Material destinado exclusivamente à classe médica. 

Produzido em: Fevereiro/2013 Ronda Propaganda

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Periodicidade: bimestral Arq Bras Oftalmol. São Paulo, v. 75, n. 5, p. 301-376, set./out. 2012 

Sumário | Contents 

305 

306 

Editorial | Editorial 

Neste fascículo dos ABO 

In this issue of the ABO 





307 

313 

316 

320 

324 

333 

Artigos Originais | Original Articles 

Study of crotoxin on the induction of paralysis in extraocular muscle in animal model 

Estudo da crotoxina na indução de paralisia da musculatura extraocular em modelo animal 

Geraldo de Barros Ribeiro, Henderson Celestino de Almeida, David Toledo Velarde, Maria Lygia Vaz de Melo Sá 

Alterações retinianas em jovens portadores de anemia falciforme (hemoglobinopatias) em hospital universitário 

no nordeste do Brasil 

Retinal impairment in young individuals with sickle cell anemia (hemoglobin ss disease) in university hospital in northeastern of Brazil 

Allisson Mário dos Santos, Gustavo Baptista de Almeida Faro, Marcus Vinicius Melo do Amaral, Cristiano de Queiroz Mendonça, 

Bruno Campelo Leal, Rosana Cipolotti 

Effect of aspherical and yellow tinted intraocular lens on blue-on-yellow perimetry 

Efeito das lentes intraoculares asféricas e com pigmentação amarela na campimetria azul-amarelo 

Rodrigo França de Espíndola, Marcony Rodrigues de Santhiago, Newton Kara-Júnior 

Reproducibility of peripapillary retinal nerve fiber layer thickness measurements using Spectral Domain OCT 

in Brazilian patients 

Reprodutibilidade da espessura da camada de fibras nervosas da retina utilizando-se o Spectral Domain OCT em pacientes brasileiros 

Daniela Araújo Toscano, Marcos Pereira de Ávila, Maria Regina Catai Chalita 

Radiation therapy for Graves’ ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials 

Radioterapia para oftalmopatia de Graves: uma revisão sistemática e meta-análise de ensaios clínicos randomizados e controlados 

Gustavo Arruda Viani, André Campiolo Boin, Ligia Issa De Fendi, Ellen Carrara Fonseca, Eduardo Jose Stefano, Jayter Silva de Paula 

Cancelamento de cirurgias de catarata em um hospital público de referência 

Cancellation of cataract surgery in a public hospital 

Micheli Patrícia de Fátima Magri, Rodrigo França de Espíndola, Marcony Rodrigues de Santhiago, Elisabeth Frolich Mercadante, Newton Kara Júnior

337 

341 

344 

348 

Implantação do exame do reflexo vermelho em crianças da região do Hospital das Clínicas da Faculdade de Medicina 

de Botucatu - SP - Brasil 

Implementation of red reflex exam in children in the area of Botucatu Medical School Clinical Hospital - São Paulo, Brazil 

Antonio Carlos Lottelli Rodrigues, Rodrigo Bueno Prado, Licério Miguel 

Prevalence and causes of blindness in an urban area of Paraguay 

Prevalência e causas de cegueira em uma população urbana do Paraguai 

Fernando Yaacov-Peña, David Jure, José Ocampos, Margarita Samudio, João Marcello Furtado, Marissa Carter, Van Charles Lansingh 

An outbreak of forty five cases of Pseudomonas aeruginosa acute endophthalmitis after phacoemulsification 

Surto de quarenta e cinco casos de endoftalmite aguda por Pseudomonas aeruginosa após facoemulsificação 

Ricardo Luz Leitão Guerra, Bruno de Paula Freitas, Cintia Maria Felix Medrado Parcero, Otacílio de Oliveira Maia Júnior, Roberto Lorens Marback 

Phacoemulsification and foldable acrylic IOL implantation in children with treated retinoblastoma 

Facoemulsificação e implante de lente intraocular acrílica dobrável em crianças com retinoblastoma 

Marcia Beatriz Tartarella, Gloria Fátima Britez-Colombi, Marcia Motono, Martha Motono Chojniak, Joao Borges Fortes Filho, Rubens Belfort Jr. 

352 

356 

358 

361 

Relatos de Casos | Case Reports 

Síndrome de Waardenburg - aspectos oftalmológicos e critérios de diagnóstico: relatos de casos 

Waardenburg syndrome - ophthalmic findings and criteria for diagnosis: case reports 

Luciano Sólia Nasser, Lívia Maris Ribeiro Paranaíba, Ana Cláudia Frota, Andreia Gomes, Gisele Versiani, Hercílio Martelli Júnior 

Optical coherence tomography image in gelatinous drop-like corneal dystrophy: case report 

Tomografia de coerência óptica na distrofia corneana gelatinosa em gotas: relato de caso 

Otávio de Azevedo Magalhães, Samuel Rymer, Diane Ruschel Marinho, Sérgio Kwitko, Isabel Habeyche Cardoso, Lúcia Kliemann 

Esclerite posterior associada à oclusão da veia central da retina e edema macular cistoide: relato de caso 

Posterior scleritis associated with central retinal vein occlusion and cystoid macular edema: case report 

Roger Wada Kamei 

Buphthalmos development in adult: case report 

Buftalmus em adulto: relato de caso 

Mônica Alves, Leonardo Tannus Malki, Eduardo Melani Rocha 

363 

Artigos de Revisão | Review Articles 

Ocular rosacea - a review 

Rosácea ocular - revisão 

Ana Carolina Cabreira Vieira, Ana Luisa Höfling-Lima, Mark J Mannis 

370 

Cartas ao Editor | Letters to the Editor 

Axonal electrovisiogram or inverse photopic skin electroretinogram? 

Eletrovisograma axonal ou eletrorretinograma fotópico inverso de pele? 

Katharina Messias, Vinicius Monteiro de Castro, Florian Gekeler, Andre Messias 

373 Instruções para os Autores | Instructions to Authors





Vários artigos originais e inéditos de grande importância clínica estão publicados nesse fascículo dos ABO, 

demonstrando que, cada vez mais, os autores reconhecem a qualidade e abrangência da nossa revista. 

A publicação com a maior casuística de endoftalmite aguda por Pseudomonas aeruginosa do mundo (1) revelou 

que 20% dos 45 olhos submetidos à vitrectomia apresentaram acuidade visual pelo menos igual a 20/200. 

Apesar da fonte do surto não ter sido identificada, todos os pacientes haviam sido submetidos à cirurgia de 

catarata por facoemulsificação em uma mesma instituição em um período determinado de dois dias. Isso induz à 

conclusão que a fonte tenha sido intraoperatória e faz com que os leitores questionem os métodos antissépticos 

atualmente utilizados nas cirurgias oftalmológicas. 

Mais uma vez o tema da medicina baseada em evidências é abordado nos ABO. A revisão sistemática dos 

riscos e benefícios da radioterapia, associada ou não ao uso de glicocorticoides, para o tratamento da oftalmopatia 

de Graves apresentada nesse fascículo é a mais completa já publicada na literatura mundial (2) . Os autores 

identificaram 359 artigos científicos sobre o assunto nas diversas fontes de dados e selecionaram os únicos oito 

que eram estudos clínicos controlados, aleatorizados e com dados disponíveis. Com a meta-análise dos 439 pacientes 

envolvidos neste estudos, os autores concluíram que a radioterapia, especialmente quando associada ao 

uso de glicocorticoides, é efetiva na fase ativa da doença e deve ser indicada nos estágios mais iniciais da mesma. 

Dois relatos de casos inéditos mundialmente são apresentados nesse fascículo: o primeiro relato de buftalmo 

em adulto (3) e a primeira publicação de imagens de tomografia de coerência óptica (OCT) da distrofia corneana 

gelatinosa em gotas (4) . O primeiro faz com que os leitores questionem a importância da avaliação elasticidade 

escleral em diferentes fases da vida e em diferentes doenças, enquanto o segundo apresenta uma excelente 

correlação das imagens de OCT com a anatomia patológica, incluindo a típica birrefringência em luz polarizada 

observada nessa distrofia. 

A prevalência das causas de cegueira no Paraguai, foi avaliada em um estudo epidemiológico realizado por 

instituições paraguaias em colaboração com autores de instituições norte-americanas e da Agência Internacional 

para Prevenção da Cegueira (IAPB) (5) . Os autores detectaram uma menor prevalência de deficiência visual em 

relação ao único estudo populacional prévio do mesmo país, realizado em 2003 (6) . A importância deste artigo 

reside no fato que, apesar de quase 10% das pessoas com cegueira bilateral viverem nas Américas, estudos 

oftalmológicos populacionais, metodologicamente adequados, são infrequentes na América Latina (7) . 

Ainda neste fascículo foram descritos, pela primeira vez, os efeitos de uma neurotoxina isolada do veneno 

de uma cobra sul-americana nos músculos oculares extrínsecos (8) . A crotoxina foi aplicada no músculo reto superior 

de coelhos e comparada com a toxina botulínica tipo A. Os autores concluíram que, quando utilizada na 

concentração de 1,5 µg, o efeito da crotoxina foi similar ao da toxina botulínica tipo A. 

Referências 

1. Guerra RLL, Freitas BP, Parcero CMFM, Maia Jr OO, Marback RL. An outbreak of forty 

five cases of Pseudomonas aeruginosa acute endophthalmitis after phacoemulsification. 

Arq Bras Oftalmol. 2012;75(5):344-7. 

2. Viani GA, Boin AC, de Fendi LI, Fonseca EC, Stefano EJ, de Paula JS. Radiation therapy 

for Graves’ ophthalmopathy: a systematic review and meta-analysis of randomized 

controlled trials. Arq Bras Oftalmol. 2012;75(5):324-32. 

3. Alves M, Malki LT, Rocha EM. Buphthalmos development in adult: case report. Arq Bras 

Oftalmol. 2012;75(5):361-2. 

4. Magalhães OA, Rymer S, Marinho DR, Kwitko S, Cardoso IH, Kliemann L. Optical coherence 

tomography image in gelatinous drop-like corneal dystrophy: case report. Arq 

Bras Oftalmol. 2012;75(5):356-7. 

5. Yaacov-Peña F, Jure D, Ocampos J, Samudio M, Furtado JM, Carter MJ, Lansingh VC. 

Prevalence and causes of blindness in an urban area of Paraguay. Arq Bras Oftalmol. 

2012;75(5):341-3. 

6. Duerksen R, Limburg H, Carron JE, Foster A. Cataract blindness in Paraguay results of 

a national survey. Ophthalmic Epidemiol. 2003;10(5):349 -57. 

7. Pascolini D, Mariotti SP. Global estimates of visual impairment - 2010. Br J Ophthalmol. 

2012;96(5):614-8. 

8. Ribeiro GB, Almeida HC, Velaverde DT, Sá MLVM. Study of crotoxin on the induction of 

para lysis in extraocular muscle in animal model. Arq Bras Oftalmol. 2012;75(5):307-12. 

Submetido para publicação: 5 de outubro de 2012 

Aceito para publicação: 5 de outubro de 2012 

1 

Médico, Departamento de Oftalmologia, Escola Paulista de Medicina - EPM, Universidade Federal 

de São Paulo - UNIFESP - São Paulo (SP), Brasil. 

Financiamento: Não houve financiamento para este trabalho. 

Divulgação de potenciais conflitos de interesse: W.Chamon, Nenhum. 

Arq Bras Oftalmol. 2012;75(5):305 

305





Several original and unpublished articles of great clinical importance are published in this issue of the ABO, 

showing that, increasingly, the authors recognize the quality and comprehensiveness of our journal. 

A publication with the highest incidence of infectious endophthalmitis by Pseudomonas aeruginosa in the 

world (1) revealed that 20% of the 45 eyes that underwent vitrectomy presented visual acuity of at least 20/200. 

Although the source of the outbreak has not been identified, all patients had undergone cataract surgery by 

phacoemulsification in a single institution in a given period of two days. This leads to the conclusion that it was 

an intraoperative source and forces readers to question the antiseptic methods currently used in eye surgery. 

Again the theme of evidence-based medicine is covered in ABO. A systematic review of the risks and benefits 

of radiotherapy, with or without the use of glucocorticoids, for the treatment of Graves’ ophthalmopathy presented 

in this issue is the most comprehensive ever published in the world literature (2) . The authors identified 359 

scientific articles on the subject in the various data sources and selected the eight ones that were randomized 

controlled trials, with data available. With the meta-analysis of 439 patients involved in these studies, the authors 

concluded that radiotherapy, especially when associated with glucocorticoid treatment, is effective in the active 

phase of the disease and must be indicated in the earlier stages of the same. 

Two unpublished case reports are presented in this issue: the first report of buphthalmos in adult (3) and the 

first publication of optical coherence tomography (OCT) images of gelatinous drop-like corneal dystrophy (4) . The 

first makes readers question the importance of assessing scleral elasticity in different stages of life and in different 

diseases, while the second shows an excellent correlation with the OCT images and pathology, including the 

typical birefringence under polarized light observed in this dystrophy. 

The prevalence of the causes of blindness in Paraguay, was evaluated in an epidemiological study conducted 

by Paraguayan institutions in collaboration with authors from U.S. institutions and from the International Agency 

for Prevention of Blindness (IAPB) (5) . The authors found a lower prevalence of visual impairment in relation the 

only previous population-based study from the same country, in 2003 (6) . The importance of this paper lies in 

the fact that, although almost 10% of people with bilateral blindness live in the Americas, methodologically 

appropriate, ophthalmic population-based studies are infrequent in Latin America (7) . 

Also in this issue, it has been described, for the first time, the effects of a neurotoxin isolated from the venom 

of a South American rattlesnake in the external ocular muscles (8) . The crotoxin was applied to the superior rectus 

muscle of rabbits and compared with botulinum toxin type A. The authors concluded that, when used at a 

concentration of 1.5 µg, the effect of the crotoxin was similar to botulinum toxin type A. 

ReferENCES 

1. Guerra RLL, Freitas BP, Parcero CMFM, Maia Jr OO, Marback RL. An outbreak of forty 

five cases of Pseudomonas aeruginosa acute endophthalmitis after phacoemulsification. 


2. Viani GA, Boin AC, de Fendi LI, Fonseca EC, Stefano EJ, de Paula JS. Radiation therapy 

for Graves’ ophthalmopathy: a systematic review and meta-analysis of randomized 

controlled trials. Arq Bras Oftalmol. 2012;75(5):324-32. 

3. Alves M, Malki LT, Rocha EM. Buphthalmos development in adult: case report. Arq Bras 

Oftalmol. 2012;75(5):361-2. 

4. Magalhães OA, Rymer S, Marinho DR, Kwitko S, Cardoso IH, Kliemann L. Optical coherence 

tomography image in gelatinous drop-like corneal dystrophy: case report. Arq 

Bras Oftalmol. 2012;75(5):356-7. 

5. Yaacov-Peña F, Jure D, Ocampos J, Samudio M, Furtado JM, Carter MJ, Lansingh VC. 

Prevalence and causes of blindness in an urban area of Paraguay. Arq Bras Oftalmol. 

2012;75(5):341-3. 

6. Duerksen R, Limburg H, Carron JE, Foster A. Cataract blindness in Paraguay results of 

a national survey. Ophthalmic Epidemiol. 2003;10(5):349 -57. 

7. Pascolini D, Mariotti SP. Global estimates of visual impairment - 2010. Br J Ophthalmol. 

2012;96(5):614-8. 

8. Ribeiro GB, Almeida HC, Velaverde DT, Sá MLVM. Study of crotoxin on the induction of 

paralysis in extraocular muscle in animal model. Arq Bras Oftalmol. 2012;75(5):307-12. 

Submitted for publication: October 5, 2012 

Accepted for publication: October 5, 2012 

1 

Physician, Department of Ophthalmology, Escola Paulista de Medicina - EPM, Universidade Federal 

de São Paulo - UNIFESP - São Paulo (SP), Brazil. 

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

Disclosure of potencial of interest: W.Chamon, None. 

306 Arq Bras Oftalmol. 2012;75(5):306

Artigo Original | Original Article 


Estudo da crotoxina na indução de paralisia da musculatura extraocular em modelo animal 

Geraldo de Barros Ribeiro 1 , Henderson Celestino de Almeida 2 , David Toledo Velarde 3 , Maria Lygia Vaz de Melo Sá 4 

ABSTRACT 

Purpose: Crotoxin is the major toxin of the venom of the South American rattlesnake 

Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at 

the neuromuscular junction. The objective of this study was to appraise the action 

and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to 

compare its effects with the botulinum toxin type A (BT-A). 

Methods: The crotoxin, with LD50 of 1.5 μg, was injected into the superior rectus 

muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 μg. 

Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The 

evaluation of the paralysis was performed using serial electromyography. After the 

functional recovery of the muscles, which occurred after two months, six rabbits were 

sacrificed for anatomopathology study. 

Results: The animals did not show any evidence of systemic toxicity. Transitory ptosis 

was observed in almost every animal and remained up to fourteen days. These toxins 

caused immediate blockade of the electrical potentials. The recovery was gradual in 

the average of one month with regeneration signs evident on the electromyography. 

The paralysis effect of the crotoxin on the muscle was proportional to its concentration. 

The changes with 1.5 μg crotoxin were similar to those produced by the botulinum 

toxin type A. The histopathology findings were localized to the site of the injection. 

No signs of muscle fiber’s necrosis were seen in any sample. The alterations induced 

by crotoxin were also proportional to the concentration and similar to botulinum 

toxin type A in concentration of 1.5 μg. 

Conclusion: Crotoxin was able to induce transitory paralysis of the superior rectus 

muscle. This effect was characterized by reduction of action potentials and non-specific 

signs of fibrillation. Crotoxin, in concentration of 1.5 μg was able to induce similar 

effects as botulinum toxin type A. 

Keywords: Crotoxin/administration & dosage; Crotalid venoms; Snakes; Botulinum 

toxins, type A/administration & dosage; Cobra neurotoxin proteins; Ophthalmople - 

gia/chemically induced; Neuromuscular junction; Comparative study 

RESUMO 

Objetivo: A crotoxina é a principal toxina do veneno da cobra cascavel sul-americana 

Crotalus durissus terrificus e causa bloqueio da neurotransmissão na junção neuromuscular. 

O objetivo deste estudo foi avaliar a ação e aplicabilidade da crotoxina na indução 

de paralisia da musculatura extrínseca ocular, e comparar seus efeitos com os da toxina 

botulínica do tipo A (TB-A). 

Métodos: A crotoxina, com DL50 de 1,5 μg, foi aplicada no músculo reto superior direito 

de dez coelhos da raça neozelandesa, em concentrações que variaram de 0,015 μg a 

150 μg. Em dois coelhos, utilizou-se 2 unidades de toxina botulínica do tipo A para análise 

comparativa. A avaliação da paralisia foi realizada através de eletromiografia seriada. 

Após a recuperação, que ocorreu em dois meses, seis coelhos foram sacrificados para 

estudo anátomopatológico. 

Resultados: Os animais não apresentaram sinais de intoxicação sistêmica. Ptose palpebral 

transitória foi observada em quase todos os animais e permaneceu por até 14 dias. As 

toxinas causaram um bloqueio imediato da captação dos potenciais elétricos. A recuperação 

foi gradativa no período aproximado de um mês, observando-se sinais evidentes 

de regeneração no registro eletromiográfico. Os efeitos da crotoxina na paralização do 

músculo injetado foram proporcionais à concentração. A crotoxina, na concentração 

de 1,5 μg, induziu alterações semelhantes às da toxina botulínica do tipo A. Os achados 

anátomo-patológicos foram localizados somente na região em que se aplicou as toxinas, 

não havendo necrose de fibras musculares em nenhuma amostra analisada. As alterações 

causadas pela crotoxina também foram proporcionais à concentração utilizada e similares 

a toxina botulínica do tipo A na concentração de 1,5 μg. 

Conclusão: A crotoxina foi capaz de induzir paralisia transitória do músculo reto superior. 

Este efeito foi caracterizado pela redução na amplitude dos potenciais de ação e sinais 

inespecíficos de fibrilação. Observou-se que a ação da crotoxina, em concentração de 1,5 μg, 

proporcionou efeito semelhante ao da toxina botulínica do tipo A. 

Descritores: Crotoxina/administração e dosagem; Venenos de crotalídeos; Serpentes; 

Toxinas botulínicas tipo A/administração e dosagem; Proteínas neurotóxicas de elapídeos; 

Oftalmolplegia/induzido quimicamente; Junção neuromuscular; Estudo comparativo 

INTRODUCTION 

Crotoxin is a b-neurotoxin, isolated from the poison of South 

American rattlesnake Crotalus durissus terrificus (1) . This toxin is a noncovalent 

oligomer, formed by two subunits: one acid and the other 

basic. The latter has phospholipase A2 activity and is neurotoxic, while 

the acid subunit is enzymatically and pharmacologically inactive, but 

it highly increases the toxicity of the basic subunit (2,3) . The acid subunit 

acts as a helper to the basic subunit, giving it specificity and increasing 

its stability. Crotoxin has molecular weight of 23.5KDa. Its basic 

subunit has molecular weight of 14.3 KDa and isoelectric point 8.9. It 

is formed by a single polypeptide branch with 123 amino acids. The 

acid subunit has molecular weight of 9.2 KDa and isoelectric point 3.8, 

and it is formed by three polypeptides (a,b,¡) linked by seven disulfide 

bridges (3-5) . Both crotoxin subunits behave in a synergic manner, but 

dissociate when they interact with synaptic membranes. The basic 

portion remains attached to the membrane, while the acid portion 

is released into solution. The binding of the basic portion to synaptic 

membranes is not specific, and it can also bind to other membranes, 

while the acid portion does not attach. While in association to the 

basic portion, the acid subunit enhances its pharmacological action, 


Accepted for publication: August 12, 2012 

Study carried out at Strabismus Clinic at São Geraldo Hospital of Universidade Federal de Minas 

Gerais - UFMG - Belo Horizonte (MG) - Brazil 

1 

Physician, Strabismus Service, Universidade Federal de Minas Gerais - UFMG - Belo Horizonte 

(MG) - Brazil. 

2 

Teacher, Universidade Federal de Minas Gerais - UFMG - Belo Horizonte (MG) - Brazil. 

3 

Biochemist, Hospital Foundation of Minas Gerais State - Fhemig - Belo Horizonte (MG) - Brazil. 

4 

Physician, Institute of Clinical Neurophysiology of Minas Gerais, Belo Horizonte (MG) - Brazil. 


Disclosure of potential conflicts of interest: G.B.Ribeiro, inventor in patent UFMG (Universidade 

Federal de Minas Gerais) involving the use of crotoxin in humans; H.C.Almeida, inventor in patent 

UFMG (Universidade Federal de Minas Gerais) involving the use of crotoxin in humans; D.T.Velarde, 

inventor in patent UFMG (Universidade Federal de Minas Gerais) involving the use of crotoxin in 

humans; M.L.V.M.Sá, None. 

Correspondence address: Geraldo de Barros Ribeiro, Av. Silviano Brandão, 1600 - Belo Horizonte - 

MG - 30015-015 - Brazil - E-mail: gbarrosribeiro@gmail.com 

Arq Bras Oftalmol. 2012;75(5):307-12 

307


by significantly reducing the non-specific binding (3-5) . Crotoxin blocks 

the release of neurotransmitter at the presynaptic motor end-plate (6) . 

Based on the crotoxin effect as a neuromuscular blocker, we decided 

to verify the possibility of using it to induce extraocular muscle 

paralysis in rabbits. The objectives of this study were: to evaluate the 

capacity of crotoxin to induce extraocular muscle paralysis in rabbits, 

analyze the duration of extraocular muscle paralysis induced by 

crotoxin; observe the duration and possible side effects of crotoxin at 

different concentrations through electromyography and anatomopathology 

exams, and finally compare crotoxin to botulinum toxin 

type A (BT-A). 

METHODS 

All procedures were conducted according to Brazilian Law n o 

6.638, May 1979. This law established regulations for the scientificdidactic 

practices of animal vivisection. It foresees that research 

should be realized always in a manner that does not cause any 

suffering to animals involved. 

In this study, 12 new-Zealand rabbits were used, with average 

weight of 2.5 kg. Rabbits were divided in 6 groups, with 2 rabbits 

in each group. Crotoxin dose initially used was based on the comparison 

of minimum lethal dose (LD50) of crotoxin and botulinum 

toxin type A in mice (1) . 

Crotoxin used had a LD50 of 1.5 μg. Toxicity was determined 

by minimum lethal dose in 50% of injected animals (LD50), using 

conventional Swiss mice, with weights from 18 to 22 g. 

Based on these calculations, it was decided to use different 

concentrations of crotoxin. Doses ranged from one hundred times 

smaller to one hundred times larger than the estimated DL50 of 

crotoxin. 

One group received 2 units of botulinum toxin type A (Botox ® ). 

Crotoxin and botulinum toxin type A were injected into the 

right superior rectus muscle of each rabbit, with an insulin syringe 

(Unijet, Plascalp Produtos Cirúrgicos Ltda., Feira de Santana, BA). The 

best place for injection was evaluated through electromyography. 

Injection was done after instillation of 0.5% proximetacaine 

chloride anesthesic eye drop (Anestalcon®-Alcon Laboratórios 

do Brasil, São Paulo, SP) and under direct visualization of the supe - 

rior rectus muscle. Needle was introduced transconjunctivally and 

inserted into the muscle. Injection was made into superior rectus 

muscle 4mm behind to the muscle insertion. Injected volume was 

100μl, except in rabbit n o 12, which received a volume of 50 μl. Solution 

applied in rabbit n o 12 contained a concentration of 150 μg in 

100μl: that means this rabbit received half the dose of rabbit n o 11. 

The dose applied in each rabbit was: 

Group I > Rabbits 1 and 2 > 0.015 μg crotoxin 

Group II > Rabbits 3 and 4 > 0.15 μg crotoxin 

Group III > Rabbits 5 and 6 > 1.5 μg crotoxin 

Group IV > Rabbits 7 and 8 > 2 U of botulinum toxin type A 

(BT-A (Botox®) 

Group V > Rabbits 9 and 10 > 15 μg crotoxin 

Group VI > Rabbits 11 and 12 > 150 μg crotoxin and 75 μg 

crotoxin (respectively) 

Rabbits were accompanied daily in the first week, watching for local 

and systemic side effects. Analysis of possible systemic side effects 

was done through observation of animal behavior. Laboratory testing 

to evaluate liver and kidney functions were not done. Afterwards, 

observation of animals was done twice a week until the end of the 

experiment. The evaluation of toxin effects was done through electromyography 

exams, and was done 2, 9, 16, 23 and 60 days after the 

injections. After the last electromyographic exam, one animal of each 

group was sacrificed for anatomopathology studies. 

Electromyographic exams were done in the Institute of Clinical 

Neurophysiology of Minas Gerais, in Belo Horizonte. Animals received 

3 drops of 0.5% proximetacaine chloride eye drop (Anestalcon ® - 

Alcon Laboratórios do Brasil, São Paulo, SP, Brasil) before the exam. 

Electromyograph used was a Neuropack Four Mini Evoked Potential 

Measuring System MEB-5304K (Nihon Kohden, Tokio, Japan). 

A concentric bipolar electrode was used, with platinum central wire 

and stainless steel cannula. Length of electrode was 37 mm; needle 

had 0.46mm diameter, and a record area of 0.07 mm (Teca Corporation, 

catalogue number 53156, New York, USA). One hook-and-loop 

fastener tape (Teca Corporation, catalogue number GE-V, New York, 

USA), soaked in saline solution, was put around the ears of the rabbits 

for grounding the system. 

Animals were sacrificed through intracardiac injection of 0.75% 

bupivacaine hydrochloride (Cristália Produtos Químicos Farmacêuticos 

Ltda., Itapira, SP, Brasil) after the last electromyographic exam. 

The right orbit of odd numbered rabbits, each one representing one 

group studied, was carefully exenterated and processed for histopathology 

exams. 

Crotoxin used in this research was given by Immunobiological 

Division of Ezequiel Dias Foundation of Belo Horizonte - MG (FUNED). 

Crotoxin was obtained in its pure form and after lyophilization, was 

dissolved in saline buffer and afterwards its toxicity was evaluated 

through LD50 testing in mice. Toxicity of this solution was determined 

through LD50 testing in mice with 18 to 22 grams, intraperitoneally. 

Male and female mice were used, in groups of 8 animals per 

dose, with reading after 48 hours. 

RESULTS 

Rabbits tolerated well the experiment, not showing any behavior 

alteration after the injection of both toxins. One day after the toxins 

injection, only rabbit 4 did not have blepharoptosis; the other animals 

had discrete ptosis, which lasted for two days in rabbits 1, 2, 3, 5 and 

6, and seven days in rabbits 7, 11 and 12. Rabbit 8 had the longest 

duration of ptosis: fourteen days. Conjunctival hyperemia on the site 

of injection was discrete in rabbits 1, 2, 3, 4, 7 and 8, lasting less than 

48 hours and moderate in rabbits 5 and 6, gradually improving in seven 

days. Rabbit 11 had the strongest reaction: besides conjunctival 

reaction, there was corneal edema, which improved after 14 days, 

but also produced permanent leukoma in the affected cornea. This 

lesion may have no relation to the application, because its location 

was distant from the area of injection. 

Results of electromyography 

Electromyographic (EMG) exams in superior recti muscles of all 

animals were normal before the injections, and they were repeated 

with 2, 9, 16, 23 and 58 days. 

Results are divided in four tables according to days of follow-up 

(Tables 1 to 4). 

At the fifty-eighth day of follow-up, the electromyography records 

were practically normal in all animals. 

Results of anatomo-pathology study 

The right orbit of six rabbits, one from each group, was exenterated 

for histological study 70 days after the injection of crotoxin or 

botulinum toxin type A. In all groups, alterations found in the superior 

rectus muscle were located 4 to 5mm posterior to the scleral muscle 

insertion and observed only at the site of injection. 

In group I (0.015 μg crotoxin), there was a discrete endomysial 

fibrosis on the injected area, the remaining muscle being normal. In 

group II (0.15 μg crotoxin), endomysial fibrosis slightly more evident 

than in group I. In group III (1.5 μg crotoxin), more evident local 

lesions as: discrete chronic inflammation, characterized by discrete 

lymphocytic mononuclear histiocytic infiltrate, myophagocytosis and 

edema with endomysial fibrosis, fibers with degenerative phenomena 

(vacuolated) and signs of muscle fibers regeneration (centralization of 

nuclei) (Figure 3). 

308 Arq Bras Oftalmol. 2012;75(5):307-12

Ribeiro GB, et al. 

Table 1. EMG with two days of follow-up 

Results of electromyographic exams 

Group I 0.015 μg crotoxin There were not any observable signs of irritability of neuromuscular membrane. 

Observed contraction potentials had normal amplitude and duration, with no significant alterations in fiber recruitment, which was only incomplete. 

Group II 0.15 μg crotoxin Although potentials were under expected limits, the amplitudes were smaller when compared to potentials of the smaller dose. 

Group III 1.5 μg crotoxin Although the signs of membrane irritability were not present, potentials obtained were rare and of diminished amplitude. Findings suggested 

a blockade of conduction between fibers. 

Group IV 2 U BT-A There were signs of irritability of neuromuscular sheaths at rest due to blockade of neuromuscular joint conduction. There was no response 

of fibers and no evidence of contraction of motor units. The presence of fibrillation potentials could indicate a functional denervation. 

Group V 15 μg crotoxin No signs of membrane irritability, but the rare potentials detected were of low amplitude, as if fibers were destroyed or blocked to stimulus 

response. 

Group VI 

150 μg crotoxin 


There was a complete silence in electromyography records. 

Table 2. EMG with nine days of follow-up 


Group I 0.015 μg crotoxin Action potentials were normal and with no signs of irritability (instability of membranes). 

Group II 0.15 μg crotoxin Similar activity as group I. 

Group III 1.5 μg crotoxin Signs of irritability were not present, but the detection of potentials (that are normal) showed that few motor units had response, such as 

happens to group IV. 

Group IV 2 U BT-A Signs of irritability of membrane remain, but with rare normal potentials during contraction. 

Group V 15 μg crotoxin Non-specific signs of irritability are present, but during contraction there were signs of asynchronous recruitment of motor units (polyphasic). 

Group VI 



In rabbit 11, which received a volume of 100 µl, the main characteristic is the complete absence of potentials, with signs of non-specific 

irritability in rest. 

In rabbit 12, which received 50 µl, irritability is lower and, despite the existence of functional units, they are rare. 

Table 3. EMG with sixteen days of follow-up 


Group I 0.015 μg crotoxin Action potentials were normal. 

Group II 0.15 μg crotoxin Similar activity as group I. 

Group III 1.5 μg crotoxin Normal potentials during contraction, with more intense signs of irritability. 

Group IV 2 U BT-A Signs of neuromuscular irritability were more intense, and potentials with normal amplitude and duration during contraction, associated 

to long polyphasic potentials, characterizing asynchronous recruitment process, typical of recent reinnervation. Although the pattern of 

recruitment was not normal, there was no rarefaction in response. 

Group V 15 μg crotoxin Normal potentials, with signs of recent reinnervation. 

Group VI 



Normal potentials during contraction, but the number of motor units was reduced. 

Table 4. EMG with twenty days of follow-up 


Group I 0.015 μg crotoxin Normal potentials and recruitment. 

Group II 0.15 μg crotoxin Signs of irritability were not present and, during contraction, units were in normal quantity, but there were signs of asynchronous recruitment, 

typical of reinnervation. 

Group III 1.5 μg crotoxin Some non-specific signs of irritability remained, and present motor units were reduced (figure 1) 

Group IV 2 U BT-A Signs of irritability were not present, and motor units presented normal amplitude and duration during contraction. The pattern of interference 

was still incomplete, but there were not long duration polyphasics (asynchrony), which indicated that the process of regeneration 

was complete (Figure 2). 

Group V 15 μg crotoxin Normal potentials during contraction, with intense signs of irritability and signs of asynchronous recruitment. 

Group VI 



Signs of neuromuscular irritability associated with long duration polyphasic potentials, which indicated process of asynchronous recruitment, 

typical of recent reinnervation. 


309


In group IV (2 U BT-A), anatomo-pathology alterations were similar 

to those found in group III (Figure 4). 

In group V (15 μg crotoxin), degenerated fibers (vacuolated), with 

loss of striation and marked endomysial fibrosis. Muscle fibers with 

signs of degeneration. 

In group VI (150 and 75 μg crotoxin), more marked signs of muscle 

fiber degeneration, such as myophagocytosis, discrete endomysial 

fibrosis and chronic inflammatory infiltrate, and also muscle fibers 

with signs of degeneration (central nucleus). There was no muscle 

necrosis. 

DISCUSSION 

Most of our current knowledge about various human pathologies 

was experimentally discovered in animals. It is necessary, 

naturally, to take care when extrapolating the analysis of results with 

animals to human beings. 

In our study, the rabbit, despite not having binocularity - vision 

axis are not parallel -, was useful for presenting extraocular muscles 

well developed, especially the superior rectus, and also because it is 

an animal of easy handling. Using only anesthetic drops, we were able 

to perform electromyography of the superior rectus muscle to evaluate 

the effects of the injected toxins and its subsequent recovery. 

The injection of toxins was well tolerated by rabbits, without 

signs of prostration or changes in feeding behavior. The main local 

side effect observed was ptosis, which occurred in eleven of twelve 

rabbits, the day after the injection. However, the ptosis was discrete 

and improved after two days in rabbits 1, 2, 3, 5 and 6, after seven days 

in rabbits 7,11 and 12 and remained for two weeks in rabbit 8, which 

received 2U of BT-A. Ptosis observed in monkeys in the first research 

with botulinum toxin lasted up to six weeks (7) . Dosing used for this 

animal was higher than used in our study. Besides, they injected a 

volume up to 500 µl, which easily diffuse to adjacent tissues. Animals 

receiving A-bungarotoxin (snake poison) on the same experiment 

showed ptosis, which improved after three days (7) . 

Conjunctival hyperemia observed after the injection was discrete, 

and improved after 48 hours in rabbits 1, 2, 3 and 4 (which were 

submitted to lower doses of crotoxin), and in rabbits 7 and 8 (which 

received 2 units of botulinum toxin type A). Rabbits 5 and 6 that had 

injections of 1.5 μg crotoxin, showed moderate hyperemia, which 

gradually improved, in seven days. Scott et al., in 1973 (7) , had also 

observed a discrete local reaction in animals submitted to injection 

of A-bungarotoxin and botulinum toxin, which improved after one 

day. A more marked local reaction, with hyperemia and purulent 

secretion, was observed in rabbits 9, 10, 11 and 12, but improved 

spontaneously, without any topic medication, in approximately one 

Figure 1. EMG of rabbit 6, twenty-three days after the injection of 1.5 μg crotoxin. 

Figure 3. Fibers with degenerative phenomena (vacuolated) and signs of muscle fibers 

regeneration (centralization of nuclei) (magnification of 400X, stained with hematoxy - 

lin-eosin) in group III (1.5 μg crotoxin). 

Figure 2. EMG of rabbit 7, twenty-three days after the injection of 2U botulinum 

toxin type A. 

Figure 4. Discrete degenerated muscle fibers (vacuolated), edema, endomysial fibrosis 

and mononuclear infiltrate (magnification of 400 X, stained with hematoxylin-eosin) in 

group IV (2 U BT-A). 


Ribeiro GB, et al. 

week. Rabbit 11, besides conjunctival reaction, had also corneal 

leukoma, which persisted until the end of the experiment. 

There are still some doubts about the mechanism of action of 

crotoxin in inducing the neuromuscular blockade. The process of 

transmission of information in synapses involves several stages. In 

a general way, stimulus activate an action potential that leads to 

alteration of ions flux, due to the opening and/or closing of ionic 

channels, ending with the release of neurotransmitters, which were 

stored in synaptic vesicles. 

Several proteins located in the plasmatic membrane of nervous 

terminal or in the membrane of synaptic vesicle, or even free in the 

neuron cytoplasm, are involved in the process of neurotransmitter 

release. They act on recycling, translocation, anchorage and fusion 

of synaptic vesicles to cell membrane. Proteins that are, so far, known 

for participating in this process, are: syntaxin, synaptosomal-associated 

protein 25 (SNAP-25), neurexin, voltage sensitive calcium 

channels, PKC, N-ethylmaleimide-sensitive factor (NSF), soluble NSF 

attachment proteins (SNAPs) a, b, g, kinase C substrate, myristoylated 

alanine-rich (MARCKS) and growth associated protein (GAP-43), 

synapsins (Ia, Ib, IIa, IIb and II1a), synaptobrevin, synaptophysin, 

synaptotagmin, CaMK I and II, dinamin, rab, GTP-binding proteins 

and rabphilin (8,9) . 

Botulinum toxin type A targets synaptosomal-associated 

protein 25 (SNAP-25), of molecular weight 25KDa. Other types of 

botulinum toxin attach themselves to different membrane proteins 

or to synaptic vesicle (8,9) . 

Crotoxin has phospholipase activity A 2 

(PLA 2 

), necessary for its 

toxic effect. The substitution of Ca 2+ ions, essential to phospolipase 

activity, for Sr 2+ , inhibits the toxic effect of crotoxin (10-12) . According 

to these authors, toxins would bind to cell membrane, dependent 

on calcium and, afterwards, would be endocyted into synaptic 

vesicles. Due to its phospholipase action on the vesicle membrane, 

they would irreversibly block vesicular endocytosis. Crotoxin also 

interferes in calcium and potassium channels, and this could reduce 

the acetylcholine release in the neuromuscular junction (13) . It alters 

also protein phosphorylation in the neuromuscular junction (14) . 

In this study, evaluation of paralysis or paresis of superior rectus 

muscles after injection of crotoxin and BT-A was done through 

electromyography. Extrinsic ocular muscles of rabbits are striated. 

This type of muscle is functionally formed of motor units in which 

axons of individual motor cells innerve several muscle fibers. Motor 

units are the smallest functional units of the locomotor apparatus. 

Information on the function of these units is obtained, mainly, from 

the use of electromyography. The sum of several action potentials 

of many motor-end plates forms the action potential of the muscle, 

which originates in the motor-end plates and is initiated from 

an afferent nervous impulse to neuromuscular joint. This nervous 

impulse is spread all over the muscle fibers, stimulating contraction. 

