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issn 0004-2749<br />

versão impressa<br />

A r q u i v o s b r a s i l e i r o s d e<br />

publicação oficial do conselho brasileiro de oftalmologia<br />

JANEIRO/FEVEREIRO 2013<br />

76 01<br />

<strong>Photocoagulation</strong> <strong>versus</strong> <strong><strong>in</strong>travitreal</strong><br />

<strong><strong>in</strong>jection</strong> <strong>in</strong> <strong>diabetic</strong> ret<strong>in</strong>opathy<br />

Body mass and <strong>in</strong>traocular<br />

pressure <strong>in</strong> children<br />

Ultrasonographic presentation<br />

of <strong>in</strong>traocular foreign bodies<br />

Cl<strong>in</strong>ical trials <strong>in</strong> Brazilian journals<br />

Radius-Maumenee syndrome<br />

<strong>in</strong>dexada nas bases de dados<br />

medl<strong>in</strong>e | embase | isi | ScielO


NOVAS LENTES DE CONTATO<br />

1-DAY ACUVUE®<br />

© Johnson & Johnson do Brasil Indústria E Comércio de Produtos Para Saúde Ltda. ABRIL/2013<br />

TRUEYE®<br />

Saúde ocular equivalente aos olhos sem lentes. 1<br />

1<br />

ª<br />

A 1ª LENTE DE USO ÚNICO<br />

DE SILICONE HIDROGEL NO BRASIL<br />

1-DAY ACUVUE® TRUEYE®. OLHOS SAUDÁVEIS<br />

E CONFORTÁVEIS, COM A PRATICIDADE DE<br />

UMA LENTE NOVA A CADA DIA. TODO DIA.<br />

ACESSE O WEBSITE EXCLUSIVO PARA OFTALMOLOGISTAS: WWW.JNJVISIONCARE.COM.BR<br />

PARA MAIS INFORMAÇÕES, LIGUE PARA 0800 7288281 OU ENVIE E-MAIL PARA OFTALMOLOGISTA@CONBR.JNJ.COM<br />

Senofilcon A - 1 ACUVUE® OASYS® com HYDRACLEAR® PLUS: Reg.ANVISA 80148620045, 2 ACUVUE® OASYS® para ASTIGMATISMO com HYDRACLEAR® PLUS: Reg.ANVISA 80148620054, 3 ACUVUE®<br />

OASYS® com HYDRACLEAR® PLUS (Bandage): Reg.ANVISA 80148620058, Galyfilcon A - 4 ACUVUE® ADVANCE® com HYDRACLEAR®: Reg.ANVISA 80148620026, Etafilcon A - 5 ACUVUE® 2: Reg.<br />

ANVISA 80148620019, 6 1-DAY ACUVUE® MOIST®: Reg.ANVISA 80148620052 , 7 1-DAY ACUVUE® MOIST® para ASTIGMATISMO: Reg.ANVISA 80148620064 , 8 ACUVUE® 2 COLOURS: Reg.ANVISA<br />

80148620013, 9 ACUVUE® CLEAR: Reg.ANVISA 80148620021 e 10 ACUVUE® BIFOCAL: Reg.ANVISA 80148620016. Caixas com 30 6,7 , 6 1,2,3,4,5,8,9,10 ou 2 8 lentes de contato (LC). Indicações: LC Esféricas 1,4,5,6,9 :<br />

Miopia, hipermetropia (presbiopia em regime de monovisão) afácica ou não afácica. LC Esféricas Coloridas 8 : Miopia, hipermetropia (presbiopia em regime de monovisão) afácica ou não afácica. LC<br />

Bifocais 10 : Presbiopia afácica ou não afácica associada ou não a miopia ou hipermetropia. LC Tóricas 2,7 : Astigmatismo afácico ou não afácico associado ou não a miopia ou hipermetropia. LC Terapêuticas 3 :<br />

As lentes de contato podem ser prescritas, em determ<strong>in</strong>adas condições ou doenças oculares, como lentes de proteção para a córnea, a fim de aliviar o desconforto e servir como uma cobertura de<br />

proteção. O médico Oftalmologista <strong>in</strong>formará se o usuário apresenta essa condição, podendo prescrever medicações adicionais ou programação de substituição para a condição específica. O usuário<br />

nunca deve tratar qualquer condição, usando lentes de contato ou medicação para os olhos, sem primeiro consultar o médico Oftalmologista. Contra-Indicações: Qualquer <strong>in</strong>flamação, <strong>in</strong>fecção, doença<br />

ocular, lesão ou anormalidade que afete a córnea, conjuntiva ou pálpebras. Qualquer doença sistêmica que venha a afetar os olhos ou ser agravada pelo uso de LC; reações alérgicas das superfícies<br />

oculares ou anexas. Qualquer <strong>in</strong>fecção ativa da córnea; olhos vermelhos ou irritados. Precauções e Advertências: Problemas oculares, <strong>in</strong>clu<strong>in</strong>do úlceras de córnea, podem se desenvolver rapidamente<br />

e causar perda da visão. Em caso de desconforto visual, lacrimejamento excessivo, visão alterada, vermelhidão nos olhos ou outros problemas, retirar imediatamente as LC e contatar o Oftalmologista.<br />

Usuários de LC devem consultar seu Oftalmologista regularmente. Não usar o produto se a embalagem estéril de plástico estiver aberta ou danificada. Reações Adversas: Ardor, coceira ou sensação de<br />

pontada nos olhos. Desconforto quando a LC for colocada pela primeira vez. Sensação de que há algo no olho (corpo estranho, área raspada). Lacrimejamento excessivo, secreções oculares <strong>in</strong>comuns<br />

ou vermelhidão dos olhos. Acuidade visual deficiente, visão embaçada, arco-íris ou halos ao redor de<br />

objetos, fotofobia, ou olho seco, podem ocorrer caso as LC sejam usadas cont<strong>in</strong>uamente ou por tempo<br />

excessivamente longo. Se o usuário relatar algum problema, deve RETIRAR IMEDIATAMENTE AS<br />

LENTES e contatar o Oftalmologista. Posologia: Uso prolongado 1,2,3,5,8,10 – Um a 7 dias/6 noites de uso<br />

contínuo, <strong>in</strong>clusive durante o sono. Uso diário 1,2,3,4,5,8,9,10 – Períodos <strong>in</strong>feriores a um dia de uso enquanto<br />

acordado. Descartáveis diárias 6,7 – uso único. VENDA SOB PRESCRIÇÃO MÉDICA REFRACIONAL<br />

(LC com grau), VENDA SOB PRESCRIÇÃO MÉDICA (LC terapêutica plana), UTILIZAÇÃO SUJEITA À<br />

PRESCRIÇÃO MÉDICA (LC colorida plana). Johnson & Johnson Industrial Ltda. Rod. Pres. Dutra, Km<br />

154 - S. J. dos Campos, SP. CNPJ: 59.748.988/0001-14. Resp. Téc.: Evelise S. Godoy – CRQ No. 04345341.<br />

Mais <strong>in</strong>formações sobre uso e cuidados de manutenção e segurança, fale com seu Oftalmologista, ligue<br />

para Central de Relacionamento com o Consumidor: 0800-7274040, acesse www.acuvue.com.br ou<br />

consulte o Guia de Instruções ao Usuário. A PERSISTIREM OS SINTOMAS, O MÉDICO DEVERÁ SER<br />

CONSULTADO.<br />

1. OS BORN, K.; VEYS, J. A new silicone hydrogel lens for contact lens-related dryeness. Part 1 - Material Properties. Optician, 2005; 6004(229):<br />

39-41.


Lançamento no Brasil!<br />

Olho Seco<br />

Pós-Cirurgia<br />

& Refrativa 1<br />

Ronda Propaganda<br />

Muco-adesivo 2,4<br />

Alta capacidade de retenção de água 2,3<br />

Hidratação prolongada<br />

Conforto prolongado<br />

Ph e osmolaridade semelhantes às do filme lacrimal normal 2 Visco-elástico 4<br />

Mais conforto ao paciente<br />

Impede a visão turva<br />

Indicado para usuários de lentes de contato 1 Melhora as propriedades de adesão <strong>in</strong>tercelular 3,4<br />

Promove rápida cicatrização pós-cirurgias<br />

Tratamento s<strong>in</strong>tomático do olho seco.<br />

Lubrificação e hidratação de lentes de contato.<br />

Referências Bibliográficas: 1) Bula do produto: Hyabak. Registro MS nº 80424140002. 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,<br />

K<strong>in</strong>oshita 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 <strong>in</strong> vitro. Br J Ophthalmol. 2004 Jun;88(6);821-5.<br />

SE PERSISTIREM OS SINTOMAS, O MÉDICO DEVERÁ SER CONSULTADO. Informações adicionais disponíveis à classe farmacêutica mediante solicitação.<br />

Bula do produto: 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 <strong>in</strong>jetáveis q.b.p. 100 mL. NOME E<br />

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 dest<strong>in</strong>ada a ser adm<strong>in</strong>istrada nos olhos ou nas lentes de contato. Foi concebido: • Para<br />

humedecimento e lubrificação dos olhos, em caso de sensações de secura ou de fadiga ocular <strong>in</strong>duzidas 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<br />

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,<br />

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 <strong>in</strong>jetar, não engolir. Não utilize o produto caso<br />

o <strong>in</strong>vólucro de <strong>in</strong>violabilidade esteja danificado. MANTER FORA DO ALCANCE DAS CRIANÇAS. INTERAÇÕES: É conveniente aguardar 10 m<strong>in</strong>utos entre a adm<strong>in</strong>istração de dois produtos oculares. COMO UTILIZAR ESTE DISPOSITIVO: POSOLOGIA: 1 gota em cada olho durante o dia, sempre que<br />

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 determ<strong>in</strong>adas<br />

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 <strong>in</strong>ferior, puxando ligeiramente a pálpebra <strong>in</strong>ferior para baixo e dirig<strong>in</strong>do o olhar para cima. O tempo<br />