The intensity of muscle contraction depends, partially, on the 

number of motor units that are being activated (recruitment) and, 

partially, on the frequency neurons are sending impulses to muscle 

fibers. In lesions of peripheral nerve, electromyography can be used 

in a previous stage than any other method to identify paralysis and 

record if regeneration is happening accordingly. If peripheral motor 

neurons that supply a muscle are completed destroyed, lesion will 

be partial, proportional to the number of affected cells. In denervated 

muscles, that lost their nerve supply, there are still some action 

potentials that can be observed on electromyography, and these 

are called fibrillation potentials, which seem to originate in isolated 

muscle fibers that lost their innervations. The origin of fibrillation is 

not completely understood, but some authors say that it is due to 

a “sensitization” of the muscle portion of the motor-end plate after 

denervation. The absence of the neurotransmitter can stimulate the 

muscle fibers to respond to a very small quantity of acetylcholine 

present in blood stream. 

Electromyographic findings demonstrated that crotoxin caused 

a reversible paralysis of muscular activity, being proportional to the 

dose injected, according to other authors (13) . Reduction in action 

potentials was observed mainly in crotoxin concentrations greater 

than 1.5 μg. Recovery of paralysis was gradual, and at the end of 

two months of follow-up, electromyographic records were almost 

normal. BT-A injected also caused a reversible paralysis. Action 

potentials of muscles injected with BT-A had its recovery starting 

after nine days, and were close to normality after two months. That 

shows that paralysis induced by known concentrations of crotoxin 

had similar duration than BT-A. 

High concentrations of crotoxin have myotoxic effect (3,15) . Mor - 

phologic alterations observed in mice, through electron microscopy, 

show that, in high doses, crotoxin affects nerve terminals, skeletal 

muscle and the axons. These effects were also observed with only the 

injection of PLA 2 

subunit from crotoxin, what was not demonstrated 

with the other subunit. First structures that are affected by crotoxin 

are: sarcolemma, mitochondria and sarcoplasmic reticulum (16,17) . In 

1984, it was evidentiated that the beginning of myonecrosis caused 

by crotoxin was provoked by a progressive loss of sarcolemma integrity, 

due to hydrolysis of phospholipid component. Regeneration of 

muscle fibers was fast (18) . 

In our experiment, one animal from each group was sacrificed 

for anatomopathology studies. Histological alterations found were 

proportional to crotoxin concentration, and located only on the site 

of injection. There was no muscle fiber necrosis in any specimen. 

At lower concentrations (0.015 and 0.15 μg), it was observed only 

discrete endomysial fibrosis and, in some regions, mononuclear 

infiltrate. At concentration of 1.5 μg of crotoxin, inflammatory process 

was also discrete, however, it was possible to observe signs of 

myophagocytosis, vacuolated fibers (degenerative sign) and fibers 

with central nucleus (regeneration sign). These alterations were 

similar to those found in rabbits that received BT-A. Some studies 

show that the injection of botulinum toxin type A causes muscle 

alterations, proportional to toxin concentration (19) . Similarly to 

studies with crotoxin, histological alterations caused by botulinum 

toxin type A were reversible (20) . Changes observed in groups V and 

VI, that received crotoxin at concentrations of 15 μg and 150 μg, 

respectively, were more marked than the changes observed in 

other groups, and it is even more evident in the group of the 

highest concentration. Signs of degenerated fibers (vacuolated), 

loss of striation and endomysial fibrosis were more marked. Signs 

of regeneration of muscle fibers (characterized by the presence of 

central nucleus) were also evident. 

CONCLUSIONS 

Muscle paralysis induced by crotoxin injection could be demonstrated 

with the help of electromyography. At concentration 

of 1.5 μg, crotoxin caused similar effects to botulinum toxin type 

A, showing only discrete local histological alterations. Based on 

these findings, we believe that the pharmacological activity of crotoxin 

can be useful to treat pathologies that have been receiving 

botulinum toxin with success. Clinical studies in human beings are 

necessary to corroborate crotoxin applicability in several areas of 

medicine. 

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de córtex de rato [tese]. Belo Horizonte, Instituto de Ciências Biológicas, Universidade 

Federal de Minas Gerais; 2000. 

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active neurotoxins. In: Eaker D, Wadstrom T, editors. Natural toxins. , Oxford: 

Pergamon Press; 1980. p.569-78. 

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38 o Congresso da 

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Alterações retinianas em jovens portadores de anemia falciforme (hemoglobinopatias) 

em hospital universitário no nordeste do Brasil 

Retinal impairment in young individuals with sickle cell anemia (hemoglobin ss disease) 

in university hospital in Northeastern of Brazil 

Allisson Mário dos Santos 1 , Gustavo Baptista de Almeida Faro 2 , Marcus Vinicius Melo do Amaral 3 , Cristiano de Queiroz Mendonça 4 , 

Bruno Campelo Leal 4 , Rosana Cipolotti 3 

RESUMO 

Objetivos: Descrever e classificar alterações retinianas encontradas em portadores 

de anemia falciforme com genótipo SS, bem com comparar métodos diagnósticos 

(mapeamento de retina e angiofluoresceinografia). 

Métodos: Neste estudo transversal foram avaliados pacientes portadores de anemia 

falciforme com idade igual ou superior a sete anos. Esses pacientes foram submetidos 

a mapeamento de retina e angiofluoresceinografia. Os achados do mapeamento de 

retina foram agrupados em três classes: sem alterações; alterações não proliferativas 

e alterações proliferativas. Os resultados à angiofluoresceinografia foram classificados 

de acordo com os estágios de Goldberg, variando de I a V e expressando gradiente 

crescente de gravidade. 

Resultados: Foram avaliados 61olhos de 31pacientes. A retinopatia falciforme foi 

encontrada em 38/61 (62,3%) dos olhos examinados. A média de idade do grupo de 

portadores de retinopatia foi menor que dos pacientes sem retinopatia (14,4 versus 

17,4 anos, p=0,04). Observou-se elevada freqüência de retinopatia não proliferativa, 

especialmente as tortuosidades vasculares (27,9%), seguidas por anastomoses arteriovenosas 

na periferia da retina (24,6%) e oclusões arteriolares (8,2%). Em um olho 

foi observado neovascularização. Em 16,4% dos olhos obteve-se resultado normal no 

mapeamento de retina e alterado à angiofluoresceinografia. 

Conclusões: As alterações retinianas do tipo não proliferativa são frequentes e precoces 

nos portadores de anemia falciforme do tipo SS, sendo a angiofluoresceinografia mais 

sensível no diagnóstico quando comparada ao mapeamento de retina. 

Descritores: Anemia falciforme; Retina/fisiopatologia; Doenças retinianas/diagnóstico; 

Angiofluoresceinografia/metodos; Oftalmoscopia 

ABSTRACT 

Purposes: To describe and categorize retinal vascular changes in patients with sickle 

cell anemia, as well as to compare diagnostic methods (indirect ophthalmoscopy and 

fluorescein angiography). 

Methods: Patients with sickle cell anemia over the age of seven were examined. Complete 

ophthalmologic examination with indirect ophthalmoscopy and angiography was 

performed in each patient. The fundoscopy results were grouped in 3 classes: normal; non- 

-proliferative retinopathy, which includes vascular tortuosity, black sunburst, salmon- patch 

and peripheral closure/anastomoses; and proliferative retinopathy, related to neovascular 

proliferation. Angiography results were classified according to Goldberg classifications 

from stage I to V. 

Results: Retinopathy related to sickle cell anemia was seen in 62.3% (38/61) of the eyes 

checked. Neovascularization was observed in one eye. The frequency of bilateral changes 

in angiography was high. Non-proliferative retinopathy was more common, especially 

vascular tortuosities (17/61), followed by arteriovenous anastomoses in the retinal periphery 

(15/61) and arterial occlusions (5/61). The mean age of retinopathy group was 14.4 years 

old, significantly lower than the mean age of non-retinopathy group, which was 17.4. The 

result was normal in16.4% (10/61) of the eyes in the fundoscopy exam, while angiography 

showed alterations. 

Conclusions: All the results pointed to the conclusion that the non-proliferative retinal 

vascular changes are frequent and precocious in patients with sickle cell anemia (SS genotype). 

Fluorescein angiography is more sensitive in the diagnosis of retinopathy when 

compared to indirect ophthalmoscopy. 

Keywords: Anemia, sickle cell; Retina/physiopathology; Retinal diseases/diagnosis; Fluo - 

rescein angiography/methods; Ophthalmoscopy 

INTRODUÇÃO 

A anemia falciforme é a doença hereditária mais prevalente no 

Brasil (1) . A hemoglobinopatia ocorre em situação de homozigose do 

gene responsável pela produção de uma hemoglobina mutante, 

a hemoglobina S, que em seu estado desoxigenado pode sofrer polimerização 

e originar hemácias falcizadas, responsáveis por anemia 

hemolítica crônica e fenômenos vasoclusivos (1-6) . 

Embora haja outros genótipos para a doença falciforme, acredita-se 

que SC, Sβ 0 talassemia, em menor grau, o SS (este o responsável pelo 

fenótipo da anemia falciforme) resultem em maior risco para complicações 

oculares (2,4,5) . 

As manifestações oculares da anemia falciforme compreendem 

alterações orbitárias, conjuntivais, uveais, papilares e, principalmente, 

retinianas (7-10) . A retina periférica e a mácula parecem ser os locais 

mais suscetíveis à oclusão vascular, onde as lesões são mais evidentes 

e destrutivas, podendo ocasionar cegueira (11-13) . 

O presente estudo objetiva descrever e classificar alterações 

retinianas encontradas em portadores de anemia falciforme, bem 

Submetido para publicação: 24 de maio de 2012 

Aceito para publicação: 17 de agosto de 2012 

Trabalho realizado na Universidade Federal de Sergipe em parceria com o Instituto de Olhos Dr. 

Cristiano Mendonça, Aracajú - Sergipe. 

1 

Médico, Departamento de Oftalmologia, Fundação Altino Ventura, Recife (PE), Brasil. 

2 

Acadêmico de Medicina, Universidade Federal de Sergipe, Aracaju (SE), Brasil. 

3 

Médico, Universidade Federal de Sergipe, Aracaju (SE), Brasil. 

4 

Médico, Instituto de Olhos Cristiano Mendonça, Aracaju (SE), Brasil. 


Divulgação de potenciais conflitos de Interesse: A.M.Santos, Nenhum; G.B.A.Faro, Nenhum; 

M.V.M.Amaral, Nenhum; C.Q.Mendonça, Nenhum; B.C.Leal, Nenhum; R.Cipolotti, Nenhum. 

Endereço de correspondência: Rosana Cipolotti, Av. Beira Mar, 2016, Apto. 402, Aracaju (SE) 

49025-040, Brasil - E-mail: rosanaci@yahoo.com 

Comitê de ética responsável pela aprovação: Comitê de Ética em Pesquisa Envolvendo Seres 

Humanos da Universidade Federal de Sergipe (CEP-UFS) N o .CAAE:0140.0.107.000-07 


313

Alterações retinianas em jovens portadores de anemia falciforme (hemoglobinopatias) em hospital universitário no nordeste do Brasil 

como comparar os métodos diagnósticos (mapeamento de retina e 

angiofluoresceinografia). 

MÉTODOS 

Foram avaliados neste estudo transversal (com dados obtidos 

prospectivamente), pacientes portadores de anemia falciforme, 

confirmada laboratorialmente por eletroforese de hemoglobina em 

pH alcalino, com idade igual ou superior a sete anos, em acompanhamento 

regular em ambulatório de Hematologia Pediátrica de 

Hospital Universitário da região nordeste do Brasil. Os pacientes foram 

consecutivamente encaminhados para avaliação oftalmológica, 

após assinatura de Termo de Consentimento Livre e Esclarecido pelo 

paciente ou seu responsável legal. 

O exame oftalmológico consistiu em medida da acuidade visual 

corrigida através dos optotipos de Snellen, tonometria de aplanação 

de Goldmann, biomicroscopia com lâmpada de fenda, oftalmoscopia 

binocular indireta, retinografia e angiografia com injeção de 

fluoresceína sódica a 20%, sendo esse três últimos após a midríase 

medicamentosa com tropicamida a 1%. Todos os pacientes foram 

submetidos a todos os procedimentos citados. 

Os achados fundoscópicos foram agrupados em: (1) sem alterações; 

(2) retinopatia não-proliferativa: tortuosidade venosa, hemorragias 

“salmon patch” (coloração alaranjada advinda da degradação 

da hemoglobina) e “blacksunburst” (lesão hiperpigmentada) (2,4,6,13) , 

pontos iridescentes, anastomoses arteriovenosas (5,14) , alterações na 

mácula e no nervo óptico (pontos escuros, pequenos e vermelhos) (15,16) ; 

(3) retinopatia proliferativa, caracterizada por neovascularização periférica 

denominada “seafun” (2,5,6,13) . 

Os achados da angiofluoresceinografia foram descritos através 

da classificação de Goldberg (14) em cinco estágios, sendo os dois 

primeiros pré-proliferativos e os três restantes proliferativos (4,6,13,15) : (I) 

oclusões arteriolares na periferia da retina; (II) anastomoses arteriovenosas 

na periferia da retina; (III) proliferações fibrosas e neovasculares; 

(IV) hemorragia vítrea; (V) descolamento da retina. 

As variáveis categóricas foram apresentadas como porcentagens 

e a comparação entre os grupos, realizada por meio do teste de Fisher. 

As variáveis contínuas foram apresentadas por meio de medidas 

de tendência central e comparadas pelo teste T ou Mann Whitney, 

con siderando-se significativos os valores de p

Santos AM, et al. 

Observou-se frequência elevada de alterações bilaterais à an - 

gio fluoresceinografia neste estudo. Downes et al. observaram a 

possibilidade de reversão para unilateral em cerca de 30% dos casos, 

o que indica que esses pacientes devem ser acompanhados clinicamente, 

mesmo não havendo indicação de intervenção terapêutica 

no momento (12) . 

Considerando-se que o paciente se mantém assintomático até 

estágios avançados, a identificação precoce de retinopatia proliferativa 

permite intervenções terapêuticas curativas. Não parece haver 

consenso com relação à idade apropriada para início do tratamento 

da retinopatia proliferativa no paciente portador de anemia falciforme, 

uma vez que existem relatos controversos sobre a eventual resolução 

espontânea do quadro (11) , que, no entanto, não foi observada 

por outros autores (9) . 

O presente estudo apresenta como limitações seu delineamento 

transversal e o reduzido tamanho da amostra estudada. Estudos 

longitudinais são necessários para ratificar achados aqui presentes e 

estabelecer fatores de risco para a retinopatia em pacientes portadores 

de anemia falciforme. 

CONCLUSÃO 

Com base nos casos estudados, que as alterações retinianas do 

tipo retinopatia não proliferativa, especialmente as tortuosidades vas - 

culares, anastomoses arteriovenosas na periferia da retina e oclusões 

arteriolares são frequentes e precoces nos portadores de anemia 

falciforme, sendo a angiofluoresceinografia mais sensível no diagnóstico 

quando comparada ao mapeamento de retina. Os achados 

indicam a necessidade de acompanhamento oftalmológico, cuja 

pe riodicidade deve ser determinada pela extensão e gravidade das 

alterações encontradas. 

REFERÊNCIAS 

1. Paiva e Silva RB, Ramalho AS, Cassorla RM. A anemia falciforme como problema 

de Saúde Pública no Brasil. Rev Saúde Pública. 1993;27(1):54-8. 

2. Freitas LG, Isaac DL, Tannure WT, Lima EV, Abud MB, Tavares RS, et al. Alterações retinianas 

apresentadas em pacientes portadores de hemoglobinopatia falciforme 

atendidos em um Serviço Universitário de Oftalmologia. Arq Bras Oftalmol. 2011; 

74(5):335-7. 

3. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997; 

337(11):762-9. 

4. Vilela RQ, Bandeira DM, Silva MA. Ocular complications in sickle cell disease. Rev 

Bras Hematol Hemoter. 2007;29(3):285-7. 

5. Gill HS, Lam WC. A screening strategy for the detection of sickle cell retinopathy in 

pediatric patients. Can J Ophthalmol. 2008;43(2):188-91. 

6. Bonanomi MT. Alterações oculares na doença falciforme. In: Agência Nacional de 

Vigilância Sanitária. Manual de diagnóstico e tratamento de doenças falciformes 

[Internet]. Brasília: ANVISA; 2002. p.97-105. [citado 2004 Jul 27]. Disponível em: 

http://bvsms.saude.gov.br/bvs/publicacoes/anvisa/diagnostico.pdf 

7. Osafo-Kwaako A, Kimani K, Ilako D, Akafo S, Ekem I, Rodrigues O, et al. Ocular 

manifestations of sickle cell disease at the Korle-bu Hospital Accra, Ghana. Eur J 

Oph thalmol. 2010;21(4):484-9. 

8. Morel C. [Retinal involvmente in hemoglobinopathy] J Fr Ophtalmol. 2001; 

24(9).967-92. French. 

9. Bisol T, Fior O, Esteves JF, Friderich JR. Sickle cell hemoglobinopathy genotypes 

and retinal manifestations in patients of a university hospital. Arq Bras Oftalmol. 

2000;63(4):273-6. 

10. Fadugbagbe AO, Gurgel RQ, Mendonça CQ, Cipolotti R, Santos AM, Cuevas LE. 

Ocular manifestations of sickle cell disease. Ann Trop Paediatr. 2010;30(1):19-26. 

11. Elagouz M, Jyothi S, Gupta B, Sivaprasad S. Sickle cell disease and the eye: old and 

new concepts. Surv Ophthalmol. 2010;55(4):359-77. 

12. Downes SM, Hambleton IR, Chuang EL, Lois N, Serjeant GR, Bird AC. Incidence and 

natural history of proliferative sickle cell retinopathy: observations from a cohort 

study. Ophthalmology. 2005;112(11):1869-75. 

13. Bonanomi MT, Cunha SL, Araújo JT. Funduscopic alterations in SS and SC hemoglobinopathies 

- Study of a Brazilian population. Ophthalmologica.1988; 197(1): 

26-33. 

14. Goldberg MF. Classification and pathogenesis of proliferative sickle cell retinopathy. 

Am J Ophthalmol. 1971;85(4):426-37. 

15. Garcia CA, Fernandes MZ, Uchôa UB, Cavalcante BM, Uchôa RA. Achados fundoscópico 

sem crianças portadoras de anemia falciforme no estado do Rio Grande 

do Norte. Arq Bras Oftalmol. 2002;65(5):615-8. 

16. Cook WC. A case of sickle cell anemia with associated subarachnoid hemorrhage. 

J Med. 1930;11:54117. 

17. Bonanomi MT, Oliveira AA, Suzuki H. Hemoglobinopatias. In: AbujamraS, Ávila M, 

Barsante C. Retina e vítreo. São Paulo: Roca; 2000. p.592-601. 


315



Efeito das lentes intraoculares asféricas e com pigmentação amarela na campimetria azul-amarelo 

Rodrigo França de Espíndola 1 , Marcony Rodrigues de Santhiago 1 , Newton Kara-Júnior 1 

ABSTRACT 

Purpose: To investigate the possible effect of aspherical or yellow tinted intraocular 

lens (IOL) on contrast sensitivity and blue-on-yellow perimetry. 

Methods: This prospective randomized bilateral double-masked clinical study included 

52 patients with visually significant bilateral cataracts divided in two groups; 

25 patients (50 eyes) received aspherical intraocular lens in one eye and spherical 

intraocular lens in the fellow eye; and 27 patients (54 eyes) received ultraviolet and 

blue light filter (yellow tinted) IOL implantation in one eye and acrylic ultraviolet 

filter IOL in the fellow eye. The primary outcome measures were contrast sensitivity 

and blue-on-yellow perimetry values (mean deviation [MD] and pattern standard 

deviation [PSD]) investigated two years after surgery. The results were compared 

intra-individually. 

Results: There was a statistically significant between-group (aspherical and spherical 

intraocular lens) difference in contrast sensitivity under photopic conditions at 12 

cycles per degree and under mesopic conditions at all spatial frequencies. There were 

no between-group significant differences (yellow tinted and clear intraocular lens) 

under photopic or mesopic conditions. There was no statistically significant difference 

between all intraocular lens in MD or PSD. 

Conclusion: Contrast sensitivity was better under mesopic conditions with aspherical 

intraocular lens. Blue-on-yellow perimetry did not appear to be affected by aspherical 

or yellow tinted intraocular lens. Further studies with a larger sample should be carried 

out to confirm or not that hypotheses. 

Keywords: Lenses, intraocular; Cataract extraction; Phacoemulsification; Glaucoma/ 

diagnosis; Visual field tests/methods; Visual fields; Lens implantation, intraocular; Con - 

trast sensitivity 

RESUMO 

Objetivo: Investigar a possibilidade de efeitos na sensibilidade ao contraste e nos resulta - 

dos da campimetria azul-amarelo com implante de uma lente intraocular (LIO) asférica 

ou de pigmentação amarela. 

Métodos: Trata-se de um estudo prospectivo, randomizado, duplo-mascarado, envolvendo 

52 pacientes portadores de catarata senil bilateral, divididos em dois grupos; 

25 pacientes (50 olhos) receberam uma LIO asférica em um olho e uma esférica no olho 

con tralateral; e 27 pacientes (54 olhos) com implante de uma LIO de pig mentação 

amarela e uma LIO convencional no olho contralateral. O principal resultado do 

estudo foi a sensibilidade ao contraste e os dados da perimetria azul-amarelo (“mean 

deviation” [MD] e “pattern standard deviation” [PSD]). Os resultados foram analisados 

interindividualmente. 

Resultados: Houve diferença estatística entre os grupos (lentes asféricas e esféricas) na 

sensibilidade ao contraste em condições fotópicas (12 ciclos por grau) e em condições 

mesópicas (todas frequências). Não houve diferença estatística na sensibilidade ao 

contraste entre as lentes de pigmentação amarela e convencionais. Não houve diferença 

estatística nos valores de MD e PSD entre os grupos. 

Conclusão: A sensibilidade ao contraste foi melhor em condições mesópicas com as lentes 

asféricas. A campimetria azul-amarelo parece não ser influenciada por LIOs asféricas e 

com pigmentação amarela. Mais estudos com uma amostra maior são necessários para 

confirmar ou afastar essa hipótese. 

Descritores: Lentes intraoculares; Extração de catarata; Facoemulsificação; Glaucoma/ 

diagnóstico; Testes de campo visual/métodos; Campos visuais; Implante de lente in - 

traocular; Sensibilidade de contraste 

INTRODUCTION 

Short-wavelength automated perimetry (SWAP) or Blue-on-Yellow 

(B/Y) perimetry has gained fairly wide acceptance as a clinical test since 

its initial use more than 10 years ago. SWAP uses moderately bright 

yellow background fields to depress visual sensitivity that is mediated 

via long and middle-wavelength-sensitive cones. This selective sensitivity 

reduction allows visual sensitivity mediated via short-wavelengthsensitive 

cones to be measured in isolation (1) . 

Previous studies suggest that visual field defects on B/Y perimetry 

occur before defects on standard automatic white-on-white perimetry 

(SAP) and exhibit progression in advance of those recorded with whi teon-white 

perimetry in both chronic open-angle glaucoma and ocular 

hypertension (2-5) . Although, Tafreshi et al., associates compared SAP, 

Matrix frequency-doubling technology (FDT) perimetry and SWAP and 

detected no significant differences in their diagnostic performance (6) . 

Changes in the absorption characteristics of the human lens with 

age and lens opacity can influence the results of SWAP (7) . Others influences 

in B/Y, such as intraocular lenses (IOLs) with ultraviolet filter, 

was reported in peer review literature (8) . Another type of intraocular lens 

(IOL) with aspherical surface, could modify the visual performance of 

patients implanted with these IOLs in relation to those implanted with 

spherical IOLs. 

It has been suggested in previous works that aspherical IOLs can 

improve contrast sensitivity and reduce the patient’s perception of halos 

and glare (9) . These theoretical changes can confound the interpretation 

of the glaucomatous visual field, and it is a great clinical importance to 

understand the aspherical IOL´s effect upon such mode of perimetry. 

The purpose of this prospective study was to investigate the 

possible effects of an aspherical and a blue-light filter (yellow tinted) 

IOLs on contrast sensitivity and B/Y perimetry measures. 

Submitted for publication: March 1, 2012 


Study conducted in Ophthalmology Department of the University of São Paulo, São Paulo, Brazil. 

1 

Ophthalmology Department, Universidade de São Paulo (USP), São Paulo, Brazil. 


Disclosure of potential conflicts of interest: R.F.Espíndola, None; M.R.Santhiago, None; N.Kara- 

-Júnior, None. 

Correspondence address: Rodrigo F. Espíndola. Praça das Hortências, 70 - Itu (SP) - 13301-689 - 

Brazil - E-mail: rodrigo166@uol.com.br 


Espíndola RF, et al. 

METHODS 

This study was conducted according to ethical standards for clinical 

research and was approved by the University Hospital’s research 

ethics committee/investigational review board. The observers who 

conducted the postoperative visual evaluations did not have access 

to the randomization code or information about the surgical procedures. 

Informed consent was obtained, and the study was conducted 

in adherence with the tenets of the Declaration of Helsinki. 

All patients involved had bilateral sequential cataract surgery 

under similar preoperative conditions using the same phacoemulsification 

technique in both eyes. Only one experienced surgeon per - 

formed all surgeries. 

Patients with visually significant bilateral cataract and no history 

of glaucoma were eligible for inclusion in the study. Exclusion criteria 

was any ocular disease, such as corneal opacities or irregularity, dry 

eye, amblyopia, anisometropia, retinal abnormalities, surgical complications, 

IOL tilt, previous or current use of medications known to 

cause color-vision deficiencies, or incomplete follow-up. 

The patients were divided in two groups: first group compromised 

25 patients (50 eyes). Each patient received a spherical foldable, 

1-piece, hydrophobic acrylic IOL (Akreos Fit, Bausch & Lomb, Inc.) in 

one eye and a 1-piece foldable, hydrophobic acrylic IOL (Akreos AO, 

Bausch & Lomb, Inc.) with aspherical anterior and posterior surface 

in the fellow eye (aberration-free). 

The second group enrolled 27 patients (54 eyes) with an ultraviolet 

and blue light filter IOL (AcrySof Natural SN60AT, Alcon) in one eye 

(yellow tinted), and an acrylic ultraviolet filter IOL (AcrySof SA60AT, 

Alcon) in the fellow eye (non-tinted). 

Approximately 30 days after the first surgery, the second eye had 

cataract surgery with implantation of another IOL model. All patients 

and observers were masked about the IOL type implanted. 

An envelope system was used to randomly assign all enrolled 

patients. Sequenced and sealed envelopes containing the first type 

of IOL (Akreos AO or Akreos Fit; SN60AT or MA60AC) were prepared 

before surgery. An unscrubbed observer in the operating room opened 

the envelopes and assigned each patient. 

The individuals met the following inclusion criteria at two years 

postoperatively: visual acuity better than 0.3 logMAR in both eyes, 

normal intraocular pressures, no evidence of posterior capsule opacity, 

and no signs of glaucoma. 

The primary outcome measures of the study were contrast sensitivity 

and B/Y perimetry values. The contralateral eye was used as 

control. Best-corrected visual acuity (BCVA) and distance uncorrected 

visual acuity (UCVA) were measured as well as B/Y values. The visual 

acuity was measured at 100% contrast using Early Treatment of 

Dia betic Retinopathy Study (ETDRS) charts (Precision Vision) under 

pho topic conditions (target luminance 85 candelas [cd]/m 2 ) at 4.0 m. 

Contrast sensitivity was measured with VCTS 6000 (Vistech Consultants 

Incorporation, Dayton, OH, USA) with best spectacle correction 

under photopic (85 cd/m 2 ) and mesopic (3 cd/m 2 ) conditions. 

Light conditions were controlled with a luxometer (Gossen-Starlite, 

Nürnberg, Germany). 

During visual field testing, optimal refractive correction was pla - 

ced before the tested eye, and the fellow eye was occluded with an 

opaque eye patch. B/Y perimetry was performed (first in right eye) 

using the Humphrey Visual Field Analyzer (Carl Zeiss Meditec, USA). 

A full-threshold algorithm (central 24-2 full-threshold strategy) was 

used with a blue (440 nm) size V (1.72°) stimulus on a yellow background 

(530 nm), with maximum brightness of 100 cd/m 2 . The measured 

levels were expressed in decibels (dB) for all points. 

Because the participants did not have previous experience with 

any visual field testing, they underwent two initials tests to minimize 

the learning curve. These tests were not included in the analysis. 

Only visual field tests with reliable results were analyzed. A reliable 

test was defined as one with fixation losses of less than 25% and 

both false-positive and false-negative responses of less than 33%. 

Statistical analysis was conducted using the software SPSS 

ver sion 15.0 (SPSS Inc., Chicago, IL, USA). Data were analyzed with 

the nonparametric Mann-Whitney U test using a 5% significance 

level and 80% power. The normality of the quantitative variables was 

verified using the Kolmogorov-Smirnov test. The level of statistical 

significance for such comparison was set a p


Table 2. Pattern standard deviation (PSD) of blue-on-yellow 

perimetry in eyes implanted with Akreos AO and Akreos Fit 

Value 

Table 4. Pattern standard deviation (PSD) of blue-on-yellow 

perimetry in eyes implanted with SN60AT and MA60AC 

Value 

MA60AC 

(dB) 

N60AT 

(dB) 

Mean 3.04 2.52 

Minimum 0.00 0.00 

Maximum 8.00 5.49 

dB= decibels; P=0.42 

Akreos AO 

(dB) 

Akreos Fit 

(dB) 

Mean 3.30 3.80 

Minimum 2.78 3.20 

Maximum 4.72 5.10 


Table 3. Mean deviation (MD) of blue-on-yellow perimetry in eyes 

implanted with SN60AT and MA60AC 

Value 

MA60AC 

(dB) 

SN60AT 

(dB) 

Mean --3.68 --5.62 

Minimum -21.70 -22.67 

Maximum --6.15 --4.65 


entire refractive system of the eye (10) . The selection of aspherical IOLs 

to compensate for corneal aberrations can improve pseudophakic 

visual quality (11) . 

After cataract removal with IOL implantation, the IOL itself 

might confound the findings of common diagnostic tests such as 

perimetry (12-14) . There are no reports on the effect of aspherical IOL 

on B/Y perimetry to our knowledge. This contralateral eye study 

was conducted to analyze the theoretical benefits of aspherical IOL 

implantation in improve contrast sensitivity and its consequences in 

B/Y parameters. Blue-filter IOLs were also taken into account. 

Under mesopic conditions, postoperative VCTS contrast sensitivity 

testing showed significant differences between the 2 groups 

(aspherical and spherical IOLs) at all spatial frequencies, indicating 

that Akreos AO performed better than Akreos Fit in larger pupil sizes. 

However, under photopic conditions, the Akreos AO IOL performed 

better than Akreos Fit only at 12 cpd. Others studies confirms this 

fin dings (9,12) . Despite this improvement in contrast sensitivity, no 

chan ges in pattern standard deviation (PSD) or mean deviation (MD) 

were found comparing aspherical and spherical IOL. 

Benefits of blue-filter IOLs that have been suggested include 

pro tection against retinal damage due to blue light, with a possible 

role in preventing the development or exacerbation of age-related 

macular degeneration. In addition, by blocking blue light, the optical 

chromatic aberration is reduced. Improvement in contrast sensitivity, 

reduced glare under photopic and mesopic conditions and reduction 

in disturbance of blue color vision are also expected. These 

changes could confound the interpretation of the glaucomatous 

visual field (15-20) . 

In our study, no statistically difference was found in contrast sensitivity 

comparing yellow tinted and clear IOLs. Even with a shorter 

follow-up, most previous studies found no detrimental effect of blue 

light-filtering IOLs on photopic or mesopic contrast sensitivity or on 

color vision between eyes with blue light-filtering IOLs and eyes with 

UV light-filtering IOLs (21,22) . 

Castro et al. (23) , using a blue light spectrum filter (simulating an 

AcriSof Natural IOL) found statistically significant reductions in MD 

and foveal threshold on SWAP, but not in SAP examinations. However, 

this study was not conducted for patients with cataract (young 

patients). Our study did not confirm these results. A previous study by 

Jang et al. (24) , had similar findings to the results of Castro et al. 

Another study on the influence of yellow IOL on SWAP, concluded 

that yellow IOLs did not affect SWAP results (25) , which is in agreement 

with our results. Ueda et al. (26) , also reported that no significant differences 

were observed between patients with yellow-tinted and clear 

IOLs for FDT perimetry results. They suggested that when interpreting 

the results of perimetry, the effect of cataract should be considered 

but that of IOL color does not need consideration. 

Some studies described a better (26,27) or worse (28,29) performance 

of blue-light- filtering IOLs. The majority of the studies, however, did 

not find any statistically significant differences in comparison with 

UV-filtering IOL (30-32) . 

In this study, no significant difference for either MD or PSD was 

found between IOLs, although, the Akreos AO group demonstrated 

better values (Table 1 and 2). In spite of no scientific agreement exists as 

to whether removing aberrations from the visual system may result in 

a better retinal image, it is also apparent that zero spherical aberration 

does not automatically provide best visual performance. 

This study has limitations that included the absence of preoperative 

B/Y perimetry data, the small number of cases, and the absence 

of concurrent standard automated perimetry. A larger number of 

cases, (proximally 100 cases in each group), could make a difference 

in the findings between each group, or confirm the result seen in 

this study. 

The fact that this study makes a contralateral comparison minimizes 

intraindividual factors that could interfere with contrast sensitivity 

and the results of B/Y perimetry. Different IOLs from the same 

manufacturer were used to minimize bias. 

CONCLUSION 

In summary, aspherical IOL showed better performance in the 

contrast sensitivity test under mesopic conditions compared with 

the spherical IOL. Blue-yellow perimetry did not appear to be affected 

by aspherical or yellow tinted IOL. Further studies with a larger 

sample size are necessary. 

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visual field loss. Invest Ophthalmol Vis Sci. 1995;36(7):1398-410. 

6. Tafreshi A, Sample PA, Liebmann JM, Girkin CA, Zagwill LM, Weinreb RN, et al. Visual 

function-specific perimetry to identify glaucomatous visual loss using three different 

definitions of visual field abnormality. Invest Ophthalmol Vis Sci. 2009;50(3):1234-40. 

7. Carrillo MM, Artes PH, Nicolela MT, LeBlanc RP, Chauhan BC. Effect of cataract 

extraction on the visual fields of patients with glaucoma. Arch Ophthalmol. 2005; 

123(7):929-32. 

8. Sirtoli MG, Santhiago MR, Parede TR, Espíndola RF, Carvalho RS, Kara-Junior N. Phacoemulsification 

versus extracapsular extraction: governmental costs. Clinics. 2010;65(4): 

357-61. 

9. Guirao A, Redondo M, Artal P. Optical aberrations of the human cornea as a function 

of age. J Opt Soc Am A Opt Image Sci Vis. 2000;17(10):1697-702. 


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10. Artal P, Berrio E, Guirao A, Piers P. Contribution of the cornea and internal surfaces to 

the change of ocular aberrations with age. J Opt Soc Am A Opt Image Sci Vis. 2002; 

19(1):137-43. 

11. Kara-Junior N, Santhiago MR. Lentes asféricas: avaliação da indicação clínica e das 

opções de lentes. Rev Bras Oftalmol. 2009;68(4):195-6. 

12. Santhiago MR, Netto MV, Barreto J Jr, Gomes BA, Mukai A, Guermandi AP, et al. Wavefront 

analysis, contrast sensitivity, and depth of focus after cataract surgery with 

aspherical intraocular lens implantation. Am J Ophtalmol. 2010;149(3):383-9. 

13. Caporossi A, Casprini F, Tosi GM, Baiocchi S. Preliminary results of cataract extraction 

with implantation of a single-piece AcrySof intraocular lens. J Cataract Refract Surg. 

2002;28(4):652-5. 

14. Kim YY, Kim JS, Shin DH, Kim C, Jung HR. Effect of cataract extraction on blue-on-yellow 

visual field. Am J Ophthalmol. 2001;132(2):217-20. 

15. Kook MS, Yang SJ, Kim S, Chung J, Kim ST, Tchah H. Effect of cataract extraction on 

frequency doubling technology perimetry. Am J Ophthalmol. 2004;138(1):85-90. 

16. Moss ID, Wild JM, Whitaker DJ. The influence of age-related cataract on blue-on-yellow 

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23. Castro LC, Souza CE, Soriano ES, Melo LA Jr, Paranhos A Jr. Influence of blue light 

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24. Jang SY, Ohn YH, Kim SW. Effect of yellow-tinted intraocular lenses on short-wavelength 

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lens. Am J Ophthalmol. 2004;138(1):138-40. 

28. Rodriguez-Galietero A, Montes-Mico R, Munoz G, Albarrán-Diego C. Blue-light filtering 

intraocular lens in patients with diabetes: contrast sensitivity and chromatic 

discrimination. J Cataract Refract Surg. 2005;31(11):2088-92. 

29. Mainster M, Sparrow. How much blue-light should an IOL transmit? Br J Ophthalmol. 

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ted intraocular lenses. J Cataract Refract Surg. 2007;33(7):1248-52. 

31. Landers J, Tan TH, Yen J, Liu H. Comparison of visual function following implantation 

of Acrisof Natural intraocular lenses with conventional intraocular lenses. Clin Experiment 

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2006;32(2):236-42. 

XIX Congresso Norte-Nordeste 

de Oftalmologia 


Enotel Resort & SPA Porto de Galinhas 

Ipojuca (PE) 


Tel.: (81) 3033-5147 

E-mail: secretaria.cnne2013@snno.com.br 

Site: www.snno.com.br 


319


Reproducibility of peripapillary retinal nerve fiber layer thickness measurements 

using Spectral Domain OCT in Brazilian patients 

Reprodutibilidade da espessura da camada de fibras nervosas da retina utilizando-se o 

Spectral Domain OCT em pacientes brasileiros 

Daniela Araújo Toscano 1 , Marcos Pereira de Ávila 2 , Maria Regina Catai Chalita 1 

ABSTRACT 

Purpose: To evaluate the reproducibility of peripapillary retinal nerve fiber layer 

(RNFL) thickness measurements in normal eyes and eyes with glaucoma using 

spectral domain optical coherence tomography (SDOCT). 

Methods: One eye of 79 normal and 72 glaucoma patients was analyzed. All 

patients underwent a complete ophthalmological examination, including visual 

acuity testing; intraocular pressure, slit-lamp examination, indirect ophthalmoscopy; 

and the glaucoma group underwent achromatic perimetry with the 24-2 

SITA Fast Humphrey Field Analyzer. All patients’ eyes were scanned using the 

spectral domain optical coherence tomography - Spectralis ® and one of them 

was cho sen randomly. Three con secutive circular B-scan centered at the optic 

disc were performed in one visit. 

Results: The intraclass correlation coefficient (ICC), coefficient of variation and 

test-retest variability for the mean retinal nerve fiber layer thickness were respectively: 

0.94, 2.56% and 4.85 µm for the normal group and 0.93, 4.65% and 6.61 µm 

for the glaucomatous group. The intraclass correlation coefficient for retinal nerve 

fiber layer thickness in all quadrants were all excellent in both groups, with the 

superior quadrant having the highest ICCs (0.964) in glaucomatous eyes and nasal 

quadrant measurements having the lowest (0.800), but still excellent in eyes without 

glaucoma. The coefficient of variation was between 2.56% - 8.74% and between 

4.65% - 11.44% in normal and glaucomatous group respectively. The test-retest 

variability was between 4.85 µm and 11.51 µm in the normal group and between 

6.61 µm and 14.24 µm in the glaucomatous group. The measurements in glaucomatous 

eyes were more variable than normal eyes. 

Conclusions: Spectral domain optical coherence tomography showed excellent 

reproducibility with regard to retinal nerve fiber layer thickness measurements in 

normal and glaucomatous eyes. 

Keywords: Diagnostic techniques, ophthalmological; Glaucoma/diagnosis; Tomography, 

optical coherence/methods; Retinal ganglion cells; Optic nerve/pathology; 

Nerve fibers; Reproducibility of results 

RESUMO 

Objetivo: Avaliar a reprodutibilidade da medida da espessura da camada de fibras 

nervosas da retina (CFNR) em olhos sem e com glaucoma utilizando-se tomografia de 

coerência óptica de domínio espectral (spectral domain OCT - SDOCT). 

Métodos: Foram analisados apenas um olho de 79 pacientes normais e 72 com glaucoma. 

Todos os pacientes realizaram um exame oftalmológico completo, incluindo 

acuidade visual, pressão intraocular, biomicroscopia, oftalmoscopia indireta e, para o 

grupo com glaucoma, perimetria acromática 24-2 SITA Fast Humphrey Field Ana ly zer. 

Foram realizados em todos os olhos e em apenas uma visita, três B-scans circulares 

centrados no disco óptico utilizando-se o SDOCT - Spectralis ® . 

Resultados: O coeficiente de correlação intraclasse (ICC), coeficiente de variação e va - 

riabilidade teste-reteste para a média de espessura da camada de fibras nervosas da 

retina foram respectivamente: 0,94, 2,56% e 4,85 µm para o grupo sem glaucoma e 0,93, 

4,65% e 6,61 µm para o grupo glaucomatoso. O coeficiente de correlação intraclasse 

foi excelente em ambos os grupos em todos os quadrantes, com o quadrante superior 

sendo o maior (0,964) no grupo glaucomatoso e o nasal sendo o menor (0,800), mas 

ainda excelente, em olhos sem glaucoma. O coeficiente de variação foi entre 2,56% - 

8,74% e entre 4,65% - 11,44%, nos grupos sem e com glaucoma, respectivamente. A 

variabilidade teste-reteste variou de 4,85 µm e 11,51 µm no grupo sem glaucoma; e 

entre 6,61 µm e 14.24 µm no com glaucoma. Olhos com glaucoma apresentaram-se 

mais variáveis que os sem glaucoma. 

Conclusão: A tomografia de coerência óptica “spectral domain” apresentou excelente 

reprodutibilidade da espessura da camada de fibras nervosas da retina em pacientes 

sem e com glaucoma. 

Descritores: Técnicas de diagnóstico oftalmológico; Glaucoma/diagnostico; Tomografia 

de coerência óptica/métodos; Células ganglionares da retina; Nervo óptico/patologia; 

Fibras nervosas; Reprodutibilidade dos testes 

INTRODUCTION 

Glaucoma is an optic neuropathy, multifactorial, characterized 

by accelerated death of the retinal ganglion cells, subsequent axonal 

loss, and visual field impairment (1) . 

Detected defects in the retinal nerve fiber layer (RNFL) years 

before arising alterations in the visual field suggests that anatomical 

alterations of the RNFL can identify progression of the glaucoma 

before it causes functional loss in the visual field (2) . 

Methods for reliably establishing glaucomatous nerve atrophy 

are limited. Optical coherence tomography (OCT) is a noninvasive, 

high-resolution imaging technique that allows in vivo measurements 

of RNFL in cross section. High-resolution imaging of retinal structure 

is clinically relevant for the diagnosis of glaucoma (3) . 

Until recently, the OCT commercially available was the time domain 

OCT (TDOCT), which provides an axial resolution of 10 μm, and 

cross sectional retinal images consisting of 512 A-scans can be acquired 



Study carried out at Department of Ophthalmology, Universidade de Brasília - UnB. 

1 

Physician, Department of Ophthalmology, Universidade de Brasília - UnB - Brasília (DF), Brazil. 

2 

Professor, Department of Ophthalmology, Universidade Federal de Goiás - UFG - Goiânia (GO), 

Brazil. 


Disclosure of potential conflicts of interest: D.A.Toscano, None; M.P.Ávila, None; M.R.C.Chalita, 

None. 

Correspondence address: Daniela Araújo Toscano. Av. Ingá, 250, Apto. 302 - João Pessoa (PB) 

58038-250 - Brazil - E-mail: danielaatoscano@gmail.com 

The study was approved by the Institutional Review Board / Ethics Committee of the University of 

Brasília (DF) Brazil (CEP-FM 057/2010). 


Toscano DA, et al. 

in 1.28 seconds. The main disadvantage of TDOCT technology is the 

limited resolution and slow acquisition time. With the spectral domain 

OCT (SDOCT) or Fourier domain, the echo time delays of light 

are measured by acquiring the interference spectrum of the light 

signal and converted to depth information by Fourier transform (4) . 

The detection method using a spectrometer allowed a considerable 

increase in imaging speed and resolution without compromising 

image quality (5) . The increase in imaging speed minimizes motion 

artifacts. Resolution is up to 5 times higher, and imaging speed 

is 60 times faster than in conventional time domain OCT (4) . 

Estimate reproducibility of RNFL thickness using OCT is essential 

for diagnostic precision and in particular, describes the smallest 

changes detectable for identifying and monitoring the progression 

of glaucoma as well as indicates therapeutic interventions (6,7) . 

Quantifying the reproducibility of the RNFL thickness measurements 

using Spectralis ® spectral domain OCT is an important step in 

evaluating the potential usefulness of this device for the diagnosis of 

glaucoma and for determining glaucomatous progression. 

To our knowledge the present study is the first to report on the 

reproducibility and test-retest variability of RNFL thickness measurements 

using Spectralis ® SD-OCT device in Brazilian population. 

The purpose of this study was to evaluate the reproducibility of 

peripapillary retinal nerve fiber layer (RNFL) thickness measurements 

in normal and glaucomatous eyes using spectral domain optical 

coherence tomography (Spectralis ® ) in Brazilian population. 

METHODS 

This prospective observational cross-sectional study was approved 

by the Institutional Review Board / Ethics Committee of the University 

of Brasília, Brasília, Brazil. All participants in this study gave their written 

informed consent. All normal and glaucoma participants were enrolled 

in this study through the glaucoma and cataract service of Brasília Center 

of Vision (CBV, Brasília, Brazil) between August and December 2010. 

A total of 151 eyes from 79 normal patients and 72 patients with moderate 

to advanced glaucoma were analyzed. All subjects underwent a 

complete ophthalmological examination, including medical and family 

history; visual acuity testing with refraction; intraocular pressure measurements 

using Goldmann applanation tonometry (GAT), a complete 

slit-lamp examination, including indirect ophthalmoscopy. Patients from 

the glaucoma group underwent achromatic perimetry using 24-2 SITA 

FAST Humphrey Field Analyzer (Humphrey- Zeiss Systems, Dublin CA). 

Inclusion criteria for both groups were: age more than or equal to 

40 years, spherical refractive error less than or equal to 5 diopters (D), 

cylindrical refractive error less or equal to 3D. 

Inclusion criteria for normal subjects were: best-corrected visual 

acuity of 20/60 or better; normal slit-lamp examination; intraocular pressure 

of 21 mmHg or less; normal appearing optic nerve heads; and no 

history of ocular surgery or laser treatments. 

Glaucoma patients were defined on the basis of having either: 

1. An abnormal Humphrey Field Analyzer, defined as having MD 

less than -12dB; Less than 50% of the points are depressed 

bellow the 5% level and less than 20 points are depressed bellow 

the 1% level on the patterns deviation plot; No points in the 

central 5 o can have a sensitivity of 0 dB; Only one hemifield may 

have a point with sensitivity of < 15 dB within 5 o of fixation (8) and 

2. Glaucoma optic disc change defined as a cup-to-disc ratio 

greater than or equal to 0.6, cup-to-disc ratio asymmetry between 

the eyes greater than or equal to 0.2, disc rim thinning, 

notching, localized pallor or nerve fiber layer defect (9) . 

All patients from the glaucoma group had primary open-angle glau - 

coma or chronic angle-closure glaucoma, being excluded any other kind 

of glaucoma. 

Exclusion criteria for both groups included other intraocular diseases, 

as well as diseases that affect the visual field, like pituitary lesion, diabetes, 

retinal conditions or secondary cause of intraocular pressure increase. 

Patients were excluded in the glaucoma group if they had unreliable 

automated perimetry results: fixation loss, false positives or false 

negatives more than 33%. Visual fields were carried out at least twice (9) . 

OCT measurements 

All patients’ eyes were scanned using the commercially available 

SDOCT Spectralis ® HRA (Heidelberg Retina Angiograph) + OCT (Heidelberg 

Engineering). This instrument uses a wavelength of 820 nm 

in the near infrared spectrum in the SLO (scanning laser ophthalmoscopy) 

mode. The light source of the SDOCT is a super luminescent 

diode with a wavelength of 870 nm. Infrared images and OCT scans 

(40,000 A-Scan/sec) of the dual laser scanning systems are acquired 

simultaneously (10) . Three consecutive circular B-scan (3.4-mm diameter, 

768 A-scans) centered at the optic disc were performed in one 

visit by the same operator. The scanning circle was centered manually 

on the optic disc first, although the participant was looking at the 

internal fixation light. The RNFL borders could be clearly identified 

and were marked automatically by the segmentation software. Ima - 

ges were judged to be of sufficient quality on the basis of subjecti - 

ve operator evaluation. Within each scan session, the instrument 

alignment and controls were not changed, unless as part of image 

acquisition process. The subject was repositioned between the scan 

measurements only when necessary. There was no specific attempt 

to reposition the subjects between scans done during the same session. 

Images were acquired through undilated pupils. 

The Spectralis ® reports the average RNFL thickness in the superior, 

temporal, inferior, nasal and overall (mean). A RNFL thickness 

graph includes the colored normative database range. 

Eyes were placed into 1 of 3 categories that indicate comparison 

versus normative database. Green: within normal limits, with values 

inside the 95% normal range. Yellow: borderline, with values outside 

95% but within 99% confidence interval of normal distribution 

(0.01

Reproducibility of peripapillary retinal nerve fiber layer thickness measurements using Spectral Domain OCT in Brazilian patients 

ICC, COV and TRV for both groups are presented in tables 3 and 

4, respectively. The lowest ICC was 0.800 in the nasal quadrant for the 

normal group and 0.827 in the temporal quadrant for the glaucomatous 

group. The highest ICC was 0.944 for the mean RNFL in the normal 

group and 0.964 for the superior quadrant in the glaucomatous group. 

Even the lower 95 % CIs were greater 0.70, indicating excellent reproducibility 

of all measurements. The overall RNFL had the lowest COV 

and the nasal quadrant the highest COV in both groups. TRV showed 

the lowest for the overall RNFL thickness, 4,85 µm in the normal group 

and 6.61 µm in the glaucomatous group. The highest TRV was observed 

in the nasal quadrant for the normal group (11.51 µm) and in the 

inferior quadrant for the glaucomatous group (14.24 µm). RNFL measurements 

in glaucomatous eyes were more variable than normal eyes. 

Table 1: Demographic characteristics 

Groups 

Number 

Male 

Gender 

Female 

Age 

Normal group 79 49.37% 50.63% 58 (range 40-86) 

Glaucomatous group 72 31.94% 68.06 % 68 (range 44-97) 

Table 2. RFNL Thickness in normal and glaucomatous groups 

Normal group 

Glaucomatous group 

Thickness 

(µm) 

Std deviation 

(µm) 

Thickness 

(µm) 

Std deviation 

(µm) 

Mean 096.25 10.28 73.14 15.37 

Temporal 071.55 11.69 62.25 12.63 

Superior 117.87 14.48 87.02 25.06 

Nasal 069.60 12.18 56.45 14.44 

Inferior 125.19 15.01 86.86 25.63 

Std= standard 

Table 3. Intraclass correlation coefficient, coefficient of variation and 

test-retest variability in normal eyes 

ICC COV (%) TRV (µm) 

Mean 0.944 (0.921) 2.56 04.85 

Temporal 0.895 (0.852) 5.93 08.41 

Superior 0.928 (0.898) 4.09 09.49 

Nasal 0.800 (0.726) 8.74 11.51 

Inferior 0.931 (0.902) 3.80 09.33 

ICC= intraclass correlation coefficient, with lower 95% CI (confidence interval) in parentheses; 

COV= coefficient of variation; TRV= test-retest variability 

Table 4. Intraclass correlation coefficient, coefficient of variation and 

test-retest variability in glaucomatous eyes 

ICC COV (%) TRV (µm) 

Mean 0.937 (0.908) 04.65 06.61 

Temporal 0.827 (0.757) 08.44 09.95 

Superior 0.964 (0.947) 07.23 11.15 

Nasal 0.877 (0.824) 11.44 11.78 

Inferior 0.855 (0.795) 08.60 14.24 

ICC= intraclass correlation coefficient, with lower 95% CI (confidence interval) in parentheses; 

COV= coefficient of variation; TRV= test-retest variability 

DISCUSSION 

In glaucoma patients the OCT is an important instrument for 

diagnosis and to follow the progression of the disease. Assessing 

the reproducibility of the RNFL thickness using OCT is of paramount 

importance for its use in clinical practice of glaucoma. 

This study showed excellent reproducibility of RNFL thickness 

measurements with Spectralis ® in patients without and with moderate 

to advanced glaucoma (generally defined as 0.75 - 1.00). The 

lowest ICCs were observed in the nasal quadrant for the patients 

without glaucoma (0.800) and in the temporal quadrant (0.827) for 

patients with glaucoma. Even the lower 95% CIs were greater 0.70, 

indicating excellent reproducibility of all measurements. 

Comparing two different SD OCTs (Cirrus TM and Spectralis ® ), excellent 

repeatability of RNFL thickness measurement was observed 

in normal participants for both devices. Using Spectralis ® in undilated 

pupils the average of TRV was 4.95, COV 1.7% and ICC 0.971 (11) . In our 

study the TRV was 4.85, COV 2.56% and ICC 0.944. These differences 

can be explained because the number and the age of the participants 

in our study were higher. 

Many other studies reported the reproducibility of RNFL thickness 

using different kinds of OCT. Blumenthal et al., in 1999 studied 10 

eyes with glaucoma and 10 normal eyes and reported, using the 

commercially available OCT, that glaucoma patients were found to 

be significantly more variable than normal subjects (P=0.03). The 

coefficient of variation for the mean RNFL thickness was significantly 

smaller (P=0.02) in normal eyes (6.9%) than in glaucomatous eyes 

(11.8%). The coefficient of variation was larger in the temporal and 

nasal quadrants than in the superior and inferior quadrants, as found 

in our study (12) . 

Studies with Stratus TM OCT showed good RNFL thickness reproducibility. 

Peripapillary RNFL thickness of 51 subjects with glaucoma 

was measured using the Standard and Fast scan protocols of Stratus TM 

OCT 3 times on the same day to determine intrasession variability and 

on 5 different days within a 2-month period to determine intersession 

variability. It was observed the RNFL thickness test-retest variability 

intrasession ranged between 5.2 µm and 17.1 µm (mean 5.2 µm) using 

standard protocol and between 5 µm and 16.7 µm (mean 5.0 µm) for 

fast protocol, for clock hours. The test-retest variability of the temporal 

quadrant and of most temporal clock hours seemed to be less than 

that of other quadrants or locations, and the Fast scanning protocol, 

ICC and COV tended also to be worst for the nasal quadrant, similar 

to our results. The best ICC was 0.98 for both protocols. Intraclass 

correlation coefficients were essentially all excellent with the mean 

Standard RNFL and Fast RNFL values having the highest of 0.98 (13) . 

Still assessing the reproducibility of the Stratus TM , Budenz et al., 

performed 3 peripapillary circulars scans in 147 subjects normal and 

with glaucoma. The ICC was excellent for both Standard (mean 0.97) 

and Fast (mean 0.95) RNFL measurements. TRV of the quadrants measurements 

ranged from 3.5 µm to 13.0 µm in normal subjects and 

5.2 µm to 13.8 µm in glaucomatous eyes analyzing standard and 

fast protocols, and four quadrants (14) . Reproducibility of Stratus TM 

OCT as also studied in 10 normal subjects that were scanned three 

consecutive times with each of the following: macular scans, RNFL 

scans, and ONH scans before dilation and three additional times for 

each scan type after dilation. Similarly, all the subjects were scanned 

on two additional days within 5 months and the inter and intravisit 

reproducibility was calculated. The ICCs for the RNFL quadrants 

were higher after dilation, ranging between 71% and 84%, with the 

exception of the superior quadrant (ICC was 79% before and 75% 

after dilation). Stratus TM OCT demonstrated reproducible measurements 

for NFL thickness, macular thickness, and optic nerve head 

parameters (15) . 

The reproducibility of macula thickness using spectral domain 

OCT (Spectralis ® ) was studied in 41 normal eyes. Intravisit reproducibility 

was analyzed by performing 3 scans in the macula. It was 


Toscano DA, et al. 

observed excellent reproducibility of retinal thickness measurements 

with mean difference among measurements of about 1 µm (6) . 

Other SDOCT were also analyzed as RTVue which the RNFL thickness 

reproducibility showed the ICC ranged between 0.91 and 0.97 for 

the healthy group (60 eyes) and 0.86 and 0.97 for the glaucomatous 

group (76 eyes) (7) . Using the SD SLO/OCT OTI the lowest ICC was 0.961 

at 3 o’clock in the normal group (98 eyes) and 0.951 at 4 o’clock in the 

glaucoma group (79 eyes) (9) . 

Bendschneider et al., analyzed the RNFL thickness in 170 healthy 

patients using the SDOCT Spectralis ® and observed that the RNFL 

thickness was significantly associated with age (1.9 µm decline in 

mean total RNFL thickness per age decade), axial length (total RNFL 

decrease of -4.79 mm per every increasing 1-mm-axial length) and 

optic disc area (with a total RNFL increase of 6.28 mm for every 

1-mm 2 -increase in disc area). The total RNFL thickness in the study 

population was 97.2 ± 9.7 µm, which is comparable to our study 

(96.25 µm ± 10.28) (10) . 

Recently, Wu et al., reported the reproducibility of Spectralis in 

45 normal patients and 33 glaucoma patients. Their ICCs ranged 

from 0.977 (temporal) to 0.990 (global and inferior-nasal sector) in 

normal eyes, and from 0.983 (temporal) to 0.997 (inferior quadrant) 

in glaucomatous eyes. CVs ranged from 1.45% (overall global) to 

2.59% (temporal quadrant) for normal participants and ranged from 

1.74% (overall global) to 3.22% (temporal quadrant) for glaucoma 

patients (16) . There were some differences between this study and the 

present study: they analyzed the RNFL thickness using more than 

four quadrants (overall global - 360 degrees), for 4 quadrants (superior, 

inferior, nasal, and temporal), and then for 4 additional sectors: 

superior-temporal (TS, 45 to 90 degrees), superior-nasal (NS, 90 to 

135 degrees), inferior-nasal (NI, 225 to 270 degrees), and inferior- 

-temporal (TI, 270 to 315 degrees); the number of participants was 

smaller than ours; the subjects had different types of glaucoma, 

in cluding pseudoexfoliation glaucoma; and they used the TruTrack 

image alignment software (i.e., the eye tracking system). Probably 

because of all these facts theirs ICC and COV were better than the 

present study, especially because of the tracking system. 

Evaluating the impact of Spectralis ® self-acting eye tracking 

system and retest software on the reproducibility of RNFL thickness 

measurements in glaucomatous and healthy eyes it was observed 

that the reproducibility can be improved by using the eye tracker, 

and this gain was significantly higher in glaucomatous than in healthy 

eyes. In healthy subjects, COVs for RNFL thickness measurements 

without using the system ranged from 3.5% to 7.4% and with the eye 

tracker and retest protocol ranged from 1.0% to 2.5%. In glaucoma 

patients measurements without the eye tracker ranged from 5.8% 

to 10.5% and with the system ranged from 1.6% to 3.8%. The improvement 

in reproducibility was significantly higher in glaucomatous 

than in healthy eyes (17) . Our study showed COV ranged from 4.65% 

to 11.44% in the glaucomatous group similar to the previous study 

without using the eye tracker system. Despite not using the eye 

tracking system, our study showed an excellent reproducibility of 

RNFL thickness in normal and glaucomatous eyes. It is necessary 

to emphasize that the patients included in the present study had 

moderate to advanced glaucoma with difficult to fixation on one or 

both eyes and it may have contributed to the high COV. 

CONCLUSION 

The Spectralis ® spectral domain OCT equipped showed excellent 

reproducibility with regards to RNFL thickness measurements in normal 

and in moderate to advanced glaucoma patients. 

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Radiation therapy for Graves’ ophthalmopathy: a systematic review and 

meta-analysis of randomized controlled trials 

Radioterapia para oftalmopatia de Graves: uma revisão sistemática e meta-análise de 

ensaios clínicos randomizados e controlados 

Gustavo Arruda Viani 1 , André Campiolo Boin 2 , Ligia Issa De Fendi 3 , Ellen Carrara Fonseca 3 , Eduardo Jose Stefano 1 , Jayter Silva de Paula 4 

ABSTRACT 

Purpose: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy 

(RT 20 Gy) in the treatment of Graves’ ophthalmopathy. 

Methods: A systematic review and meta-analysis of randomized controlled trials 

was performed comparing RT 20 Gy with or without glucocorticoid to cli nical 

treatments for Graves’ ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library 

databases and recent relevant journals were searched. Relevant reports were 

reviewed by two reviewers. Response to radiotherapy was defined as clinical 

success according to each trial. We also evaluated the quality of life and whether 

RT to produce fewer side effects than other treatments. 

Results: A total of 8 randomized controlled trials (439 patients) were identified. 

In the subgroup analysis, the overall response to treatment rates was better for: 

RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, 

p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus 

intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 

1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other 

fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without 

glucocorticoids showed an improvement in diplopia grade, visual acuity, optic 

neuropathy, lid width, proptosis and ocular motility. No difference was seen for 

costs, intraocular pressure and quality of life. 

Conclusion: Our data have shown that RT 20 Gy should be offered as a valid the - 

rapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness 

of orbital radiotherapy can be increased by the synergistic interaction with 

glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, 

excluding intraocular pressure, without any difference in quality of life and costs. 

Keywords: Graves ophthalmopathy; Exophthalmos; Radiotherapy; Meta-analysis, 

Review 

RESUMO 

Objetivo: Avaliar a eficácia da radioterapia (RT) com dose total de 20 Gy (RT 20 Gy) 

no tratamento da oftalmopatia de Graves. 

Métodos: Uma revisão sistemática e meta-análise de ensaios clínicos randomizados 

foram realizadas comparando RT 20 Gy, com ou sem glicocorticoides a tratamentos 

clinicos para a oftalmopatia de Graves. O MEDLINE, EMBASE, bases de dados da 

Biblioteca Cochrane e recentes de revistas relevantes foram pesquisados. Relatórios 

relevantes foram revisados por dois revisores. A resposta à radioterapia foi definida 

através do sucesso clinico de acordo a cada ensaio clínico. Nós também avaliamos a 

qualidade de vida e se a radioterapia produzia menos efeitos colaterais comparados 

a outras intervenções. 

Resultados: Um total de 8 ensaios clínicos randomizados (439 pacientes) foram iden - 

tificados. Na análise de subgrupo, a resposta global para as taxas de tratamento foi 

melhor para: RT 20 Gy além de glicocorticoides vs glicocorticoides sozinhos, OR=17,5 

(IC95% 1,85-250, p=0,04), RT 20 Gy vs sham RT, OR=3,15 (IC95% 1,59-6,23, p=0,003) e 

RT 20 Gy além de glicocorticoides por via intravenosa RT 20 Gy além de glicocorticoides 

orais, OR=4,15 (IC95% 1,34-12,87, p=0,01). Não houve diferenças entre RT 20 Gy contra 

outros fracionamentos e 20 Gy RT contra glicocorticoides sozinhos. RT 20 Gy, com 

ou sem glicocorticoides mostraram uma melhoria no grau de diplopia, acuidade 

visual, neuropatia óptica, abertura palpebral, proptose e da motilidade ocular. Não 

foi observada diferença para os custos, a pressão intraocular e a qualidade de vida. 

Conclusão: Nossos dados mostraram que 20 Gy RT deve ser oferecida como uma opção 

terapêutica válida para pacientes com moderada a severa oftalmopatia de Graves. A 

eficácia da radioterapia orbital pode ser aumentada pela interação sinérgica com os 

glicocorticoides. Além disso, RT 20 Gy é útil para melhorar vários sintomas oculares, 

excluindo a pressão intraocular, sem qualquer diferença de qualidade de vida. 

Descritores: Oftalmopatia de Graves; Exoftalmia; Radioterapia; Meta-análise, Revisão 

INTRODUCTION 

Graves’ ophthalmopathy is a debilitating disease impairing the 

quality of life of the affected individuals. Despite recent progress in 

the understanding of its pathogenesis, treatment is often not sa - 

tisfactory. In mild cases, local therapeutic measures (artificial tears 

and ointments, sunglasses, nocturnal eyes taping, prisms) can control 

symptoms and signs. In severe forms of the disease, aggressive 

measures are required. The management strategy for moderate tosevere 

Graves’ ophthalmopathy is controversial. Systemic steroids are 

often effective (1-4) , but relapse is common when they are tapered or 

withdrawn (5) . A number of retrospective studies have reported the 

efficacy of orbital irradiation (6,7) but prospective studies have shown 

conflicting results (8-10) . Some investigators have suggested that ste - 

roids provide excellent improvement in orbital inflammation in the 

short term, whereas the effects of orbital irradiation take longer to 

appear (11) . Studies that have compared combination therapy of or - 

bi tal irradiation and systemic steroids with steroids alone therapy 

have produced conflicting results (12-18) . The accomplishment of a 

sys tematic review is the best manner for describing the state of our 

knowledge, and hence becomes the best way of obtaining high 

qua lity scientific evidence. Consequently, this systematic review was 

proposed to analyze the results from clinical trials that compared ra - 

diotherapy to any other treatment. 

Submitted for publication: February 6, 2012 


Study carried out at Faculty of Medicine of Marília, Department of Radiation Oncology. 

1 

Physician, Radiation Oncology Department, Escola de Medicina de Marília, Marília (SP), Brazil. 

2 

Medical Student, Escola de Medicina de Marília, Marília (SP), Brazil. 

3 

Department of Ophthalmology, Escola de Medicina de Marília, Marília (SP), Brazil. 

4 

Physician, Department of Ophthalmology, Escola de Medicina de Ribeirão Preto, Universidade de 

São Paulo - USP - Ribeirão Preto (SP), Brazil. 


Disclosure of potential conflicts of interest: G.A.Viani, None; A.C.Boin, None; L.I.De Fendi, None; 

E.C.Fonseca, None; E.J.Stefano, None; J.S.de Paula, None. 

Correspondence address: Gustavo Arruda Viani. Rua Coronel José Brás, 205/72 - Marília (SP) - 

17501-570 - Brazil - E-mail-gusviani@gmail.com 


Viani GA, et al. 

METHODS 

Types of studies 

This systematic review properly included randomized controlled 

clinical trials. Any trial including only patients with mild Graves 

ophthalmopathy (GO), or any trial including patients with moderate-severe 

GO were included. The participants of studies included 

patients with GO diagnosis for the first time, not resistant to previous 

treatment and with no age limit. The intervention criteria to be included 

in this review was any trial in which radiotherapy with total 

dose of 20 Gy associated or not to glucocorticoid (of any kind) was 

the primary treatment compared to radiotherapy (RT) with total 

dose different of 20 Gy, no radiotherapy or any another treatment. 

The efficacy of radiotherapy was evaluated following measures 

after treatment. The lid width was measured as the widest vertical 

dimension, proptosis was measured by an exophthalmometer, ocular 

motion was measured in degrees or constancy of diplopia, intraocular 

pressure measured using an applanation tonometer, optic nerve 

function was assessed by recording of the corrected visual acuity 

or fundoscopy. Response to radiotherapy was defined as clinical 

suc cess according to each trial. We also evaluated the quality of life 

and whether RT produced fewer side effects than other treatments. 

Medline and manual searches were done (completed independently 

and in duplicate) to identify all published (manuscripts and abstracts) 

randomized controlled trials (RCTs) that compared radiotherapy for 

GO to any treatment. The Medline search was done between 1966 

and 2006 with no language restrictions, using the search terms 

“ophthalmopathy,” orbitopathy” and “Graves’ ophthalmopathy,” “radiotherapy” 

or “orbital radiotherapy,” and “retro ocular radiotherapy”. 

The second search was done through EMBASE and the Cochrane Li - 

brary to identify randomized trials published between January 1998 

and July 2006, using MeSH headings (ophthalmopathy, orbipathy, 

Graves’ ophthalmopathy, orbital radiotherapy, retro ocular radiotherapy 

/sc {Secondary}, ex-lode Clinical Trials, clinical trial {publication 

type}) and text words (retro ocular radiotherapy radiotherapy, Graves’ 

ophthalmopathy, trial, and study) without language restrictions. All 

the searched abstracts were screened for relevance. Manual searches 

were done by reviewing articles and abstracts cited in the reference 

lists of identified RCTs, by reviewing the first author’s article, abstract 

file, from reference lists of retrieved papers, textbooks and review 

articles. Hand searches were carried out in the following journals 

between January Ophthalmology; Lancet; Ophthalmology; International 

Journal of Radiation Oncology, Biology, and Physics; and Journal of 

Clinical endocrinology and metabolism. Reference lists from identified 

studies and other relevant publications were scrutinized. Colleagues, 

collaborators, and other experts were contacted about ongoing and 

unpublished trials. From the titles and abstracts, relevant RCTs were 

identified. Two independent reviewers (V.A.G., A.C.B.) then assessed 

the RCTs to establish if predetermined inclusion criteria were met. 

Study suitableness was assessed using QUOROM criteria (19) . The RCTs 

were also independently assessed for quality according to predetermined 

criteria (method of randomization, blinding, statistical methods, 

quality of life assessment, data completeness, follow-up), and 

the data extracted and tabulated. Discrepancies between the two 

reviewers were resolved by discussion. The intention was to carry out 

a meta-analysis of outcomes if there were enough trials of sufficient 

quality and homogeneity. 

Statistics 

The efficacy of radiotherapy treatment with total dose of 20 Gy 

was measured through the response to treatment described in each 

trial. Responders to treatment were defined as patients who presented 

overall response to radiotherapy or other treatment, according 

to clinical success defined according to each trial. The data analyses 

were made with Review Manager Version 5.1 provided by The Cochrane 

Collaboration. All analyses were carried out on an intention 

to treat basis; that is, all patients randomly assigned to a treatment 

group were included in the analyses according to the assigned treatment, 

irrespective of whether they received the treatment or were 

excluded from analysis by the investigators. For categorical variables, 

weighted risk ratios and their 95% confidence interval were calculated 

using RevMan 5.1 software according to the Peto method (20) . 

Results were tested for heterogeneity at significance level of P


RT: radiation therapy; RCT: randomized controlled trial. 

Figure 1. Flowchart according to QUOROM statement criteria. 

three RCTs, (12,13,16) only one trial (13) showed benefit for RT 20 Gy arms. 

Diplopia was assessed in five RCTs (9,10,12,14,15) of these studies Prummel 

et al., (15) and Mourits et al. (9) founded significant differences between 

radiotherapy versus sham radiotherapy for changes in diplopia, in 

the other studies it was not seen. Intraocular pressure was tested in 

two RCTs (12,16) , one performed by Ng et al. (16) , and another by Kahaly 

et al. (12) , in both studies no benefit was seen in combined orbital 

irradiation and systemic steroids or using low dose of radiotherapy. 

Mar cocci et al. (14) , was the only trial to assess the efficacy of radiotherapy 

to improve optic neuropathy. In this study combined orbital 

irradiation and systemic steroids were associated with significant 

difference to improve optic neuropathy. 

Ocular motility and clinical response was tested in all RCTs (8-10,12-16) . 

RT 20 Gy with or without glucocorticoid achieved significant statistical 

difference in five of the eight trials evaluated for clinical response. 

Ocular motility was improved in six trials (8,9,13-16) comparing RT 20 Gy 

with other treatments. Table 2 summarizes the parameters evaluated 

and the treatment results. According to the Jadad criteria, we 

assessed the quality of the randomized and comparative trials with 

regard to: a) method of randomization, b) treatment allocation, c) 

similarity between groups, d) specification of eligible criteria, e) blinded 

outcome of assessor, care provider and patient (22) . Applying these 

criteria made clear that the quality of the trials was high, as showed 

in the table 3 which describes in details the trials design, aim, study 

question, results, and conclusions. 

Response to treatment 

All the studies reported response to treatment as one of the out - 

comes. The criterions for evaluation of the response to treatment 

were heterogeneous between the trials. Altogether, the analyses 

included 8 trials with 439 patients (9, 10, 12-16) . The individual odds ratios 

ranged from 0.87 to 17.5 with a pooled odds ratio for all of the trials 

of 2.14 with a 95% confidence interval of 1.44 to 3.18. The test for 

heterogeneity was not statistically significant with p value 0.14, which 

indicates that the pooling of the data was valid. The overall odds ratio 

suggests that there is difference between RT 20 Gy arms and other 

treatments in terms of response to treatment rate with p value 0.0002, 

as shown in the figure 2. 

Radiotherapy versus sham radiotherapy 

Three trials (9,10,15) with 190 patients evaluated response to treatment 

comparing radiotherapy versus sham radiotherapy. The in - 

dividual odds ratios ranged from 1 to 3.5 with a pooled odds ratio 

for all of the trials of 3.15 with a 95% confidence interval of 1.59 to 

6.23. The test for heterogeneity was not statistically significant with 

p value 0.28, which indicates that the pooling of the data was valid. 



Table 1. Characteristics of the patients, parameters of the treatment, status of GO and end points of the studies included in this meta-analysis 

Trial (year) 

Prummel et al., 

(2004) 

Marcocci et al., 

(2001) 

Kahaly et al., 

(2000) 

Patients/ 

treatment 

88 

RT: 44 

NO RT: 44 

82 

RT+IVGC:41 

RT+ORGC:41 

62 

A=18 1 Gray/week 

20 Gray/20 weeks 

B=22 1 Gray/day 


C=22 2 Gray/day 


Ng et al., (2005) 16 

RT+GC:8 

GC:8 

Bartalena et al., 

(1983) 

Gorman et al., 

(2002) 


(1993) 

Mourits et al., 

(2000) 

48 

RT+GC36 

GC:12 

42 

RT:21 

NO RT:21 

56 

RT:28 

GC:28 

60 

RT: 30 

NO RT: 30 

Diagnostic 

Signs and symptoms with 

enlarged extraocular eye muscles on 

coronal computed tomography scan 

of the orbits 

Signs and symptoms with enlarged 

extraocular eye muscles on coronal 

computed tomography scan of the 

orbits 


extraocular eye muscles on magnetic 

resonance imaging (MRI) 


extraocular eye muscles on 

computed tomography or 

magnetic resonance imaging (MRI) 


extraocular eye muscles 


extraocular eye muscles on 

computed tomography 


extraocular eye muscles 


extraocular eye muscles on coronal 

computed tomography scan of the 

orbits 

Status GO/treatment 

hypertireoidism 

Mild, antithyroid drugs, 

TSH supression 

Moderate-to-severe 

methimazole 

for 3-4 months before 

radioiodine therapy 

Mild to moderate eye 

disease, euthyroidism, 

antithyroid drugs 


ophthalmopathy, 

anti-thyroid drugs, 

radioactive iodine, 

thyroidectomy 





thyroidectomy 

Mild to moderate 

ophthalmopathy 



thyroidectomy 

Moderate 

ophthalmopathy 



thyroidectomy 





thyroidectomy 

RT: radiation therapy; NO RT: no radiation therapy; GC: glucocorticoid; IV: intravenous; TSH: thyroid-stimulating hormone. 

Equipament 

Dose/angle/field 

Linear accelerator/ 

20Gy/3 grade anterior/ 

5 X 5 cm 

Linear accelerator/20Gy10 

degrees anterior/ 

4 X 4 cm 

Linear accelerator/20Gy-10 

Gy/3 degrees anterior/ 

5 X 6 cm 



4 X 4 cm 

Cobalt -60/20Gy-10 Gy/10 

degrees anterior/ 

4 X 4 cm 



4 X 4 cm 

Linear accelerator or cobalt 

-60/20Gy-10 Gy/10 degrees 

anterior/ 

5 X 5 cm 



4 X 4 cm 

End point 

After 12 months, motility in 

degrees, 

proptosis, lid aperture, 

diplopia, quality life, cost 

After 12 months, motility in 

degrees, 

proptosis, lid aperture, optic 

neuropathy, diplopia 

After 12 months, lid aperture, 

proptosis, motility in degrees, 

diplopia, intraocular pressure 

After 12 months, motility 

in degrees, 

proptosis, lid aperture 

After 12 months, 

ophthalmic index, 

proptosis, optic neuropathy 

After 6 months, motility 

in degrees, 

proptosis, lid aperture, 

clinical activity scores 


eye score and a decrease in 

eye-muscle volume 


eyelid aperture, proptosis, 

eye movements, subjective 

eye score, and clinical-activity 

Table 2. Ocular parameters and results post treatment evaluated in randomized clinical trails 

Trial 

Prummel 

1993 

Marcocci* 

2000 

Bartalena 

1983 

Ng 

2005 

Kahaly 

2000 

Mourits 

2001 

Prummel 

2004 

Gorman 

2001 

Parameter 

Quality of life 0 0 0 0 0 0 = 0 

Proptosis (mm) = + 0 0 0 0 0 0 

Lid width (mm) 0 + 0 0 0 0 0 0 

Visual acuity 0 0 0 = = 0 0 0 

Diplopia 0 = 0 0 = + + = 

Intraocular pressure = = = 0 0 0 0 0 

Optic neuropathy 0 + + 0 0 0 0 0 

Ocular motility + + + + = + + = 

Clinical response = + + + = + + = 

Cost 0 0 0 0 0 0 = 0 

Side effects - - + = - + + + 

*= Marcocci trial + was used for RT 20 Gy plus iv glucocorticoid and 0 was used for RT 20 Gy plus oral glucocorticoid; += significant for radiotherapy 20 Gy arms with or without glucocorticoids 

when compared to the other treatment; -= significant for another treatment; (=)= no difference between the arms of study; 0= no evaluation. 


327


Table 3. Description of the design, aim, question, results and conclusion of the studies included in this meta-analysis 

Author Year 


2004 

Ng et al., 

2005 


1993 

Marcocci et al., 

2001 

Gorman et al., 

2001 

Double-blind 

randomized trial 

Design /aim/ 

study question Results Conclusions/comments 

To compared RT efficacy with sham 

irradiation in mild ophthalmopathy 

Double-blind 


To assess the efficacy and safety 

of combined orbital irradiation 

and systemic steroids in the 

management of moderate-tosevere 

Graves’ ophthalmopathy 

Double-blind 


Randomized trial 

To assess the efficacy and safety of 

orbital radiotherapy combined with 

either oral (prednisone; starting 

dose, 100 mg/d; withdrawal after 5 

months) or iv (methylprednisolone; 

15 mg/kg for four cycles and then 

7.5mg/kg for four cycles; each 

cycle consisted of two infusions 

on alternate days at 2-wk intervals) 

glucocorticoids 

Prospective, randomized, internally 

controlled, double-blind clinical trial 

To evaluate the efficacy of 

radiotherapy for GO 

RT was successful in 23 of 44 (52%) irradiated patients vs. 12 of 

44 (27%) sham-irradiated patients at 12 months after treatment 

(relative risk, 1.9; 95% CI, 1.1 - 3.4; P =0.02). was effective in 

improving eye muscle motility and decreasing the severity of 

diplopia. Quality of life improved similarly in both groups. In the 

radiotherapy group there was less need for follow-up treatment; 

66% vs. 84% of the patients needed further treatment (P=0.049) 

Total eye score improved earlier in the SRT group, achieving 

statistical significance (P


OR: odds ratio. 

Figure 2. Treatment response comparing radiation therapy 20 Gy to other treatments in the randomized controlled trial. 

The overall odds ratio suggests that there is difference between RT 

20 Gy arms and no RT 20 Gy arms in terms of response to treatment 

rate with p value 0.003, as shown in table 4. 

Radiotherapy plus glucocorticoid versus glucocorticoid 

One randomized study (16) (15 patients) compared the efficacy of 

combined orbital irradiation and systemic steroids in the management 

of moderate-to-severe Graves’ ophthalmopathy. The odds ratio 

for this trial was of 17.50 with a 95% confidence interval of 1.85 to 

250. The test for heterogeneity was not statistically significant with p 

value 0.42, which indicates that the pooling of the data was valid. The 

overall odds ratio suggests that there is difference between RT 20 Gy 

arms and glucocorticoid arms in terms of response to treatment rate 

with p value 0.04, as demonstrated in the table 4. 