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: <strong>in</strong>stilar uma gota de HYABAK® na concavidade da lente. FREQUÊNCIA E MOMENTO EM QUE O PRODUTO DEVE SER ADMINISTRADO: Distribuir as <strong>in</strong>stilações<br />

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 <strong>in</strong>ferior a 25ºC. Depois de aberto, o frasco não<br />

deve ser conservado mais de 8 semanas.<br />

UNIÃO QUÍMICA FARMACÊUTICA NACIONAL S/A<br />

Divisão GENOM<br />

Unidade Brasília: Trecho 01 Conjunto 11 Lote 6 a 12<br />

Pólo de Desenvolvimento JK<br />

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


Referências Bibliográficas: 1. Katz LJ, et al. Twelve-Month, Randomized, Controlled Trial of Bimatoprost 0.01%, 0.0125%, and 0.03% <strong>in</strong> Patients with Glaucoma or Ocular Hypertension.<br />

American Journal of Ophthalmology 2009; 149(4):661-671. 2. Pfennigsdorf S, et al. Multicenter, prospective, open-label, observational study of bimatoprost 0.01% <strong>in</strong> patients with primary<br />

open-angle glaucoma or ocular hypertension. Cl<strong>in</strong>ical Ophthalmology 10/May/2012:6. 739-746. 3. LUMIGAN® RC 0,01% - Bula do Produto. Allergan Produtos Farmacêuticos. 4. Carney LG,<br />

et al. Buffer<strong>in</strong>g <strong>in</strong> human tears: pH responses to acid and base challenge. Invest Ophthalmol vis Sci. 1989 30(4): 747-754.<br />

LUMIGAN® RC (bimatoprosta 0,01%) USO ADULTO. Indicações: LUMIGAN® RC é <strong>in</strong>dicado para o tratamento e prevenção do aumento da pressão dentro dos olhos em pacientes com glaucoma de ângulo aberto,<br />

glaucoma de ângulo fechado em pacientes submetidos previamente a iridotomia e hipertensão ocular.Advertências/Precauções: tem sido relatadas alterações de pigmentos dos tecidos com a utilização de solução<br />

oftálmica de bimatoprosta. Os relatos mais freqüentes têm sido os escurecimentos da íris, das pálpebras e cílios. Houve relatos de ceratite bacteriana associada com o uso de recipientes de doses múltiplas de<br />

produtos oftálmicos de uso tópico. Gravidez e Lactação: não foram realizados estudos controlados em gestantes. LUMIGAN® RC apenas deve ser utilizado em gestantes se os potenciais benefícios para a mãe<br />

justificarem os potenciais riscos para o feto. Posologia e modo de usar: você deve aplicar o número de gotas da dose recomendada pelo seu médico em um ou ambos os olhos. A dose usual é de 1 gota aplicada no(s)<br />

olho(s) afetado(s), uma vez ao dia, (de preferência à noite), com <strong>in</strong>tervalo de aproximadamente 24 horas entre as doses. A dose não deve exceder a uma dose única diária, pois foi demonstrado que adm<strong>in</strong>istração<br />

mais freqüente pode dim<strong>in</strong>uir o efeito do medicamento sobre a pressão <strong>in</strong>tra-ocular elevada. Reações adversas oculares relatadas mais comumente com LUMIGAN® RC por ordem de freqüência foram: Reação<br />

muito comum (> 10%): hiperemia conjuntival. A hiperemia conjuntival ocorre geralmente nos primeiros dias de tratamento, sendo transitória. Reação comum (>1% e < 10%): coceira nos olhos, dor ocular, irritação<br />

ocular, crescimento e escurecimento dos cílios, escurecimento da pele ao redor dos olhos ente outros. Reg. ANVISA/MS - 1.0147.0155 - Farm. Resp.: Dra. Flávia Reg<strong>in</strong>a Pegorer CRF-SP nº 18.150 VENDA SOB<br />

PRESCRIÇÃO MÉDICA. Para maiores <strong>in</strong>formações, consultar a bula completa do produto. Fabricado por ALLERGAN PRODUTOS FARMACÊUTICOS LTDA: Av. Guarulhos, 3272 - CEP 07030-000 – Guarulhos/<br />

SP - CNPJ nº 43.426.626/0009-24 - Indústria Brasileira - ® Marca Registrada.<br />

VENDA SOB PRESCRIÇÃO MÉDICA<br />

www.allergan.com.br<br />

BR/0713/2012c - fev/2013


PUBLICAÇÃO OFICIAL DO<br />

CONSELHO BRASILEIRO<br />

DE OFTALMOLOGIA<br />

CODEN - AQBOAP<br />

PUBLICAÇÃO OFICIAL DO CONSELHO BRASILEIRO DE OFTALMOLOGIA<br />

Publicação <strong>in</strong><strong>in</strong>terrupta desde 1938<br />

ISSN 0004-2749<br />

(Versão impressa)<br />

ISSN 1678-2925<br />

(Versão eletrônica)<br />

Periodicidade: bimestral Arq Bras Oftalmol. São Paulo, v. 76, n. 1, p. 1-62, jan./fev. 2013<br />

Conselho Adm<strong>in</strong>istrativo<br />

Marco Antônio Rey de Faria<br />

Harley E. A. Bicas<br />

Roberto Lorens Marback<br />

Rubens Belfort Jr.<br />

Wallace Chamon<br />

Editor-Chefe<br />

Wallace Chamon<br />

Editores Anteriores<br />

Waldemar Belfort Mattos<br />

Rubens Belfort Mattos<br />

Rubens Belfort Jr.<br />

Harley E. A. Bicas<br />

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José Álvaro Pereira Gomes<br />

Editores Associados<br />

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Internacional<br />

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ABO – Arquivos Brasileiros de Oftalmologia • publicação bimestral do Conselho Brasileiro de Oftalmologia (CBO)<br />

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Capa: Fotografia gonioscópica de paciente com neovascularização de seio camerular. Autor da Fotografia: Dr. Sérgio Hen -<br />

rique Teixeira (Setor de Glaucoma do Departamento de Oftalmologia da UNIFESP, Brasil).<br />

Cover: Gonioscopic photograph of a patient present<strong>in</strong>g anterior chamber angle neovascularization. Photographer: Sérgio Hen ­<br />

rique Teixeira, MD (Glaucoma Sector, Department of Ophthalmology, UNIFESP, Brazil).


PUBLICAÇÃO OFICIAL DO<br />

CONSELHO BRASILEIRO<br />

DE OFTALMOLOGIA<br />

PUBLICAÇÃO OFICIAL DO CONSELHO BRASILEIRO DE OFTALMOLOGIA<br />

ISSN 0004-2749<br />

(Versão impressa)<br />

ISSN 1678-2925<br />

(Versão eletrônica)<br />

• ABO<br />

arquivos Brasileiros de Oftalmologia<br />

www.abonet.com.br<br />

www.freemedicaljournals.com<br />

www.scielo.org<br />

• Copernicus<br />

www.copernicusmarket<strong>in</strong>g.com<br />

www.periodicos.capes.gov.br<br />

www.scirus.com<br />

• ISI Web of Knowledge (SM)<br />

• MEDLINE<br />

• LILACS<br />

Literatura Lat<strong>in</strong>o-americana<br />

em Ciências da Saúde<br />

Diretoria do CBO - 2011-2013<br />

Marco Antônio Rey de Faria (Presidente)<br />

Milton Ruiz Alves (Vice-Presidente)<br />

Carlos Heler Ribeiro D<strong>in</strong>iz (1º Secretário)<br />

Nilo Holzchuh (Secretário Geral)<br />

Mauro Nishi (Tesoureiro)<br />

Sociedades Filiadas ao Conselho Brasileiro de Oftalmologia<br />

e seus respectivos Presidentes<br />

Centro Brasileiro de Estrabismo<br />

Sociedade Brasileira de Adm<strong>in</strong>istração em Oftalmologia<br />

Sociedade Brasileira de Catarata e Implantes Intra-Oculares<br />

Sociedade Brasileira de Cirurgia Plástica Ocular<br />

Sociedade Brasileira de Cirurgia Refrativa<br />

Sociedade Brasileira de Ecografia em Oftalmologia<br />

Sociedade Brasileira de Glaucoma<br />

Sociedade Brasileira de Laser e Cirurgia em Oftalmologia<br />

Sociedade Brasileira de Lentes de Contato, Córnea e Refratometria<br />

Sociedade Brasileira de Oftalmologia Pediátrica<br />

Sociedade Brasileira de Oncologia em Oftalmologia<br />

Sociedade Brasileira de Ret<strong>in</strong>a e Vítreo<br />

Sociedade Brasileira de Trauma Ocular<br />

Sociedade Brasileira de Uveítes<br />

Sociedade Brasileira de Visão Subnormal<br />

Maria de Lourdes Fleury F. Carvalho Tom Back<br />

Flávio Rezende Dias<br />

Armando Stefano Crema<br />

Ricardo Mörschbacher<br />

Renato Ambrósio Júnior<br />

Norma Allemann<br />

Vital Paul<strong>in</strong>o Costa<br />

Caio V<strong>in</strong>icius Saito Regatieri<br />

César Lipener<br />

Rosa Maria Graziano<br />

Priscilla Luppi Ballalai Bordon<br />

Walter Yukihiko Takahashi<br />

Nilva Simeren Bueno Moraes<br />

Wilton Feitosa de Araújo<br />

Mayumi Sei<br />

Apoio:


PUBLICAÇÃO OFICIAL DO<br />

CONSELHO BRASILEIRO<br />

DE OFTALMOLOGIA<br />

PUBLICAÇÃO OFICIAL DO CONSELHO BRASILEIRO DE OFTALMOLOGIA ISSN 0004-2749<br />

(Versão impressa)<br />

ISSN 1678-2925<br />

(Versão eletrônica)<br />

Periodicidade: bimestral Arq Bras Oftalmol. São Paulo, v. 76, n. 1, p. 1-62, jan./fev. 2013<br />

Sumário | Contents<br />

V<br />

VII<br />

Editorial | Editorial<br />

A questão do idioma nas Revistas Oftalmológicas Brasileiras<br />

The language issue <strong>in</strong> Brazilian Ophthalmological Journals<br />

Wallace Chamon<br />

The language issue <strong>in</strong> Brazilian Ophthalmological Journals<br />

A questão do idioma nas Revistas Oftalmológicas Brasileiras<br />

Wallace Chamon<br />

1<br />

6<br />

10<br />

13<br />

18<br />

21<br />

Artigos Orig<strong>in</strong>ais | Orig<strong>in</strong>al Articles<br />

Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia<br />

Increased VEGFR-1 immunoreactivity <strong>in</strong> the choroid-scleral complex <strong>in</strong> hypercholesterolemia experimental model<br />

Rogil José de Almeida Torres, Lucia de Noronha, Antonio Marcelo Barbante Casella, Regiane do Rocio de Almeida Torres, Isabela de Carvalho Mart<strong>in</strong>s, Rafael Zotz,<br />

Andréa Luch<strong>in</strong>i, Conrado Roberto Hoffmann Filho, Dalton Bertolim Précoma<br />

The need for artificial tears <strong>in</strong> glaucoma patients: a comparative, retrospective study<br />

O uso de lágrimas artificiais em pacientes com glaucoma: um estudo retrospectivo e comparativo<br />

Vital Paul<strong>in</strong>o Costa, Renata Siqueira da Silva, Renato Ambrósio Jr.<br />

The correlation between body mass <strong>in</strong>dex and <strong>in</strong>traocular pressure <strong>in</strong> children<br />

Correção entre o índice de massa corpórea e a pressão <strong>in</strong>traocular em crianças<br />

Luciano Lira de Albuquerque, Maria Isabel Lynch Gaete, José Natal Figueiroa, João Guilherme Bezerra Alves<br />

Composition of <strong>in</strong>traocular foreign bodies: experimental study of ultrasonographic presentation<br />

Composição de corpos estranhos <strong>in</strong>traoculares: estudo experimental da apresentação ultrassonográfica<br />

Márcio Augusto Nogueira Costa, Patrícia Novita Garcia, Letícia Fernandes Barroso, Marco Antonio Ferreira, Érika Araki Okuda, Norma Allemann<br />

Panret<strong>in</strong>al photocoagulation <strong>versus</strong> <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong> retreatment pa<strong>in</strong> <strong>in</strong> high-risk proliferative <strong>diabetic</strong> ret<strong>in</strong>opathy<br />

Dor em panfotocogulação ret<strong>in</strong>iana <strong>versus</strong> <strong>in</strong>jeção <strong>in</strong>travítrea em pacientes com ret<strong>in</strong>opatia diabética proliferativa de alto risco<br />

Célia Reg<strong>in</strong>a Farias de Araújo Lucena, José Afonso Ramos Filho, André Márcio Vieira Messias, José Aparecido da Silva, Felipe Piacent<strong>in</strong>i Paes de Almeida, Ingrid Ursula Scott,<br />

Jefferson Augusto Santana Ribeiro, Rodrigo Jorge<br />

Cl<strong>in</strong>ical trials <strong>in</strong> Brazilian journals of ophthalmology: where we are<br />

Ensaios clínicos em periódicos brasileiros de oftalmologia: onde estamos<br />

Rodrigo Pessoa Cavalcanti Lira, Franz Schubert Leal, Fauze Abdulmassih Gonçalves, Fernando Henrique Ramos Amorim,<br />

João Paulo Fernandes Felix, Carlos Eduardo Leite Arieta


26<br />

29<br />

33<br />

38<br />

Influence of English language <strong>in</strong> the number of citations of articles published <strong>in</strong> Brazilian journals of Ophthalmology<br />

Influência do idioma <strong>in</strong>glês no número de citações de artigos publicados em periódicos brasileiros de Oftalmologia<br />

Rodrigo Pessoa Cavalcanti Lira, Rafael Marsicano Cezar Vieira, Fauze Abdulmassih Gonçalves, Maria Carol<strong>in</strong>a Alves Ferreira, Diana Maziero,<br />

Thais Helena Moreira Passos, Carlos Eduardo Leite Arieta<br />

Censo Brasileiro de Cirurgia Refrativa<br />

Brazilian Trends <strong>in</strong> Refractive Surgery<br />

Marcelo Vieira Netto, Rodrigo França de Espíndola, Rafael Garcia Fernandes Nogueira, Mauro Campos, Renato Ambrósio Jr., Newton Leitão de Andrade<br />

Lentes progressivas - análise dos campos <strong>in</strong>termediário e de perto por deflexometria<br />

Progressive addition lenses - analysis of <strong>in</strong>termediate and near vision zones by deflectometry<br />

Celso Marcelo Cunha, Renato José Bett Correia, Antonio Augusto Sard<strong>in</strong>ha Neto<br />

Assessment of ocular surface toxicity after topical <strong>in</strong>stillation of nitric oxide donors<br />

Avaliação da toxicidade na superfície ocular após <strong>in</strong>stilação tópica de doadores de óxido nítrico<br />

Angel<strong>in</strong>o Julio Cariello, Gabriela Freitas Pereira de Souza, Márcia Serva Lowen, Marcelo Ganzarolli de Oliveira, Ana Luisa Höfl<strong>in</strong>g-Lima<br />

42<br />

45<br />

48<br />

50<br />

Relatos de Casos | Case Reports<br />

Bilateral acute depigmentation of the iris (BADI): first reported case <strong>in</strong> Brazil<br />

Despigmentação aguda bilateral da íris (BADI): primeiro relato de caso no Brasil<br />

Heloisa Andrade Maestr<strong>in</strong>i, Angela Andrade Maestr<strong>in</strong>i, Danuza de Oliveira Machado, Daniel Vitor Vasconcelos Santos, Homero Gusmão de Almeida<br />

Idiopathic dilated episcleral vessels (Radius-Maumenee syndrome): case report<br />

Dilatação idiopática dos vasos episclerais (síndrome de Radius-Maumenee): relato de caso<br />

Ricardo Alexandre Stock, Natalie Lucas Fernandes, Nathan Lopes Pastro, Rafaela Sant<strong>in</strong>i de Oliveira, Elcio Luiz Bonamigo<br />

Topiramate-associated acute, bilateral, angle-closure glaucoma: case report<br />

Glaucoma agudo de ângulo fechado, bilateral, desencadeado pelo topiramato: relato de caso<br />

Lucas Barasnevicius Quagliato, Kleyton Barella, José Maria Abreu Neto, Elizabeth Maria Aparecida Barasnevicius Quagliato<br />

Essential trichomegaly: case report<br />

Tricomegalia essencial: relato de caso<br />

Julia Dutra Rossetto, Heloisa Nascimento, Crist<strong>in</strong>a Muccioli, Rubens Belfort Jr.<br />

52<br />

Artigos de Revisão | Review Articles<br />

Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento<br />

Fungal keratitis: review of diagnosis and treament<br />

Felipe Mellado, Tomás Rojas, Cristián Cumsille<br />

57<br />

Cartas ao Editor | Letters to the Editor<br />

Abnormal vascular regulation <strong>in</strong> the ophthalmic artery of chronic heart failure patients<br />

Alteração na regulação vascular da artéria oftálmica em pacientes com <strong>in</strong>suficiência cardíaca crônica<br />

Daniel Meira-Freitas, Daniela B. Almeida-Freitas, Augusto Paranhos Jr.<br />

59 Instruções para os Autores | Instructions to Authors


Editorial | Editorial<br />

A questão do idioma nas Revistas Oftalmológicas Brasileiras<br />

The language issue <strong>in</strong> Brazilian Ophthalmological Journals<br />

Wallace Chamon 1<br />

Nesta edição do Arquivos Brasileiros de Oftalmologia (ABO), Lira et al., estudaram a qualidade dos periódicos<br />

oftalmológicos brasileiros por meio do número de citações em fontes <strong>in</strong>dexadas no Science Citation Index<br />

Expanded (SCIE) após dois anos da publicação (Fator de Impacto ® ) e da qualidade dos artigos de acordo com<br />

o Consolidated Standards for Report<strong>in</strong>g Trials (CONSORT) (1,2) . As publicações são excelentes em demonstrar que<br />

os manuscritos de qualidade, escritos em <strong>in</strong>glês são bem mais citados (e provavelmente mais lidos) do que as<br />

suas contrapartes.<br />

É importante entendermos que não existem bases de dados universais, cada análise aplica-se apenas para<br />

a amostra avaliada pelo seu provedor de banco de dados. Portanto, deve-se entender o Universo que foi considerado<br />

como base para os relatórios de citação. Web of Science é um dos serviços prestados pela Thomson<br />

Reuters ® , uma empresa <strong>in</strong>glesa fundada por um imigrante alemão em 1851 (3) . A Thomson Reuters ® foi criada<br />

pela fusão de duas empresas de um mesmo grupo (Thomson Corporation e Reuters Group) que entrou em vigor<br />

em 2009. A Thomson Reuters ® tem 17.621 revistas <strong>in</strong>dexadas em seu banco de dados e o subconjunto de SCIE<br />

conta com 8.630 títulos, sendo 59 revistas oftalmológicas.<br />

Outras empresas oferecem bases de dados científicas e de conhecimento para competir neste mercado. Scopus<br />

® é um banco de dados pesquisável de manuscritos avaliados por pares, oferecidos pela Elsevier ® , que <strong>in</strong>clui<br />

mais de 19.500 revistas (4) . SciELO ® é uma <strong>in</strong>iciativa brasileira desenvolvida pela FAPESP (Fundação de Amparo à<br />