Radiotherapy plus IV glucocorticoid versus radiotherapy plus 

oral glucocorticoid 

One study (14) (82 patients) compared the efficacy radiotherapy 

plus IV glucocorticoid versus radiotherapy plus oral glucocorticoid. 

The odds ratio of this study was 4.15 with 95% confidence interval 

of 1.34 to 12.87, suggesting that there is difference between 

radiotherapy plus IV glucocorticoid versus radiotherapy plus oral 

glucocorticoid in terms of response to treatment with p value 0.01, 

shown in table 4. 

Radiotherapy with 20 Gy versus other fractionations 

One study (12) (66 patients) compared the efficacy of radiotherapy 

with a total dose of 20 Gy versus others fractionations. The odds ratio 

of this study was 1.10 with 95% confidence interval of 0.39 to 3.10, 

suggesting that there is no difference between radiotherapy with a 

total dose of 20 Gy versus others fractionations for response to treatment, 

as demonstrated in table 4. 

Quality of life and costs 

One study of Prummel et al., (15) (88 patients) evaluated the quality 

of life and costs and did not evidence differences in quality of life 

or costs between patients submitted to radiotherapy versus sham 

radiotherapy for GO. 

Radiotherapy versus glucocorticoid 


with a total dose of 20 Gy versus glucocorticoid. The odds ratio of 

this study was 0.87 with 95% confidence interval of 0.30 to 2.87, 

suggesting that there is no difference between radiotherapy with a 

total dose of 20 Gy versus glucocorticoid for response to treatment, 

as described in table 4. 

Radiotherapy plus IV glucocorticoid versus radiotherapy alone 


plus IV glucocorticoid versus radiotherapy alone. The odds ratio this 

study was 3 with 95% confidence interval of 0.68 to 13.31, suggesting 

that there is no difference between radiotherapy with a total dose of 

20 Gy plus glucocorticoid versus radiotherapy alone for response to 

treatment, as shown in table 4. 

Quality of studies 

The median of the quality scores was of 4 points (in a 5-point 

scale), with none study scoring 0, 1, 2, or 3. There was complete agreement 

in scoring by the two assessors. The quality scores were high, 

five trials scored 5 points (8-10,15,16) and three trials scored 4 points in the 

Jada scale. This fact occurred because of the importance placed on 

blinding in the scoring system, and the inherent difficulty in blinding 

a treatment such as radiation, as shown in the table 3. 

Evaluation of publication Bias 

The funnel plot of the log ORs versus the inverse of their variances 

of the individual studies is displayed in figure 3. The plot formed a very 

distinct funnel shape with the log ORs evenly distributed around the 

meta-analysis OR regardless the study variance. Therefore, there was 

no indication of an asymmetry in the study findings by the variance 

or size of the studies and, thus, little evidence for publication bias. 

DISCUSSION 

External radiotherapy has been used for GO for around 60 years 

and it still represents a mainstay in the management of the disease (23) . 

The rationale for the use of radiotherapy for GO resides both in its 


329


Table 4. Odds ratio calculated according to the response to treatment 

for the trials included in this meta-analysis 

Response to treatment (n=439) 

RT 20 Gy vs sham RT (n=190) 

Prummel et al., 2004 (15) 

Mourits et al., 2000 (9) 

Gorman et al., 2001 (10) 

RT 20 Gy plus glucocorticoid vs 

glucocorticoid (n=15) 

Ng et al., 2005 (16) 

RT 20 Gy IVGC vs RT ORGC * (n=82) 

Marcocci et al., 2001 (14) 

RT 20 Gy vs glucocorticoid (n=56) 

Prummel et al., 1993 (8) 

RT 20 Gy vs Low dose RT (n=66) 

Kahaly et al., 2000 (12) 

RT 20 Gy plus glucocorticoid vs 

RT 20 Gy (n=30) 

Marcocci et al., 1991 (13) 

Estimated OR (95% CI), p value 

3.15 (1.59 - 6.23), p=0.003 

2.92 (1.2 - 7.1) 

3.50 (1.2 - 10.2) 

1.00 (0.26 - 3.87) 

17.5 (1.22 - 250), p=0.04 

4.15 (1.34 - 12.87), p=0.01 

0.87 (0.30 - 2.47), p=0.79 

1.10 (0.39 - 3.10), p=0.86 

3.00 (0.68 - 13.31), p=0.15 

OR= odds ratio; CI= confidence interval; NR= not reported; RT= radiotherapy. 

*= iv methylprednisoloneacetate (IVGC) or oral prednisone (ORGC). 

SE: size effect; OR: odds ratio. 

Figure 3. Funnel plot for response to treatment using radiotherapy for Graves’ ophthalmopathy. 

nonspecific anti-inflammatory effect and in the high radio sensitivity 

of lymphocytes infiltrating the orbital space (24) . Lymphocytes are generally 

suppressed with relatively low doses of radiation, and the helper/suppressor 

T lymphocyte ratio is also altered by radiotherapy (23) . 

In addition, radiotherapy might also reduce glycosaminoglycans 

production by orbital fibroblasts (25) . Whether the reported effectiveness 

of orbital radiotherapy in GO is related either to its nonspecific 

anti-inflammatory action, or to specific immunosuppressive effects, 

both need to be clarified. Our review of papers published between 

1983 and 2006 showed that positive results were obtained using RT. 

According to most studies, orbital radiotherapy is especially effective 

on soft tissue inflammatory changes and recent extraocular muscle 

involvement, producing improvement in the ocular parameters as 

visual acuity, diplopia, proptosis, lid width, ocular motility and optic 

neuropathy, but without any benefit on intraocular pressure. It 

should be mentioned that all studies were randomized, controlled 

and of high quality. The latest 5 years have witnessed important discussions 

on the role of orbital radiotherapy, in particular questioning 

its effectiveness and safety (26-32) . 

Most authors agree that orbital radiotherapy is a safe procedure. 

If the technique of radiation is correct, it seems not to increase the 

risk of cataract and retinopathy, except for patients with diabetic and 

hypertensive retinopathy (33,34) . The two latter conditions, especially 

if associated, should be considered as relative contraindications 

to orbital radiotherapy, in particular when signs of retinopathy are 

present before irradiation. It is worth noting that, even after a very 

long follow-up, orbital radiotherapy does not seem to bear a risk of 

radiation-induced tumors (35-40) . Thus, the safety of orbital radiotherapy 

is not a major matter of argument, but there is a controversy about 

its real effectiveness. This debate has been revitalized by a randomized, 

placebo-controlled, double-blind study from the Mayo Clinic (10) . 

In the original experimental design of this study, only one orbit of 

42 patients with moderately severe GO was irradiated, whereas the 

contralateral orbit served as an internal control. A detailed analysis of 

objective measures was provided; leading the authors to conclude 

that orbital radiotherapy is ineffective and therefore, should not be 

offered to GO patients (10) . Although Gorman et al. should be congratulated 

on the major effort they made, our point about this study is 

that it has some structural errors. 

One of them was the fact that a lot of patients had a longstan 

ding ophthalmopathy and had been already treated before, 

apparently not well succeeded, by systemic glucocorticoids (10) . The 

second one involves timing of therapy, and the therapeutic goals 

of orbital radiation therapy. The authors in their study included 

pa tients between 0.2 and 16 years, with a median of 1.3 years with 

onset from the eye symptoms. The authors made no attempt to 

treat patients in the active progressive phase of thyroid eye disease. 

This phase disease is characterized by infiltration of the extra-ocular 

muscles with lymphocytes, and it is the prime radiation sensitive 

period. Patients who do not respond to glucocorticoids are unlikely 

to show any benefit from orbital radiotherapy. In addition, the 

obser vation that the untreated orbit did not show any improvement 

or worsening during the 6-months period of further observation 

suggesting that enrolled patients had stable, non progressive, 

i.e. inactive (“burnt-out”) eye disease. The third vital error was the 

stated goal of orbital radiation. In many institutions the stated goal 

of therapy is to halt or reverse severe progressive thyroid ophthalmopathy. 

The author’s therapeutic objectives of treating patients 

who had chronic fibrotic thyroid ophthalmopathy established 

were unclear. This article seemed to evaluate if radiation therapy 

reversed such findings as orbital volume in patients with chronic 

thyroid ophthalmopathy. Our final concern about this article was 

the unusual port design for radiation therapy. This design may be 

useful as a research data, on the other hand, being human studies 

it can be considered as worrisome. Treating with their wedge pair 

field design to spare the contralateral eye, the authors increased the 

volume of normal tissue significantly, including the frontal lobes 

and parotid glands, exposed to radiation compared to the standard 

opposed lateral fields. Although the risks of a secondary malignancy 

in the treatment of those patients are slight, increasing the volume 

would be expected to increase this risk. But the long-term effects 

of a low dose radiation in a larger volume of the frontal lobe may 

have subtle effects in the higher brain functions. 

What did the other randomized controlled trials tell us about 

the efficacy of orbital radiotherapy for GO? In 1993, a randomized 

double-blind trial of prednisone vs. orbital radiotherapy in patients 

with moderately severe GO (8) demonstrated that the proportion of 

responders in prednisone-treated (14 of 28, 50%) and irradiated (13 of 

28, 46%) patients (18%) was similar. That time, there were no doubts 

that glucocorticoid was an effective treatment for GO. Ho wever, from 

this study through non direct comparison RT has star ted to be also 

considered effective. In addition, the study above also demonstrated 

a decrease in the eye muscle volume, as assessed by the eye muscle 

score (8) . In 2000 those data were confirmed for a double-blind ran- 



domized study which included 60 patients with moderately severe 

GO who were submitted to either orbital radiotherapy or sham-irradiation 

(9) . The qualitative treatment outcome was successful in 60% 

of irradiated patients and in only 31% of sham irradiated patients (9) . 

Improvement was mainly confined to eye movements; it should also 

be noted that 25% of irradiated patients were saved from additional 

strabismus surgery (9) . In 2004 a new important information (15) about 

the use of orbital radiotherapy was provided for GO by Prummel et 

al. This double-blind, randomized clinical trial was the first to address 

the question of whether orbital radiotherapy has a place in the management 

of nonsevere GO. Based on the evaluation of changes in 

major and minor criteria prespecified, primary therapeutic outcome 

was successful in 52% of irradiated patients and in only 27% of 

sham-ir radiated patients (15) , with improvement in the eye muscle 

function and diplopia. It should also be noted that the orbital radiotherapy 

was not associated with a greater improvement of quality of 

life, compared to sham irradiation (15) . This paper also provides valuable 

information that orbital radiotherapy did not prevent progression 

to more severe expressions in about 15% of the patients. The reason 

why the severe forms of GO develop is still un clear nowadays, but it 

seems that environmental factors play a decisive role in this progression 

(40) . Thus, if the study by Prummel et al. (15) , lends further support 

to the concept that orbital radiotherapy is in general an effective 

treatment for GO, it also suggests that the commonly adopted policy 

of “wait-and-see” in cases of mild GO should be maintained, including 

the cost/benefit considerations. At present, most centers utilize linear 

accelerators delivering 4-6 megavolts and use a 4 x 4-cm lateral field 

slightly angled posteriorly to avoid as much as possible irradiation 

to the contralateral lens. The use of higher energy sources has not 

proven to be particularly advantageous. The most common delivered 

dose is 20 grays (Gy) per eye (30) ; this cumulative dose is usually 

fractionated in 10 daily doses over a 2-week period to reduce the 

cataractogenic effect of irradiation (27) . The importance of dose was 

evaluated by Kahaly et al., (12) , using different radiation doses. It reported 

that a therapeutic scheme of 1 Gy per week over a 20-week period 

was equally effective and possibly better tolerated than the classi cal 

2-week scheme. The use of higher cumulative doses of radiation 

(30 Gy vs. 20 Gy) does not produce any increase in the effectiveness 

of treatment (41) . Irrespective of small differences observed using 

low-dose vs. high-dose radiotherapy, beneficial effects of radiotherapy 

were observed in all the three groups of patients in 55 to 67% of 

cases. In summary, what is the message to the reader, based on the 

present systematic review? 

CONCLUSION 

Our data has shown that orbital radiotherapy still has an impor - 

tant role in the management of GO. Although there are a lot of 

avai lable studies in the literature, they have a limited impact owing 

to selection bias and lack of an appropriate ophthalmological assessment. 

In the era of evidence-based medicine it cannot be denied 

that six of eight randomized and controlled studies showed that orbital 

radiotherapy is effective on GO, especially on extraocular muscle 

involvement. Orbital radiotherapy, in burning out eye disease, 

can also make eye muscle and/or eyelid corrective surgery possible 

in earlier stages. The effectiveness of orbital radiotherapy can be increased 

by the synergistic interaction with glucocorticoids. Orbital 

radiotherapy should still be offered as a valid therapeutic option to 

patients with moderate to severe GO. The selection of patients is 

fundamental, be cause patients with inactive (“burnt-out”) GO are 

unlikely to respond to irradiation (as well as to glucocorticoids). 

The use of orbital radiotherapy in the early stage of the disease 

(possibly less than 1 year from the onset) is recommended. The real 

efficacy of orbital radiotherapy should come from well-designed, 

multicenter, randomized and controlled studies enrolling a large 

number of patients. 

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Cancellation of cataract surgery in a public hospital 

Micheli Patrícia de Fátima Magri 1 , Rodrigo França de Espíndola 2 , Marcony Rodrigues de Santhiago 2 , Elisabeth Frolich Mercadante 3 , Newton Kara Júnior 2 

RESUMO 

Objetivo: Analisar a incidência e causas de cancelamento de cirurgias de catarata 

em um hospital público de referência. 

Métodos: Trata-se de um estudo retrospectivo em que foram analisados o número 

de cancelamentos de facectomias durante o ano de 2009. Foram analisados sexo, 

idade, tipo de procedimento suspenso (facoemulsificação ou extração extracapsular 

do cristalino), tipo de anestesia, convênio (Sistema Único de Saúde ou convênio/particular) 

e motivo de suspensão da cirurgia (causas clínicas, institucionais ou pessoais). 

Resultados: Foram agendadas no período 2.965 cirurgias de catarata, havendo 650 

cancelamentos (21,92%). Dentre as principais razões para a suspensão do procedimento 

destacaram-se as causas clínicas (86,90%). Os meses de inverno apresentaram 

os maiores índices de suspensão de cirurgias de catarata. 

Conclusão: A taxa de cancelamento de cirurgia de catarata em serviços públicos 

parece ser a mesma que há 10 anos. A principal causa de suspensão deve-se por 

condições clínicas (hipertensão, diabetes, falta de exames, etc.). 

Descritores: Catarata; Extração de catarata; Facoemulsificação; Cegueira/prevenção 

& controle; Hospitais públicos; Procedimentos cirúrgicos eletivos; Eficiência organizacional; 

Pacientes desistentes do tratamento 

ABSTRACT 

Purpose: To report the incidence and causes of cataract surgery cancellations in a public 

hospital. 

Methods: This is a retrospective study, which examined the number of cancellations 

of cataract surgery during 2009. We analyzed the type of procedure suspended (phacoemulsification 

or extracapsular extraction), type of anesthesia, gender, age, covenant 

(public/private) and the main reasons for suspension of the surgeries (clinical causes, 

institutional or personal). 

Results: We analyzed 2,965 scheduled cataract surgeries, with 650 cancellations (21.92%). 

The main reason for the suspension of the procedure was clinical causes (86.90%). The 

winter months had the highest suspension rates of cataract surgery. 

Conclusion: The cancellation rate of cataract surgery in Brazilian public system seems 

to be the same as 10 years ago. The main cause of the suspension should be in clinical 

conditions (hypertension, diabetes, lack of exams, etc.). 

Keywords: Cataract; Cataract extraction; Phacoemulsification; Blindness/prevention & 

control; Hospitals, public; Surgical procedures, elective; Efficiency, organizational; Patient 

dropouts 

INTRODUÇÃO 

A cirurgia da catarata apresenta alta eficiência, favorável custobenefício 

no tratamento e na reabilitação visual e oferece grande im - 

pacto para a sociedade (1-3) . 

Nos países em desenvolvimento, o acesso de pacientes necessitados 

à cirurgia de catarata é dificultado devido aos fatores so - 

cioe co nômicos e culturais, além de obstáculos criados pelo próprio 

sistema de saúde, o que impede a realização de mais procedimentos 

cirúrgicos (3-6) . Mesmo quando estes obstáculos são superados, algumas 

cirurgias de catarata são canceladas, ocasionando um impacto 

negativo para o paciente e para a comunidade, além de diminuir a 

eficiência do serviço prestado e gerar aumento dos custos (7) . 

O cancelamento de cirurgias gera insatisfação e prejuízo aos pa - 

cientes em condições clínicas favoráveis para a realização do procedimento 

(7) . A taxa de suspensão de cirurgias ambulatoriais varia mui to 

de hospital para hospital, dependendo do critério que a define e 

como os dados são coletados (8) . 

As cirurgias ambulatoriais são fundamentais para qualquer sis - 

tema de saúde. A baixa complexidade, a rápida recuperação pós- 

-operatória e a segurança do procedimento, fazem com que os 

pro cedimentos ambulatoriais estejam cada vez mais em evidência 

nas instituições de saúde. Para que isso ocorra é necessário que haja 

uma otimização na quantidade de cirurgias realizadas, o que só será 

possível se houver reconhecimento de seus benefícios e potencial 

econômico, pessoal e material (9) . 

Com o crescimento dos custos na área da saúde e as limitações 

orçamentárias, tornou-se necessária a adoção de um sistema que 

forneça informações capazes de evitar desperdícios, aprimorar os 

serviços e impulsionar a melhoria contínua do gerenciamento das 

ações (10) . 

A utilização máxima da capacidade cirúrgica, em muitos casos, 

constitui uma das principais medidas que visam à eficiência do uso 

de verbas em uma unidade hospitalar (11) . Uma das estratégias que 

podem ser adotadas como ação é a realização de um maior número 

de cirurgias, diminuindo o número de cancelamentos de procedimentos 

(12) . 

O Hospital Regional de Divinolândia (CONDERG) firma-se como 

referência regional do Sistema Único de Saúde (SUS) nas especialidades 

de oftalmologia, otorrinolaringologia, ortopedia e cirurgia geral, 

além da reabilitação neurológica, sendo referência para 16 cidades 

na região de São João da Boa Vista (SP), interior do Estado de São 

Paulo. Uma população de aproximadamente 480 mil habitantes são 

assistidas pelo CONDERG sendo 97% do atendimento realizado pelo 

SUS e o restante por convênios/particular. 

Submetido para publicação: 12 de abril de 2012 

Aceito para publicação: 28 de agosto de 2012 

Trabalho realizado no CONDERG - Hospital Regional de Divinolândia - UNICAMP - em conjunto com 

o Hospital das Clínicas da Universidade de São Paulo - HC-FMUSP - e a Faculdade de Medicina 

do ABC - FM-ABC. 

1 

Mestre em Gerontologia. Pontifícia Universidade Católica de São Paulo, São Paulo (SP), Brasil. 

2 

Médico, Departamento de Oftalmologia, Universidade de São Paulo - USP - São Paulo (SP), Brasil. 

3 

Professor, Pontifícia Universidade Católica de São Paulo - PUCSP - São Paulo (SP), Brasil. 


Divulgação de potenciais conflitos de interesse: M.P.F.Magri, Nenhum; R.F.Espíndola, Nenhum; 

M.R.Santhiago, Nenhum; E.F.Mercadante, Nenhum; N.Kara.Júnior, Nenhum. 

Endereço para correspondência: Rodrigo França de Espíndola, Praça das Hortências, 70 - Cond. 

Portal de Itu - Itu (SP) 13301-689 - Brasil - E-mail: rodrigoespindola@usp.br 


333


O objetivo deste estudo é analisar a incidência e as principais 

causas de cancelamento de cirurgias de catarata em um hospital referência 

do SUS que podem ter contribuído para diminuir a eficiência 

do sistema de saúde. 

MÉTODOS 

Trata-se de um estudo retrospectivo na qual foi avaliado o número 

de suspensões de facectomia do centro cirúrgico ambulatorial 

de oftalmologia. Foram incluídos no estudo todos os pacientes com 

cirurgias agendadas e canceladas em 2009, de acordo com dados 

obtidos em arquivos e prontuários do Hospital Regional de Divinolândia. 

A pesquisa foi aprovada pelo Comitê de Ética e Pesquisa 

de Enfermagem e Medicina do CONDERG. 

A região assistida pelo CONDERG (16 municípios) apresenta uma 

população de idosos (>60 anos) de 51.799 pessoas, o que representa 

um percentil de 12,70%. Destes 3,70% possuem de 60 a 64 anos, 

3.20% de 65 a 69 anos, 2,70% de 70 a 74 anos e 3,10% possuem 75 

anos ou mais (Fonte: IBGE, Senso 2000). 

Os seguintes dados foram coletados nos arquivos do centro cirúrgico: 

tipo de procedimento (facoemulsificação [FACO] ou facectomia 

extracapsular [FEC]), tipo de anestesia (local, sedação ou geral), sexo, 

idade, convênio (SUS ou convênio/particular) e causas de suspensão 

da cirurgia. 

As cirurgias suspensas foram divididas conforme demonstrado 

abaixo: 

A. Causas clínicas: hipertensão arterial, tosse ou resfriado, falta de 

exames solicitados na consulta pré-operatória, más condições 

clínicas, hipoglicemia ou hiperglicemia - relaciona-se com as 

con dições de atendimento nos municípios de origem, devido ao 

paciente não comparecer com a(s) doença(s) de base controladas; 

B. Causas institucionais: falta de condições da unidade hospitalar 

de saúde: material, pessoal, estrutural, falta de horário - relaciona-se 

com as condições de atendimento do hospital, que por 

alguma justificativa não apresentou as condições necessárias 

para a realização do procedimento cirúrgico; 

C. Causas pessoais: ingestão de anticoagulante, desistência, falta ou 

recusa - relaciona-se com as condições de saúde de cada indivíduo. 

Ao final da primeira fase de coleta de dados foi realizado o cálculo 

dos indicadores e a análise dos mesmos acima mencionados. Para 

tanto, foi utilizado a metodologia descrita no Manual de indicadores 

de enfermagem do Controle de Qualidade Hospitalar CQH (2006). 

Os dados foram tabulados e analisados em três partes: tabulação 

dos dados, elaboração de indicadores de qualidade e análise dos 

indicadores. Foram analisados os seguintes indicadores: 

- Taxa de suspensão de cirurgia 

A taxa de suspensão de cirurgias foi calculada através da razão 

entre a quantidade de cirurgias suspensas e o total de cirurgias 

agendadas em cada mês, sendo o resultado multiplicado por 

100 e expresso em números relativos. 

- Taxa de aproveitamento das cirurgias 

A taxa de aproveitamento das cirurgias foi calculada através da 

razão entre a quantidade de cirurgias realizadas e agendadas em 

cada mês, sendo o resultado multiplicado por 100 e expresso em 

porcentual. 

A equipe multidisciplinar do centro cirúrgico incluí 1 enfermeira, 

22 técnicos em enfermagem, 4 instrumentadoras, 4 auxiliares de 

serviços, 2 anestesistas e equipe médica de residentes, preceptores e 

contratados. A grade cirúrgica é pré-definida com um agendamento 

de cirurgias eletivas realizadas nas 12 horas disponíveis no centro cirúrgico, 

de segunda a sexta-feira, ou através de mutirões que ocorrem 

em alguns finais de semana. 

A amostragem baseou-se em todos os casos de cancelamento 

de cirurgias de catarata durante o ano de 2009. Os dados foram analisados 

descritivamente e tabulados usando o auxílio do programa 

Microsoft Excel (versão 2010). 

RESULTADOS 

Foram agendadas no período analisado 2.965 cirurgias de catarata, 

havendo 650 cancelamentos (21,92%). A tabela 1 demonstra 

o número de agendamentos, cirurgias realizadas e cancelamentos 

durante o período analisado. Todas as cirurgias foram financiadas 

pelo SUS. 

Com relação ao sexo e idade, dos 650 cancelamentos, 353 eram 

do sexo feminino (54,30%) e 25,00% encontrava-se na faixa de 60 - 64 

anos de idade com uma média de 63 ± 1,21 anos e 297 eram do sexo 

masculino (45,70%) e 30,00% encontrava-se na faixa de 60 - 64 anos 

de idade com uma média de 64 ± 1,43 anos. 

Dos cancelamentos, 640 seriam por FACO (98,40%) e 10 seriam 

por FEC (1,60%). Considerando o tipo de anestesia programada, 

a grande maioria dos cancelamentos foi com anestesia local (646 

pacientes [99,40%]) seguidos por sedação (2 pacientes [0,30%]) e 

anestesia geral (2 pacientes [0,30%]). 

Analisando-se as causas de cancelamentos de cirurgia de catarata, 

a grande maioria foi devido a causas clínicas (86,90%) como 

demonstrado na tabela 2. A Tabela 3 mostra a distribuição das causas 

de suspensão de facectomias. 

O gráfico 1 demonstra as taxas de cancelamento e aproveitamento 

de cirurgias durante o ano de 2009. Verifica-se que a taxa 

Tabela 1. Distribuição do número de cancelamentos, agendamentos e de cirurgias de catarata realizadas no centro cirúrgico ambulatorial durante 2009 

2009 Jan Fev Mar Abr Mai Jun Jul Ago Set Out Nov Dez Total Média 

Cancelamentos 044 054 063 037 055 063 071 064 048 064 050 037 0.650 054.10 

Agendamentos 202 205 235 241 248 278 276 278 278 296 239 180 2.956 246.30 

Cirurgias realizadas 158 151 172 204 193 215 205 214 230 232 189 143 2.306 192.10 

Tabela 2. Número de cancelamentos de cirurgias de catarata de acordo com causas clínicas, institucionais e pessoais durante 2009 

Causas Jan Fev Mar Abr Mai Jun Jul Ago Set Out Nov Dez Total % 

Clínicas 39 45 55 33 52 51 69 62 39 57 35 27 564 86.90 

Institucionais 01 02 00 01 01 05 01 01 00 01 10 02 025 003.80 

Pessoais 04 07 08 03 02 07 01 01 09 06 05 08 061 009.30 

Total 44 54 63 37 55 63 71 64 48 64 50 37 650 100.00 


Magri MPF, et al. 

Tabela 3. Causas gerais de cancelamento de cirurgia de catarata durante 

o ano de 2009 

Causas de cancelamento N % 

Hipertensão arterial* 369 56,70 

Falta de exames 113 17,30 

Tosse/resfriado 40 6,10 

Más condições clínicas 33 5,07 

Hipo/hiperglicemia 29 4,46 

Tomou AAS** 21 3,23 

Remarcado para cirurgião R4 (com mais experiência) 11 1,60 

Recusa do paciente 9 1,38 

Faltou tempo 7 1,07 

Contra indicado pelo anestesista 4 0,60 

Não identificado 4 0,60 

Falta de jejum 4 0,60 

Falta de médico 3 0,46 

Indicação questionada pelo cirurgião 3 0,46 

Total 650 100,00 

*= pressão arterial ≥ 140 X 90 mmHg; **= acido acetil-salicílico. 

Gráfico 1. Distribuição das taxas de cancelamento e de aproveitamento das cirurgias 

de catarata durante o ano de 2009. 

de aproveitamento cirúrgico variou de 73,20% a 84,70%, com uma 

média de 78,95% segundo o agendamento. Através dos indicadores 

de suspensões de facectomias, podemos observar que houveram 

variações entre 15,30% a 26,30%, com uma média de 20,80%. 

DISCUSSÃO 

O estudo nacional mais recente que avaliou causas de cancelamento 

de cirurgia de catarata no Brasil aconteceu há mais de 10 

anos. Lira et al., (11) detectaram uma taxa de suspensão de facectomia 

de 19,50%. Arieta et al., (13) em 1992, detectaram 22.80% de cancelamento. 

No presente estudo a taxa de cancelamento no ano de 2009 

foi de 21,92%, semelhante aos levantamentos anteriores. Nota-se que 

esses valores encontram-se praticamente inalterados ao longo dos 

anos, apesar dos esforços no sentido de otimizar os centros cirúrgicos 

ambulatoriais. 

Estudos em outros países mostram taxas de cancelamento muito 

inferiores aos do Brasil, variando entre 5 - 12% (14,15) . As principais causas 

citadas nestes estudos também foram clínicas, como por exemplo 

hipertensão arterial, diabetes e resfriado. Alguns autores revelam que 

até 80% das causas de cancelamento seriam preveníveis (14) . 

Causas relacionadas à condição clínica do paciente (causas pessoais) 

levaram à suspensão de 4,50% das cirurgias no último estudo 

nacional (11) . Isso demonstra que esse mesmo índice encontrado no 

presente estudo (9,30%), demonstrado na tabela 2, está acima dos 

encontrados na literatura e que os clientes estão chegando de seus 

municípios com nível pressórico muito alto e/ou com falta de exames 

laboratoriais solicitados para a realização da cirurgia de catarata. 

O resultado da cirurgia e a recuperação da visão traz benefícios 

econômicos e sociais para o indivíduo, sua família e comunidade 

se gundo os estudos anteriores (13,16) . Desta maneira, todas as partes 

envolvidas com o impacto que a baixa visão por catarata acarreta são 

beneficiadas quando a saúde ocular é restabelecida. 

Para tanto, é necessário conhecer a instituição e o serviço, levantar 

dados e analisar os indicadores de qualidade. Elevadas taxas de 

cancelamentos refletem diretamente no atendimento prestado à 

comunidade. Para melhorarmos a taxa de aproveitamento do centro 

cirúrgico ambulatorial (diminuição do número de cancelamentos) 

algumas medidas foram tomadas: 

1. Os dados seriam apresentados ao Departamento Regional de 

Saúde de São João da Boa Vista (DRS XIV), um dos 17 departamentos 

do Estado de São Paulo, juntamente com os municípios 

participantes para propor ações em conjunto e diminuir 

estes índices; 

2. Criação de um protocolo estabelecendo os parâmetros de 

suspensão em relação aos exames pedidos como por exemplo, 

glicemia acima de 200 mg/dl, pressão arterial acima de 150 X 

90 mmHg e etc.; 

3. Criar um espaço para orientações pré-operatória para retirar as 

dúvidas e explicar as cirurgias; 

4. Realizar uma triagem através da equipe de enfermagem para 

reforçar as orientações pré-operatórias e verificar os exames 

antes do dia agendado para a cirurgia; 

5. Priorização do atendimento aos idosos que já tiveram a sua 

cirurgia suspensa por algum motivo; 

6. Monitorar os indicadores de suspensão de cirurgia mensalmente. 

Desta maneira toda a equipe do CONDERG, os municípios e os 

clientes estarão interligados com medidas que tentam eliminar as 

principais causas de suspensão de cirurgia. 

Os meses de abril e dezembro apresentaram menor número de 

suspensões, e o mês de julho obteve a maior expressão de suspensão. 

Diferentemente, o agendamento possuí o menor índice em dezembro 

e o maior em outubro (Tabela 1). Tais dados podem representar 

expressivamente os períodos sazonais na qual julho é o mês com um 

período mais frio, elevando a pressão arterial, proporcionando assim 

os maiores índices de suspensão cirúrgica, o que está de acordo 

com a literatura (11) . Em dezembro, com diminuição da produtividade 

devido ao período de festividade, houve menos agendamento de 

cirurgias. 

CONCLUSÃO 

A taxa de cancelamento de cirurgia de catarata em serviços 

públicos parece ser a mesma que há 10 anos. A principal causa de 

suspensão deve-se por condições clínicas (hipertensão, diabetes, 

falta de exames, etc.). Não somente o hospital de referência (local da 

cirurgia), mas o município de origem dos pacientes devem interagir 

para diminuir o número de cancelamentos e assemelhar-se aos padrões 

internacionais. 

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catarata senil: óbices para o paciente. Arq Bras Oftalmol. 1996;59(6):573-7. 


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Oftalmol. 2010;73(6):491-3. 

XVII Congresso da 

Sociedade Brasileira de Uveítes 



E-mail: wiltonfeitosa@hotmail.com 



Implantação do exame do reflexo vermelho em crianças da região do 

Hospital das Clínicas da Faculdade de Medicina de Botucatu - SP - Brasil 

Implementation of red reflex exam in children in the area of Botucatu Medical School Clinical Hospital - 

São Paulo, Brazil 

Antonio Carlos Lottelli Rodrigues 1 , Rodrigo Bueno Prado 1 , Licério Miguel 2 

RESUMO 

Objetivo: Descrever a implantação do teste de reflexo vermelho nas 30 cidades 

de inserção do Hospital das Clínicas da Faculdade de Medicina de Botucatu, 

HC/FMB/UNESP (480.337 habitantes), a criação de um centro para referência 

de crianças com reflexo vermelho alterado ou duvidoso, a Triagem do reflexo 

vermelho e outro para o tratamento da catarata infantil, o Centro de tratamento 

da catarata infantil. 

Métodos: O exame do reflexo vermelho foi divulgado em 30 cidades da região de 

Botucatu. Foram realizadas palestras aos municípios, convocados pelo Departamento 

Regional de Saúde VI do estado de São Paulo (DRS VI). Foram distribuídos 109 “pen 

torch ophthalmoscope”, às maternidades e Unidades Básicas de Saúde (UBSs) das 

cidades. A Triagem do reflexo vermelho recebeu os casos de reflexo vermelho alterado 

ou duvidoso e estabeleceu o diagnóstico oftalmológico. O Centro de tratamento da 

catarata infantil realizou o exame pré-operatório, o tratamento cirúrgico e o acompanhamento 

das crianças com catarata. 

Resultados: Após um ano de funcionamento a Triagem do reflexo vermelho 

aten deu 29 crianças, 17 do sexo masculino e 12 do feminino, com idade média e 

desvio padrão (dp) de 10,09 ± 20,35 meses (7 dias - 98 meses). 16 pacientes foram 

encaminhados com reflexo vermelho alterado, idade média e dp de 13,17 ± 24,14 

meses (7 dias - 98 meses), a alteração foi confirmada em todos os casos, 13 deles 

apresentavam catarata. Em 13 encaminhamentos com reflexo duvidoso, idade mé - 

dia e dp de 6,29 ± 14,46 meses (7 dias - 98 meses), a alteração não se confirmou. A 

incidência de alterações do reflexo vermelho encontradas foi de 9,2/10.000 nascidos 

vivos e a incidência the catarata foi de 7,9/10.000 nascidos vivos. 

Conclusão: Descrevemos a implantação do Teste do reflexo vermelho na Região de 

Botucatu, a criação da Triagem do reflexo vermelho e do Centro de tratamento da 

catarata infantil e dificuldades encontradas. 

Descritores: Catarata/diagnóstico; Catarata/congênita; Oftalmoscópios; Reflexo 

pupilar; Vision tests; Criança 

ABSTRACT 

Purpose: To describe the implantation of the red reflex test in 30 cities in the area of 

Botucatu Medical School Clinical Hospital, (480,337 inhabitants) and the creation of a 

reference Center for children with red reflex changes, the Red reflex screening and another 

Center for treatment of childhood cataract. 

Methods: The red reflex exam was released in 30 cities of the surrounding Botucatu 

area, lectures were done in the cities invited to participate by the Regional Department 

of Health.109 pen torch ophthalmoscopes were distributed to the hospital maternities 

and primary care units. The Red reflex screening attended cases of altered or doubtful 

red reflex and established the diagnosis. The Center for treatment of childhood cataract 

performed the preoperative examination, surgical treatment and follow-up of children 

with cataracts. 

Results: After one year the Red reflex screening attended 29 children, 17 males and 

12 females, mean age and pattern deviation (PD) of 10.09 ± 20.35 months (7 days - 98 

months old). 16 patients were referred with altered red reflex, with a mean age and 

pattern deviation of 13.17 ± 24.14 months (7 days - 98 months old). The alteration was 

confirmed in all of these cases. 13 children had cataract. In 13 children with doubtful 

exam, with a mean age and PD of 6.29 ± 14.46 months (7 days - 54 months old), the 

alteration was not confirmed in any of these patients. The incidence of negative red 

reflex found among newborns was 9.2/10,000 and the incidence cataracts in this 

same group was 7.9/10,000. 

Conclusion: We described the implantation of the red reflex exam in the Botucatu area, 

and the creation of a reference Center for eye examination of children with changes in 

the red reflex, and the creation of a reference Center for treatment of childhood cataract 

and difficulties. 

Keywords: Cataract/diagnosis; Cataract/congenital; Ophthalmoscopes; Reflex, pupillary; 

Child 

INTRODUÇÃO 

Algumas das importantes afecções oculares que ocorrem no re - 

cém-nascido e na criança como a catarata, o retinoblastoma e outras 

alterações da córnea ou do polo posterior, podem ser detectadas 

usando um teste prático, conhecido como exame do reflexo vermelho 

ou teste do reflexo de Bruckner. O exame consiste na visualização 

da pupila da criança, usando oftalmoscópio direto, colocado há cerca 

de um braço de distância (1) . 

Para ser considerado normal, o examinador deve ver através da 

pupila dos dois olhos um reflexo vermelho e simétrico. Qualquer 

alteração no reflexo vermelho como manchas escuras, ausência ou 

assimetria de reflexo, ou presença de reflexo branco (leucocoria) são 

motivos para se suspeitar de doenças oculares, devendo a criança ser 

referida para exame especializado com um oftalmologista (1) . 

Tradicionalmente o oftalmoscópio é usado para o exame do 

reflexo vermelho. No entanto, o uso de modelos simplificados como 

Submetido para publicação: 28 de março de 2012 

Aceito para publicação: 9 de agosto 2012 

Trabalho realizado no Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e 

Pescoço - Uni versidade Estadual Paulista “Júlio de Mesquita Filho” - Faculdade de Medicina de 

Botucatu, Botucatu (SP), Brasil. 

1 

Médico, Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Fa - 

culdade de Medicina de Botucatu, Botucatu (SP), Brasil. 

2 

Acadêmico de Medicina, Faculdade de Medicina de Botucatu, Botucatu (SP), Brasil. 

Financiamento: Fundação de Auxílio à Pesquisa do Estado de São Paulo FAPESP, Secretaria de 

Saúde do Estado de São Paulo, Ministério da Saúde, Conselho Nacional de Desenvolvimento 

Científico e Tecnológico (CNPQ) (Programa de Pesquisa para o SUS - PPSUS). 

Divulgação de potenciais conflitos de interesse: A.C.L.Rodrigues, Nenhum; R.B.Prado, Nenhum; 

L.Miguel, Nenhum. 

Endereço de correspondências: Antonio Carlos Lottelli Rodrigues. Departamento de Oftalmologia, 

Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, UNESP - Distrito de Rubião Jr - Botucatu - 

SP - 18618-970 - Brasil - E-mail: eye_acr@fmb.unesp.br 

Projeto número 2363/2007, aprovado pelo comitê de ética e pesquisa da Faculdade de Medicina 

de Botucatu. 


337

Implantação do exame do reflexo vermelho em crianças da região do Hospital das Clínicas 

da Faculdade de Medicina de Botucatu - SP - Brasil 

o “pen torch ophthalmoscope” (PTO) (Apramed Indústria e Comércio 

de Aparelhos Médicos Ltda.) podem representar uma alternativa 

barata e possibilitam o uso por profissionais de saúde não médicos 

treinados na detecção de anormalidades do reflexo vermelho (2) . 

A causa mais frequente de alteração do reflexo vermelho na in - 

fância é a catarata infantil, doença tratável que apresenta resultado 

visual favorável desde que diagnosticada e tratada precocemente (3) . 

A catarata infantil é aquela presente ao nascimento (congênita) 

ou que se desenvolve até os 12 anos de idade (4) . Sua prevalência 

é muito variável sendo de 1 a 4/10.000 nascidos em países desenvolvidos 

e 5 a 15/10.000 nascidos em países em desenvolvimento. 

A relação inversa entre prevalência e índice de desenvolvimento é 

resultado da melhor assistência pré-natal e melhor prognóstico visual 

sempre que o diagnóstico e o tratamento adequados são realizados 

precocemente. A catarata é responsável por 14% das crianças cegas 

do mundo (5) . 

No Brasil, as estatísticas são insuficientes e nos últimos anos, por 

força de leis o exame do reflexo vermelho começa a ser realizado nas 

maternidades brasileiras. A primeira lei que obriga o teste do reflexo 

vermelho na maternidade foi aprovada em 5 de setembro de 2002 no 

estado do Rio de Janeiro, desde então várias cidades e estados vêm 

criando leis municipais e estaduais obrigando a realização do exame. 

No estado de São Paulo, somente em 2007 a Lei Estadual n o 12.551 de 

5 de março, tornou obrigatório o exame nas maternidades do estado. 

Além da importância de se pesquisar o reflexo vermelho nas ma - 

ternidades, sua pesquisa é preconizada pela American Academy of 

Pe diatrics nas consultas pediátricas de rotina com um, dois, quatro, 

seis e nove meses, um, dois, três, quatro, cinco, seis, oito, 10 e 12 anos (6) . 

O Hospital de Clínicas da Faculdade de Medicina de Botucatu - 

UNESP é referência para 30 municípios (480.337 habitantes) na região 

centro-oeste do estado de São Paulo. Existiam obstáculos fundamentais 

para que o exame fosse realizado e para que o diagnóstico precoce 

trouxesse efetivamente benefício às crianças. Muitas maternidades 

não dispunham de oftalmoscópio, os profissionais envolvidos não 

haviam sido capacitados para realização técnica e interpretação do 

exame e o serviço de referência dos pacientes não estava estruturado. 

Diante do exposto, justificou-se a necessidade da criação de um 

projeto com ações que viabilizassem: a concretização do teste do 

reflexo-vermelho, a criação de um serviço de referência para exame 

oftalmológico e o tratamento da catarata infantil. O objetivo deste 

artigo é descrever: a implementação do teste do reflexo vermelho 

nas 30 cidades de inserção do Hospital das Clínicas da Faculdade de 

medicina de Botucatu, HC/FMB/UNESP (480.337 habitantes), a criação 

de um Centro para referência de crianças com reflexo vermelho 

alterado ou duvidoso, a Triagem do reflexo vermelho (TRV) e outro 

para o tratamento da catarata infantil, o Centro de tratamento da catarata 

infantil (CTCI), as dificuldades encontradas e resultados obtidos 

após um ano de funcionamento. 

agentes pertencentes aos “Programas de Saúde da Família” (PSF). 

Após a palestra realizamos treinamento prático utilizando o PTO. A 

palestra e o treinamento prático foram repetidos por mais duas vezes 

no município de Botucatu, para as cidades que não responderam à 

primeira convocação. 

Nas palestras foram entregues 109 PTO para cada uma das 17 maternidades 

e 92 unidades básicas de saúde dos municípios presentes 

(Figura 1). Estes instrumentos foram montadas ao custo de R$ 200,00, 

valor três vezes menor que o de um oftalmoscópio direto simples 

(valores de janeiro de 2008). 

Orientamos o encaminhamento dos casos detectados com re fle xo 

alterado ou duvidoso a um serviço de triagem criado para receber estas 

crianças no HC/FMB/UNESP, a TRV. Esta triagem passou a atender 

a partir de julho de 2008, em um dia fixo da semana. Desde então, 

toda criança que comparece com diagnóstico de reflexo alterado ou 

duvidoso é atendida, sem necessidade de agendamento prévio. As 

crianças atendidas no primeiro ano de funcionamento da triagem 

foram divididas por idade, sexo, motivo do encaminhamento (reflexo 

alterado ou duvidoso), se a alteração foi confirmada ou não e o 

diagnóstico. 

Foi criado um centro especializado no tratamento da catarata 

infantil o CTCI composto por ambulatório próprio e centro cirúrgico 

especializado. As crianças com catarata infantil triadas pela Triagem 

do reflexo vermelho foram avaliadas pelo CTCI e divididas em relação 

à idade, sexo, lateralidade e necessidade de tratamento clínico ou 

cirúrgico. As crianças submetidas à cirurgia foram examinadas, sob 

anestesia geral, com medida da pressão intraocular (PIO) utilizando 

tonômetro de Perkins, ceratometria média utilizando ceratômetro 

portátil (Retinomax K plus 2, Righton) e comprimento axial utilizando 

biômetro de contato (Microscan Model 100A + , Sonomed). 

RESULTADOS 

Das 30 cidades convocadas para as reuniões, uma delas, com 

1.741 habitantes (0,36% da população da região), não compareceu 

para ouvir a palestra, receber o treinamento e o PTO embora tenha 

sido reconvocada pela DRS VI por mais duas vezes. Em um ano de funcionamento 

a TRV atendeu 29 crianças, 17 do sexo masculino e 12 do 

sexo feminino, com idade média e desvio padrão (dp) de 10,09 ± 20,35 

meses (7 dias - 96 meses), destas 17 (58,6%) tinham idade igual ou 

menor que 3 meses, 16 pacientes foram encaminhados com refle xo 

vermelho alterado, com idade média e dp de 13,17 ± 24,14 meses (7 

MÉTODO 

Em parceria com o Departamento Regional de Saúde VI (DRS VI) 

do estado de São Paulo, regional em que se insere o HC/FMB/UNESP, 

divulgamos o teste do reflexo vermelho através de uma matéria 

publicada em jornal regional, duas entrevistas em rádios regionais e 

uma entrevista televisiva também regional. Foram confeccionados 

e distribuídos pela DRS VI 5.000 folhetos explicativos à população e 

aos profissionais de saúde. Esses folhetos foram distribuídos pelos 

postos de saúde das cidades. As cidades foram divididas em quatro 

grupos de acordo com a localidade, para cada grupo foi ministrada 

uma palestra abordando a importância da realização do exame e 

quais doenças poderiam ser detectadas, com uma breve explicação 

sobre cada uma delas. Foi enfatizada a importância de se realizar o 

exame não só nas maternidades, mas em toda consulta pediátrica (1) . 

Também foi orientado e estimulado a realização do exame com o 

PTO por outros profissionais de saúde não médicos, principalmente 

Figura 1. Esquema ilustrativo do funcionamento de um “pen torch ophthalmoscope” 

(PTO), à esquerda e foto do aparelho distribuído. 


Rodrigues ACL, et al. 

dias - 96 meses) e 13 com reflexo duvidoso, com idade média e dp de 

6,29 ± 14,46 meses (7 dias - 54 meses). A alteração foi confirmada nos 

16 pacientes encaminhadas com reflexo alterado e não se confirmou 

em nenhum paciente encaminhado com reflexo duvidoso. Dos 16 

pacientes com reflexo alterado uma menina de 4 meses apresentava 

leucoma corneano no olho direito, um menino de 28 meses apresentava 

descolamento de retina no olho esquerdo e outro de 96 

meses apresentava catarata traumática também no olho esquerdo, 

13 crianças (81,25%) apresentavam catarata congênita/juvenil, sendo 

destas, 6 com catarata bilateral e 7 com catarata unilateral. 

Para o cálculo da incidência considerou-se que as crianças com 

alterações detectadas nas maternidades deveriam chegar ao serviço 

pelo menos até os 3 meses de idade e que o número de nascidos 

vivos na região neste período ficou em torno de 7.600 segundo o “Datasus” 

do ministério da saúde, considerou-se também que recebemos 

sete pacientes com reflexo alterado nesta faixa etária, assim teremos 

uma incidência de exame do reflexo vermelho alterado, detectado na 

maternidade, de 9,2/10.000 nascidos vivos. Desses, 6 tinham catarata 

(7,9/10.000 nascidos vivos) sendo 4 com catarata bilateral (5,3/10.000 

nascidos vivos). 

A média e dp de idade dos pacientes com catarata congênita/ 

ju venil foi de 6,50 ± 6,97 meses (0,3 - 22,26 meses), dos pacientes 

com catarata congênita/juvenil bilateral foi de 7,74 ± 7,13 meses (1,4 

meses - 18,8 meses) e unilaterais 6,37 ± 7,57 meses (0,3 - 22,26 meses). 

A média e dp do comprimento axial dos olhos com catarata foi de 

18,97 ± 1,94 milímetros (17,20 - 23,12 mm), e a média e dp da ceratometria 

média foi de 46,93 ± 3,26 dioptrias (43,00 - 52,75 D) (Gráfico 1). 

A média e dp da PIO nestes olhos foi de 9,63 ± 1,89 milímetros de 

mercúrio (7 - 12 mmHg). 

DISCUSSÃO 

O desinteresse de algumas secretarias municipais de saúde é 

desestimulante, no entanto a maioria é bastante interessada e 

atuan te. O público que compareceu às palestras era composto em 

sua maioria por enfermeiros, auxiliares de enfermagem e agentes de 

saúde do “Pro grama de Saúde da Família” (PSF), e poucos pediatras. 

Este fato inicialmente nos frustrou, no entanto, percebemos que o 

esclarecimento das pessoas envolvidas, mesmo que não médicas, 

geram cobranças, fazendo com que médicos busquem informações 

sobre o assunto. 

Grande parte das crianças encaminhadas (41,37%), tanto como 

suspeitas como com reflexo alterado não eram recém-nascidos que 

tiveram exame alterado ou duvidoso realizado na maternidade. 

Estes encaminhamentos provavelmente decorreram da ação de 

profissionais não médicos e não de pediatras nos atendimentos 

Gráfico 1. Gráfico de dispersão dos valores de comprimento axial e ceratometria 

média de olhos com catarata infantil em relação à idade e linha de tendência em 

es cala logarítmica. 

am bulatoriais, pois a frequência destes profissionais nas palestras foi 

pequena e sabemos das dificuldades em mudar hábitos de profissionais 

médicos, principalmente acrescentando “trabalho extra” e não 

obrigatório, aos atendimentos ambulatoriais do serviço público. Em 

relação ao encaminhamento de recém-nascidos, acreditamos que 

tenha sido sim pela ação dos pediatras nas maternidades, obrigados 

a realizar o exame por força da lei n o 12.551 do Estado de São Paulo. 

O grande número de pacientes encaminhados com reflexo duvidoso 

provavelmente se deveu a dúvidas e dificuldades encontradas 

por profissionais iniciantes na prática do exame. Estas dúvidas e dificuldades 

são ainda maiores em crianças recém-nascidas o que pode 

ser uma das justificativas para que a média de idade das crianças 

encaminhadas com reflexo duvidoso fosse menor que as encaminhadas 

com reflexo alterado. Outro fator que pode ter influenciado neste 

dado é a obrigatoriedade da realização do exame na maternidade. 

Isto é apenas uma tendência já que não encontramos diferença 

es tatística entre os dois grupos (p=0,181; teste de Mann-Whitney). 

Infelizmente em nosso estudo não pesquisamos em detalhes a 

origem dos exames que geraram os encaminhamentos, nem quantos 

foram feitos por profissionais médicos ou não médicos. 

Não encontramos dados na literatura quanto à incidência de reflexo 

vermelho alterado em recém-nascidos, na verdade eles se confundem 

com dados de incidência de catarata devido a sua grande 

frequência. Em relação à incidência de catarata, no que consideramos 

como recém-nascido, foi quase duas vezes maior (7,9/10.000 nascidos 

vivos) do que esperávamos para uma região considerada de - 

senvol vida e bem assistida em relação à saúde, comparada a média 

brasileira e ficando dentro da faixa de países em desenvolvimento (5) . 

Te mos que considerar ainda que provavelmente nem todas as crian ças 

nascidas foram examinadas e que crianças detectadas com reflexo 

alterado podem não ter chegado serviço. Não criamos mecanismos 

de controle para garantir isto, no entanto estes dados podem servir 

de parâmetro para estudos futuros, pois a literatura, principalmente 

brasileira é muito pobre em relação a eles. Estas incidências, que consideramos 

alta, por outro lado mostra indiretamente o cumprimento 

de nossos objetivos de viabilizar o teste do reflexo vermelho na região 

e centralizar o encaminhamento destas crianças. 

A catarata foi a principal causa de alteração do reflexo vermelho, 

corroborando com a literatura (7) . O gráfico da distribuição dos valores 

de comprimento axial e média ceratométrica destes pacientes em 

relação à idade, possuem linha de tendência logarítmico como era de 

se esperar (7-8) . 

No Brasil o uso do oftalmoscópio é competência médica. No entanto, 

o exame do reflexo vermelho é um exame tecnicamente fácil 

e que pode ser realizado por paramédicos treinados, como acontece 

em outros países (2) . Profissionais não médicos treinados utilizando o 

PTO podem auxiliar no diagnóstico de alterações no reflexo vermelho 

que se manifestem após o nascimento. Os agentes de saúde dos 

PSFs também poderiam exercer um importante papel neste sentido. 

Além disso os PTO distribuídos não são oftalmoscópios, portanto não 

existe nenhuma restrição legal ao seu uso. 

A Organização Mundial de Saúde (OMS) propõe o “Vision 2020 - 

The Right to Sight”, uma iniciativa global para eliminação da cegueira 

prevenível até o ano de 2020 (9) . A criação de uma lei federal que 

torna obrigatório o exame do reflexo vermelho nas maternidades 

brasileiras contribuiria para prevenção da cegueira infantil em nosso 

país. Precisamos sim concentrar esforços neste sentido, no entanto 

não podemos nos esquecer que as doenças que levam a alterações 

do reflexo vermelho podem estar presentes ao nascimento ou se 

manifestar posteriormente (10) . Devemos criar nos pediatras o hábito 

de examinar os olhos e realizar o exame do reflexo vermelho em toda 

consulta de rotina (6) , assim como examina o ouvido e a garganta. 

Isso não é ensinado em nossas escolas médicas. O exame do reflexo 

vermelho na maternidade é necessário, mas não suficiente. 

A TRV continua recebendo crianças com reflexo vermelho alterado 

e duvidoso, assim como o CTCI a tratar a catarata infantil, estes 


339

Implantação do exame do reflexo vermelho em crianças da região do Hospital das Clínicas 

da Faculdade de Medicina de Botucatu - SP - Brasil 

serviços estão se fortalecendo, aumentaram sua área de abrangência 

para toda DRS IV e já começam a receber crianças das DRSs vizinhas. A 

criação e fortalecimento desses centros são de extrema importância 

para organização do serviço público de saúde, servindo de base para 

a criação de redes de encaminhamento. 

CONCLUSÃO 

Descrevemos o processo para implementação do projeto que viabilizou 

a realização do teste do reflexo vermelho na região de Botucatu. 

A sua implementação permitiu a triagem de cerca de 7.600 crianças 

tendo sido recebidas 29 para avaliação em Centro de referência 

sendo 16 crianças portadoras de doenças oculares e destas, 13 por - 

tadoras de catarata congênita/juvenil. 

O estudo também mostra que o “Pen torch ophthalmoscope” (PTO) 

pode ser uma ferramenta importante na disseminação do exame do 

reflexo vermelho e combate da cegueira na infância. 

REFERÊNCIAS 

1. Red reflex examination in infants. Section on Ophthalmology. American Academy of 

Pediatrics. Pediatrics. 2002;109(5):980-1. 

2. Pon JA, Bevin TH, Herbison P, Taylor BJ, Sanderson G. A novel instrument for assessing 

the retinal red reflex for non-ophthalmic health professionals. Clin Exp Optom. 2005; 

88(3):160-4. 

3. Meier P, Sterker I, Tegetmeyer H. [Leucocoria in childhood]. Klin Monbl Augenheilkd. 

2006;223(6):521-7. German. 

4. Robinson GC, Jan JE, Kinnis C. Congenital ocular blindness in children, 1945 to 1984. 

Am J Dis Child. 1987;141(12):1321-4. 

5. Foster A, Gilbert C. Cataract in children. Acta Paediatr. 2003;92(12):1376-8. Comment 

on: Acta Paediatr. 2003;92(12):1468-73. 

6. Recommendations for preventive pediatric health care. Committee on Practice and 

Ambulatory Medicine. Pediatrics. 1995;96(2 Pt 1):373-4 

7. Trivedi RH, Wilson ME. Biometry data from caucasian and african-american cataractous 

pediatric eyes. Invest Ophthalmol Vis Sci. 2007;48(10):4671-8. 

8. Trivedi RH, Wilson ME. Keratometry in pediatric eyes with cataract. Arch Ophthalmol. 

2008;126(1):38-42. 

9. VISION 2020: the right to sight. Global initiative for the elimination of avoidable 

blindness [Internet]. Geneva: World Health Organization; revised February 2000. 

Fact Sheet 213. [cited 2011 Jan 24]. Available from: https://apps.who.int/inf-fs/en/ 

fact213.html 

10. Committee on Practice and Ambulatory Medicine and Section on Ophthalmology; 

American Association of Certified Orthoptists; American Association for Pediatric 

Ophthalmology and Strabismus; American Academy of Ophthalmology. Eye examination 

in infants, children, and young adults by pediatricians. Pediatrics. 2003; 

111(4 Pt 1): 902-7. 

XI Congresso Sul-Brasileiro de Oftalmologia 

XVII Simpósio de Atualização em Oftalmologia 

22 e 23 de março de 2013 

Majestic Palace Hotel 

Florianópolis (SC) 


Site: www.oftalmosul.com.br/2013 




Prevalência e causas de cegueira em uma população urbana do Paraguai 

Fernando Yaacov-Peña 1 , David Jure 1 , José Ocampos 1 , Margarita Samudio 2 , João Marcello Furtado 3 , Marissa Carter 4 , Van Charles Lansingh 5 

ABSTRACT 

Purpose: To determine the prevalence and causes of blindness in Piribebuy, Paraguay. 

Methods: A population based study was conducted from September to November 

2007 in Piribebuy, Paraguay. Based on the city map, seven clusters were randomly 

selected, containing 22 to 36 squares (423 to 578 houses) each, where all subjects 

≥ 40 years old who agreed to participate were included in the study. Presenting 

vision acuity (VA) was obtained for each eye, with ‘E’ Snellen charts 6 meters far from 

the patient with appropriate light. Eyes with VA ≤20/60 were also tested with the 

pinhole. Objective and subjective refraction was performed, followed by examination 

of anterior segment under the slit-lamp, Goldmann applanation tonometry, 

and pupil dilatation with 0.5% tropicamide plus 0.5% phenylephrine, followed by 

evaluation of the posterior pole. Best corrected visual acuity was used to classify the 

patients as follows: blindness was defined as visual acuity of the better eye


The aim of the present study is to determine the prevalence and 

causes of blindness and low vision in Piribebuy, Paraguay, and compare 

the findings with available data in the literature. 

Methods 

The Piribebuy Eye Study is a population-based study performed 

in Piribebuy, Paraguay, from September to November 2007, to determine 

the prevalence and causes of blindness in the area. Piribebuy 

is a small town located 72 km east from Asunción. Data from the 

last national census described a total of 22,807 inhabitants, 2,626 of 

them being 40 years old or above. Demographic and socioeconomic 

characteristics from Piribebuy are representative from the entire Cordillera 

Department. Also, the distribution of the age groups is similar 

to the rest of the country (7,8) . 

To calculate the sample size, based on a previous publication (6) 

we estimated a prevalence of blindness ranging from 2 to 3.2% in 

individuals aged 40 or older, which results in a sample of 436 subjects 

(95% CI) through the use of the Epi Info 2000 software. 

Based on the Piribebuy city map, seven clusters were randomly 

selected, containing 22 to 36 squares (423 to 578 houses) each 

(Table 1). 

All individuals aged 40+ years old living in these squares were 

notified prior to eye exam. The aim of the study and the examination 

procedure were explained to the subjects, and those who gave verbal 

consent were examined. 

Eye examination was performed by three third-year residents 

in ophthalmology from Fundación Visión, under the supervision of 

an experienced ophthalmologist. In a local ophthalmological clinic, 

presented vision acuity (VA) was obtained for each eye, with ‘E’ 

Snellen charts 6 meters far from the patient with appropriate light. 

Objective and subjective refraction was performed and also best 

corrected visual acuity (BCVA) was obtained, followed by examination 

of anterior segment under the slit-lamp, Goldmann applanation 

tonometry, pupil dilatation with 0.5% tropicamide plus 0.5% phenylephrine 

and evaluation of the posterior pole with a 90D lens and 

with indirect ophthalmoscope and 20D lens. Patients who could not 

attend the ophthalmological appointment were submitted to visual 

acuity (VA) measurement, refraction, eye examination with a portable 

slit-lamp and indirect ophthalmoscope with a 20D lens in their 

houses. Best corrected VA was used to classify the patients as follows: 

blindness was defined as VA of the better eye

Yaacov-Peña F, et al. 

recorded if they contributed equally to visual loss, and this likely 

biased the findings toward cataract. Patients having dense cataracts 

could also have some pathology in the posterior pole such as glaucoma 

or diabetic retinopathy that could not be assessed. Also, a 

healthier lifestyle (e.g.: eating habits) could also contribute for these 

findings. 

The ProyectoVer, performed with Hispanics living in Arizona, USA, 

also found cataract was the main cause of visual impairment (best 

corrected vision in the better eye worse than 20/40), (12) but the lead 

cause of blindness (best corrected vision in the better eye ≤20/200) 

was glaucoma, while in the present study no blind subjects due to 

this disease were found. 

Surveys using the rapid assessment of avoidable blindness (RAAB) 

or the rapid assessment of cataract surgical services (RACSS) methodology 

examines subjects ≥50 years old, (10,13) while the Los Angeles 

Latino Eye Study (LALES) (14) and the Proyecto Ver (12) examined individuals 

aged 40 or above. In the present study, only one subject (0.7%) 

aged


An outbreak of forty five cases of Pseudomonas aeruginosa acute endophthalmitis 

after phacoemulsification 

Surto de quarenta e cinco casos de endoftalmite aguda por Pseudomonas aeruginosa após facoemulsificação 

Ricardo Luz Leitão Guerra 1 , Bruno de Paula Freitas 2 , Cintia Maria Felix Medrado Parcero 2 , Otacílio de Oliveira Maia Júnior 1 , Roberto Lorens Marback 3 

ABSTRACT 

Purpose: To describe an outbreak of Pseudomonas aeruginosa endophthalmitis 

post cataract surgery. Clinical findings, treatment and outcome are discussed. 

Methods: Clinical charts review of forty-five patients treated for endophthalmi tis 

in a two-day period. The patients underwent primary vitrectomy, anterior chamber 

irrigation and intravitreous antibiotic injection. Cultures from vitreous and anterior 

chamber samples were performed in all patients. 

Results: Forty-five patients (twenty-three men and twenty-two women) were identified. 

The average age was 71.2 years (range, 56-83 years). The right eye (62%) was 

affected more often than the left eye (38%). The median interval between surgery 

and endophthalmitis onset was 5.5 days (range, 5-6 days). The visual acuity at the 

diagnosis was better than 20/40 in one patient (2%), from 20/40 to 20/200 in one 

patient (2%), from 20/400 to counting fingers in two patients (4%), hand movements 

in eleven patients (24%), and light perception in thirty patients (68%). Pseudomonas 

aeruginosa was the isolated agent in twenty-six vitreous samples and in three 

anterior chamber samples. Overall, one patient (2%) achieved a final visual acuity 

better than 20/40; eight patients (18%) achieved a final visual acuity from 20/40 to 

20/200; six patients (13%) achieved a final visual acuity from 20/400 to counting 

fingers; eleven patients (25%) achieved a final acuity of hand movements; thirteen 

patients (29%) achieved a final acuity of light perception and six (13%) patients 

had no light perception at the last examination. None of these eyes underwent 

evisceration or enucleation in a three-month follow-up period. 

Conclusion: Even with all the safety that cataract surgery has achieved, today, 

en dophthalmitis remains a risk and a fearful complication of this procedure. In the 

present study, it was impossible to identify the source of the outbreak. 

Keywords: Phacoemulsification/adverse effects; Endophthalmitis/etiology; Pseu - 

domonas aeruginosa; Vitrectomy; Pseudomonas, infections; Equipment conta - 

mination 

RESUMO 

Objetivo: Descrever surto de endoftalmite por Pseudomonas aeruginosa após fa - 

cectomia. Os achados clínicos, o tratamento e o resultado são discutidos. 

Métodos: Revisão dos prontuários de quarenta e cinco pacientes tratados para endoftalmite 

em um período de dois dias. Todos os pacientes foram tratados por vitrectomia 

primária, irrigação da câmara anterior e injeção vítrea de antibióticos. Culturas do 

vítreo e de amostras de câmara anterior foram realizadas em todos os pacientes. 

Resultados: Quarenta e cinco pacientes (23 homens e 22 mulheres) foram identificados. 

A idade média foi 71,2 anos (variação, 56-83 anos). O olho direito (62%) foi mais 

afetado do que o esquerdo (38%). O intervalo médio entre a cirurgia e a apresentação 

da endoftalmite foi de 5,5 dias (intervalo de 5-6 dias). A acuidade visual no momento 

do diagnóstico foi melhor que 20/40 em um paciente (2%), de 20/40 a 20/200 em um 

paciente (2%), de 20/400 para contar dedos em dois pacientes (4%), movimento de mão 

em onze pacientes (24%), percepção de luz em trinta pacientes (68%). Pseudomonas 

aeruginosa foi o agente isolado em 26 amostras de vítreo e em três amostras da câmara 

anterior. No geral, um paciente (2%) obteve acuidade visual final melhor que 20/40, 

oito pacientes (18%) obtiveram acuidade visual final de 20/40 a 20/200, seis pacientes 

(13%) obtiveram acuidade visual final de 20/400 para contar os dedos; onze pacientes 

(25%) obtiveram acuidade visual final de movimento de mão; treze pacientes (29%) 

obtiveram acuidade visual final de percepção de luz e seis (13%) pacientes não havia 

percepção luminosa no último exame. Nenhum olho foi submetido à evisceração ou 

enucleação em três meses de acompanhamento. 

Conclusão: Mesmo com toda a segurança da cirurgia de catarata nos dias atuais, 

endoftalmite permanece um risco e uma complicação temível deste procedimento. 

No presente estudo não foi possível identificar a fonte do surto. 

Descritores: Facoemulsificação/efeitos adversos; Endoftalmite/etiologia; Pseudomonas 

aeruginosa; Vitrectomia; Infecções por pseudomonas; Contaminação de 

equipamentos 

INTRODUCTION 

Acute endophthalmitis is the most serious complication of cataract 

surgery and intraocular lens implantation, with an incidence 

of 0.07% to 0.12% (1) . Endophthalmitis occurring within 1 to 14 days 

postoperatively is classified as acute. The most common cultured 

or ganism is Staphylococcus epidermidis, accounting for 60% to 80% 

of cases (1) . Gram-negative bacteria are responsible for 6% to 29% 

of cases, however, the rapid progression of infection and their 

virulence often result in a poor visual outcome despite prompt 

treatment (2-4) . 

The most common ocular infection caused by Pseudomonas aeruginosa 

is contact lens-related keratitis, but it may also cause endophthalmitis 

(5) . Outbreaks of postoperative P. aeruginosa endophthalmitis 

have been described in the literature (6-14) . The association with 

intrinsic contamination of ophthalmic solutions and contaminated 

instruments or equipment has been reported (6-13) . 

The purpose of this study is describing an outbreak of Pseudomonas 

aeruginosa endophthalmitis after cataract surgery, which occurred 

at one ophthalmological center of Eunapólis city, Bahia, Brazil. 

Clinical findings, treatment and outcome are discussed. 


Accepted for publication: July 30, 2012 

Study carried out at Retina and Vitreous Service, Hospital São Rafael - Fundação Monte Tabor - Salvador 

(BA) - Brazil. 

1 

Physician, Department of Ophthalmology, Hospital São Rafael, Fundação Monte Tabor, Salvador 

(BA), Brazil. 

2 

Physician. 

3 

Professor, Department of Ophthalmology, Hospital São Rafael, Fundação Monte Tabor, Salvador 

(BA), Brazil. 


Disclosure of potential conflicts of interest: R.L.L.Guerra, None; B.P.Freitas, None; C.M.F.M.Parcero, 

None; O.O.Maia Jr, None; R.L.Marback, None. 

Correspondence address: Otacilio O. Maia Jr. Retina and Vitreous Service, Department of Ophthalmology. 

Hospital São Rafael - Fundação Monte Tabor. Av. São Rafael, 2142 - Salvador - BA - 

41253-190 – Brazil - E-mail: omaiausp@uol.com.br 


Guerra RLL, et al. 

METHODS 

A retrospective study based on medical records analysis of for tyfive 

patients with diagnosis of acute endophthalmitis after cataract 

surgery performed in two consecutive days at one ophthalmological 

center of Eunapólis city, Bahia, Brazil, and treated at São Rafael Hos - 

pital in a two consecutive day period. All patients underwent pha - 

coemulsification and foldable single piece intraocular lens implantation 

in the capsular bag. Exclusion criteria were incomplete data or 

less than a ninety day follow-up period. No patient was excluded from 

the study. The cases occurred in September, 2009. 

The study protocol was approved by the Institutional Ethics Review 

Board of the São Rafael Hospital- Fundação Monte Tabor (CAAE 

- 00901112.5.0000.0048), and conducted by the Retina and Vitreous 

Service of the same institution. 

Three vitreoretinal specialists submitted all the patients to oph - 

thalmologic examination. The same specialists collected the data. 

Data reviewed included demographic information, affected eye, 

pertinent systemic medical problems, interval between surgery and 

onset, signs and symptoms, treatment performed and outcome of 

visual acuity and eye preservation. The ophthalmologic examination 

at the ninetieth day after treatment was considered as the last 

ophthalmological examination. 

All patients were treated for endophthalmitis on the day of presentation. 

Anterior chamber irrigation, administration of intravitreous 

antibiotics (vancomycin and ceftazidime) and primary vitrectomy 

we re performed in all the patients. Secondary vitrectomy (reoperation) 

was performed in the cases with poor response to the treatment. 

Perioperative images of different patients are shown in figure 1. 

A 

C 

E 

Figure 1. Perioperative images of different patients. A) Appearance 

before the surgery. B) Mechanical removal of membrane from the anterior 

chamber. C) Mechanical removal of membrane from the posterior 

chamber. D) Removal of opacities from the anterior vitreous and posterior 

capsule. E) Vitrectomy in a mild case. F) Vitrectomy in a severe case. 

B 

D 

F 

Vitreous and anterior-chamber fluid aspirates were collected in 

the operating room using a sterile syringe prior to vitrectomy and 

intravitreal antibiotic injection and were sent immediately to the 

mi crobiology laboratory (at the same hospital) for analysis. A micro - 

biologist inoculated the samples on blood agar, chocolate agar, Mac - 

conkey agar and Sabouraud agar. 

Following the protocol of the hospital, susceptibility to amikacin, 

ampicillin, ampicillin sulbactam, aztreonam, cephalothin, cefepime, 

ce fotaxime, cefoxitin, ceftazidime, gentamicin, imipenem, meropenem, 

piperacillin-tazobactam and trimethoprim-sulfa were tested. 

RESULTS 

Forty-five patients (twenty-three men and twenty-two women) 

presenting acute P. aeruginosa endophthalmitis post phacoemulsification 

were identified. The average age was 71.2 years (range, 56-83 

years). The right eye (62%) was more often affected than the left 

eye (38%). Associated systemic medical findings included arterial 

hy pertension (53%) and type 2 diabetes mellitus (11%). The median 

interval between surgery and endophthalmitis onset was 5.5 days 

(range, 5-6 days). 

Visual acuity at diagnosis was better then 20/40 in one patient 

(2%), from 20/40 to 20/200 in one patient (2%), from 20/400 to 

coun ting fingers in two patients (4%), hand movements in eleven 

patients (24%) and light perception in thirty patients (68%). The most 

significant findings at the diagnosis were decreased visual acuity 

(96%), pain (84%), hyperemia (73%), eyelid edema (42%), headache 

(4%), foreign body sensation (4%) and fever (2%). Additional clinical 

findings at the diagnosis were conjunctival hyperemia (100%), anterior 

chamber inflammatory reaction (91%), hypopyon (82%), corneal 

edema (76%), pupillary membrane (64%), chemosis (56%), vitreous in 

anterior chamber (4%), conjunctival purulent secretion (4%), hyphema 

(2%) and shallow anterior chamber (2%) - table 1. 

Cultures were positive for Pseudomonas in twenty-six patients 

(57.8%), three (6.6%) anterior chamber samples and twenty-six 

(57.8%) vitreous samples. Nineteen patients (42.2%) had negative 

cul tures. Antibiotic resistance test were similar in all cases, sensitive 

to amikacin, aztreonam, cefepime, cefotaxime, ceftazidime, gentami - 

cin, imipenem, meropenem, piperacillin-tazobactam and trimetho - 

Table 1. The most significant findings at the diagnosis 

Ocular finding Incidence (%) 

Hyperemia 100 

Decreased visual acuity 096 

Anterior chamber reaction 091 

Pain 084 

Hypopyon 082 

Corneal edema 076 

Pupillary membrane 064 

Chemosis 056 

Eyelid edema 042 

Vitreous in anterior chambre 004 

Purulent secretion 004 

Headache 004 

Foreing body sensation 004 

Fever 002 

Hyphema 002 

Shallow anterior chamber 002 


345

An outbreak of forty five cases of Pseudomonas aeruginosa acute endophthalmitis after phacoemulsification 

prim-sulfa, and resistant to ampicillin, ampicillin sulbactam, cefoxitin 

and cephalothin. 

One patient (2%) achieved a final visual acuity better than 20/40; 

eight patients (18%) achieved a final visual acuity from 20/40 to 

20/200; six patients (13%) achieved a final visual acuity from 20/400 

to counting fingers; eleven patients (25%) achieved a final acuity of 

hand movements; thirteen patients (29%) achieved a final acuity 

of light perception and six patients (13%) were no light perception 

at the last follow-up. Five patients were submitted to a secondary 

vitrectomy. None of the studied eyes underwent evisceration or 

enu cleation in a three-month follow-up period. Best corrected visual 

acuity before and after treatment is shown in figure 2. 

Discussion 

The largest Pseudomonas endophthalmitis outbreak post ca - 

taract surgery that we were able to find in the literature involved 

twenty eyes of twenty patients in a six-week period (14) . In the current 

study we had forty-five eyes of forty-five patients (twenty-six culture 

positive for Pseudomonas) in a two consecutive day period. Endophthalmitis 

suspect cases cultures turn out to be positive in a range 

of 24% to 85% according to different studies (15) . 

Pseudomonas aeruginosa is one of the most common Gramne 

gative pathogens associated with nosocomial infections (14) . The 

epidemics seem to be related to contaminated intraocular irrigating 

solutions (6,7,9,12,14) . Pseudomonas was also identified in povidone-io - 

dine solution (14) , at the fluid pathways of a phacoemulsifier (9) , water 

of autoclave (12) and air-conditioning system (14) . Technics as high-re - 

solution fluorescent amplified fragment length polymorphism 

ana lysis can identify the source of the outbreak to help preventing 

new ones (16) . It was impossible to identify the source of the outbreak 

because all the patients were referred from another hospital (500 

miles away) and no cultures of the phacoemulsification fluids and 

oph thalmic solutions were performed. 

According to the Endophthalmitis Vitrectomy Study (EVS), the re - 

commended treatment for endophthalmitis is primary vitrectomy 

only for cases with light perception, any acuity better than this should 

be submitted to intravitreous antibiotic injection after intraocular 

fluid aspiration for culture (2) . Chen et al., suggests that vitrectomy 

(pri mary or secondary) reduces the likelihood of evisceration (17) . In 

the current study all the patients underwent primary vitrectomy, five 

of them needed a secondary vitrectomy and no patient underwent 

evisceration or enucleation in a three-month follow-up. The EVS protocol 

was not followed in this outbreak. The aggressive clinical as pect 

at the diagnosis of endophthalmitis was crucial for the choice of the 

treatment performed. 

Generally the visual prognosis is poor despite of the treatment 

with intravitreal antibiotics even in cases in which the isolates 

Figure 2. Best corrected visual acuity before and after treatment. 

were sensitive (14) . In a nine patient reported outcome, five of them 

reached final acuity of no light perception and no patient reached 

acuity better then 20/400 (4) . In the EVS, four of the four hundred and 

twenty patients had confirmed Pseudomonas endophthalmitis and, 

three of these, had final acuity worse then 20/400 (2) . In the current 

study, nine patients had final acuity 20/200 or better, six patients 

between 20/400 and counting fingers, eleven had hand movements, 

thirteen had light perception and six no light perception. None of 

these eyes underwent primary or secondary evisceration. Maybe the 

better visual outcome in some of these cases could be attributed 

to the treatment performed (primary vitrectomy, anterior chamber 

irrigation and intravitreal antibiotics) in all patients at the diagnosis 

despite the visual acuity. 

The choice of antibiotics for injection at the first moment, prior 

to culture results, aims to cover gram positive and gram negative 

bacteria. The safety and effectiveness of vancomycin and ceftazidime 

combined has been reported in experimental studies using mice and 

confirmed in humans case series (4,18) . To treat ocular Pseudomonas infection 

we must take into consideration the increasing prevalence of 

antibiotic-resistant isolates. Reviewing the literature we have found 

reports of resistance to various antibiotics as cefazolin, ampicillin, 

cephalothin, neomycin, chloramphenicol, tetracycline, aminoglycosides, 

and fluoroquinolones (14) . In the current study, resistance 

to am picillin, ampicillin-sulbactam, cephalothin and cefoxitin was 

ob served. The other antibiotics tested (amikacin, aztreonam, cefepime, 

cefotaxime, ceftazidime, gentamicin, imipenem, meropenem, 

piperacillin-tazobactam and trimethoprim-sulfa) were effective on 

the isolated strain of Pseudomonas. 

CONCLUSION 

Even with all the safety cataract surgery has achieved, today, 

en dophthalmitis remains a risk and a fearful complication of the 

procedure. The proper cleaning and sterilization of surgical instruments, 

surgical quality inputs, and correct prophylaxis are crucial to 

prevention. In the present study, it was impossible to identify the 

source of the outbreak. 

Another fact that caught the attention of the authors was the 

high level of preservation of the eyeball and some useful vision as 

compared to the results of other case series found in literature. It 

might have been due to the early treatment with primary vitrectomy 

and subsequent intravitreal antibiotic injection at the time of 

endophthalmitis diagnosis. Further study is needed to sustain this 

hypothesis. 

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17. Chen KJ, Sun MH, Lai CC, Wu WC, Chen TL, Kuo YH, et al. Endophthalmitis caused by 

Pseudomonas aeruginosa in Taiwan. Retina. 2011;31(6):1193-8. 

18. Yoshizumi MO, Bhavsar AR, Dessouki A, Kashani A. Safety of repeated intravitreous 

injections of antibiotics and dexamethasone. Retina. 1999;19(5):437-41. 

4 a Jornada Paulista de Oftalmologia 


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347


Phacoemulsification and foldable acrylic IOL implantation in children with 

treated retinoblastoma 

Facoemulsificação e implante de lente intraocular acrílica dobrável em crianças com retinoblastoma 

Marcia Beatriz Tartarella 1 , Gloria Fátima Britez-Colombi 1 , Marcia Motono 2 , Martha Motono Chojniak 2 , Joao Borges Fortes Filho 3 , Rubens Belfort Jr. 1 

ABSTRACT 

Purpose: To study the results of cataract surgery in children with radiation-induced 

cataract after treatment for retinoblastoma. 

Methods: Retrospective interventional case series. Six consecutive patients diagnosed 

with secondary cataracts due to radiation therapy for retinoblastoma. Intervention: Pha - 

coemulsification and foldable acrylic intraocular lens implantation. Outcomes mea sured: 

Visual acuity, binocular indirect ophthalmoscopy and slit-lamp biomicroscopy. 

Aspirated lens material and aqueous humor samples were collected during surgery. 

Results: Six uniocular children between 3 to 5 years of age at time of surgery were 

studied. The mean time interval between radiotherapy and cataract diagnosis was 

22.3 months. The mean follow-up after surgery was 17.2 months (range: 12 to 23 

months). All eyes achieved a clear visual axis after surgery allowing monitoring of 

the tumor status. None developed recurrence or retinoblastoma dissemination. 

His topathological analysis of the aspired material showed no tumoral cells in all 

sam ples. All patients improved vision after cataract surgery. 

Conclusions: Phacoemulsification with acrylic intraocular lens implantation seems to 

be a safe, feasible, and effective method for the removal of radiation-induced cataracts 

in patients with treated retinoblastoma. 

Keywords: Retinoblastoma/cirurgia; Retinoblastoma/radiotherapy; Retinal neoplasms/radiotherapy; 

Cataract/etiology; Eye enucleation; Radiation injuries; Radiotherapy/adverse; 

Lens implantation, intraocular; Humans; Child 

RESUMO 

Objetivos: Estudar os resultados da cirurgia da catarata induzida pela radioterapia para 

o tratamento do retinoblastoma em crianças. 