Pesquisa do Estado de São Paulo), em 1998 (5) . A SciELO ® apenas <strong>in</strong>clui fontes que dão acesso livre e não aceita<br />

qualquer embargo, como adiar o acesso livre aos manuscritos após a publicação. O banco de dados da SciELO ®<br />

<strong>in</strong>clui 1.021 fontes, provenientes da África do Sul, Argent<strong>in</strong>a, Brasil, Chile, Colômbia, Costa Rica, Cuba, Espanha,<br />

México, Portugal e Venezuela. Quatro revistas da SciELO ® estão relacionadas especificamente à oftalmologia.<br />

Hoje em dia, o ABO aceita artigos escritos em <strong>in</strong>glês, português e espanhol. Usando a mesma base de dados<br />

Lira et al., o gráfico 1 mostra que nos últimos anos o número de submissões em português dim<strong>in</strong>uiu e, desde<br />

o ano passado, a maioria dos manuscritos são enviados em <strong>in</strong>glês. Quando se analisa o porcentual de citações<br />

durante os dois anos segu<strong>in</strong>tes à publicação pode-se notar o aumento importante desde 2008.<br />

Gráfico 1. Idioma de publicação e porcentagem de citações em relação ao tempo nos Arquivos<br />

Brasileiros de Oftalmologia (ABO). Notar que neste banco de dados foram <strong>in</strong>cluídos todos os artigos<br />

(não apenas os citáveis) e que alguns artigos podem ter sido citados mais de uma vez.<br />

Submetido para publicação: 8 de junho de 2013<br />

Aceito para publicação: 8 de junho de 2013<br />

1<br />

Médico, Departamento de Oftalmologia, Universidade Federal de São Paulo - UNIFESP - São Paulo<br />

(SP), Brasil.<br />

F<strong>in</strong>anciamento: Não houve f<strong>in</strong>anciamento para este trabalho.<br />

Divulgação de potenciais conflitos de <strong>in</strong>teresse: W.Chamon, Nenhum.<br />

V


A questão do idioma nas Revistas Oftalmológicas Brasileiras<br />

A equipe editorial do ABO tem focado fortemente na seleção de melhores manuscritos para a publicação, a<br />

nossa decisão foi dim<strong>in</strong>uir o número de artigos publicados por ano e aumentar a sua qualidade. Considerando-se<br />

os artigos orig<strong>in</strong>ais, relatos de casos, artigos de revisão, cartas ao editor e editoriais, o número de artigos<br />

por ano caiu de cerca de 200, em 2008, para 100 nos últimos três anos. Isso pode ter contribuído para a melhoria<br />

da qualidade, observada pelo porcentual de artigos citados. Além disso, o aumento natural de artigos publicados<br />

em Inglês, bem como os resultados de Lira et al., levam ao questionamento sobre o ABO considerar apenas a<br />

aceitação de manuscritos escritos em <strong>in</strong>glês (2) .<br />

Referências<br />

1. Lira RPC, Leal FS, Gonçalves FA, Amorim FHR, Felix JPF, Arieta CEL. Cl<strong>in</strong>ical trials <strong>in</strong><br />

Bra zilian journals of ophthalmology: where we are. Arq Bras Oftalmol. 2013;76(1):21-5.<br />

2. Lira RPC, Vieira RMC, Gonçalves FA, Ferreira MCA, Maziero D, Passos THM, Arieta CEL.<br />

Influence of English language <strong>in</strong> the number of citations of articles published <strong>in</strong><br />

Brazilian journals of Ophthalmology. Arq Bras Oftalmol. 2013;76(1):26-8.<br />

3. Thomson Reuters [Internet]. New York: Thomson Reuters. [cited 2013 Jun 8]. Available<br />

from: http://thomsonreuters.com/scientific-search-and-discovery/<br />

4. Scopus [Internet]. Amsterdam: Elsevier. [cited 2013 Jun 8]. Available from: http://<br />

www.<strong>in</strong>fo.sciverse.com/scopus<br />

5. SciELO [Internet]. Sao Paulo: SciELO. [cited 2013 Jun 8]. Available from: http://www.<br />

scielo.org/php/<strong>in</strong>dex.php<br />

VI


Editorial | Editorial<br />

The language issue <strong>in</strong> Brazilian Ophthalmological Journals<br />

A questão do idioma nas Revistas Oftalmológicas Brasileiras<br />

Wallace Chamon 1<br />

In this issue of Arquivos Brasileiros de Oftalmologia (ABO), Lira et al., studied the quality of Ophthalmological<br />

Brazilian Journals by means of the number of citations <strong>in</strong> sources <strong>in</strong>dexed at Science Citation Index Expanded<br />

(SCIE) after two years of publication (Impact Factor ® ) and the quality of report<strong>in</strong>g accord<strong>in</strong>g the Consolidated<br />

Standards for Report<strong>in</strong>g Trials (CONSORT) (1,2) . Their work is excellent <strong>in</strong> po<strong>in</strong>t<strong>in</strong>g out that well quality papers<br />

written <strong>in</strong> English are well more cited (and probably read more often) than their counterparts.<br />

It is important do understand that there are no universal databases; each analysis applies only for the sample<br />

evaluated by its database provider. Therefore, one should understand the Universe that was considered as<br />

the background for citation reports. Web of Science is one of the services provided by Thomson Reuters ® , an<br />

English company founded by a German immigrant <strong>in</strong> 1851 (3) . Thomson Reuters ® was created as a fusion of two<br />

companies form the same group (Thomson Corporation and Reuters Group) that took effect <strong>in</strong> 2009. Thomson<br />

Reuters ® has 17,621 Journals <strong>in</strong>dexed on its database and the subset of SCIE <strong>in</strong>dexes 8,630, be<strong>in</strong>g 59 ophthalmological<br />

journals.<br />

Other companies offer scientific and knowledge databases to compete for this market. Scopus ® is a searchable<br />

database of peer-reviewed literature, offered by Elsevier ® , that <strong>in</strong>cludes more than 19,500 journals (4) . SciELO ®<br />

is a Brazilian <strong>in</strong>itiative developed by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), <strong>in</strong> 1998 (5) .<br />

SciELO ® only <strong>in</strong>dexes sources that provide open access and does not accepts any embargo, such as postpon<strong>in</strong>g<br />

the free access to the manuscripts after publication. SciELO ® database <strong>in</strong>cludes 1,021 sources, from Argent<strong>in</strong>a,<br />

Brazil, Chile, Colombia, Costa Rica, Cuba, México, Portugal, Spa<strong>in</strong>, South Africa and Venezuela. Four journals from<br />

SciELO ® are related specifically to ophthalmology.<br />

Nowadays, ABO accepts papers written <strong>in</strong> English, Portuguese and Spanish. Us<strong>in</strong>g the same database as Lira<br />

et al., graph 1 shows that dur<strong>in</strong>g the last years the number of submissions <strong>in</strong> Portuguese has decreased and,<br />

s<strong>in</strong>ce last year, most of the manuscripts are <strong>in</strong> English. When analyz<strong>in</strong>g the percentage of citations dur<strong>in</strong>g the<br />

next two years of publication one can notice the important <strong>in</strong>crease s<strong>in</strong>ce 2008.<br />

Graph 1. Language of publication and percentage of citations over time at the Arquivos Brasileiros<br />

de Oftalmologia (ABO). Notice that for this database all publications were <strong>in</strong>cluded (not only citable<br />

ones) and the same manuscript may have been cited more than once.<br />

Submitted for publication: June 8, 2013<br />

Accepted for publication: June 8, 2013<br />

1<br />

Physician, Department of Ophthalmology, Federal University of São Paulo - UNIFESP - São Paulo<br />

(SP), Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potencial of <strong>in</strong>terest: W.Chamon, None.<br />

VII


The language issue <strong>in</strong> Brazilian Ophthalmological Journals<br />

ABO’s editorial team has focused strongly <strong>in</strong> select<strong>in</strong>g better manuscripts for publication, our decision was<br />

to lessen the number of published papers per year and <strong>in</strong>crease their quality. Consider<strong>in</strong>g orig<strong>in</strong>al articles,<br />

case reports, review articles, letters to the editor and editorials, the number of papers per year dropped from<br />

approximately 200, <strong>in</strong> 2008, to 100 dur<strong>in</strong>g the last three years. This may have accounted for the improvement<br />

of quality, observed by the percentage of cited papers. Also, the natural <strong>in</strong>crease of papers published <strong>in</strong> English<br />

as well as the f<strong>in</strong>d<strong>in</strong>gs of Lira et al., leads to the question<strong>in</strong>g of if ABO should consider accept<strong>in</strong>g only English<br />

written manuscripts (2) .<br />

REFERENCES<br />

1. Lira RPC, Leal FS, Gonçalves FA, Amorim FHR, Felix JPF, Arieta CEL. Cl<strong>in</strong>ical trials <strong>in</strong><br />

Bra zilian journals of ophthalmology: where we are. Arq Bras Oftalmol. 2013;76(1):21-5.<br />

2. Lira RPC, Vieira RMC, Gonçalves FA, Ferreira MCA, Maziero D, Passos THM, Arieta CEL.<br />

Influence of English language <strong>in</strong> the number of citations of articles published <strong>in</strong><br />

Brazilian journals of Ophthalmology. Arq Bras Oftalmol. 2013;76(1):26-8.<br />

3. Thomson Reuters [Internet]. New York: Thomson Reuters. [cited 2013 Jun 8]. Available<br />

from: http://thomsonreuters.com/scientific-search-and-discovery/<br />

4. Scopus [Internet]. Amsterdam: Elsevier. [cited 2013 Jun 8]. Available from: http://<br />

www.<strong>in</strong>fo.sciverse.com/scopus<br />

5. SciELO [Internet]. Sao Paulo: SciELO. [cited 2013 Jun 8]. Available from: http://www.<br />

scielo.org/php/<strong>in</strong>dex.php<br />

VIII


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em<br />

modelo experimental de hipercolesterolemia<br />

Increased VEGFR-1 immunoreactivity <strong>in</strong> the choroid-scleral complex <strong>in</strong> hypercholesterolemia<br />

experimental model<br />

Rogil José de Almeida Torres 1 , Lucia de Noronha 2 , Antonio Marcelo Barbante Casella 3 , Regiane do Rocio de Almeida Torres 4 ,<br />