Métodos: Estudo retrospectivo intervencional em série de casos onde seis pacientes consecutivos 

apresentaram catarata secundária à terapia por radiação para o retinoblastoma. 

Intervenção: Facoemulsificação e implante de lente intraocular acrílica dobrável. Foram 

avaliadas: acuidade visual, oftalmoscopia binocular indireta e biomicroscopia. Material 

para análise histológica do cristalino e do humor aquoso foi coletado durante as cirurgias. 

Resultados: Seis crianças, entre 3 e 5 anos de idade, com catarata secundária à radiação 

para tratamento de retinoblastoma foram submetidas à cirurgia de facoemulsificação 

com implante de lente intraocular. A média do intervalo de tempo decorrido entre a 

radioterapia e o diagnóstico da catarata foi 22,3 meses. O período médio de seguimento 

após a cirurgia foi de 17,2 meses (intervalo: 12 a 23 meses). Todos os olhos melhoraram a 

visão e mantiveram eixo visual livre permitindo a fundoscopia para monitorar o tumor. 

Nenhum paciente evoluiu com recorrência ou disseminação do retinoblastoma. A análise 

histopatológica do material colhido resultou em ausência de células tumorais nas amostras. 

Conclusões: A cirurgia de facoemulsificação com implante de lente intraocular acrílica 

dobrável mostrou ser um procedimento seguro e efetivo para o tratamento da catarata 

induzida pela radioterapia em pacientes portadores de retinoblastoma. 

Descritores: Retinoblastoma/cirurgia; Retinoblastoma/radioterapia; Neoplasisas da 

retina/radioterapia; Catarata/etiologia; Enucleação ocular; Lesões por radiação; Radioterapia/efeitos 

adversos; Implante de lente intraocular; Humanos; Criança 

INTRODUCTION 

Retinoblastoma (RB) is the most common intraocular malignancy 

in childhood, occurring in approximately 1 of 20,000 live births (1) . 

The goals of management of RB are, first, to preserve life and, second, 

to salvage the eye and restore vision if possible (2) . Earlier diagnosis 

coupled with new therapeutic modalities such as External Beam Radiotherapy 

(EBRT), radioactive plaque and brachytherapy have allowed 

successful treatment avoiding enucleation in many cases (1-5) . 

About 20% to 87% of the patients treated with radiotherapy can 

develop a radiation-induced secondary cataract blocking the visual 

axis and therefore causing severe reduction of visual acuity (VA) (6-8) . 

Maintenance of a clear visual axis is important in order to allow 

the examination of the eye fundus and to observe the regressed re - 

tinoblastoma lesions (9) . 

The purpose of this study was to evaluate the visual outcome and 

ocular complications of the cataract surgery by phacoemulsification 

and foldable acrylic intraocular lens implantation (IOL) in children 

with radiation-induced cataract after treatment for RB. 

METHODS 

Six uniocular patients with secondary cataract due to radiation 

therapy for RB treatment were submitted to phacoemulsification 

and IOL implantation at the Congenital Cataract Section, Department 

of Ophthalmology, Federal University of Sao Paulo SP, Brazil. During 

surgery, a sample of aqueous humor (0.2 ml) was collected from the 

anterior chamber for analysis. Aspirated lens material (0.2 ml) was also 

sent for histopathological analysis. 

Table 1 presents the age (in months) of patients at RB diagnosis, 

the different prescribed treatments, and the time interval between 

radiotherapy and the diagnosis of cataract. All patients had bilateral 

RB, and all of them had one eye previously enucleated. All eyes had 

Submitted for publication: April 4, 2012 


Study carried out at Department of Ophthalmology, Universidade Federal de São Paulo - UNIFESP - São 

Paulo (SP), Brazil. 

1 

Physician, Department of Ophthalmology, Universidade Federal de São Paulo - UNIFESP - São 


2 

Physician, Ocular Oncology Department, Hospital A C Camargo, São Paulo (SP), Brazil. 

3 

Physician, Department of Ophthalmology, Universidade Federal do Rio Grande do Sul - UFRS - 

Porto Alegre (RS), Brazil. 


Disclosure of potential conflicts of interest: M.B.Tartarella, None; G.F.Britez-Colombi, None; 

M.Motono, None; M.M.Chojniak, None; J.B.Fortes Filho, None; R.Belfort Jr, None. 

Correspondence address: João Borges Fortes Filho. School of Medicine, Department of Ophthalmology. 

Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul. Rua Ramiro 

Barcelos, 2350 - Porto Alegre (RS) 90035-903 - Brazil - E-mail: jbfortes@cursohbo.com.br 


Tartarella MB, et al. 

inactive tumors when they presented for cataract surgery. Lens opa - 

cities hindered fundus examination in all patients. 

Visual acuity was measured with Snellen acuity cards, Teller Acuity 

Cards or Lea Hyvarigen Acuity Cards depending on patient collaboration. 

Final best corrected visual acuity (BCVA) was obtained at the 

last followup visit. 

Calculation of the IOL power was based on previous studies of 

axial length growth in pseudophakic eyes of children with lamellar 

cataract, as follows: children aged 3 to 4 years had a 10% reduction 

of the calculated IOL power. Children between 4 and 6 years had an 

addition of 0.75% on the preoperative axial length in order to calculate 

the final IOL diopter (10) . 

The same surgeon (MBT) operated on all cases using the same 

technique. A clear corneal tunnel incision was performed and a lateral 

paracentesis was used to allow the introduction of any additional instrument 

during phacoemulsification. Viscoelastic substance (Viscoat ® ) 

was used to fill the anterior chamber. An anterior continuous circular 

capsulorhexis followed by hydrodissection and hydrodeliniation were 

performed. Phacoemulsification or phacoaspiration of the lens was 

performed followed by a meticulous aspiration of lens material. A 

foldable acrylic IOL (AcrySof ® ) was implanted within the capsular bag. 

Next step included aspiration of the viscoelastic substance from the 

anterior chamber and injection of a miotic drug (Miostat ® ). One or two 

single sutures (mononylon 10-0) were used to achieve a safe closure of 

the corneal incision. Subconjuntival dexamethasone (0.5 mg/1 ml) and 

gentamicin (40 mg/1 ml) were injected at the end of surgery. Topical 

antibiotics and corticosteroids were applied for the first two weeks 

after surgery and tapered during 2 months of follow-up. 

Visual acuity, binocular indirect ophthalmoscopy and slit lamp 

examination were assessed on all postoperative visits. 

RESULTS 

Patients were between 3 and 5 years-old (mean 4.9 years-old) at 

the time of cataract surgery. Three eyes presented nuclear cataract 

and three eyes presented posterior sub-capsular cataract. Mean time 

between radiotherapy and cataract diagnosis was 22.3 months. All 

patients included in this study showed initial VA worse than 20/200. 

All children improved VA after surgery (Table 2). Mean postoperative 

follow-up was 17.2 months (12 to 23 months). 

A posterior paracentral capsule opacification (PCO) was observed 

during surgery in three eyes (patients #2, #4 and #5) but the capsule 

was left intact. No patient needed a Neodimium YAG laser posterior 

capsulotomy. 

Patient #4 presented an inflammatory membrane anterior to the 

IOL that disappeared within two weeks after surgery. 

One eye (patient #3) developed a paracentral mild PCO during 

the follow-up. This PCO did not affect VA or eye fundus examination 

(Figure 2). 

Five eyes received a three-piece acrylic hydrophobic foldable IOL 

(MA60AC, Alcon AcrySof ® ) and one eye received a single-piece IOL 

(SA30AL Alcon AcrySof ® ). 

Intraocular lens power ranged from +21 to +29 (mean +25.5 D). 

Refraction was obtained and glasses with protective polycarbonate 

multifocal lenses were prescribed for all patients. 

Slit lamp examination postoperatively showed severe dry eye 

with fluorescein staining in two eyes. 

All eyes achieved a clear visual axis after cataract surgery, allowing 

monitoring tumoral status (Figure 1, patient #6). None had recurrence 

or spread of the tumor during the follow-up time of this study. Histopathological 

analysis of aqueous humor and aspirated lens material 

showed no tumoral cells in the samples of all patients. 

DISCUSSION 

Retinoblastoma is the most frequent intraocular tumor in child hood (1) 

and early detection and treatment is essential. Erwenne and Franco (11) 

found that advanced age and delayed diagnosis increase the chance 

for extraocular disease that mandates significantly more aggressive 

treatment. 

Time range between the appearance of first RB signs and the 

initial treatment as well as the management of RB influence the outcomes 

(4) . 

In the past, standard treatments for RB consisted of enucleation 

and EBRT. Systemic chemotherapy was generally reserved for 

patients with invasion of the optic nerve, choroid, orbit or with metastatic 

disease (1) . Nowadays, chemoreduction has been widely used 

to avoid EBRT (1,5) . Other management options in children include ra- 

Table 2. Visual acuity before and after cataract surgery 

Patient 

Age at surgery 

(years) 

VA before 

cataract surgery 

Follow-up 

(months) 

Final 

BCVA 

1 3 20/570 23 20/400 

2 5 20/200 12 20/30 

3 4 CF 2 m 19 20/70 

4 4 CF 50 cm 13 20/200 

5 5 LP 16 20/60 

6 5 LP 20 20/40 

VA= visual acuity; Final BCVA= best corrected VA at last follow-up; CF= counting fingers 

vision; LP= light perception vision. 

Table 1. Retinoblastoma diagnosis, therapy and time interval between 

radiotherapy and cataract development 

Patient Age* TTT Cryo Photo Brachy Chemo RXT Cataract † 

1 10 + + + 0 + + 14 

2 04 0 0 + 0 0 + 40 

3 02 + + + 0 + + 25 

4 02 + + + + 0 + 14 

5 22 + 0 + 0 + + 14 

6 20 + 0 0 + 0 + 24 

*= age in months at retinoblastoma diagnosis; TTT= transpupillary thermotherapy; Cryo= 

cryotherapy; Photo= phototherapy; Brachy= brachytherapy; Chemo= chemotherapy; 

RXT= radiotherapy; += therapy yes; 0= therapy no; † = time interval between radiotherapy 

and radiation-induced cataract (in months). 

Figure 1. Patient # 6 - Eye fundus with inactive retinoblastoma: tumor status 20 months 

after cataract surgery and IOL implantation. 


349

Phacoemulsification and foldable acrylic IOL implantation in children with treated retinoblastoma 

Figure 2. Patient #3 - posterior capsule opacification. 

diation therapy, photocoagulation, cryotherapy, and chemotherapy. 

Focal treatment modalities, as radioactive plaques, have promising 

prospects (4,9) . 

Radiotherapy has been a useful modality in the treatment of RB, 

but lens irradiation may cause cataract induction, usually occurring 2 

to 12 years after treatment (12) . In our study we found a mean latency 

period of 22.3 months from radiotherapy to cataract diagnosis. 

Treatment of radiation-induced cataracts is similar to treatment 

for pediatric cataracts. The implantation of an IOL by itself may not 

increase the risk of recurrence of RB or systemic metastasis and could 

be considered for providing optimal visual rehabilitation after cataract 

surgery. All patients in this series improved VA, although other 

factors as tumor size and location, age of the patient and amblyopia 

may influence the final visual results. 

Samples of aqueous humor and aspirated lens material were 

easily obtained during cataract surgery. Hadjistilianou et al., analyzed 

aqueous humor proteins in patients with RB and reported an increase 

in protein content in eyes with RB (13) . In order to investigate malignant 

cells, the samples were collected and a histopathological analysis was 

performed. The results of our study showed the absence of malignant 

cells in the samples. 

The role of posterior capsulotomy in spreading tumor cells is yet 

unknown but Brooks et al. (3) , recommended avoiding posterior capsulotomy 

to prevent an eventual seeding of the tumor. Although posterior 

capsulorrhexis in children is advisable, we preferred to main tain 

the posterior capsule in order to respect the anatomical barrier between 

anterior and posterior eye segments. All children were older than 3 

years-age at the time of surgery and might be able to collaborate to 

perform Neodimiun- YAG laser posterior capsulotomy if necessary. 

Miller et al. (14) , described good results after pars plana lensectomy 

and IOL implantation in radiation-induced cataracts in children with RB. 

Same authors (15) reported a series of eleven eyes that underwent 

a primary IOL implantation after RB treatment. They concluded that 

IOL implantation seemed to be a safe method for aphakia correction. 

The authors advised penetrating the anterior chamber through a 

clear corneal incision to avoid direct contact with conjunctival blood 

vessels, scleral tissues, and vitreous management in order to reduce 

the risk of spreading tumoral cells (15) . 

Besides tumoral spread or recurrences, the complications expected 

in the removal of radiation-induced cataracts are similar to 

pediatric cataract surgery (3,9,16-17) . In this case series no complications 

related to the RB occurred. All eyes studied did not develop tumor 

recurrence or dissemination during the follow-up period. Attention 

to dry eye signs and symptoms is a must in those irradiated eyes. 

Artificial tear drops and ointments were prescribed to two patients 

diagnosed with dry eye. 

In three eyes a partial PCO was detected at the end of surgery, but 

posterior capsulotomy was not performed due to the risk of tumor 

dissemination. Despite the capsular opacification, indirect ophthalmoscopy 

was feasible and VA improved after surgery. Maintenance 

of a clear visual axis was obtained, allowing adequate view of the 

posterior pole in order to monitor the regressed tumoral lesions. 

Intraocular lenses choice was important, IOL material and model 

are related to biocompatibility in adults (18,19) and children (20-22) . This 

study showed good results with acrylic hydrophobic IOLs. 

Refractive results were within the expected calculated diopters. 

Future changes in refraction may occur in these growing eyes. IOL 

power calculation was based on previous data on axial lengths in 

children with cataracts (10) . There are no studies of ocular growth in 

eyes with RB and cataracts. Predictive IOL power calculation and axial 

growth in eyes with RB need further investigation. 

Hoehn et al. (23) , showed the effectiveness of cataract surgery to 

improve quality of life in affected children. The children in our study 

were all uniocular patients and achieved an improvement of vision 

that could lead to better ambulation and better integration in the 

community and school. 

CONCLUSION 

No tumor spread or recurrences were observed in this series and 

improvement of VA was obtained in all patients. We conclude that 

although the long term risk-benefit is still unknown, phacoemulsification 

and foldable acrylic IOL implantation in eyes with previously 

treated RB seems to be a feasible, safe and effective treatment for 

radiation-induced cataracts, but the number of included patients is 

too low in order to establish an outcome complication profile. 

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1. Brichard B, De Bruycker JJ, De Potter P, Neven B, Vermylen C, Cornu G. Combined chemotherapy 

and local treatment in the management of intraocular retinoblastoma. 

Med Pediatr Oncol. 2002;38(6):411-5. 

2. Honavar SG, Singh AD, Shields CL, Meadows AT, Demirce H, Cater J, et al. Postenucleation 

adjuvant therapy in high-risk retinoblastoma. Arch Ophthalmol. 2002; 

120(7):923-31. 

3. Brooks HL Jr, Meyer D, Shields JA, Balas AG, Nelson LB, Fontanesi J. Removal of 

radiation-induced cataracts in patients treated for retinoblastoma. Arch Ophthalmol. 

1990;108(12):1701-8. 

4. Balmer A, Munier F, Zografos L. Nouvelles stratégies dans le traitement du rétinoblastome. 

J Fr Ophtalmol. 2002;25:187-93. 

5. Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Singh A, et al. Chemoreduction 

plus focal therapy for retinoblastoma: factors predictive of need for treatment 

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Comment in: Am J Ophthalmol. 2002;134(4):633; author reply 633-4. 

6. Anteby I, Ramu N, Gradstein L, Miskin H, Pe’er J, Benezra D. Ocular and orbital complications 

following the treatment of retinoblastoma. Eur J Ophthalmol. 1998;8(2): 

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7. Blach LE, McCormick B, Abramson DH. External beam radiation therapy and retinoblastoma: 

long-term results in the comparison of two techniques. Int J Radiat Oncol 

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8. Fontanesi J, Pratt CB, Kun LE, Hustu HO, Coffey D, Meyer D. Treatment outcome and 

dose-response relationship in patients younger than 1 year treated for retinoblastoma 

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9. Honavar SG, Shields CL, Shields JA, Demirci H, d Naduvilath TJ. Intraocular surge ry 

after treatment of retinoblastoma. Arch Ophthalmol. 2001;119:1613-21. 

10. Tartarella MB. Estudo do comprimento axial em olhos de crianças portadoras de 

catarata lamelar bilateral [Tese]. São Paulo: Universidade Federal de São Paulo; 1998. 

11. Erwenne CM, Franco EL. Age and lateness of referral as determinants of extraocular 

retinoblastoma. Ophthalmic Pediatr Genet. 1989;10(3):179-84. 

12. Egbert PR, Donaldson SS, Moazed K, Rosenthal AR. Visual results and ocular 

complications following radiotherapy for retinoblastoma. Arch Ophthalmol. 1978; 

96(10):1826-30. 

13. Hadjistilianou T, Giglioni S, Micheli L, Vannoni D, Brogi E, Cevenini G, et al. Analysis of 

aqueous humour proteins in patients with retinoblastoma. Clin Experiment Ophthalmol. 

2012;40(1):e8-e15. 

14. Miller DM, Murray TG, Cicciarelli NL, Capo H, Markoe AM. Pars plana lensectomy and 

intraocular lens implantation in pediatric radiation-induced cataracts in retinoblastoma. 

Ophthalmology. 2005;112(9):1620-4. 


Tartarella MB, et al. 

15. Portellos M, Buckley EG. Cataract surgery and intraocular lens implantation in patients 

with retinoblastoma. Arch Ophthalmol. 1998;116(4):449-52. 

16. Sinha R, Titiyal JS, Sharma N, Vajpayee RB. Management of radiotherapy-induced 

cataracts in eyes with retinoblastoma. J Cataract Refract Surg. 2004;30(5):1145-6. 

17. Osman IM, Abouzeid H, Balmer A, Gaillard MC, Othenin-Girard P, Pica A, et al. Modern 

cataract surgery for radiation-induced cataracts in retinoblastoma. Br J Ophthalmol. 

2011;95(2):227-30. 

18. Hollick EJ, Spalton DJ, Ursell PG, Pande MV, Barman SA, Boyce JF, et al. The effect of 

polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular 

opacification 3 years after cataract surgery. Ophthalmology. 1999;106(1):49-55. 

19. Sundelin K, Friberg-Riad Ylva, Östberg A, Sjöstrand J. Posterior capsule opacification 

with AcrySof® and poly(methylmethecrylate) intraocular lenses - comparative study 

with a 3-year follow-up. J Cataract Refract Surg. 2001;27(10):1586-90. 

20. Verçosa IMC, Tartarella MB. Catarata na criança. Fortaleza, CE: Celigráfica, 2008. 319p. 

21. Hosal BM, Biglan AW. Risk factors for secondary membrane formation after removal 

of pediatric cataract. J Cataract Refract Surg. 2002;28(2):302-9. 

22. Wilson ME, Elliot L, Johnson B, Peterseim MM, Rah S, Werner L, et al. AcrySof acrylic 

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14(3):232-4. 

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351

Relatos de Casos | Case Reports 

Síndrome de Waardenburg - aspectos oftalmológicos e critérios de diagnóstico: 

relatos de casos 

Waardenburg syndrome - ophthalmic findings and criteria for diagnosis: case reports 

Luciano Sólia Nasser 1 , Lívia Maris Ribeiro Paranaíba 1 , Ana Cláudia Frota 2 , Andreia Gomes 3 , Gisele Versiani 4 , Hercílio Martelli Júnior 1 

RESUMO 

Objetivo: Descrever as características clínicas e imaginológicas de duas famílias com 

a síndrome de Waardenburg, sendo uma do tipo I e outra do tipo II, enfatizando as 

manifestações oftalmológicas, bem como o padrão de herança genética. 

Método: Realizou-se um estudo clínico envolvendo as duas famílias afetadas pela sín - 

dro me de Waardenburg, sendo, através dos heredogramas, determinado o padrão de 

herança genética presente. Também foram realizadas análises oftalmológicas abordando 

a me dida da acuidade visual, a presença de distopia cantorum (telecanto), a avaliação da 

coloração da íris e o mapeamento de retina, além de exames otológicos e dermatológicos. 

Resultados: O heredograma da família afetada pela síndrome de Waardenburg tipo I 

revelou um modo autossômico dominante de transmissão. A condição estava presente 

em 85,71% dos pacientes. A distopia cantorum foi a alteração mais frequente, seguida 

pela mecha branca na pele da fronte, hipopigmentação da íris e da retina e surdez 

neurossensorial. A família com síndrome de Waardenburg tipo II apresentou 33,33% 

dos familiares com a alteração. Nenhum membro apresentou distopia cantorum e 

hipopigmentação de íris. Três pacientes apresentaram surdez neurossensorial (12,5%), 

associada ao topete branco e manchas acrômicas confluentes pelo corpo. 

Conclusão: O presente estudo mostra a importância do oftalmologista no auxílio do 

diagnóstico desta rara condição genética, uma vez que inclui alterações oftalmológicas 

como telecanto, hipopigmentação da íris e retina. A distopia cantorum é o principal 

critério diagnóstico para diferenciar o tipo I do II e deve ser feita por oftalmologista 

treinado. As famílias encontram-se em acompanhamento multiprofissional, tendo 

recebido orientações genéticas e os cuidados referentes à proteção ocular. 

Descritores: Síndrome de Waardenburg; Doenças da íris; Doenças retinianas; Acon - 

selhamento genético; Surdez; Pálpebras/anormalidades; Nariz/anormalidades; Relatos 

de casos 

ABSTRACT 

Purpose: To describe the clinical and imaginological features of two families with Waardenburg 

syndrome: type I and II, with emphasis on ophthalmic manifestations, as well as 

the pattern of genetic inheritance. 

Methods: We conducted a clinical study involving two families affected by Waardenburg 

syndrome, and through the pedigree, determined the present pattern of genetic inheritance. 

Analyses were performed including the measurement of visual acuity, the presence of 

dystopia cantorum (telecanthus), evaluation of iris color and retinal mapping, as well as 

dermatological and otological examinations. 

Results: The pedigree of the family affected by the Waardenburg syndrome type I showed 

an autosomal dominant mode of transmission. The syndrome was present at 85.71% of 

patients. The dystopia cantorum was the most frequent feature, followed by the white 

streak on the skin of the forehead, hypopigmentation of the iris and retina and deafness. 

The Waardenburg syndrome family type II had 33.33% of family members affected by 

the syndrome. No member had dystopia cantorum and hypopigmentation of the iris. 

Three patients had sensorineural hearing loss (12.5%), associated with white forelock and 

achromatic spots confluent by the body. 

Conclusion: This study shows the importance of the ophthalmologist in aiding the 

diagnosis of this rare genetic condition, since it includes ocular disorders such as telecanthus, 

hypopigmentation of the iris and retina. The cantorum dystopia is the main 

diagnostic criterion to differentiate type I and II syndrome and should be done by a trained 

ophthalmologist. The families are in medical monitoring, receiving genetic guidelines 

and care related to eye protection. 

Keywords: Waardenburg’s syndrome; Iris diseases; Retinal diseases; Genetic counseling; 

Deafness; Eyelids/abnormalities; Nose/abnormalities; Case reports 

INTRODUÇÃO 

Síndrome de Waardenburg (SW; MIM #193500) é uma alteração 

do sistema melanocítico-pigmetário resultante de uma desordem na 

diferenciação, sobrevivência e migração dos melanócitos derivados 

da crista cristal no período embriogênico (1) . A SW apresenta distribuição 

universal, sem predileção por raça e gênero e sua prevalência 

estimada é de 1:42.000 nativivos na população geral (2) . 

Análise histológica das estruturas afetadas na SW mostra ausência 

de melanócitos teciduais como na região frontal do cabelo 

(topete branco), pele, íris e estria vascular da cóclea (surdez neurosensorial) 

(3) . Além destas alterações de pigmentação, pode ocorrer a 

distopia cantorum ou telecanto, um deslocamento lateral dos cantos 

internos dos olhos (2) . Características menos frequentes associadas 

são, a presença de manchas acrômicas da pele, a confluência dos 

supercílios (sinófris) e uma base larga do nariz (4) . Diante desta diversidade 

clínica, foram propostos os critérios diagnósticos maiores para 

a SW: perda auditiva neurossensorial, alterações na pigmentação da 

íris, hipopigmentação do cabelo (topete branco ou cabelos grisalhos 

surgidos antes dos 30 anos de idade) e distopia cantorum, além de 

critérios menores: sinófris, hipopigmentação da pele e uma base larga 

do nariz (4-8) . Para ter a confirmação da SW o paciente deve apresentar 

dois critérios maiores e um menor (4) . 

Submetido para publicação: 26 de julho de 2012 


Trabalho realizado na Universidade Estadual de Montes Claros, Unimontes, Montes Claros, Minas 

Gerais, Brasil. 

1 

Programa de Pós-graduação em Ciências da Saúde, Universidade Estadual de Montes Claros, 

Unimontes, Montes Claros, Minas Gerais, Brasil. 

2 

Estudante de Medicina, Universidade Estadual de Montes Claros, Unimontes, Montes Claros, 

Minas Gerais, Brasil. 

3 

Estudante de Odontologia, Universidade Estadual de Montes Claros, Unimontes, Montes Claros, 

Minas Gerais, Brasil. 

4 

Departamento de Fonoaudiologia do Hospital Universitário Clemente de Faria da Universidade 

Estadual de Montes Claros, Unimontes, Minas Gerais, Brasil. 


Divulgação de potenciais conflitos de interesse: L.S.Nasser, Nenhum; L.M.R. Paranaíba, Nenhum; 

A.C.Frota, Nenhum; A.Gomes, Nenhum; G.Versiani, Nenhum; H.Martelli.Jr., Nenhum. 

Endereço para correspondência: Luciano Sólia Násser. Rua Walter F. Barreto, 57 - Montes Claros 

(MG) 39401-347 - Brasil - E-mail: solianasser@gmail.com 

Comitê de Ética: Unimontes 2781/2011. 


Nasser LS, et al. 

De acordo com a combinação dessas alterações clínicas, a SW 

é classificada em 4 tipos, SW1, SW2, SW3 e SW4. O tipo I (SW1; MIM 

#193500) é a forma clássica com distopia cantorum, o tipo II (SW2; 

MIM #193510) caracterizado pela presença de tecidos com distúrbios 

de pigmentação e surdez, porém, sem a presença de distopia cantorum, 

o tipo III (síndrome de Klein-Waardenburg; MIM #148820) é 

similar ao tipo I com anormalidades musculoesqueléticas adicionais; 

enquanto o tipo IV (síndrome de Shah-Waardenburg ou doença de 

Waardenburg- Hirschsprung, MIM #277580) é caracterizada pela presença 

de megacolon congênito (4) . A tabela 1 mostra os critérios de 

diagnóstico para a SW. 

O objetivo do presente estudo foi descrever as características 

clínicas e imaginológicas em 2 famílias brasileiras com a SW (tipo I e 

tipo II), enfatizando as manifestações oftalmológicas. 

MÉTODOS 

Família 1 

Paciente de 2 anos, masculino, procedente de Montes Claros, 

Mi nas Gerais, acompanhado de seus pais, apresentava surdez total 

bilateral desde o nascimento. Foi avaliado no departamento de oftalmologia 

da Universidade Estadual de Montes Claros, Unimontes, 

Minas Gerais, Brasil, por apresentar queixa principal de fotofobia e os 

olhos extremamente claros. Ao exame clínico, observou-se uma mecha 

branca na região cutânea da fronte, uma mancha hipocrômica no 

braço direito, íris extremamente azuis e telecanto (Figura 1). Diante 

da clínica observada, o diagnóstico presuntivo foi de SW. Iniciou-se 

um estudo envolvendo toda a família do paciente, composta por 15 

membros nas últimas quatro gerações, para determinar o padrão de 

herança e a expressividade da doença (Figura 2). 

Os pacientes afetados tinham idade entre 2 e 55 anos (média de 

18,27 anos). A avaliação clínica incluiu anamnese e exame físico completo. 

O estudo oftalmológico abordou a medida da acuidade visual, 

a presença de distopia cantorum (telecanto), a análise da coloração da 

íris e o mapeamento de retina com retinografia colorida (Figura 3). A 

medida da distopia cantorum foi obtida através do cálculo do índice W, 

resultante de uma análise envolvendo a medida de três pontos anatômicos 

entre os dois olhos, conforme a figura 4. A distopia está presente 

quando o índice W resulta em valor maior ou igual a 1,95 mm (4) . 

Exames otológicos envolveram otoscopia, impedanciometria e 

audiometria computadorizada. Análise de imagens, incluindo fotografias 

do telecanto, hipopigmentação da íris e retina (retinografia 

colorida), além de alterações na pigmentação do cabelo e pele foram 

realizadas. 

Família 2 

Paciente de 53 anos, feminino, procedente de Capitão Enéas, Minas 

Gerais, foi avaliada no mesmo Serviço da família 1, pois apresentava 

pterígio bilateral com crises de inflamação recorrente. A paciente 

apresentava uma mecha branca na região frontal, manchas acrômicas 

em membros inferiores e surdez moderada (Figura 1). Por meio de uma 

avaliação auditiva e uma audiometria, detectou-se a presença de surdez 

neurossensorial. Como a paciente não apresentava distopia cantorum, 

confirmou-se o diagnóstico de SW tipo II. Iniciou-se um estudo 

envolvendo toda a família da paciente, composta por 24 membros, 

nas últimas quatro gerações, para determinar o padrão de herança e a 

expressividade da doença (Figura 5). 

Os pacientes afetados tinham idade entre 4 e 53 anos (média 

de 25,3 anos). A avaliação clínica incluiu anamnese e exame físico. 

O estudo oftalmológico abordou a medida da acuidade visual, presença 

de distopia cantorum (telecanto), análise da coloração da íris 

e mapea mento de retina. Exames otológicos envolveram otoscopia, 

impedanciometria e audiometria computadorizada. Análise de imagens, 

incluindo fotografias do telecanto e alterações na pigmentação 

do cabelo e pele foram realizadas. 

O estudo foi submetido e aprovado pelo Comitê de Ética Institucional. 

Consentimento informado, livre e esclarecido foi obtido de 

cada paciente ou seu responsável legal, antes da inclusão no estudo. 

Tabela 1. Critérios diagnósticos para a síndrome de Waardenburg 

tipos I e II 

Critérios maiores 

1-Distopia cantorum 

2-Alterações na pigmentação da íris 

3-Hipopigmentação do cabelo (topete 

branco ou cabelos grisalhos surgidos 

antes dos 30 anos de idade) 

Critérios menores 

1-Hipopigmentação da pele 

2-Confluência dos supercílios (sinófris) 

3-Base alta e alargada do nariz 

4- Perda auditiva neurossensorial 4-Hipoplasia das asas do nariz 

SW tipo I = Dois critérios maiores 

SW tipo II = Dois critérios maiores, exceto a distopia cantorum 

Read, Newton (4) . Waardenburg syndrome: syndrome of the month. 

A 

C 

Figura 1. Pacientes com síndrome de Waardenburg tipo I (A e B): notam-se iris extrememente 

azuladas, dystopia cantorum, sinófris e base alargada do nariz. Pacientes com 

SW tipo II (C e D): notam-se manchas acrômicas espalhadas pelo corpo e topete branco. 

Figura 2. Heredograma da família com síndrome de Waardenburg tipo I. 

B 

D 


353

Síndrome de Waardenburg - aspectos oftalmológicos e critérios de diagnóstico: relatos de casos 

RESULTADOS 

Família 1 

O exame clínico das últimas quatro gerações da família revelou 

que dos 15 membros (4 homens e 11 mulheres), 11 (73,33%) apresentaram 

ca racterísticas da SW. Desses 11 pacientes, a distribuição por 

sexo foi de 3 (27,27%) masculino e 8 (72,72%) do feminino. Não havia 

história de consanguinidade na família. O heredograma da família revelou 

um padrão de transmissão autossômico dominante com penetrância 

incompleta e expressividade variável (Figura 2). Dez membros 

apresentaram dystopia cantorum. Desses 10, 2 apresentaram surdez 

neurossensorial, 6 hipopigmentação da íris confirmada por uma significativa 

hipoplasia do epitélio pigmentado observado no exame de 

biomicroscopia e 6 topete branco, caracterizando o tipo I da SW por 

possuírem dois critérios maiores, segundo Read, Newton (4) . Sinófris 

foi observado em 4 pacientes afetados pela síndrome. O probando 

foi submetido à cirurgia para implante coclear bilateral aos 2 anos e 

já responde a comandos verbais e fala com dicção compreensível. 

Todos os pacientes portadores de hipopigmentação da íris receberam 

óculos solares com filtro contra UV-A e UV-B, além da correção 

óptica, quando necessário. 

Figura 3. Retinografia do probando com síndrome de Waardenburg tipo I. Ob - 

ser va-se a intensa rarefação do epitélio pigmentado da retina. 

Família 2 

Nesta família, composta por 24 descendentes distribuídos em 

quatro gerações, características da SW estiveram presentes em 33,33% 

(6 homens e 2 mulheres) (Figura 1). A primeira geração foi considerada 

pelos relatos dos membros das gerações seguintes. Desses 8, 

a distribuição por sexo foi de 2 (25%) masculino e 6 (75%) feminino. 

Não havia história de consanguinidade na família. O heredograma da 

família revelou um padrão autossômico dominante (Figura 5). Ne nhum 

membro apresentou distopia cantorum. Três pacientes apresentaram 

surdez neurossensorial associada a topete branco e manchas acrômicas 

confluentes pelo corpo, caracterizando o tipo II da SW por possuírem 

dois critérios maiores e ausência de distopia, segundo alguns 

autores (5) . A probanda foi submetida a implante de prótese auditiva 

com recuperação dos limiares auditivos normais e à exérese do pterígio 

no olho esquerdo. 

Figura 4. Medidas oculares para o diagnóstico da distopia cantorum. Distância entre 

os cantos mediais (a), distância interpupilar (b), distância entre os cantos laterais (c). 

Cálculo: X= (a - 0,2119c - 3.909)/c; 

Y= (a - 0,2479b - 3.909)/b; 

Índice W= X+Y+ a/b. 

Partington MW (1964). Waardenburg`s syndrome and heterochromia iridum in a deaf 

school population (13) . 

Figura 5. Heredograma da família com síndrome de Waardenburg tipo II. 

DISCUSSÃO 

A SW é uma doença de distribuição universal, sem predileção para 

raça e gênero (4) . A prevalência estimada do tipo I foi de 1:42.000 na 

população geral e 1:143 (1,43%) em portadores de surdez congênita (4) . 

A SW apresenta um padrão de herança autossômica dominante com 

penetrância incompleta e expressividade variável, especialmente nos 

tipos I e II (9) . A expressiva heterogeneidade clinica da SW é atribuída a 

uma rede complexa de interação entre seis genes identificados até o 

momento: o gene PAX3, principal responsável pela SW tipo I e III, os 

genes MITF, SOX10 e SNAI2 na SW tipo II e os genes EDN3 e EDNRB na 

SW tipo IV. Todos esses seis genes estão envolvidos dentro de uma rede 

de interações que determinam falhas na embriogênese das células derivadas 

da crista neural e caracterizam a diversidade fenotípica da SW (1) . 

No presente estudo, relatou-se duas famílias, ambas do norte do 

estado de Minas Gerais. A primeira apresentou o padrão clínico tipo 

I, e segunda família, tipo II. A distopia cantorum é a característica mais 

comum da SW tipo I, podendo ter uma incidência de 99% nesse 

sub grupo (4) . Este deslocamento lateral do canto interno dos olhos se 

tornou o recurso diagnóstico mais confiável para classificação do tipo 

I, devido a sua elevada frequência (1) . Já a hipertricose medial das sobrancelhas 

(sinófris) é mais frequente no tipo I (85%) do que no tipo II 

(25%) (5) . A família com SW tipo I apresentou 78,57% dos seus membros 

com distopia cantorum e 28,57% deles com sinofris. A segunda família, 

formada por indivíduos com a SW tipo II, apresentou um padrão de 

transmissão autossômica dominante com penetrência incompleta e 

expressividade variável. Nenhum membro desta família apresentou 

distopia cantorum e hipopigmentação da íris. 


Nasser LS, et al. 

A heterocromia de íris pode ser completa ou parcial (5) . Na parcial, 

existe a presença de cores diferentes em um mesmo olho. Alguns 

autores encontraram heterocromia parcial em 4,2% dos indivíduos 

com SW tipo I e em 27,5% dos indivíduos com SW tipo II (5) . Ohno et al., 

descreveram a presença de heterocromia de íris completa ou parcial 

em 30% dos indivíduos com SW tipo I e II (10) . Iris extremamente azul bilateralmente 

pode fazer parte do quadro ocular em 10% de todos os 

pacientes com diagnóstico de SW e esta coloração é devido à intensa 

hipoplasia do seu epitélio pigmentado (1) . No presente estudo, hipopigmentação 

da íris esteve presente em 42,85% na família com SW 

tipo I. Uma característica desta alteração é que a hipopigmentação da 

íris se apresentou simetricamente entre os dois olhos e no probando 

com SW tipo I foram observadas íris extremamente azuladas (Figura 

1). Neste paciente foi observada uma significativa rarefação e mobilização 

do epitélio pigmentado da retina nos dois olhos, alteração 

descrita na literatura e que geralmente correspondente ao mesmo 

território alterado na íris (10) . 

A perda auditiva na SW é neurossensorial, de caráter congênito, 

não progressivo, podendo ser uni ou bilateral e variar em níveis de intensidade 

(4) . Outros autores, encontraram uma penetrância de perda 

auditiva neurossensorial na SW tipo I de 69% e de 87% na SW tipo II (11) . 

A hipoacusia decorre de uma degeneração cocleossacular e ausência 

completa de pigmentação na estria vascular da cóclea culminando 

em uma atrofia do órgão de Corti (3,12) . No presente estudo a surdez 

neurossensorial esteve presente em 14,28% dos indivíduos com SW 

tipo I e em 12,50% na família com SW tipo II. 

Em relação à mecha branca frontal, esta pode estar presente 

desde o nascimento ou surgir na primeira infância, como também 

pode desaparecer com a idade adulta (4) . Pingault et al., relatam que a 

alteração da cor dos cabelos está presente em pelo menos um terço 

dos tipos I e II (1) . No presente estudo o topete branco esteve presente 

em 50% na família com SW tipo I e 29,16% na SW tipo II. 

A expressividade da SW varia amplamente na literatura, sendo 

apresentada de forma diferente em cada família acometida. Na 

avaliação das famílias apresentadas neste estudo foram encontradas 

características clínicas diferentes na forma de apresentação e nas 

suas prevalências. Por exemplo, a penetrância de distopia cantorum 

e hipopigmentação da íris foram expressivas na família com SW tipo 

I (78,57 e 50%, respectivamente), mas a perda auditiva foi limitada 

(14,28%) e observada apenas em dois indivíduos (III-6 e IV-7) dos 14 

membros da família. Na família com SW tipo II, não foram observadas 

alterações oftalmológicas, apenas surdez e manchas hipocrômicas 

no cabelo e na pele. 

A presença de alterações oftalmológicas na SW tipo I exige uma 

abordagem oftalmológica direcionada a todos os membros da família 

baseada na prevenção de doenças oculares e na reabilitação visual 

destes pacientes com deficiência de pigmentação em dois tecidos de 

suma importância na fisiologia visual, a íris e a retina. Todos os pacientes 

foram submetidos a exame refracional e receberam a prescrição da 

correção. Nos casos de emetropia, foram indicados óculos solares com 

filtros contra os raios ultravioletas. 

CONCLUSÃO 

O presente estudo mostra a importância do oftalmologista no 

auxílio do diagnóstico deste raro quadro sistêmico, uma vez que inclui 

alterações oftalmológicas como distopia cantorum, hipopigmentação 

da íris e da retina. A distopia cantorum é o principal critério diagnóstico 

para diferenciar o tipo I do II e deve ser feita por oftalmologista treinado. 

Aconselhamento genético e cuidados para proteger um olho com 

deficiência de pigmentação na íris e na retina foram oferecidos aos 

pacientes. Investigações envolvendo amostras maiores, com enfoque 

em bases genéticas e moleculares são necessárias para elucidar as consequências 

destas alterações clínicas e melhorar nossa compreensão 

sobre os mecanismos envolvidos nesta patologia, a fim de podermos 

oferecer um aconselhamento genético criterioso e um tratamento 

mais completo aos pacientes. 

REFERÊNCIAS 

1. Pingault V, Ente D, Dastoto-Le Moal F, Goossens M, Marlin S, Bondurand N. Review 

and update of mutations causing Waardenburg syndrome. Human Mutat. 2010;31(4): 

391-406. 

2. Waardenburg PJ. A new syndrome combining developmental anomalies of the 

eyelids, eyebrowns and nose root with pigmentary defects of the iris and head hair 

and with congenital deafness. Am J Hum Genet. 1951;3(3):195-253. 

3. Nakashima S, Sando I,Takahashi H, Hashida Y. Temporal bone histopathologic findings 

of the Waardenburg`s syndrome: a case report. Laryngoscope. 1992;102(5):563-67. 

4. Read AP, Newton VE. Waardenburg syndrome. J Med Genet. 1997;34(8):656-65. 

5. Liu XZ, Newton VE, Read AP. Waardenburg syndrome type 2: phenotypic findings and 

diagnostic criteria. Am J Med Genet. 1995;55(1):95-100. 

6. Farrer LA, Grundfast KM, Amos J, Arnos KS, Asher JH Jr, Beithton P, et al. Waardenburg 

syndrome (WS) tipe 1 is caused by defects at multiple loci, one of which is near ALPP 

on chromosome 2: first report of the WS Consortium. Am J Hum Genet. 1992;50(5): 

902-13. 

7. Hageman MJ, Delleman JW. Heterogeneity in Waardenburg syndrome. Am J Hum 

Genet. 1977;29(5):468-85. 

8. Fraser Gr. The cause of profound deafness in childhood. Baltimore: John Hopkins 

University Press; 1976 

9. Arias S. Genetic heterogeneity in the Waardenburg syndrome. Birth Defects Orig Artic 

Ser. 1971;7(4):87-101. 

10. Ohno N, Kiyosawa M, Wang WF, Takase H, Mochizuki M. Clinical findings in Japanese 

patients with Waardenburg syndrome type 2. Jpn J Ophthalmol. 2003;47(1):77-84. 

11. Newton VE, Read AP. Waardenburg Syndrome. Audiol Med. 2003;1(1):77-88. 

12. Steel KP, Barkway C. Another role for melanocytes: their importance for normal stria vas - 

cularis development in the mammalian inner ear. Development. 1989;107(3):453-63. 

13. Partington MW. Waardenburg`s syndrome and heterochromia iridum in a deaf school 

population. Can Med Assoc J. 1964;90:1008-17. 


355

Relato de Caso | Case Report 

Optical coherence tomography image in gelatinous drop-like corneal dystrophy: 

case report 

Tomografia de coerência óptica na distrofia corneana gelatinosa em gotas: relato de caso 

Otávio de Azevedo Magalhães¹, Samuel Rymer 2 , Diane Ruschel Marinho 2 , Sérgio Kwitko 2 , Isabel Habeyche Cardoso 3 , Lúcia Kliemann 4 

ABSTRACT 

Gelatinous drop-like corneal dystrophy is a rare disorder with few cases described 

in the present literature. The following report will show how difficult it is to 

diagnose this disease in early stages. Modern image exams, such as optical co - 

he rence tomography helps to diagnose and can be crucial to establish the best 

treatment. We will present the histopathological changes and clinical features in 

this unusual dystrophy. 

Keywords: Corneal dystrophies, hereditary/diagnosis; Tomography, optical coheren - 

ce/methods; Corneal opacity; Case report; Humans; Child 

RESUMO 

A distrofia corneana gelatinosa em gotas é uma desordem rara e pouco descrita em 

nossa literatura. O caso apresentado demonstra a dificuldade de realizar o diagnóstico 

nas fases mais iniciais da doença. O uso de modernos exames de imagem, como a 

to mografia de coerência óptica de segmento anterior, auxilia no diagnóstico e pode 

ser crucial para definir a melhor conduta terapêutica. Apre sentaremos as alterações 

histopatológicas e as características clínicas desta incomum distrofia. 

Descritores: Distrofias hereditárias da córnea/diagnóstico; Tomografia de coerência 

óptica/métodos; Opacidade da córnea; Relato de caso; Humanos; Criança 

INTRODUCTION 

Gelatinous drop-like corneal dystrophy is a rare disorder also 

known as primary familial amyloidosis of the cornea (1) . It usually 

occurs in the first decade of life and its clinical appearance can simulate 

other diseases such as band keratopathy (2) . Symptoms include 

photophobia, tearing and poor vision. Bilateral corneal opacification 

increases with age. Microscopic findings include subepithelial deposits 

that resemble a mulberry shape without any inflammatory 

component. The genetic inheritance pattern is not well established (3) , 

but it is believed to be autosomal recessive. Bowman’s membrane 

can be absent at the histopathological analysis and characteristic 

ap ple-green birefringence is viewed in polarized light (4) . 

CASE REPORT 

A five-year-old girl was referred to our Cornea and External Disea - 

se Department because of bilateral corneal opacity and low vision. 

Her past medical history was negative for any systemic disease, trauma 

or prenatal disorders. Similar findings were found in her 8-year-old 

brother, who had the same biomicroscopic characteristic but milder 

symptoms. Her best corrected visual acuity was counting fingers at 

1 meter in both eyes. Slit lamp examination revealed a total lack of 

transparency, epithelial edema with bubbles and a thin layer of calcification 

(Figure 1). The main initial diagnostic hypothesis was congenital 

hereditary endothelial dystrophy (CHED) and a penetrating 

keratoplasty (PK) was indicated in the right eye. Histopathological 

analysis revealed amyloid nodules in the subepithelial layer and in the 

anterior portion of the corneal stroma that stained with Congo Red 

(Figure 2) and formed apple-green birefringence when combined 

with polarized light (Figure 3). Bowman’s membrane was absent, there 

was no significant posterior stromal edema and Descemet´s membrane 

was normal. Histopathological findings were consistent with 

the diagnosis of gelatinous drop-like corneal dystrophy and showed 

that our first hypothesis of CHED was mistaken. Optical Coherence 

Tomography (OCT - Optovue Fourier-Domain System ® ) was performed 

in the opposite eye that had the same clinical appearance. This exam 

showed increased anterior reflectivity with nodules measuring about 

327 microns in thickness. Total central corneal width was 1070 microns. 

There were no significant changes in the posterior stroma and 

Descemet’s membrane (Figure 4). 

DISCUSSION 

There are few descriptions of this type of dystrophy and no reports 

of anterior OCT images. Had we performed a corneal OCT exam 

before PK of the right eye, we could have made a different surgical 

approach since the OCT showed only anterior stromal alterations. 

Submitted for publication: June 12, 2012 

Accepted for publication: July 27, 2012 

Study carried out at the Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Gran de 

do Sul. 

1 

Physician, Setor de Córnea e Doenças Externas, Serviço de Oftalmologia, Hospital de Clínicas de 

Porto Alegre, Universidade Federal do Rio Grande do Sul - UFRS - Porto Alegre (RS), Brasil. 

2 

Physician, Serviço de Oftalmologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do 

Rio Grande do Sul - UFRS - Porto Alegre (RS), Brasil. 

3 

Physician, Porto Alegre (RS), Brasil. 

4 

Physician, Serviço de Patologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio 

Grande do Sul - UFRS - Porto Alegre (RS), Brasil. 


Disclosure of potential conflicts of interest: O.A.Magalhães, employee of Hospital Nossa Senhora 

da Conceição; S.Rymer, None; D.R.Marinho, employee of Hospital de Clínicas de Porto Alegre; 

S.Kwitko, None; I.H.Cardoso, None; L.Kliemann, 

Correspondence address: Otávio de Azevedo Magalhães. Rua Mostardeiro, 333/401 - Porto Alegre 

(RS) - 90430-001 - Brazil - E-mail: otaviomaga@yahoo.com.br 


Magalhães OA, et al. 

Figure 1. Gelatinous drop-like dystrophy biomicroscopic findings - grayish, mulberry-like 

and protruding subepithelial deposits. 

Figure 3. Apple-green birefringence when viewed with polarized light. 

Figure 2. Red Congo stain showing anterior amyloid nodular deposits. 

Figure 4. OCT image showing hypereflective nodular formation in the anterior corneal 

layer. 

During the diagnostic investigation, it is essential to use this kind of 

technology. That way, invasive procedures with high rates of rejection 

can be avoided. Anterior lamellar procedures or phototherapeutic 

keratectomy (PTK) (5) can be better options for this disease. 

REFERENCES 

1. Nakaizumi K. A rare case of corneal distrophy. Acta Soc Ophthal Jpn. 1914;18:949-50. 

2. Kanai A, Kaufman HE. Electron microscopic studies of primary band-shaped keratopathy 

and gelatinous drop-like corneal dystrophy in two brothers. Ann Ophthalmol. 

1982;14(6):535-9. 

3. Kawasaki S, Kinoshita S. Clinical and basic aspects of gelatinous drop-like corneal 

dys trophy. Dev Ophthalmol. 2011;48:97-115. 

4. Garner A. Amyloidosis of the cornea. Br J Ophthalmol. 1969;53(2):73-81. 

5. Ito M, Takahashi J, Sakimoto T, Sawa M. [Histological study of gelatinous drop-like 

dys trophy following excimer laser phototherapeutic keratectomy]. Nihon Ganka 

Gakkai Zasshi. 2000;104(1):44-50. Japanese. 


357


Esclerite posterior associada à oclusão da veia central da retina 

e edema macular cistoide: relato de caso 

Posterior scleritis associated with central retinal vein occlusion and cystoid macular edema: case report 

Roger Wada Kamei 1 

RESUMO 

Apresentamos um caso de esclerite posterior associada à oclusão da veia central 

da retina e edema macular cistoide. Com esse caso, observamos como a doença 

pode ser agressiva e como a acuidade visual pode ser comprometida. No entanto, 

o tratamento correto pode melhorar as alterações oculares com melhora visual. 

Aler tamos também para os cuidados que devem ser tomados em relação ao uso 

de altas doses de corticosteroides. 

Descritores: Esclerite/quimioterapia; Oclusão da veia retiniana; Edema macular; 

Uveítes; Angiofluoresceinografia; Metilprednisolona/uso terapêutico; Relato de caso; 

Humanos; Idoso; Feminino 

ABSTRACT 

A case of posterior scleritis associated with central retinal vein occlusion and cystoid 

macular edema is reported. With this case, we noticed how the disease can be aggressive 

and how the visual acuity can be compromised. However, the correct treatment can 

improve the ocular changes with visual improvement. We also alert to the care with the 

use of high doses of corticosteroids. 

Keywords: Scleritis/drug therapy; Retinal vein occlusion; Macular edema; Uveitis; 

Fluo rescein angiography; Methylprednisolone/therapeutic use; Case report; Humans; 

Aged; Female 

INTRODUÇÃO 

A esclerite posterior é uma forma rara de esclerite que, apesar 

da sua grande morbidade, apresenta uma grande dificuldade no seu 

diagnóstico. Definida como um processo inflamatório da esclera posterior 

até a ora serrata com sintomas que, frequentemente, simulam 

outras condições, sendo uma doença pouco diagnosticada (1-3) . 

Como em outras formas de esclerites, a dor é um sintoma importante 

e a visão pode ser gravemente afetada. Além do quadro 

clínico, a ecografia B mostra-se de grande utilidade para confirmar o 

diagnóstico, achados ecográficos são muito comuns e fundamentais 

para o acompanhamento desses casos (1,2) , principalmente quando 

não há sinais fundoscópicos. 

Em geral acomete mais mulheres (60 a 70%) que homens, entre 

40 e 59 anos, sendo bilateral em 5% dos casos e com recorrências 

frequentes. Podendo estar associada à esclerite anterior em 43,5%, 

principalmente na forma difusa (4-6) . 

A esclerite posterior pode ser idiopática ou estar associada a uma 

doença sistêmica em até 40% dos casos. Causas infecciosas podem 

estar presentes, como herpes zoster, herpes simples, tuberculose e 

sí filis. Porém, a artrite reumatóide é descrita como sendo a associação 

mais comum. Outras vasculites sistêmicas como granulomatose de 

Wegener também podem ser uma causa (7,8) . 

O tratamento depende do diagnóstico correto e, em casos mais 

graves e não responsivos ao tratamento convencional com drogas 

anti-inflamatórias, pode ser necessário o uso de drogas imunossupressoras 

para o controle do quadro ocular (9,10) . 

Uma abordagem multidisciplinar desses casos, muitas vezes, é 

necessária. Sendo uma avaliação clínica geral e uma investigação 

laboratorial precoce de extrema importância. O encaminhamento 

para o reumatologista é aconselhável para cooperação no diagnóstico 

e tratamento. 

O processo inflamatório escleral pode ser potencialmente devastador. 

O não reconhecimento e não tratamento dessa condição pode 

comprometer a visão de maneira rápida e irreversível. 

RELATO DE CASO 

A.M.B., sexo feminino, 71 anos. Iniciou quadro de baixa acuidade 

visual (AV), hiperemia e dor no olho direito (OD) há dois meses, desde 

então, com diagnóstico e tratamento de conjuntivite. Referia ser 

“pré-diabética” controlada com dieta, sem uso de medicação hipoglicemiante. 

Negava hipertensão arterial sistêmica e trauma. 

A AV era de movimentos de mãos frente os olhos em OD e de 

20/25 em OE. À biomicroscopia, o OD apresentava quadro de esclerite 

anterior difusa, com grande congestão dos vasos episclerais superficiais 

e profundos, ausência de reação de câmara anterior (RCA), 

pressão intraocular normal e pseudofacia sem complicações. O olho 

esquerdo (OE) mostrava-se sem alterações. 

A fundoscopia do OD (Figura 1) mostrava um descolamento 

se roso da retina com descolamento periférico da coroide e ausência 

de roturas retinianas. O vítreo estava claro com raras células 

in flamatórias. Havia um edema do disco óptico importante com 

si nais compatíveis com oclusão da veia central da retina (OVCR) 

com he morragias retinianas superficiais, dilatação e ingurgitamento 

ve noso significativo, alguns exsudatos algodonosos e mácula sem 

edema. OE normal. 

Submetido para publicação: 21 de março de 2012 


Trabalho realizado no Instituto Penido Burnier. 

1 

Médico, Setor de Retina e Vítreo, Uveítes e AIDS, Instituto Penido Burnier, Campinas (SP), Brasil. 


Divulgação de potenciais conflitos de interesse: R.Kamei, Nenhum. 

Endereço para correspondência: Roger Kamei. Rua Coelho Neto, 15 - Apto. 54 - Campinas (SP) - 

13023-020 - Brasil - E-mail: rwkamei@gmail.com 


Kamei RW 

O ultrassom mostrava um vítreo pouco acometido e sem trações 

vitreorretinianas anormais, descolamento de coroide periférico, descolamento 

seroso da retina e edema do disco óptico perceptível ao 

exame. A coroide apresentava um espessamento importante e difuso 

sem, no entanto, apresentar acúmulo de líquido no espaço subtenoniano. 

Não foi observado o característico “sinal do T invertido”. O 

exame também afastou a presença de massas e demais alterações 

da parede ocular. 

A angiofluoresceinografia (AGF) mostrava o grande comprometimento 

vascular retiniano e ausência de edema macular (Figura 2). 

Neste momento, foram solicitados exames laboratoriais infecciosos 

e reumatológicos, assim como uma avaliação clínica para liberação 

para pulsoterapia com metilprednisolona endovenosa por três 

dias consecutivos. Os exames laboratoriais mostraram negatividade 

para toda a investigação sorológica e as condições clínicas da paciente 

permitiram a realização da pulsoterapia. O tratamento foi realizado 

em regime de internação hospitalar e monitorização clínica. 

Com a medicação endovenosa, obteve-se resolução total do des - 

colamento da coroide e parcial do descolamento seroso da retina. 

Sendo programada a manutenção do tratamento com prednisona 

oral 1 mg/kg/dia, porém os índices glicêmicos da paciente se elevaram 

para valores acima de 300 mg/dL. Assim, permaneceu internada 

para controle da glicemia por 20 dias, tendo alta com uso de insulina 

diária três vezes ao dia e hipoglicemiantes orais, mantendo glicemia 

de 200 mg/dl e 20 mg de predinisona por dia. Neste momento, OD 

estava com a retina totalmente colada, mantendo o edema do disco 

óptico e melhora parcial dos sinais da OVCR, porém com AV de 20/200. 

Com a realização da tomografia de coerência óptica (OCT) e 

nova AGF, notou-se um edema macular de 1.075 µm na área central 

(Figu ra 4), também evidenciado pelo exame angiográfico. 

Devido às condições clínicas da paciente, optou-se pelo tratamento 

do edema macular com aplicação de corticosteroide intraocular 

de acetato de triancinolona. Após a realização de duas injeções com 

intervalo de 40 dias, o edema macular apresentou completa resolução 

(245 µm) e a AV melhorou para 20/25. Ao final, a retina estava totalmente 

colada, sem edema do disco óptico e sinais de OVCR (Figura 3). 

CONCLUSÃO 

Com esse relato, podemos perceber como a esclerite posterior 

pode ser agressiva e exigir um tratamento intenso a base de corticosteroide. 

No entanto, essa condição pode ser erroneamente diagnosticada 

e levar a sérias complicações decorrentes da inflamação ocular. 

Em relação ao tratamento com corticosteroides, nota-se um gran - 

de cuidado principalmente em pacientes idosos e com comorbidades. 

Atenção especial deve ser dada à diabetes melito e hipertensão 

arterial sistêmica. Nesses casos, pode-se pensar em outras opções 

de tratamento, como a aplicação intra e peri-ocular e imunossupres- 

Figura 1. Retinografia colorida do OD inicial. 

Figura 3. Retinografia colorida do OD após tratamento. 

OCT inicial 

Após primeira injeção 

Após segunda injeção 

Figura 2. Angiofluoresceinografia do OD. 

Figura 4. Evolução do edema macular pelo OCT durante o tratamento. 


359

Esclerite posterior associada à oclusão da veia central da retina e edema macular cistoide: relato de caso 

sores sistêmicos. Dessa forma, uma abordagem multidisciplinar com 

um reumatologista e um clínico geral é de extrema importância para 

o manejo da medicação e acompanhamento desses casos. 

Apesar do quadro agressivo que a esclerite posterior pode proporcionar, 

o correto tratamento com altas doses de corticosteroides 

pode apresentar grande melhora e até resolução das alterações 

oculares. 

Percebe-se, assim, a importância do diagnóstico precoce e pron to 

tratamento da esclerite posterior. Sendo uma condição grave, onde 

medicações sistêmicas e uma abordagem multidiscipli nar podem ser 

necessárias para uma melhor resposta do quadro inflamatório ocular. 

REFERÊNCIAS 

1. McCluskey PJ, Watson PG, Lightman S, Haybittle J, Restori M, Branley M. Posterior 

scleritis: clinical features, systemic associations, and outcome in a large series of pa - 

tients. Ophthalmology. 1999;106(12):2380-6. 

2. Benson WE. Posterior scleritis. Surv Ophthalmol. 1988;32(5):297-316. 

3. Machado DO, Curi AL, Bessa TF, Campos WR, Oréfice F. Esclerite posterior: características 

clínicas, associação sistêmica, tratamento e evolução de 23 pacientes. Arq Bras 

Oftalmol. 2009;72(3):321-6. 

4. Parra AG, Miyazaki FH, Ribeiro RM, Gehlen ML, Skare, T. Análise de 29 casos de 

esclerite. Experiência de um serviço de Reumato-Oftalmologia. Arq Bras Oftalmol. 

2010;73(3):250-3. 

5. Machado DO, Curi AL, Fernandes RS, Bessa TF, Campos WR, Oréfice F. Esclerite: características 

clínicas, associação sistêmica, tratamento e evolução de 100 pacientes. Arq 

Bras Oftalmol. 2009;72(2):231-5. 

6. La Maza MS, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical 

characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology 

2012;119(1):43-50. Comment in: Ophthalmology. 2012;119(8):1715-1715.e.1. 

7. Raiji VR, Palestine AG, Parver DL. Scleritis and systemic disease association in a com - 

munity-based referral practice. Am J Ophthalmol. 2009;148(6):946-50. 

8. Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for 

systemic disease. Ophthalmology. 2004;111(3):501-6. Comment in: Ophthalmology. 

2007;114(6):1232. 

9. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and 

treatment results. Am J Ophthalmol. 2000;130(4):469-76. 

10. Doctor P, Sultan A, Syed S, Christen W, Bhat P, Foster CS. Infliximab for the treatment 

of refractory scleritis. Br J Ophthalmol. 2010;94(5):579-83. 

Mais informações em: http://www.oftalmo.epm.br/simasp2013 




Buftalmus em adulto: relato de caso 

Mônica Alves 1 , Leonardo Tannus Malki 1 , Eduardo Melani Rocha 1 

ABSTRACT 

To report a case of extensive globe enlargement due to secondary glaucoma in 

a young adult suffering from ocular surface disorders related to hypohidrotic 

ectodermal dysplasia. To the best of our knowledge, this is the first report of bu - 

phthalmos in the adulthood. 

Keywords: Hydrophthalmos; Ectodermal dysplasia 1, anhidrotic; Dry eye syndromes; 

Case report; Humans; Male; Adult 

RESUMO 

Relato de caso do aumento extenso do globo ocular decorrente de glaucoma secundário 

e disfunção de superfície ocular em um paciente adulto jovem portador de displasia 

ectodérmica anidrótica. Primeiro relato de caso de buftalmo em adulto. 

Descritores: Hidroftalmos; Displasia ectodérmica anidrótica tipo 1; Síndromes do olho 

seco; Relato de caso; Humanos; Masculino; Adulto 

INTRODUCTION 

The growth of the human eye occurs more extensively in the postnatal 

period and is limited to the initial five years (1) . Anomalous growth 

is called buphthalmos and is related to high intraocular pressure in the 

initial months of life (2) . 

Gordon et al., in a cross-sectional study including premature, fullterm 

newborns and patients from 2 months to 36 years old, showed 

the progressive changes during the first years of life. According to their 

results, the main increase in axial length occurs until the age of 4, then 

slows to 0.4 mm/year and after 5 years of age, it grows approximately 

only 1 mm to its final length in adulthood. No significant increase in 

human eye length is expected after 10-15 years of age (1,3) . 

The term buphthalmos is used to describe a visible enlargement 

of the globe at birth or soon thereafter, mostly due to congenital glaucoma. 

The name buphthalmos comes from the Greek meaning “oxeyed“ 

and its first formal mention is uncertain and could have been 

used to highlight clinical diagnoses made by the simple inspection a 

large globe. Historically, it was just after the 19 th century with the invention 

of the ophthalmoscope and the tonometer that the etiology 

of the buphthalmos was related to glaucoma and its distinction of 

the normally sized protuding globe and other forms eye enlargement 

were consistently made (2) . 

We report a case of extensive globe enlargement due to secondary 

glaucoma in a young adult suffering from ocular surface disorders 

related to hypohidrotic ectodermal dysplasia. To the best of our knowledge, 

this is the first report of buphthalmos in adulthood. 

CASE PRESENTATION 

A 17-year-old caucasian male patient was referred for evaluation 

of painful ocular surface disorders and uncontrolled and progressive 

secondary glaucoma. He had been diagnosed with hypohidrotic 

ectodermal dysplasia in childhood, based on sparse, fine hair, brow 

and eyelashes hypotrichosis, poor tolerance to heat due to low ability 

to sweat. At birth his eyes were normal and he developed normal 

visual acuity. However, he had a long-term history of ocular irritation 

and frequent use of topical corticosteroids, antibiotics, lubricants and 

subsequently antiglaucoma medications. 

At an ophthalmological evaluation he presented poor visual 

acuity and dry eye, indicated by tear film instability, low Schirmer test 

measurements, corneal opacities and peripheral neovacularization 

and punctate keratitis in both eyes (4) . In addition, the patient presented 

a 3 mm epithelial defect in his left eye (OS) and subcapsular cataract 

OU. The average intraocular pressure (IOP) was 46 mmHg in the 

right eye (5) and 30 mmHg in OS, with advanced disc cup in both eyes 

despite maximum topical antiglaucoma therapy. A trabeculectomy 

was performed in OD, with severe wound healing problems during 

the follow-up (Figure 1A). 

After six years of follow-up, the ocular surface disorders were 

properly controlled with preservative free lubricants and autologous 

serum applications. The extensive and prolonged use of preserved 

antiglaucoma eyedrops contributed to ocular irritation, reducing 

tolerance and compliance to treatment. Once the high IOP persisted 

in OS, we observed an enlargement of the globe, from 31mm in 2003 

to more than 36 mm of axial length in 2010 (Figures 1B and D). The 

OS evolved to no light perception which, combined with patient 

dissatisfaction with the facial aspect, eventually led to OS evisceration 

and a prosthesis adaptation. 

DISCUSSION 

Ectodermal dysplasia (ED) is a congenital syndrome characterized 

in general terms by sparse hair, severe oligodontia, missing or 

scanty eye brows, lashes and reduced sweating. It is considered a 


Accepted for publication: June 25, 2012 

Study carried out at Department of Ophthalmology, Otorrinolaringology and Head & Neck Surgery, 

Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - USP. 

1 

Physician, Department of Ophthalmology, Otorrinolaringology and Head & Neck Surgery, Faculdade 

de Medicina de Ribeirão Preto, Universidade de São Paulo - USP - Ribeirão Preto (SP), Brazil. 

Funding: This study was supported by FAPESP. 

Disclosure of potential conflicts of interest: M.Alves, None; L.T.Malki, None; E.M.Rocha, None. 

Correspondence address: Mônica Alves. Department of Ophthalmology, Otorrinolaringology and 

Head & Neck Surgery. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Av. 

Bandeirantes, 3900 - Ribeirão Preto (SP) - 14049-900 - Brazil - E-mail: monicalves@fmrp.usp.br 


361


A 

B 

Ocular surface manifestations of ED include reduction of 

eyebrows and lashes, lid keratinization, recurrent epithelial defect, 

trichiasis, superficial and deep corneal vascularization, limbal deficiency, 

meibomian glands dysfunction and dry eye (8,9) . 

Our patient has suffered from ocular surface dysfunction related 

to ED and developed glaucoma and cataracts secondary to chronic 

corticosteroid use. We hypothesize that there was a close relation 

between ED, high IOP and OS globe length growth in this case. The 

absence of buphthalmos in OD, in which effective IOP control was 

obtained following trabeculectomy, is an additional evidence of the 

association of globe length growth and increased IOP in ED patients. 

The present work describes a case of ED with challenging management 

problems that culminated with a unique event of buphthalmos 

in adulthood. 

C 

Figure 1. A) External appearance at first examination, loss of eye brow and lashes, depressed 

nasal bridge, epithelial corneal defect in the right eye and buphthalmos at left. 

B) External appearance after 6 years, showing the progression of the buphthalmos of 

the left globe. C and D) A-scan ultrasound images of both eyes showing an axial length 

of approximately 25 mm of the right eye and more than 36 mm of the left. 

large and complex group of genetic disorders defined by the abnormal 

development of two or more structures of the ectodermal layer. 

Nearly 200 different conditions have been described as ED, however, 

to the best of our knowledge, no previous association with glaucoma 

or uncontrollable eye growth has been reported (6,7) . 

D 

REFERENCES 

1. Gordon RA, Donzis PB. Refractive development of the human eye. Arch Ophthalmol 

1985;103:785-9. 

2. Mark HH. Buphthalmos: early glaucoma history. Acta ophthalmologica 2011;89:591-4. 

3. Sorsby A, Benjamin B, Sheridan M, Stone J, Leary GA. Refraction and its components 

during the growth of the eye from the age of three. Memo Med Res Counc 1961; 

301(Special):1-67. 

4. Chen HB, Yamabayashi S, Ou B, Tanaka Y, Ohno S, Tsukahara S. Structure and composition 

of rat precorneal tear film. A study by an in vivo cryofixation. Invest Ophthalmol 

Vis Sci 1997;38:381-7. 

5. Macsai MS, Agarwal S. Staphylococcal endophthalmitis following cataract extraction 

in a patient with Darier’s disease. Cornea 1998;17:335-7. 

6. Itin PH, Fistarol SK. Ectodermal dysplasias. Am J Med Genet C Semin Med Genet 2004; 

131C:45-51. 

7. Mikkola ML. Molecular aspects of hypohidrotic ectodermal dysplasia. Am J Med Ge - 

net A 2009;149A:2031-6. 

8. Kaercher T. Ocular symptoms and signs in patients with ectodermal dysplasia syndromes. 

Graefes Arch Clin Exp Ophthalmol 2004;242:495-500. 

9. Alves M, Dias AC, Rocha EM. Dry eye in childhood: epidemiological and clinical as - 

pects. Ocul Surf 2008;6:44-51. 


Artigo de Revisão | Review Article 


Rosácea ocular - revisão 

Ana Carolina Cabreira Vieira 1 , Ana Luisa Höfling-Lima 1 , Mark J Mannis 2 

ABSTRACT 

Rosacea is a prevalent chronic cutaneous disorder with variable presentation and 

severity. Although considered a skin disease, rosacea may evolve the eyes in 58-72% 

of the patients, causing eyelid and ocular surface inflammation. About one third of 

the patients develop potentially sight-threatening corneal involvement. Untreated 

rosacea may cause varying degrees of ocular morbidity. The importance of early 

diagnosis and adequate treatment cannot be overemphasized. There is not yet a 

diagnostic test for rosacea. The diagnosis of ocular rosacea relies on observation 

of clinical features, which can be challenging in up to 90% of patients in whom 

accompanying roseatic skin changes may be subtle or inexistent. In this review, 

we describe the pathophysiologic mechanisms proposed in the literature, clinical 

features, diagnosis and management of ocular rosacea, as well as discuss the need 

for a diagnostic test for the disease. 

Keywords: Rosacea/diagnosis; Eye manifestations; Eye diseases; Rosacea/drug therapy; 

Doxycycline; Visual acuity 

RESUMO 

A rosácea é uma condição cutânea crônica, que possui apresentações clínicas variáveis. 

Apesar de considerada uma doença dermatológica, os olhos podem ser acometidos em 

58-72% dos casos, causando inflamação palpebral e da superfície ocular. Aproximadamente 

um terço dos pacientes desenvolve acometimento corneano, podendo causar 

baixa visual significativa. Diagnóstico precoce e tratamento adequado são de extrema 

importância, devido à significativa morbidade ocular que a doença pode causar. Não 

há, até o momento, um teste diagnóstico para rosácea. O diagnóstico da rosácea ocular 

depende da observação das manifestações clínicas, o que pode ser bastante desafiador 

em até 90% dos pacientes, em que os achados cutâneos são discretos ou inexistentes. 

Nesta revisão, descrevemos os mecanismos fisiopatológicos propostos na literatura, 

manifestações clínicas, diagnóstico e tratamento da rosácea ocular, assim como abordamos 

a necessidade de um teste diagnóstico. 

Descritores: Rosácea/diagnóstico; Manifestações oculares; Oftalmopatias; Rosácea/qui - 

mioterapia; Doxiciclina; Acuidade visual 

INTRODUCTION 

Rosacea is a widely prevalent chronic cutaneous disorder with 

variable presentation and severity. It primarily affects blood vessels 

and pilosebaceous units of the central facial skin (cheeks, chin, 

nose, and central forehead), causing transient or persistent erythema, 

telangiectasias, papules, pustules, and phymatous changes 

(Fi gu re 1) (1) . 

Although considered a skin disease, rosacea may evolve the eyes 

in up to 58-72% of the patients, causing eyelid and ocular surface 

inflammation (1,2) . About one third of the patients develop corneal 

involvement, which may be sight-threatening (1,3) . 

Rosacea, albeit common, is often overlooked by general practitioners 

and ophthalmologists (4) . Mild rosacea patients may not seek 

medical help and may not be diagnosed in clinical practice. Ocular 

rosacea, in particular, is frequently underdiagnosed. Its symptoms 

and signs can be quite non-specific, and in up to 90% of patients, 

accompanying roseatic skin changes may be very subtle. More 

importantly, in 20% of the cases, ocular signs may even precede characteristic 

skin involvement (3) . Patients often do not mention ocular 

symptoms in a dermatology clinic, unless directly asked about them. 

Conversely, skin manifestations are uncommonly examined during 

ophthalmology consults. As a result, a certain number of cases remain 

undetected (3) . 

Chronic, untreated rosacea may cause varying degrees of ocular 

morbidity, facial disfigurement, emotional distress, and social impairment 

(5,6) . The importance of early diagnosis and adequate treatment 

cannot be overemphasized due to the negative impact this disorder may 

have on the quality of life of patients and the potential sight-threatening 

complications of this disease. 

Epidemiology 

Rosacea affects over 16 million Americans (7) , and a Swedish survey 

revealed a prevalence as high as 10% (8) . A recent large observational 

study on the epidemiology of rosacea in the United Kingdom revealed 

an incidence rate of 1.65/1,000 person-years as diagnosed by general 

practitioners (9) . Women are more commonly diagnosed with rosacea 

than men, and they tend to be diagnosed earlier. A possible explanation 

for this is that women may seek medical care more often and earlier than 

men. On the other hand, men are more prone to phymatous changes (9,10) . 

Rhinophyma is most commonly seen in men over 40 years of age, in 

more advanced stages of the disease (11,12) . 

Ocular rosacea affects both genders equally (9) . The incidence of 

ocular rosacea varies among ophthalmologic and dermatologic studies, 

ranging from 6-72%, being more prevalent in ophthalmology 

clinics (2,3,13) . 

Rosacea may be found in early childhood as well as in the elderly, 

but it most commonly affects middle-aged adults (14) . Spoendlin et 

al., found that 80% of rosacea patients in the UK were at or above 30 

years of age, with a peak in the incidence rate between the ages of 

40 and 59 years (9) . Pediatric rosacea is thought to be rare, but may be 

underreported since the dermatologic features are often absent or 

difficult to identify (15-17) . 

Submitted for publication: August 7, 2012 


Study carried out at Universidade Federal de São Paulo - UNIFESP - São Paulo (SP), Brazil. 

1 

Physician, Department of Ophthalmology, Universidade Federal de São Paulo - UNIFESP - São 


2 

Physician, Department of Ophthalmology, University of California, Davis, CA, USA. 


Disclosure of potential conflicts of interest: A.C.C.Vieira, None; A.L.Höfling-Lima, employee of 

Federal Governement of Brazil; M.J.Mannis, None. 

Correspondence address: Ana Carolina Cabreira Vieira, Rua Visconde de Silva, 52/503 - Rio de 

Janeiro - RJ - 22271-092 - Brazil - E-mail: anacarolinavieira31@gmail.com 


363


Figure 1. Cutaneous manifestations of rosacea with characteristic involvement of central 

facial skin (cheeks, nose, and central forehead). 

Fair-skinned patients of European descent are more commonly 

affected by rosacea; however, any ethnicity can be afflicted with the 

disease. It has been suggested that skin pigmentation may obscure 

identification of the characteristic findings, contributing to underdiagnosis 

in dark skinned patients (18) . 

Etiology and pathophysiology 

The precise etiology and pathophysiologic mechanisms of cutaneous 

and ocular rosacea remain unknown, although different theories 

have been proposed. Several studies confirm the inflammatory 

nature of the disease. An elevated concentration of interleukin-1a 

and b and a greater activity of gelatinase B (metalloproteinase -9) and 

colagenase-2 (MMP-8) have been found in tear fluids of patients with 

ocular rosacea (19-22) . Doxycycline, used in the treatment of cutaneous 

and ocular rosacea, decreases both MMP-8 and MMP-9 activity (21,22) . 

Tumor necrosis factor (TNF-alfa) was also elevated in rosacea (23) . 

Significant overexpression of ICAM-1 (intercellular adhesion molecule 

1) and HLA-DR, inflammatory markers, was observed in conjunctival 

epithelial cells of patients with rosacea (24) . 

Recently, studies have shown that disease exacerbation is stimulated 

by normal external environmental factors, leading to unique 

activation of pro-inflammatory systems as well as innate immune 

responses (23,25,26) . Molecular studies propose that the enhanced 

sensitivity of patients with rosacea may be caused by abnormal 

recognition of common environmental stimuli. Factors that trigger 

the innate immune system lead to an increase in the expression of 

certain cytokines and anti-microbial molecules in the skin (25,27) . Cathelicidin, 

one of these antimicrobial peptides, has both vasoactive 

and pro-inflammatory actions and is implicated in the pathogenesis 

of this disorder. Based on the observation of a single molecule that 

presents both vasoactive and pro-inflammatory actions, researchers 

decided to study the behavior of such molecule in rosacea. As hypothesized, 

these peptides were found in greater levels in the skin of 

individuals with rosacea than in normal facial skin (25,27,28) . Moreover, 

the cathelicidin peptides found in rosacea patients were not only 

more abundant but were different from those found in normal individuals 

(25) . These forms of cathelicidin peptides are known for its role 

in natural host defense against infections and in promoting leukocyte 

chemotaxis, angiogenesis, and extracellular matrix component 

expression (27) . Supporting this theory, gene array studies found that 

mRNA expression levels of cathelicidin were found to be significantly 

increased in all subtypes of rosacea (29) . Additionally, local proteases 

(serine protease KLK5) that control the production of cathelicidin in 

epidermis were also abnormally expressed in rosacea patients (25,27) . 

To further test their hypothesis, researchers injected abnormal 

cathelicidin or protease that produce these peptides in the skin 

of mice and observed similar inflammatory features of the disease 

found in humans (27) . Observation of higher amounts of receptors of 

the recognition system, Toll-like receptor 2 (TLR2), in the epidermis 

of patients with rosacea explained the overreaction of these patients 

to environmental stimuli, since enhanced action of TLR2 in keratinocytes 

leads to an increase in serine protease KLK5 and cathelicidin 

production (23,25) . Interestingly, tetracyclines, which improve signs and 

symptoms of rosacea, are known to inhibit expression and activity of 

several matrix metalloproteinases (21) , as well as a class of proteases 

that activate cathelicidin, sustaining this theory (26,27) . Furthermore, a 

recent study found elevated concentrations of 5 molecules involved 

in the innate immune response (interleukin-1b, interleukin-16, stem 

cell factor, monocyte chemotactic protein (MCP)-1, and monokine 

induced by g-interferon) in cutaneous biopsy specimens taken from 

ocular rosacea patients, supporting the concept that ocular rosacea 

is a disorder of innate immunity (30) . 

Vascular dilation and incompetence contribute to the signs and 

symptoms of rosacea. The characteristic facial flushing, persistent 

erythema and telangiectasia may be caused by altered cutaneous 

neurovascular homeostasis. Studies have demonstrated increased 

blood flow in the face and larger and more numerous vessels in the 

face than in other areas of the body (31) . Significantly dilated blood 

and lymphatic vessels were reported in all subtypes of rosacea (29) . 

Studies further demonstrated an up-regulation of genes involved 

in vasoregulation and neurogenic inflammation and suggested that 

dysregulation of mediators and receptors implicated in neurovascular 

and neuroimmune communication may be crucial at early stages 

of rosacea (26,29,32) . Improvement of erythema and flushing in rosacea 

by topical administration of a-adrenergic receptor agonists, oxymetazoline 

and xylometazoline, helps support this theory (25,33,34) . 

Cathelicidin causes endothelial changes (26) . Angiogenesis induced 

by cathelicidin is mediated by an increase in vascular endothelial 

growth factor (VEGF) in epidermal keratinocytes, and could represent 

an explanation for these vascular events in rosacea (25) . An increase in 

expression of VEGF and its receptors was demonstrated in the skin of 

patients with rosacea (35,36) . 

Group IIA phospholipase A 2 

, an antimicrobial protein capable of 

killing Gram-positive bacteria, is secreted into the tears by lacrimal 

glands and plays a role in innate host defense. A decreased concentration 

of group IIA phospholipase A 2 

was found in tears of patients 

with ocular rosacea (37) . 