Isabela de Carvalho Mart<strong>in</strong>s 5 , Rafael Zotz 5 , Andréa Luch<strong>in</strong>i 6 , Conrado Roberto Hoffmann Filho 7 , Dalton Bertolim Précoma 8<br />

RESUMO<br />

Objetivo: O objetivo deste trabalho é <strong>in</strong>vestigar a expressão do fator de crescimento<br />

vascular endotelial (VEGF) na coroide e esclera, utilizando um modelo<br />

experimental de hipercolesterolemia.<br />

Método: Coelhos New Zealand foram organizados em dois grupos: O grupo dieta<br />

normal (GN), composto por 8 coelhos (8 olhos), recebeu ração padrão para coelhos,<br />

durante 4 semanas; e o grupo hipercolesterolêmico (GH), composto por 13 coelhos<br />

(13 olhos), recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a<br />

dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum<br />

no <strong>in</strong>ício do experimento e no momento da eutanásia. Ao f<strong>in</strong>al da 8 a semana para<br />

o GH e 4 a semana para o GN foi realizada a eutanásia dos animais e os olhos foram<br />

submetidos à análise imuno-histoquímica com os anticorpos RAM-11 e VEGFR-1.<br />

Resultados: Observou-se significativo aumento do colesterol total e triglicerídeos<br />

do GH em relação ao GN (p


Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia<br />

ret<strong>in</strong>a sensorial, o EPR e a coriocapilar entram em hipóxia (9,10) . Sabe-se<br />

que a hipóxia é o pr<strong>in</strong>cipal estímulo para liberação do fator de crescimento<br />

endotelial vascular (VEGF) (11) , responsável pela formação de<br />

neovasos sub-ret<strong>in</strong>ianos (2) .<br />

Cl<strong>in</strong>icamente, a perda da visão central na DMRI pode ocorrer<br />

pela atrofia geográfica de coroide, denom<strong>in</strong>ada DMRI seca, e/ou<br />

pe lo desenvolvimento de membrana neovascular sub-ret<strong>in</strong>iana, denom<strong>in</strong>ada<br />

DMRI úmida. A DMRI seca reduz progressivamente e lentamente<br />

a acuidade visual (AV). Até o momento, preconiza-se o uso<br />

de antioxidantes s<strong>in</strong>téticos, dieta antioxidante e mudança de hábitos<br />

de vida para estabilizar ou atenuar o avanço da atrofia geográfica da<br />

coroide (12) . Por outro lado, a DMRI úmida pode provocar metamorfopsia<br />

e queda abrupta da visão. Atualmente, o pr<strong>in</strong>cipal alvo terapêutico<br />

da DMRI úmida é o VEGF, maior estimulador de neovascularização<br />

ocular (2,13) . Várias drogas têm sido utilizadas para neutralizar este fator<br />

de crescimento angiogênico com o <strong>in</strong>tuito de promover a regressão<br />

da neovascularização sub-ret<strong>in</strong>iana e manter a visão central, porém<br />

o prognóstico visual permanece ruim (14) .<br />

Sendo assim, o conhecimento de fatores que estimulam a produção<br />

do VEGF é importante para a prevenção da doença macular<br />

degenerativa. Desta forma, a criação de modelos experimentais<br />

que possam <strong>in</strong>duzir a liberação deste fator de crescimento vascular<br />

aprimora o conhecimento fisiopatogênico desta temível doença e<br />

propicia pesquisas terapêuticas experimentais que podem ser úteis<br />

futuramente no combate à DMRI.<br />

O objetivo deste trabalho é <strong>in</strong>vestigar a expressão do VEGF na<br />

coroide e esclera, utilizando um modelo experimental de hipercolesterolemia.<br />

MÉTODOS<br />

Para a realização deste estudo, o protocolo foi aprovado pela<br />

Co missão de Ética em Experimentação Animal da Pontifícia Universidade<br />

Católica do Paraná, segu<strong>in</strong>do os pr<strong>in</strong>cípios da Declaração de<br />

Hels<strong>in</strong>que (1964).<br />

Ambiente de experimentação<br />

Os procedimentos deste estudo foram realizados nas dependências<br />

do laboratório de Técnica Operatória da PUC-PR e do Centro<br />

de Estudos do Hospital Angel<strong>in</strong>a Caron (HAC). Os animais foram<br />

mantidos no biotério em macroambiente com ciclos de ilum<strong>in</strong>ação<br />

12/12 horas, com trocas de ar e temperatura controlada de 19 a 23ºC<br />

e receberam durante o experimento água e ração específica para a<br />

espécie Nuvital ® (Nuvital, Colombo, Brasil) de forma ad libitum.<br />

Animais utilizados e del<strong>in</strong>eamento experimental<br />

Foram utilizados 21 coelhos machos alb<strong>in</strong>os (Oryctolagus cunicullus),<br />

da l<strong>in</strong>hagem New Zealand, procedentes do Biotério Central<br />

da Pontifícia Universidade Católica do Paraná, com idade média aproximada<br />

de 110 dias e peso médio de 2.770 gramas. Os animais foram<br />

divididos em dois grupos: grupo 1 (GN), composto por 8 coelhos, e<br />

grupo 2 (GH) composto por 13 coelhos. O GN, ou grupo de deita nor -<br />

mal, recebeu ração padrão para coelhos de laboratório Nuvital ® (Nuvital,<br />

Colombo, Brasil) e foi submetido à eutanásia em quatro sema nas.<br />

O GH, ou grupo hipercolesterolêmico, recebeu ração padrão para<br />

coelhos de laboratório Nuvital ® (Nuvital, Colombo, Brasil), acrescida<br />

de colesterol a 1%, em todo o período do estudo (ração suplementar).<br />

Este grupo foi submetido à eutanásia ao f<strong>in</strong>al de oito semanas.<br />

Cada coelho foi submetido à dosagem sérica de colesterol total,<br />

triglicerídeos, HDL colesterol, glicemia de jejum no <strong>in</strong>ício do experimento<br />

e no momento da eutanásia. As coletas das amostras sanguíneas<br />

foram realizadas através de punção da veia marg<strong>in</strong>al auricular<br />

magna sob anestesia geral com <strong>in</strong>jeção <strong>in</strong>tramuscular de ketam<strong>in</strong>a<br />

5 mg/kg e xylaz<strong>in</strong>a 35 mg/kg. As dosagens plasmáticas de glicemia,<br />

colesterol total, colesterol HDL e triglicerídeos foram realizados pelo<br />

método enzimático colorimétrico automatizado (Architec ® - Abbott).<br />

Uma soroteca com 500 microlitros de cada animal foi congelada para<br />

análises futuras. O peso dos coelhos foi aferido em rot<strong>in</strong>a semanal.<br />

Os animais foram sacrificados com <strong>in</strong>jeção endovenosa de 5 ml<br />

de pentobarbital e os olhos imediatamente fixados em paraformaldeído<br />

a 4% (Merck, Darmstadt, Germany), em 0,1 M fosfato/pH 7,4 por<br />

4 horas, para análise imuno-histoquímica.<br />

Preparo da ração suplementar<br />

A ração hipercolesterolêmica a 1%, utilizada nas oito semanas do<br />

experimento, apresentava 200 gramas de colesterol (Sigma-Aldrich<br />

à 95% ® ) dissolvido em 800 mililitros de clorofórmio (Biotec ® ), distribuídos<br />

homogeneamente em 20 quilogramas de ração Nuvital ®<br />

(Nuvital, Colombo, Brasil). Antes de adm<strong>in</strong>istrar a ração aos coelhos,<br />

esperou-se um período mínimo de 24 horas para adequada evaporação<br />

do clorofórmio. A quantidade diária ofertada para cada animal<br />

foi de 600 gramas ao dia (15) .<br />

Preparação do tecido e análise imuno-histoquímica<br />

Os dois olhos de cada animal (total de 42) foram removidos e submetidos<br />

à fixação, porém somente um foi escolhido para o estudo,<br />

de forma aleatória. Depois da fixação os espécimes foram avaliados<br />

macroscopicamente, sendo feito uma secção axial ao nível do nervo<br />

óptico, divid<strong>in</strong>do os bulbos oculares em duas metades iguais (superior<br />

e <strong>in</strong>ferior). A metade <strong>in</strong>ferior foi estocada para estudos posteriores.<br />

Já a metade superior foi submetida à desidratação, diafanização<br />

e impregnação em paraf<strong>in</strong>a, com histotécnico da marca Leica ® (Leica,<br />

Wetzlar, Germany), modelo TP 1020. Para a confecção dos blocos de<br />

paraf<strong>in</strong>a utilizou-se o <strong>in</strong>clusor Leica ® , modelo EG1160. Estes blocos foram<br />

cortados com micrótomo, marca Leica ® modelo RM2145 (Leica,<br />

Wetzlar, Germany), a 5 µ para obtenção dos cortes histológicos (total<br />

de 42). Estes cortes foram pescados em lâm<strong>in</strong>a de vidro com album<strong>in</strong>a,<br />

corados com hematoxil<strong>in</strong>a-eos<strong>in</strong>a e montados com lamínula de<br />

vidro de 24x90 mm Entellan, Merck ® (Merck, Darmstadt, Germany).<br />

Os cortes histológicos foram desparaf<strong>in</strong>izados e re-hidratados,<br />

sen do feito posteriormente o bloqueio da peroxidase endógena. Posteriormente<br />

foram lavados em água deionizada sendo <strong>in</strong>cubados em<br />

câmara úmida a 95ºC por 20 m<strong>in</strong>utos para recuperação antigênica.<br />