Microbial organisms such as Helicobacter pylori, Demodex folliculorum, 

Demodex brevis and Staphylococcus epidermidis have been 

appointed as other possible causative factors in exacerbation of the 

disease; however this remains a controversy (23,26,31,38-43) . The prevalence 

of H. pylori infection was found higher in patients with rosacea when 

compared to the general population, and its eradication has been 

shown to influence the clinical outcome of this disease (31,39,44-46) . However, 

other studies have not found such difference (41,47-49) . Demodex, 

a microscopic mite found in hair follicles and sebaceous glands, is 

the most common ectoparasite in humans. Studies support its role 

in the activation of immune mechanisms in certain subtypes of 

rosacea, especially papulopustular rosacea (32) . The Demodex count 

was shown significantly higher in patients with facial rosacea, and 

a study demonstrated a strong correlation between positive serum 

immunoreactivity and ocular Demodex infestation in facial rosacea 

and lid margin inflammation (41,50,51) . Another proposed mechanism 


Vieira ACC, et al. 

is that Demodex mites may act as vectors for other microorganisms 

such as Bacillus olenorium, which may be responsible for initiation of 

inflammatory response in rosacea, through production of antigenic 

proteins and stimulation of Toll-like receptor 2 (TLR2) (23,25,38,42,50) . 

Diagnosis 

The diagnosis of rosacea is clinical and relies on observation of 

skin manifestations. In cases in which these are only very subtle, the 

diagnosis can become very challenging and the disease may remain 

undiagnosed. In addition, manifestations of ocular rosacea are by no 

means specific to the disorder alone and other ophthalmologic diseases 

may present with similar findings, making the diagnosis even 

more difficult and the search for a diagnostic test quite important. 

Lack of diagnostic test 

Unfortunately, there is not yet a diagnostic test available for either 

cutaneous or ocular rosacea (15) . No serologic or histologic markers 

have been described to date. A diagnostic marker may enable earlier 

diagnosis and treatment, as well as contribute with an etiologic explanation 

for this troublesome disorder. Our group has been working 

on the glycomic profile of tears and saliva of roseatic patients, as an 

initial step in the long pathway towards the search for a biomarker for 

the disease. We have previously shown a high abundance of O-linked 

oligosaccharides in the tears of patients with rosacea (52) . More recently, 

we published our results on glycomic analysis of tears and saliva, 

and previous results were confirmed in both fluids with N-glycans 

dramatically decreased in roseatic tear and saliva samples (53) . Furthermore, 

we described highly novel glycans that may be potential 

biomarkers for rosacea (53) . 

Classification and grading of rosacea 

To aid in diagnosis, in 2002, an expert committee of the American 

National Rosacea Society published a standard classification system 

for rosacea (54) . As well as serving as a diagnostic tool, this classification 

facilitates communication among dermatologists, researchers and 

other specialists (54,55) . This important publication describes primary 

and secondary features of rosacea and defines 4 subtypes (erythematotelangiectatic, 

papulopustular, phymatous and ocular rosacea) 

and 1 variant (granulomatous rosacea) of the disease (54) . The primary 

Table 1. Primary and secondary features of rosacea. Adapted from 

the Standard Classification of Rosacea, proposed by the National 

Rosacea Society Expert Committee, 2002 (54) 

Primary features 

Flushing (transient erythema) 

Nontransient erythema 

Papules and pustules 

Telangiectasia 

Secondary features 

Burning or stinging sensations 

Elevated plaques 

Dry appearance 

Edema 

Ocular manifestations 

Peripheral location 

Phymatous changes 

Description 

Frequent blushing or flushing 

Persistent redness of the facial skin 

Red papules with or without pustules. Nodules 

may also occur 

Telangiectases are common but not necessary 

for a rosacea diagnosis 

Description 

Dry appearance of central facial skin 

Facial edema 

and secondary features are listed in table 1. The presence of one or 

more of the primary signs with an axial facial distribution is indicative 

of rosacea. One or more of the secondary features may or may not 

be present. 

Later, in 2004, the National Rosacea Society Expert Committee 

published a grading system to assess the severity of disease. Primary 

features were graded on a scale from 0 to 3 whether they were absent, 

mild, moderate, or severe, and most secondary features were 

graded as absent or present (56) . 

Diagnosis of ocular rosacea 

The diagnosis of ocular rosacea relies on observation of one or 

more of the following signs and symptoms: watery or bloodshot 

appearance (interpalpebral conjunctival hyperemia), foreign body 

sensation, burning or stinging, dryness, itching, light sensitivity, 

blurred vision, telangiectases of the conjunctiva and lid margin, lid 

and periocular erythema. Anterior blepharitis, meibomian gland dysfunction 

and irregularity of the eyelid margins may also be present (54) . 

Diagnosis of pediatric rosacea 

The clinical features of pediatric rosacea are similar to those observed 

in adults (16) . However, in children, the dermatologic findings 

are often absent, making the diagnosis even more challenging and 

the identification of ocular manifestations especially important (15,17,57) . 

A study revealed ocular symptoms to precede skin features in 55% 

of children (58) . Ophthalmologists should maintain high suspicion in 

children with ocular surface disease, with or without cutaneous features, 

to avoid misdiagnosis and complications (59) . A positive family 

history of cutaneous rosacea and previous episodes of chalazia may 

be helpful in establishing the diagnosis (17) . 

Clinical findings 

Rosacea 

Symptoms may show periods of exacerbation and remission; 

however, the disease usually progresses over time. Some factors are 

known to worsen symptoms of rosacea and are referred to as trigger 

factors. Some examples of triggers are sun exposure, spicy foods, 

alcohol consumption, extreme temperatures, physical exercise, menopause 

and emotional distress such as anger and embarrassment. 

These factors tend to be specific to each individual. A recent large 

epidemiologic study revealed that alcohol consumption is associated 

with only a small increase in risk of developing rosacea, whereas 

smoking may actually substantially reduce such risk (9) . 

Figure 2. Eyelid margin of a patient with ocular rosacea showing meibomian gland 

dysfunction and telangiectases. 


365



Patients with ocular rosacea may complain of foreign body sensation, 

dryness, itching, photophobia and tearing (10,60) . Decreased visual 

acuity may result when corneal involvement is present. 

Ocular manifestations are usually bilateral and, as previously 

mentioned, can be non-specific (15) . The severity of ocular rosacea 

symptoms is often not related to the severity of cutaneous manifestations 

(15,31,51,60,61) . One study found a significant relationship between 

ocular involvement and the severity of telangiectasia (62) . 

Eyelids and tear film 

Blepharitis and meibomian gland dysfunction are common 

findings (3,15) . Slit-lamp examination of the eyelid margins reveals 

telangiectases (Figure 2), dilated meibomian glands, excessive seborrheic 

secretion and collarettes around the eyelashes (15) . Excessive 

meibomian secretion may lead to a soapy aspect of the inferior tear 

meniscus. Debris in the tear film may also be present. Recurrent 

hordeolum/chalazion and tear film insufficiency are commonly 

observed as a consequence of meibomian gland dysfunction (9,15) . 

Dry eyes, with abnormal Schirmer test, were reported in 56-62.5% 

of patients with ocular rosacea (24,51,63) . Diminished tear break-up time 

(TBUT) has also been reported in a large majority of patients with 

ocular rosacea (24,51,60) . 

Facial edema is an uncommon manifestation (64) . Periorbital edema 

has been reported in the literature and in one particular case, 

eyelid edema was severe enough to cause visual impairment (65,66) . 

Conjunctiva 

Chronic conjunctivitis characterized by interpalpebral bulbar 

conjunctival hyperemia may be present (13,15) , as well as a chronic papillary 

reaction (3) . Cicatricial conjunctivitis involving the lower lid was 

described by Akpek et al. as one of the most common ocular surface 

findings in rosacea (67) . Chronic cicatrizing conjunctivitis affecting 

mainly the upper eyelids, mimicking the classic findings in trachoma, 

has also been reported (68) . Pinguecula and conjunctival fibrosis have 

been reported in up to 20% of patients with ocular rosacea (69,70) . Starr 

and McDonald described a characteristic “arcade” of dilated vessels in 

the superficial limbal plexus, usually present in the inferior quadrants 

and not extending into the cornea (1) . 

Symblepharon formation following surgical excision of a pyogenic 

granuloma in a patient with ocular rosacea has been reported (71) . 

Cornea 

Corneal manifestations may occur in up to 33% of patients with 

rosacea (1,3) . The inferior cornea is usually affected (15) . Corneal involvement 

typically starts with superficial punctate keratitis on the lower 

third of the cornea. Peripheral neovascularization associated with 

subepithelial marginal triangular infiltrates along the advancing 

vascular border can also occur (Figure 3) (1) . If left untreated, these 

infiltrates may progress centrally and lead to stromal ulceration and 

even perforation (15,72,73) . 

Recurrent corneal epithelial erosions have been reported in patients 

with ocular rosacea (67,74,75) . Other uncommon corneal findings 

include pseudodendritic ulcer and pseudokeratoconus, presenting 

with inferior corneal thinning and high astigmatism (76-78) . Secondary 

infectious keratitis has been reported (79,80) . 

Decreased visual acuity may result from epithelial ulceration, 

surface irregularities and corneal scarring. 

Other ocular findings 

Other ocular findings include iritis, episcleritis and scleritis (5,15) . We 

have previously published a case of spontaneous scleral perforation 

in a patient with rosacea (Figure 4) (81) . 

Pediatric rosacea 

The most common ocular signs in pediatric rosacea include 

meibomian gland dysfunction, telangiectasia, recurrent chalazia, 

conjunctival hyperemia, superficial punctate epitheliopathy involving 

the inferior cornea, as well as corneal infiltrates, pannus and 

neovascularization (16,58) . Phlyctenular keratoconjunctivitis has also 

been associated with ocular rosacea in children (17) . Corneal scarring 

and opacification are possible complications of more advanced 

disease (17) . Donaldson et al., found that 90% of the children in their 

series had some degree of corneal involvement at the time of presentation 

(17) . 

Differential diagnosis of ocular rosacea 

The differential diagnosis of ocular rosacea may include staphylococcal 

and seborrheic blepharokeratoconjunctivitis, and sebaceous 

gland carcinoma. Given that there is currently no diagnostic test 

for rosacea, distinguishing ocular rosacea from staphylococcal and 

seborrheic blepharoconjunctivitis in patients in which ocular signs 

precede skin findings may be difficult. Sebaceous gland carcinoma 

Figure 3. Corneal involvement in a patient with ocular rosacea: peripheral neovascularization 

associated with subepithelial marginal infiltrates along the advancing vascular border. 

Figure 4. Scleral perforation in a patient with ocular rosacea. 



is often misdiagnosed as chalazion and early recognition is often 

challenging. For this reason, recurrent chalazia should be excised 

and sent to histopathology. 

Treatment 

Rosacea treatment should be initiated as early as possible in order 

to slow progression of inflammation and decrease development of 

irreversible fibrosis and ocular morbidity. The severity of the clinical 

findings and subtypes will help guide therapy. It is important to note 

that it is not uncommon for patients to present with an overlap of 

signs, showing features of more than one subtype of the disease (82) . 

Clinicians should therefore identify the clinical features of the individual 

patient in order to guide the treatment, rather than try to 

fit the patient into one specific category. Treatment of eye-related 

symptoms alone may not be effective unless the underlying rosacea 

is diagnosed and adequately treated. 

General measures 

Initial management includes identification and avoidance of 

trig ger factors (10) . These factors are usually specific to each individual. 

Broad-spectrum sunscreen should be used daily for photoprotection 

(11) . Appropriate use of concealing makeup may help 

disguise upsetting facial features (83) . Patients should be informed 

about the need and importance of regular eye exams (4) . 

Medical treatment 

Cutaneous rosacea 

There are several treatment options available for rosacea but it is 

unclear which are the most effective. Early stages of rosacea may be 

controlled with topical regimens. Medications such as topical metronidazole 

(0.75% and 1% formulations) and azelaic acid (15% gel 

or 20% cream) are approved for the treatment of mild to moderate 

papulopustular rosacea, showing similar results (15,61,82,84-88) . Sodium 

sulfacetamide 10%/sulfur 5% preparations have also been used 

with satisfactory results; however, its association with metronidazole 

cream showed superior efficacy(89). Other topical treatments 

used “off-label” include clindamycin, erythromycin, pimecrolimus, 

tacrolimus and tretinoin (61,86,89) . 

When topical treatment alone is not sufficient, systemic therapy 

should be initiated. Oral tetracyclines (500 mg b.i.d.) and 

do xycycline (40-100 mg daily from 8-16 weeks) have been shown 

to safely improve the signs and symptoms of rosacea (84) . In 2006, 

the FDA approved a daily formulation of 40 mg doxycycline mo - 

nohydrate (Oracea®, Galderma) for the treatment of rosacea, although 

other approved formulations of doxycycline are available. 

In unresponsive cases and when tetracyclines are contra-indicated 

or not tolerated, oral azithromycin (500 mg/day for 2 weeks) has 

been considered a good option (2,90,91) . Oral isotretinoin (0.3 to 1.0 

mg/kg/day) is recommended in more severe intractable cases. The 

biggest disadvantage of this drug is the risk of teratogenicity and, 

therefore, all female patients in childbearing age should use proper 

contraception (92) . 

Diffuse and persistent erythema in erythematotelangiectatic 

rosacea has been successfully treated with topical oxymetazoline 

0.05% and xylometazoline 0.05%, alpha-adrenergic receptor agonists 

with strong vasoconstrictive properties (33,34) . It is important 

to note that these medications are not yet FDA-approved for the 

treatment of rosacea, but have been published in case reports. 

Another α-agonist currently in study showing promising results for 

the treatment of facial erythema is brimonidine tartrate, a highly 

selective α2-adrenoreceptor agonist (82,93) . Vascular laser therapy 

and intense pulsed light can be used for treatment of resistant 

skin telangiectasias and persistent erythema (15,61,93,94) . 


Management of mild ocular rosacea requires local measures such 

as warm compresses, lid hygiene with neutral baby shampoo and 

instillation of lubricating drops (2,83) . Thicker lubricating agents, such 

as gels and ointments, may be prescribed for more symptomatic 

dry eyes to promote longer-lasting relief. Topical cyclosporine 0.05% 

helps increase tear production and quality (95) . Antibiotic ointments 

prescribed daily, at bedtime, decreases eyelid flora and helps soften 

collarettes (61) . 

Moderate ocular rosacea may require systemic therapy (96) . Oral 

tetracycline and doxycycline have been used to successfully treat 

ocular rosacea as an adjunct therapy to topical treatment (60,61,83,97) . 

As in the management of skin rosacea, tetracyclines may be initially 

administered 500 mg b.i.d. for 2-3 weeks, and then tapered according 

to clinical response. Doxycycline possesses anti-angiogenic and anti- 

-inflammatory properties as well as fewer side effects than first generation 

tetracyclines. Doxycycline may be prescribed in a regimen 

of 100 mg once or twice daily for 6 to 12 weeks. Many patients may 

present flare-ups once the medication is discontinued and may therefore 

require long-term maintenance therapy. However, long-term 

use of the drug at this dosage has side effects that may compromise 

regular treatment, such as gastrointestinal intolerance. As previously 

mentioned, the FDA approved a 40 mg doxycycline formulation 

(Oracea®, Galderma) for the treatment of rosacea. It contains 30 mg 

immediate-release and 10 mg delayed-release doxycycline that 

should be administered once daily (98) . Significant improvement of 

ocular rosacea was obtained with regular use of controlled-release 

doxycycline 40 mg, with no side effects leading to discontinuation 

of therapy (85,99) . Azithromycin improved eye symptoms and was considered 

a good alternative therapy for ocular rosacea, when other 

drugs are not tolerated (2) . Long-term oral consumption of omega 

3 fatty acids has been shown to improve the quality of meibomian 

gland secretion (15) . 

In cases where persistent ocular surface inflammation, episcleritis, 

scleritis, iritis and sterile keratitis are present, topical corticosteroids 

or cyclosporine may prove beneficial (15,61,85,95,100) . Topical cyclosporine 

0.05%, used twice daily, was also beneficial in reducing inflammation 

in posterior blepharitis (15) . Long-term use of steroids should be avoided 

due to the potential side effects, such as glaucoma and cataracts, 

in which case the use of topical cyclosporine is preferable (15) . 

In cases of secondary infectious keratitis, antimicrobial agents 

should be initiated promptly and topical steroids avoided or used 

with care, along with specific antimicrobial therapy (15,79) . 

Pediatric ocular rosacea 

Initial treatment should include local measures such as warm 

compresses and eyelid hygiene with neutral baby shampoo. This 

routine may be difficult to maintain in children; however, the importance 

of these measures should be reinforced to the parents. Topical 

erythromycin ointment may also be used on the eyelid margins (58) . 

Low-dose corticosteroid drops may be necessary to control ocular 

surface inflammation and treat keratitis, peripheral corneal vascularization 

and scarring (17) . 

As in adults, those patients with resistant disease should be prescribed 

oral therapy. Systemic treatment of ocular childhood rosacea 

is very similar to that in adults, although one important difference 

is that tetracyclines are contra-indicated in children younger than 

7 years of age (58) . Tetracycline and doxycycline, commonly used for 

therapy in adults, may result in depressed bone growth and dental 

staining in this age range (17) . In these cases, erythromycin (20 mg/kg/ 

day) is preferable (16,17,101) . Doxycycline (100 mg once or twice daily) is 

considered a good therapeutic option for older children, since it is 

usually better tolerated than tetracycline. Long-term treatment with 

systemic erythromycin and doxycycline proved beneficial in children 

with ocular rosacea (16) . Azithromycin improved eye symptoms and 


367


may also be considered in young children, where tetracyclines cannot 

be prescribed (2) . 

Surgical treatment 

Punctal occlusion may be beneficial in the management of moderate 

to severe dry eyes. Persistent chalazia may require surgical 

management and specimen should be sent to pathology. 

Corneal thinning and perforations in ocular rosacea patients 

have been managed using simple corneal sutures, tissue adhesive, 

amniotic membrane transplantation, and conjunctival flaps (73,102-104) . 

Lamellar or full-thickness keratoplasty are other options when surgical 

intervention becomes necessary, in cases of corneal perforation or 

opacification (15) . Gracner and Gracner chose to perform a keratoplasty 

to successfully treat an extensive cornealscleral perforation (72) . 

Conclusion and future perspectives 

Rosacea is a prevalent disorder that may be disfiguring and cause 

significant social impairment, as well as various degrees of ocular 

morbidity, if not diagnosed and managed appropriately. Ocular 

rosacea is often left undiagnosed and no specific diagnostic test is 

available to date. For this reason, diagnosis relies on a high level of 

suspicion and clinical observation of characteristic skin manifestations 

(54) . This becomes very challenging in up to 20% of the patients, 

when ocular symptoms and signs precede cutaneous features (3) . In 

these cases, a diagnostic test would be of great importance. Future 

studies may provide a biomarker and an etiologic explanation for this 

troublesome disorder. 

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French. 


369

Cartas ao Editor | Letters to the Editor 

Axonal electrovisiogram or inverse photopic skin electroretinogram? 

Eletrovisograma axonal ou eletrorretinograma fotópico inverso de pele? 

Katharina Messias 1 , Vinicius Monteiro de Castro 1 , Florian Gekeler 2 , Andre Messias 1 

Dear Editor, 

We would like to discuss the very interesting article “Axonal electrovisiogram 

as an electrophysiological test to evaluate optic nerve 

and inner retina electrical potentials: findings in normal subjects”, 

published in the 74(1) issue of Arquivos Brasileiros de Oftalmologia (1) . 

In this work, authors recorded electrophysiological potentials using 

the Axonal electrovisiogram (AxEvg) paradigm, which is a method 

developed by Sabadel et al. (2) , to record pre-chiasmatic electric potentials, 

in normal subjects. 

The study is well designed and is nicely reported in the article, 

but some major concerns must be made about the origin of these 

electrical responses. 

In this experiment an interference of retinal electric potentials 

- the electroretinogram (ERG) - cannot be ruled out, since AxEvg is 

recorded with electrodes placed very closely to the eye, in a similar 

configuration used for skin ERG (sERG) (3,4) . 

Interestingly, the difference between electrode placement for 

AxEvg and sERG is that the electrode placed closest to the eye is the 

negative pole, which might explain the waveform configuration 

found in AxEvg recordings. Figure 1 shows electrode placements for 

AxEvg and sERG. 

In matter of fact, placing the negative pole as the closest electrode 

to the eye, regardless of the position of the positive pole (placed 

on ear lobe in case of AxEvg or placed below the eye in case of sERG), 

and stimulating the retina with a strong light flash (2.5 cd.s/m 2 ) using 

a Ganzfeld bowl, one cannot avoid the hypothesis of the electrical 

response to be generated by the retina and presenting as an ERG 

with inverse polarity. 

Interestingly, the waveform shown by Cella et al. (1) , presents the 

same characteristics of a photopic ERG response, but recorded with 

inverse polarity, with P1 being the a-wave and N1 the b-wave. 

To investigate the origin of these electrical potentials we performed 

recordings using the same electrode configuration and 

stimulus parameters used by Cella et al. in a patient with optic chiasm 

dissection after a tuberculum sellae meningioma surgery 1 year 

earlier (no light perceptions in both eyes ever since). To proof the 

retinal origin of the AxEvg the electrodes in left eye were placed as 

mentioned by Cella at al., whereas, the electrodes in right eye were 

placed at the conjunctiva (DTL electrodes were used as negative 

pole) and at the earlobe (positive pole) (demonstrated in Figure 1). 

Two single flash stimulus intensities were used to proof relationship 

between stimulus intensity and amplitude. Finally, 30 Hz flicker was 

performed. 

Figure 1. Electrode placement for AxEvg and sERG. (Left) AxEvg: ground electrode is placed on patient´s forehead, negative electrode at the outer 

eye canthus and positive electrode at ipsilateral earlobe. (Right) sERG: ground electrode is placed at earlobe, negative electrode is placed at outer 

eye canthus and the positive electrode is placed below the eye. 

Submitted for publication: September 2, 2012 

Accepted for publication: September 30, 2012 

1 

Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine 

of Ribeirão Preto - Universidade de São Paulo - USP - Ribeirão Preto (SP), Brazil. 

2 

Center for Ophthalmology, University of Tübingen, Schleichstraße 12-16, D-72076 Tübingen, 

Germany. 


Disclosure of potential conflicts of interest: K.Messias, None; V.M.de castro, None; F.Gekeler, None; 

A.Messias, None. 


Messias K, et al. 

Figure 2. Potentials recorded from patient with dissected chiasm using AxEvg (red line) and inverted sERG techniques (blue line). (Top) 2.5 cd.s/m 2 stimulus; (Middle) 3 cd.s/m 2 

stimulus; (Bottom) 30 Hz Flicker stimulus. 

Interestingly, we can observe the same potential configuration, in 

both eyes even though we performed the AxEvg in the left eye and 

a modified sERG in the right eye. Latencies for P1 and N1 are corresponding 

in both eyes (see Figure 2). Because of the greater spatial 

proximity of the DTL electrode to the retina, amplitudes in the right 

eye are higher when compared to left eye. As the patient does not 

posses any functional optic nerve at neither of both sides, the only 

explicable origin of the measured potentials must be the retina. As 

we placed the negative electrode in contact with the eye rather than 

the positive, as it is use in ERG recording, we have a negative potential 

configuration. Note the corresponding latencies of the inverted ERG 

in figure 2. Furthermore, we can observe stimulus intensity correlation 

of the recorded potential, which speaks strongly in favor for 

electroretinographic origin of the measured potential. 

In conclusion, this data shows that the recorded electrical potentials 

using electrode placement proposed by Sabadel et al. (2) , for assessment 

of pre-chiasmatical potentials or evaluation of optic nerve 

function, and carried out by Cella et al. (1) , originate in the retina and 

are not optic nerve potentials. Future users should be aware of the 

electrical potentials generation to better understand its applications. 

The normative data shown by Cella et al., is still very valuable, since 

sERG can be very useful, especially for retinal function evaluation in 

children. 

With kind regards, 

Katharina Messias 

Vinicius de Castro 

Florian Gekeler 

André Messias 

References 

1. Cella W, Dantas AM, Lima AV, Avila MP. Axonal electrovisiogram as an electrophysiological 

test to evaluate optic nerve and inner retina electrical potentials: findings in 

normal subjects. Arq Bras Oftalmol. 2011;74(1):37-43. 

2. Sabadel A, Dalens H, Sole P. [Axonal electrovisiogram. Recording technic-clinical 

value]. Bull Soc Ophtalmol Fr. 1983;83(5):739-44. French. 

3. Giltrow-Tyler JF, Crews SJ, Drasdo N. Electroretinography with noncorneal and corneal 

electrodes. Invest Ophthalmol Vis Sci. 1978;17(11):1124-27. 

4. McCulloch DL, Van Boemel GB, Borchert MS. Comparisons of contact lens, foil, fiber 

and skin electrodes for patterns electroretinograms. Doc Ophthalmol. 1997;94(4): 

327-40. 


371

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373

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pela Internet, na interface apropriada do ABO. As normas que se 

seguem foram baseadas no formato proposto pelo Inter na tional 

Com mittee of Medical Journal Editors (ICMJE) e publicadas no artigo: 

Uniform Requirements for Manuscripts Submitted to Bio medical Journals. 

O respeito às instruções é condição obrigatória para que o tra - 

balho seja considerado para análise. 

O texto deve ser enviado em formato digital, sendo aceitos 

apenas os formatos .doc. ou .rtf. O corpo do texto deve ser digitado 

em espaço duplo, fonte tamanho 12, com páginas numeradas em 

al garismos arábicos, iniciando-se cada seção em uma nova pági na. 

As seções devem se apresentar na sequência: Página de Rosto, 

Abstract e Keywords, Resumo e Descritores, Introdução, Métodos, 

Resultados, Discussão Agradecimentos (eventuais), Referências, Tabelas 

(opcionais) e Figuras (opcionais) com legenda. 

1. Página de Rosto. Deve conter: a) título em inglês (máximo 

de 135 caracteres, incluindo espaços); b) título em português ou 

es panhol (máximo de 135 caracteres, incluindo espaços); c) tí tulo 

resumido para cabeçalho (máximo 60 caracteres, incluindo os 

es paços); d) nome científico de cada autor; e) titulação de cada 

autor (área de atuação profissional*, cidade, estado, país e, quando 

houver, depar tamento, escola, Universidade); f ) nome, endereço, 

telefone e e-mail do autor correspondente; g) fontes de auxilio 

à pesquisa (se hou ver); h) número do projeto e instituição responsável 

pelo parecer do Co mitê de Ética em Pesquisa; i) declaração dos 

conflitos de in teresses de todos os autores; j) número do registro 

dos ensaios clí nicos em uma base de acesso público. 

*Médico, estatístico, enfermeiro, ortoptista, fisioterapeuta, estudante etc. 

Aprovação do Comitê de Ética em Pesquisa. Todos os estudos 

que envolvam coleta de dados primários ou relatos clínico-cirúrgicos, 

sejam retrospectivos, transversais ou prospectivos, de vem 

indicar, na página de rosto, o número do projeto e nome da Instituição 

que forneceu o parecer do Comitê de Ética em Pes quisa. 

As pesquisas em seres humanos devem seguir a Declaração de 

Helsinque, enquanto as pesquisas envolvendo animais devem 

seguir os princí pios propostos pela Association for Research in Vision 

and Oph thal mo logy (ARVO). 

É necessário que o autor correspondente envie, como documento 

suplementar, a aprovação do Comitê de Ética em Pesquisa ou seu 

parecer dispensando da avaliação do projeto pelo Comitê. Não cabe 

ao autor a decisão sobre a necessidade de avaliação pelo Comitê de 

Ética em Pesquisa. 

Declaração de Conflito de Interesses. A página de rosto deve 

conter a declaração de conflitos de interesse de todos os autores 

(mesmo que esta seja inexistente). Para maiores informações sobre 

os potenciais conflitos de interesse acesse: Chamon W, Melo LA Jr, 

Paranhos A Jr. Declaração de conflito de interesse em apresentações 

e publicações científicas. Arq Bras Oftalmol. 2010;73(2):107-9. 

É necessário que todos os autores enviem os Formulários para Declaração 

de Conflitos de Interesse como documentos suplementares. 

Ensaios Clínicos. Todos os Ensaios Clínicos devem indicar, na pá gina 

de rosto, número de registro em uma base internacional de re gis - 

tro que permita o acesso livre a consulta (exemplos: U.S. Na tional 

Ins ti tutes of Health, Australian and New Zealand Clinical Trials 

Registry, Inter national Standard Randomised Controlled Trial Num ber 

- ISRCTN, University Hos pital Medical Information Net work Clinical Trials 

Registry - UMIN CTR, Ne derlands Trial Register). 

2. Abstract e Keywords. Resumo estruturado (Purpose, Methods, 

Re sults, Conclusions) com, no máximo, 300 palavras. Resumo não 

estruturado com, no máximo, 150 palavras. Citar cinco descritores 

em inglês, listados pela National Library of Medicine (MeSH - Medical 

Subject Headings). 

3. Resumo e Descritores. Resumo estruturado (Objetivos, Méto - 

dos, Resultados, Conclusões) com, no máximo 300 palavras. Resumo 

não estruturado com, no máximo, 150 palavras. Citar cinco descritores, 

em português listados pela BIREME (DeCS - Descritores 

em Ciências da Saúde). 

4. Introdução, Métodos, Resultados e Discussão. As citações no 

texto devem ser numeradas sequencialmente, em números arábi - 

cos sobrescritos e entre parênteses. É desaconselhada a citação 

no minal dos autores. 

5. Agradecimentos. Colaborações de pessoas que mereçam 

re conhecimento, mas que não justificam suas inclusões como 

auto res, devem ser citadas nessa seção. Estatísticos e editores médicos 

po dem preencher os critérios de autoria e, neste caso, de vem 

ser reconhecidos como tal. Quando não preencherem os critérios 

de autoria, eles deverão, obrigatoriamente, ser citados nesta 

seção. Não são aceitos escritores não identificados no manus - 

crito, portanto, escritores profissionais devem ser reconhecidos 

nes ta seção. 

6. Referências. A citação (referência) dos autores no texto deve 

ser numérica e sequencial, na mesma ordem que foram citadas 

e identificadas por algarismos arábicos sobrescritos. A apresen tação 

deve estar baseada no formato proposto pelo International 

Com mittee of Medical Journal Editors (ICMJE), conforme os exem - 

plos que se seguem. 

Os títulos de periódicos devem ser abreviados de acordo com o 

estilo apresentado pela List of Journal Indexed in Index Medicus, da 

National Library of Medicine. 

Para todas as referências, cite todos os autores, até seis. Nos traba - 

lhos com sete ou mais autores, cite apenas os seis primeiros, 

seguidos da expressão et al. 

Exemplos de referências: 

Artigos de Periódicos 

Costa VP, Vasconcellos JP, Comegno PEC, José NK. O uso da mitomicina 

C em cirurgia combinada. Arq Bras Oftalmol. 1999; 62(5):577-80. 

Livros 

Bicas HEA. Oftalmologia: fundamentos. São Paulo: Contexto; 1991. 


Capítulos de livros 

Gómez de Liaño F, Gómez de Liaño P, Gómez de Liaño R. Exploración 

del niño estrábico. In: Horta-Barbosa P, editor. Estrabismo. Rio de 

Ja neiro: Cultura Médica; 1997. p. 47-72. 

Anais 

Höfling-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. 

Teses 

Schor P. Idealização, desenho, construção e teste de um cera tô - 

metro cirúrgico quantitativo [tese]. São Paulo: Universidade Federal 

de São Paulo; 1997. 

Documentos Eletrônicos 

Monteiro MLR, Scapolan HB. Constrição campimétrica causada por 

vigabatrin. Arq Bras Oftalmol. [periódico na Internet]. 2000 [citado 

2005 Jan 31]; 63(5): [cerca de 4 p.]. Disponível em:http://www.scielo. 

br/scielo.php?script=sci_arttext&pid=S0004-274920000005000 

12&lng=pt&nrm=iso 

7. Tabelas. A numeração das tabelas deve ser sequencial, em algarismos 

arábicos, na ordem em que foram citadas no texto. Todas 

as tabelas devem ter título e cabeçalho para todas as colunas 

e se rem apresentadas em formatação simples, sem linhas verticais 

ou preen chimentos de fundo. No rodapé da tabela deve constar 

legenda para todas as abreviaturas (mesmo que definidas previamente 

no texto) e testes estatísticos utilizados, além da fonte 

bi bliográfica quando extraída de outro trabalho. Todas as tabelas 

devem estar contidas no documento principal do manuscrito após 

as referências bibliográficas, além de serem enviadas como documento 

suplementar. 

8. Figuras (gráficos, fotografias, ilustrações, quadros). A nu - 

meração das figuras deve ser sequencial, em algarismos arábi - 

cos, na ordem em que foram citadas no texto. O ABO publicará as 

figuras em preto e branco sem custos para os autores. Os manus - 

critos com figuras coloridas apenas serão publicados após o 

pagamento da respectiva taxa de publicação de R$ 500,00 por 

manuscrito. 

Os gráficos devem ser, preferencialmente, em tons de cinza, com 

fundo branco e sem recursos que simulem 3 dimensões ou profundidade. 

Gráficos do tipo torta são dispensáveis e devem ser substituídos 

por tabelas ou as informações serem descritas no texto. 

Fotografias e ilustrações devem ter resolução mínima de 300 DPI 

para o tamanho final da publicação (cerca de 2.500 x 3.300 pixels, 

para página inteira). A qualidade das imagens é considerada na 

avaliação do manuscrito. 

Todas as figuras devem estar contidas no documento principal do 

manuscrito após as tabelas (se houver) ou após as referências bibliográficas, 

além de serem enviadas como documento suplementar. 

No documento principal, cada figura deve vir acompanhada de sua 

respectiva legenda em espaço duplo e numerada em algarismo 

arábico. 

Os arquivos suplementares enviados podem ter as seguintes extensões: 

JPG, BMP, TIF, GIF, EPS, PSD, WMF, EMF ou PDF, e devem 

ser nomeados conforme a identificação das figuras, por exemplo: 

“grafico_1.jpg” ou “figura_1A.bmp”. 

9. Abreviaturas e Siglas. Quando presentes, devem ser precedidas 

do nome correspondente completo ao qual se referem, quando 

ci tadas pela primeira vez, e nas legendas das tabelas e figuras 

(mesmo que tenham citadas abreviadas anteriormente no texto). 

Não devem ser usadas no título e no resumo. 

10. Unidades: Valores de grandezas físicas devem ser referidos de 

acordo com os padrões do Sistema Internacional de Unidades. 

11. Linguagem. A clareza do texto deve ser adequada a uma 

pu blicação científica. Opte por sentenças curtas na forma direta e 

ati va. Quando o uso de uma palavra estrangeira for absolutamente 

ne cessário, ela deve aparecer com formatação itálica. Agentes 

te ra pêuticos devem ser indicados pelos seus nomes genéricos 

seguidos, entre parênteses, pelo nome comercial, fabricante, cidade, 

es tado e país de origem. Todos os instrumentos ou apare - 

lhos de fabricação utilizados devem ser citados com o seu nome 

comercial, fabricante, cidade, estado e país de origem. É necessária 

a colocação do símbolo (sobrescrito) de marca registrada ® ou 

em todos os nomes de instrumentos ou apresentações comerciais 

de drogas. Em situações de dúvidas em relação a estilo, terminologia, 

medidas e assuntos correlatos, o AMA Manual of Style 10th 

edition deverá ser consultado. 

12. Documentos Originais. Os autores correspondentes devem ter 

sob sua guarda os documentos originais como a carta de aprovação 

do comitê de ética institucional para estudos com humanos ou 

animais; o termo de consentimento informado assinado por todos 

os pacientes envolvidos, a declaração de concordância com o conteúdo 

completo do trabalho assinada por todos os autores e declaração 

de conflito de interesse de todos os autores, além dos re gistros 

dos dados colhidos para os resultados do trabalho. 

13. Correções e Retratações. Erros podem ser percebidos após a 

publicação de um manuscrito que requeiram a publicação de 

uma correção. No entanto, alguns erros, apontados por qualquer 

leitor, podem invalidar os resultados ou a autoria do manuscrito. 

Se al guma dúvida concreta a respeito da honestidade ou fidedignidade 

de um manuscrito enviado para publicação for levantada, 

é obri gação do editor excluir a possibilidade de fraude. Nestas 

si tuações o editor comunicará as instituições envolvidas e as agências 

financiadoras a respeito da suspeita e aguardará a decisão 

final desses órgãos. Se houver a confirmação de uma publicação 

frau dulenta no ABO, o editor seguirá os protocolos sugeridos pela 

In ter na tional Committee of Medical Journal Editors (ICMJE) e pelo 

Com mittee on Publication Ethics (COPE). 

Lista de Pendências 

Antes de iniciar o envio do seu manuscrito o autor deve confir - 

mar que todos os itens abaixo estão disponíveis: 

□ Manuscrito formatado de acordo com as instruções aos autores. 

□ Limites de palavras, tabelas, figuras e referências adequados 

para o tipo de manuscrito. 

□ Todas as figuras e tabelas inseridas no documento principal 

do manuscrito. 

□ Todas as figuras e tabelas na sua forma digital para serem 

enviadas separadamente como documentos suplementares. 

□ Formulário de Declaração da Participação dos Autores 

preen chido e salvo digitalmente, para ser enviado como 

do cumento suplementar. 

□ Formulários de Declarações de Conflitos de Interesses de 

todos os autores preenchidos e salvos digitalmente, para 

serem enviados como documentos suplementares. 

□ Número do registro na base de dados que contem o proto - 

colo do ensaio clínico constando na folha de rosto. 

□ Versão digital do parecer do Comitê de Ética em Pesquisa 

com a aprovação do projeto, para ser enviado como documento 

suplementar. 


375

Lista de Sítios da Internet 

Interface de envio de artigos do ABO 

http://www.scielo.br/ABO 

Formulário de Declaração de Contribuição dos Autores 

http://www.cbo.com.br/site/files/Formulario Contribuicao dos Autores.pdf 

International Committee of Medical Journal Editors (ICMJE) 

http://www.icmje.org/ 

Uniform requirements for manuscripts submitted 

to biomedical journals 

http://www.icmje.org/urm_full.pdf 

Declaração de Helsinque 

http://www.wma.net/en/30publications/10policies/b3/index.html 

Princípios da Association for Research in 

Vision and Ophthal mo logy (ARVO) 

http://www.arvo.org/eweb/dynamicpage.aspx?site=arvo2& 

webcode=AnimalsResearch 

Chamon W, Melo LA Jr, Paranhos A Jr. Declaração de conflito de 

interesse em apresentações e publicações científicas. 


http://www.scielo.br/pdf/abo/v73n2/v73n2a01.pdf 

Princípios de Autoria segundo ICMJE 

http://www.icmje.org/ethical_1author.html 

Formulários para Declaração de Conflitos de Interesse 

http://www.icmje.org/coi_disclosure.pdf 

U.S. National Institutes of Health 

http://www.clinicaltrials.gov 

Australian and New Zealand Clinical Trials Registry 

http://www.anzctr.org.au 

International Standard Randomised Controlled 

Trial Number - ISRCTN 

http://isrctn.org/ 

University Hospital Medical Information Network 

Clinical Trials Registry - UMIN CTR 

http://www.umin.ac.jp/ctr/index/htm 

Nederlands Trial Register 

http://www.trialregister.nl/trialreg/index.asp 

MeSH - Medical Subject Headings 

http://www.ncbi.nlm.nih.gov/sites/entrez?db=mesh&term= 

DeCS - Descritores em Ciências da Saúde 

http://decs.bvs.br/ 

Formatação proposta pela International Committee 

of Medical Journal Editors (ICMJE) 

http://www.nlm.nih.gov/bsd/uniform_requirements.html 

List of Journal Indexed in Index Medicus 

http://www.ncbi.nlm.nih.gov/journals 

AMA Manual of Style 10th edition 

http://www.amamanualofstyle.com/ 

Protocolos da International Committee of 

Medical Journal Editors (ICMJE) 

http://www.icmje.org/publishing_2corrections.html 

Protocolos da Committee on Publication Ethics (COPE) 

http://publicationethics.org/flowcharts 

Editada por 

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Diretora Comercial: Helen Suzana Perlmann; Diretora de Arte: Elza Rudolf; 

Editoração Eletrônica, CTP e Impressão: Ipsis Gráfica e Editora S.A. 

Periodicidade: Bimestral; Tiragem: 7.450 exemplares 

Publicidade 

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R. Casa do Ator, 1.117 - 2º andar - Vila Olímpia - 

São Paulo - SP - CEP 04546-004 

Contato: Fabrício Lacerda 

Fone: (5511) 3266-4000 - Fax: (5511) 3171-0953 

E-mail: assessoria@cbo.com.br 


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