Após esta fase, foi realizado novo bloqueio da peroxidase endóge na.<br />

Os cortes foram cobertos pelo anticorpo primário monoclonal pro -<br />

duzido em camundongo VEGF receptor 1 (VEGFR 1), da marca THER-<br />

MOscientific ® (diluição 1:100) e pelo anticorpo monoclonal pri mário<br />

RAM-11, da marca Dako ® (DakoCytomation, Carp<strong>in</strong>teria, CA, EUA), na<br />

diluição 1/400. Posteriormente, foi recoberto com anticorpo secundário,<br />

polímero marcado-HRP anti-camundongo advance ® System<br />

(DakoCytomation, Inc., Carp<strong>in</strong>teria, CA) e <strong>in</strong>cubados, à temperatura<br />

ambiente, por 30 m<strong>in</strong>utos. A seguir foram submetidos ao gotejamento<br />

de substrato misto recém preparado DAB (DakoCytomation,<br />

Inc., CA, USA). Novamente foram <strong>in</strong>cubados por 3 até 5 m<strong>in</strong>utos. Os<br />

cortes foram contra-corados com hematoxil<strong>in</strong>a de Mayer e depois<br />

montados.<br />

Controles positivos e negativos foram usados em todas as mar -<br />

cações e as lâm<strong>in</strong>as foram primeiramente analisadas por um<br />

observador, sem conhecimento prévio do grupo de identificação<br />

(análise mascarada). Nesta análise, foi anotada a presença ou não de<br />

positividade para os marcadores VEGFR 1 e RAM 11. As áreas positivas<br />

adquiriram coloração acastanhada e foram analisadas pelo método<br />

da morfometria de cores. Para tanto, foram capturadas imagens de<br />

c<strong>in</strong>co campos consecutivos, de pars plana a pars plana contralateral,<br />

em objetiva de 40x, utilizando a câmera Olympus BX50, modelo<br />

DXC-107A e o software Image Pró Plus. Tal software permitiu que as<br />

áreas positivas fossem selecionadas e coloridas por um observador.<br />

A área imunorreativa foi automaticamente calculada pelo software<br />

e expressa em micrômetros². Estes dados foram registrados no programa<br />

Microsoft Excel (Redmond, WA) em forma de planilhas para<br />

2 Arq Bras Oftalmol. 2013;76(1):1-5


Torres RJA, et al.<br />

análise estatística. A variável área imunorreativa refere-se à somatória<br />

de todas as áreas positivas em cada um dos c<strong>in</strong>co campos analisados.<br />

Análise estatística<br />

Para a comparação dos grupos def<strong>in</strong>idos pelo tratamento em<br />

relação às variáveis quantitativas, foi considerado o teste t de Student<br />

para amostras <strong>in</strong>dependentes. Para a comparação entre as avaliações<br />

<strong>in</strong>ício e eutanásia dentro de cada grupo, foi usado o teste t de Student<br />

para amostras pareadas. A condição de normalidade foi avaliada pelo<br />

teste de Shapiro-Wilks. Variáveis que não apresentaram a condição de<br />

simetria foram submetidas a uma transformação logarítmica. Valores<br />

de p


Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia<br />

Tabela 2. Área total imunorreativa ao anticorpo VEFGR-1, em micrômetros², obtida com a técnica de morfometria de cores<br />

Variável Grupo n Média Mediana Mínimo Máximo Desvio padrão Valor de p<br />

VEGFR-1 GH 13 61559406 58728731 35881479 94418194 17402678<br />

GN 08 28770288 24866275 18942711 52270525 13368328 0,002<br />

GH= grupo dieta rica em colesterol; GN= grupo dieta normal.<br />

*= teste t de Student para amostras <strong>in</strong>dependentes, p


Torres RJA, et al.<br />

Pharmacol Rep [Internet]. 2006 [cited 2010 Jul 21];58(3):353-63. Available from: http://<br />

www.if-pan.krakow.pl/pjp/pdf/2006/3_353.pdf ]<br />

6. Guidry C, Medeiros NE, Curcio CA. Phenotypic variation of ret<strong>in</strong>al pigment epithelium<br />

<strong>in</strong> age-related macular degeneration. Invest Ophthalmol Vis Sci [Ínternet]. 2002[cited<br />

2011 Oct 15]; 43(1):267-73. Available from: http://www.iovs.org/content/43/1/267.long<br />

7. Lutty G, Grunwald J, Majji AB, Uyama M, Yoneya S. Changes <strong>in</strong> choriocapillaris and<br />

ret<strong>in</strong>al pigment epithelium <strong>in</strong> age-related macular degeneration. Mol Vis [Internet].<br />

1999[cited 2011 Mar 21];5:35. Available from: http://www.molvis.org/molvis/v5/a35/<br />

8. Korte GE, Reppucci V, Henk<strong>in</strong>d P. RPE destruction causes choriocapillary atrophy.<br />

Invest Ophthalmol Vis Sci [Internet]. 1984 [cited 2012 Apr 21]; 25:1135-45. Available<br />

from: http://www.iovs.org/content/25/10/1135.long<br />

9. Friedman E. The role of the atherosclerotic process <strong>in</strong> the pathogenesis of age-related<br />

macular degeneration. Am J Ophthalmol [Internet]. 2000[cited 2010 Jul<br />

21];130(5):658-63. Comment on: Am J Ophthalmol. 1997;124(5):677-82. Available from:<br />

http://goo.gl/G44rG<br />

10. Fisher R. The <strong>in</strong>fluence of age on some ocular basement membranes. Eye (Lond)<br />

[Internet]. 1987[cited 2012 Aug 25];1(Pt 2):184-9. Available from: http://www.nature.<br />

com/eye/journal/v1/n2/abs/eye198735a.html<br />

11. Shweiki D, It<strong>in</strong> A, Soffer D, Keshet E. Vascular endothelial growth factor <strong>in</strong>duced<br />

by hypoxia may mediate hypoxia-<strong>in</strong>itiated angiogenesis. Nature. 1992; 359(6398):<br />

843-5.<br />

12. Torres RJ, Maia M, Muccioli C, W<strong>in</strong>ter G, Souza GK, Pasqualotto LR, et al. [Modifiable<br />

risk factors for age-related macular degeneration]. Arq Bras Oftalmol [Internet].<br />

2009[cited 2010 Feb 21];72(3):406-12. Portuguese. Available from: http://www.scielo.<br />

br/pdf/abo/v72n3/v72n3a27.pdf<br />

13. Krzystolik MG, Afshari MA, Adamis AP, Gaudreault J, Gragoudas ES, Michaud NA, et<br />

al. Prevention of experimental choroidal neovascularization with <strong><strong>in</strong>travitreal</strong> antivas<br />

cular endothelial growth factor antibody fragment. Arch Ophthalmol [Internet].<br />

2002[cited 2012 Jun 21];120(3):338-46. Available from: http://archopht.jamanetwork.<br />

com/article.aspx?articleid=269871<br />

14. van Wijngaarden P, Coster DJ, Williams KA. Inhibitors of ocular neovascularization:<br />

promises and potential problems. JAMA. 2005;293(12):1509-13.<br />

15. Sun YP, Lu NC, Parmley YW, Hollenbeck CB. Effects of cholesterol diets on vascular<br />

function and atherogenesis <strong>in</strong> rabbits. Proc Soc Exp Biol Med. 2000; 224(3):166-171.<br />

16. Carmeliet P. Angiogenesis <strong>in</strong> health and disease. Nat Med [Internet]. 2003[cited 2010<br />

Jun 21];9(6):653-60. Available from: http://www.nature.com/nm/journal/v9/n6/full/<br />

nm0603-653.html<br />

17. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med<br />

[Internet]. 2003[cited 2010 jul 12];9(6):669-76. Available from: http://www.nature.<br />

com/nm/journal/v9/n6/full/nm0603-669.html<br />

18. Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM. Vascular permeability factor/<br />

vascular endothelial growth factor and the significance of microvascular hyperpermeability<br />

<strong>in</strong> angiogenesis. Curr Top Microbiol Immunol. 1999;237:97-132.<br />

19. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific<br />

growth factors and blood vessel formation. Nature [Internet]. 2000; [cited 2010 Jun<br />

21]407(6801):242-8. Available from: http://www.nature.com/nature/journal/v407/<br />

n6801/full/407242a0.html<br />

20. Marneros AG, Fan J, Yokoyama Y, Gerber HP, Ferrara N, Crouch RK, et al. Vascular<br />

endothelial growth factor expression <strong>in</strong> the ret<strong>in</strong>al pigment epithelium is essential<br />

for choriocapillaris development and visual function. Am J Pathol [Internet]. 2005<br />

[cited 2011 Jun 21];167(5):1451-9. Available from: http://www.ncbi.nlm.nih.gov/pmc/<br />

articles/PMC1603772/<br />

21. Yamada H, Yamada E, Kwak N, Ando A, Suzuki A, Esumi N, et al. Cell <strong>in</strong>jury unmasks<br />

a latent proangiogenic phenotype <strong>in</strong> mice with <strong>in</strong>creased expression of FGF2 <strong>in</strong> the<br />

ret<strong>in</strong>a. J Cell Physiol. 2000;185(1):135-42.<br />

22. Schmidt-Erfurth U, Rudolf M, Funk M, Hofmann-Rummelt C, Franz-Haas NS, Aherrahrou<br />

Z, et al. Ultrastructural changes <strong>in</strong> a mur<strong>in</strong>e model of graded Bruch membrane<br />

lipoidal degeneration and correspond<strong>in</strong>g VEGF164 detection. Invest Ophthalmol Vis<br />

Sci [Internet]. 2008[cited 2012 Jan 12]; 49:390-8. Available from: http://www.iovs.org/<br />

content/49/1/390.long<br />

23. Rudolf M, W<strong>in</strong>kler B, Aherrahou Z, Doehr<strong>in</strong>g LC, Kaczmarek P, Schmidt-Erfurth U.<br />

Increased expression of vascular endothelial growth factor associated with accumulation<br />

of lipids <strong>in</strong> Bruch’s membrane of LDL receptor knockout mice. Br J Ophthalmol<br />

[Internet]. 2005[cited 2009 Oct 21];89(12):1627-30. Comment <strong>in</strong>: Br J Ophthalmol.<br />

2005;89(12):1549-51. Available from: http://bjo.bmj.com/content/89/12/1627.long<br />

24. Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K, et al. The potencial angiogenic<br />

role of macrophages <strong>in</strong> the formation of choroidal neovascular membranes. Invest<br />

Ophthalmol Vis Sci [Internet]. 1999[cited 2010 Jun 21];40(9):1891-8. Available from:<br />

http://www.iovs.org/content/40/9/1891.long<br />

25. Salazar JJ, Ramírez AI, de Hoz R, Rojas B, Ruiz E, Tejer<strong>in</strong>a T, et al. Alterations <strong>in</strong> the choroid<br />

<strong>in</strong> hypercholesterolemic rabbits: reversibility after normalization of cholesterol<br />

levels. Exp Eye Res [Internet]. 2007[cited 2010 Jun 21];84(3):412-22. Available from:<br />

http://www.sciencedirect.com/science/article/pii/S0014483506004192<br />

26. Torres RJ, Maia M, Noronha L, Farah ME, Luch<strong>in</strong>i A, Brik D, et al. Evaluation of choroid<br />

and sclera early alterations <strong>in</strong> hypercholesterolemic rabbits: histologic and histomorphometric<br />

study. Arq Bras Oftalmol [Internet]. 2009[cited 2010 Nov 21]; 72(1):68-74.<br />

Portuguese. Available from: http://www.scielo.br/pdf/abo/v72n1/v72n1a14.pdf<br />

27. Blann AD, Belgore FM, Constans J, Conri C, Lip GY. Plasma vascular endothelial growth<br />

factor and its receptor Flt-1 <strong>in</strong> patients with hyperlipidemia and atherosclerosis and<br />

the effects of fluvastat<strong>in</strong> or fenofibrate. Am J Cardiol [Internet]. 2001[cited 2010 Apr<br />

21];87(10):1160-3. Available from: http://www.sciencedirect.com/science/article/pii/<br />

S0002914901014862<br />

28. Moreira EF, Larrayoz IM, Lee JW, Rodriguez IR. 7-Ketocholesterol is present <strong>in</strong> lipid<br />

deposits <strong>in</strong> the primate ret<strong>in</strong>a: potential implication <strong>in</strong> the <strong>in</strong>duction of VEGF and CNV<br />

formation. Invest Ophthalmol Vis Sci [Internet]. 2009[cited 2010 Apr 23]; 50(2):523-32.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811433/<br />

29. Kantor B, Ashai K, Holmes DR Jr, Schwartz RS. The experimental animal models for<br />

assess<strong>in</strong>g treatment of restenosis. Cardiovasc Radiation Med [Internet]. 1999 [cited<br />

2010 Jan 21];1(1):48-54. Available from: http://www.sciencedirect.com/science/<br />

article/pii/S1522186598000055<br />

30. Triviño A, Ramírez AI, Salazar JJ, de Hoz R, Rojas B, Padilla E, et al. A cholesterol-enriched<br />

diet <strong>in</strong>duces ultrastructural changes <strong>in</strong> ret<strong>in</strong>al and macroglial rabbit cells. Exp<br />

Eye Res [Internet]. 2006 [cited 2010 Feb 3];83(2):357-66. Available from: http://www.<br />

sciencedirect.com/science/article/pii/S0014483506001436<br />

Arq Bras Oftalmol. 2013;76(1):1-5<br />

5


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

The need for artificial tears <strong>in</strong> glaucoma patients: a comparative, retrospective study<br />

O uso de lágrimas artificiais em pacientes com glaucoma: um estudo retrospectivo e comparativo<br />

Vital Paul<strong>in</strong>o Costa 1 , Renata Siqueira da Silva 2 , Renato Ambrósio Jr. 2<br />

ABSTRACT<br />

Purpose: To evaluate the need for artificial tears by glaucoma patients under<br />

topical hypotensive treatment and to identify risk factors associated with it.<br />

Methods: The charts of 175 glaucoma patients under medical treatment and 175<br />

age-matched controls were reviewed. Age, gender, use of artificial tears, number<br />

of glaucoma medications used, and duration of treatment were recorded.<br />

Results: Significantly more glaucoma patients (n=92; 52.6%) used artificial tears<br />

compared to age-matched controls (n=31; 17.7%) (p5 years (OR=2.93) were<br />

risk factors for the use of artificial tears (p


Costa VP, et al.<br />

The purpose of this study is to evaluate the need for artificial tears<br />

among glaucoma patients under topical treatment, and to identify<br />

risk factors associated with it. We hypothesize that, s<strong>in</strong>ce the use of<br />

antiglaucoma medication is associated with OSD, this may <strong>in</strong>crease<br />

the necessity of artificial tears <strong>in</strong> these patients.<br />

METHODS<br />

This was a retrospective, comparative study approved by the<br />

Ethics Committee/Investigational Review Board of the University of<br />

Camp<strong>in</strong>as, Brazil. The charts of 175 consecutive glaucoma patients<br />

and 175 age-matched (+2 years) controls followed at two private offices<br />

(VPC and RA) were reviewed. Both Institutions followed patients<br />

with glaucoma and patients without glaucoma.<br />

The follow<strong>in</strong>g characteristics were listed as <strong>in</strong>clusion criteria for<br />

the glaucoma group: diagnosis of glaucoma (primary open-angle,<br />

primary angle-closure, pigmentary glaucoma, or pseudoexfoliative<br />

glaucoma), and use of antiglaucoma medications. Patients <strong>in</strong>cluded<br />

<strong>in</strong> the control group were followed for other ocular conditions, <strong>in</strong>clud<strong>in</strong>g<br />

refractive errors and cataract. Patients with previous <strong>in</strong>traocular<br />

surgery (i.e phacoemulsification, trabeculectomy, implant device,<br />

etc), previous laser surgery (except laser iridotomy), or use of contact<br />

lens were excluded from both groups. Patients previously diagnosed<br />

with dry eyes were not excluded from the study.<br />

The follow<strong>in</strong>g data was retrieved from the charts of both groups:<br />

age, gender, use of systemic drugs associated with dry eye (anti-histam<strong>in</strong>ics,<br />

antidepressants, anti-hypertensives, chol<strong>in</strong>ergic agents),<br />

use of artificial tears, use of topical cyclospor<strong>in</strong>e, and <strong>in</strong>sertion of<br />

la crimal plug at the last exam<strong>in</strong>ation. In the glaucoma group, we<br />

also evaluated the type of glaucoma, number and type of glaucoma<br />

medications, and duration of glaucoma treatment.<br />

We compared the frequency of use of artificial tears <strong>in</strong> both<br />

po pulations us<strong>in</strong>g the Chi square or the Fisher exact test. We also<br />

<strong>in</strong>vestigated risk factors associated with the use of artificial tears <strong>in</strong><br />

both groups and specifically <strong>in</strong> the glaucoma population apply<strong>in</strong>g<br />

the Cox-proportional hazard test. P values of less than 0.05 were<br />

considered statistically significant.<br />

RESULTS<br />

Table 1 lists the demographics of both populations. There were<br />

no significant differences regard<strong>in</strong>g mean age, distribution of gender,<br />

or race between the groups (p>0.05). Most of the glaucoma patients<br />

had primary open-angle glaucoma (POAG) (82%), and used one an -<br />

Table 1. Demographics of both populations<br />

Age (years)<br />

Glaucoma<br />

N=175<br />

Mean ± SD 66.6 ± 13.0 64.3 ± 13.8<br />

Controls<br />

N=175 P<br />

Range 18 - 90 18 - 91 0.11*<br />

Gender<br />

Race<br />

Male 076 43.4% 067 38.3%<br />

Female 099 56.6% 108 61.7% 0.38**<br />

Caucasian 154 88.0% 155 88.6%<br />

Mixed 011 06.3% 009 05.1%<br />

Asian 006 03.4% 005 02.9% 0.90***<br />

African-american 004 02.8% 006 04.0%<br />

SD= standard deviation; *= ANOVA; **= Chi Square test; ***= Fisher Exact test.<br />

tiglaucoma topical medication (55%) (Table 2). Patients <strong>in</strong> the glaucoma<br />

group had been treated for a mean of 4.4 + 4.6 years (range: 1<br />

month to 38 years). Prostagland<strong>in</strong> analogues alone (46%) were used<br />

more frequently than other antiglaucoma medications. However, be -<br />

tablockers were also used by a large group of patients either alone<br />

(23%) or <strong>in</strong> fixed comb<strong>in</strong>ations with other drugs (50%).<br />

Significantly more glaucoma patients (n=92; 52.6%) used artificial<br />

tears compared to age-matched controls (n=31; 17.7%) (p


The need for artificial tears <strong>in</strong> glaucoma patients: a comparative, retrospective study<br />

Table 3. Univariate analysis of risk factors associated with the use of<br />

artificial tears <strong>in</strong>clud<strong>in</strong>g glaucoma patients and age-matched controls<br />

Variable OR CI P<br />

Glaucoma 5.148 3.16 - 5.89


Costa VP, et al.<br />

Spanish. Available from: http://www.oftalmo.com/seo/archivos/maquetas/F/350<br />

415A1-04F3-FF09-73C4-000049E3D6EF/articulo.pdf<br />

10. Rosenberg ES, Asbell PA. Essential fatty acids <strong>in</strong> the treatment of dry eye. Ocul Surf.<br />

2010;8(1):18-28.<br />

11. Erv<strong>in</strong> AM, Wojciechowski R, Sche<strong>in</strong> O. Punctal occlusion for dry eye syndrome. Cochrane<br />

Database Syst Rev [Internet]. 2010 [cited 2011 Aug 25];8(9):CD006775. http://<br />

onl<strong>in</strong>elibrary.wiley.com/doi/10.1002/14651858.CD006775.pub2/full<br />

12. Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclospor<strong>in</strong>e: pharmacology and<br />

cl<strong>in</strong>ical uses. Surv Ophthalmol [<strong>in</strong>ternet] 2009[cited 2012 Jun 21];54(3):321-38. Comment<br />

<strong>in</strong>: Surv Ophthalmol. 2010;55(2):189. Available from: http://www.sciencedirect.<br />

com/science/article/pii/S003962570900037X<br />

13. Abelson MB, Ousler GW 3 rd , Maffei C. Dry eye <strong>in</strong> 2008. Curr Op<strong>in</strong> Ophthalmol. 2009;<br />

20(4):282-6.<br />

14. Ambrosio R Jr, Tervo T, Wilson SE. LASIK-associated dry eye and neurotrophic epitheliopathy:<br />

pathophysiology and strategies for prevention and treatment. J Refract Surg.<br />

2008;24(4):396-407.<br />

15. Fonseca EC, Arruda GV, Rocha EM. [Dry eye: etiopathogenesis and treatment]. Arq<br />

Bras Oftalmol [Internet]. 2010[cited 2012 Jun 21];73(2):197-203.Portuguese. Available<br />

from: http://www.scielo.br/pdf/abo/v73n2/v73n2a21.pdf<br />

16. Schmier JK, Covert DW. Characteristics of respondents with glaucoma and dry eye <strong>in</strong><br />

a national panel survey. Cl<strong>in</strong> Ophthalmol [Internet] 2009[cited 2010 Dec 21];3:645-50.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788591/<br />

17. Martone G, Frezzotti P, Tosi GM, Traversi C, Mittica V, Malandr<strong>in</strong>i A, et al. An <strong>in</strong> vivo confocal<br />

microscopy analysis of effects of topical antiglaucoma therapy with preservative<br />

on corneal <strong>in</strong>nervation and morphology. Am J Ophthalmol. 2009;147(4):725-35e1.<br />

18. Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, Dua HS, Hom M, Karpecki<br />

PM, Laibson PR, Lemp MA, Meisler DM, Del Castillo JM, O’Brien TP,Pflugfelder SC,<br />

Rolando M, Sche<strong>in</strong> OD, Seitz B, Tseng SC, van Setten G, Wilson SE, Yiu SC; Dysfunctional<br />

tear syndrome study group. Dysfunctional tear syndrome: a Delphi approach to<br />

treatment recommendations. Cornea. 2006;25(8):900-7. Comment <strong>in</strong>: Cornea. 2007;<br />

26(7):901.<br />

19. Dogru M, Stern ME, Smith JA, Foulks GN, Lemp MA, Tsubota K. Chang<strong>in</strong>g trends <strong>in</strong><br />

the def<strong>in</strong>ition and diagnosis of dry eyes. Am J Ophthalmol 2005;140(3):507-8.<br />

20. Herrero-Vanrell R, Peral A. [International Dry Eye Workshop (DEWS). Update of the<br />

disea se]. Arch Soc Esp Oftalmol [Internet]. 2007[cited 2009 Aug 21];82(12):733-4.<br />

Spanish. Available from: http://www.oftalmo.com/seo/archivos/maquetas/F/388144<br />

D4-E886-0149-62B8-00003843D50F/articulo.pdf<br />

21. Yenice O, Temel A, Orum O. The effect of artificial tear adm<strong>in</strong>istration on visual field<br />

test<strong>in</strong>g <strong>in</strong> patients with glaucoma and dry eye. Eye (Lond) [Internet]. 2007[cited 2010<br />

Nov 21];21(12):214-7. Available from: http://www.nature.com/eye/journal/v21/n2/<br />

full/6702252a.html<br />

22. Rossi GC, T<strong>in</strong>elli C, Pas<strong>in</strong>etti GM, Milano G, Bianchi PE. Dry eye syndrome-related<br />

quality of life <strong>in</strong> glaucoma patients. Eur J Ophthalmol. 2009;19(4):572-9.<br />

23. Kuppens EV, van Best JA, Sterk CC, de Keizer RJ. Decreased basal tear turnover <strong>in</strong> patients<br />

with untreated primary open-angle glaucoma. Am J Ophthalmol. 1995;120(1):<br />

41-6.<br />

24. Jaenen N, Baudou<strong>in</strong> C, Pouliquen P, Manni G, Figueiredo A, Zeyen T. Ocular symptoms<br />

and signs with preserved and preservative-free glaucoma medications. Eur J<br />

Ophthalmol. 2007;17(3):341-9.<br />

25. Uusitalo H, Chen E, Pfeiffer N, Brignote-Baudou<strong>in</strong> F, Kaamiranta K, Le<strong>in</strong>o M, et al.<br />

Switch<strong>in</strong>g from a preserved to a preservative-free prostagland<strong>in</strong> preparation <strong>in</strong><br />

topical glaucoma medication. Acta Ophthalmol [Internet]. 2010 [cited 2012 Sep 15];<br />

88(3):329-36. Available from: http://onl<strong>in</strong>elibrary.wiley.com/doi/10.1111/j.1755-3768.<br />

2010.01907.x/pdf<br />

26. Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved,<br />

polyquad-preserved, and sofZia-preserved topical glaucoma medications on human<br />

ocular epithelial cells. Adv Ther [Internet]. 2010 [cited 2012 Oct 15];27:837-45. Available<br />

from: http://l<strong>in</strong>k.spr<strong>in</strong>ger.com/article/10.1007%2Fs12325-010-0070-1<br />

Simpósio Internacional de Córnea<br />

do Hospital de Olhos de Sorocaba<br />

24 a 26 de outubro de 2013<br />

Sorocaba (SP)<br />

Organização:<br />

Hospital de Olhos de Sorocaba<br />

Informações:<br />

Tel.: (15) 3212-7077<br />

E-mail: s<strong>in</strong>bos@bos.org.br<br />

Arq Bras Oftalmol. 2013;76(1):6-9<br />

9


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

The correlation between body mass <strong>in</strong>dex and <strong>in</strong>traocular pressure <strong>in</strong> children<br />

Correção entre o índice de massa corpórea e a pressão <strong>in</strong>traocular em crianças<br />

Luciano Lira de Albuquerque 1 , Maria Isabel Lynch Gaete 2 , José Natal Figueiroa 3 , João Guilherme Bezerra Alves 1<br />

ABSTRACT<br />

Purpose: There is evidence from some studies that support an association between<br />

obesity <strong>in</strong> adults and higher <strong>in</strong>traocular pressure (IOP). However, this association<br />

has not been completely studied <strong>in</strong> children. Our aim is to evaluate the association<br />

between child body mass <strong>in</strong>dex (BMI) and IOP.<br />

Methods: N<strong>in</strong>ety-six children attend<strong>in</strong>g the Instituto de Medic<strong>in</strong>a Integral Prof.<br />

Fer nando Figueira (IMIP) <strong>in</strong> Brazil were studied. Thirty-three were overweight/<br />

obese with a mean BMI of 29.7 ± 5.2 and 63 with a mean BMI of 20.8 ± 3.3. IOP<br />

was measured us<strong>in</strong>g the Goldmann applanation tonometer and was corrected for<br />

corneal thickness. The coefficient of correlation between BMI and IOP was calculated.<br />

Results: There was no significant difference <strong>in</strong> the IOP of children with or without<br />

overweight/obesity. The mean IOP was 13.5 and 13.0 mmHg for the right eye and<br />

13.1 and 12.9 mmHg for left eye, respectively (p=0.38 and p=0.71). The results<br />

rema<strong>in</strong>ed the same after correction by pachymetry; 13.0 and 13.1 mmHg for<br />

the right eye and 12.4 and 12.9 mmHg for the left eye, respectively (p=0.88 and<br />

p=0.41). The coefficient of correlation between BMI and IOP was 0.070 (p=0.496).<br />

Conclusion: These results do not show a correlation between body mass <strong>in</strong>dex and<br />

IOP <strong>in</strong> children. Further studies are warranted to clarify the association between<br />

BMI and IOP <strong>in</strong> children.<br />

Keywords: Intraocular pressure; Tonometry; Body mass <strong>in</strong>dex; Obesity; Overweight;<br />

Child<br />

RESUMO<br />

Objetivo: Alguns estudos apontam para uma associação entre obesidade e aumento<br />

da pressão <strong>in</strong>traocular em adultos. Entretanto, essa associação a<strong>in</strong>da não foi completamente<br />

estudada em crianças. O objetivo do estudo é avaliar a associação entre<br />

o índice de massa corpórea (IMC) e a pressão <strong>in</strong>traocular em crianças.<br />

Métodos: Noventa e seis crianças atendidas no Instituto de Medic<strong>in</strong>a Integral Prof.<br />

Fernando Figueira (IMIP), Brasil, foram estudadas. Tr<strong>in</strong>ta e três apresentavam excesso<br />

de peso ou obesidade com uma média de IMC de 29,7 ± 5,2 e os outros 63 t<strong>in</strong>ham uma<br />

média de IMC de 20,8 ± 3,3. A pressão <strong>in</strong>traocular foi medida por meio do tonômetro<br />

de aplanação de Goldmann, corrigida pela espessura da córnea. O coeficiente de<br />

cor relação entre o IMC e a pressão <strong>in</strong>traocular foi calculado.<br />

Resultados: Não foi observada diferença significativa na pressão <strong>in</strong>traocular entre<br />

as crianças com e sem excesso de peso/obesidade. A média da pressão <strong>in</strong>traocular foi<br />

de 13,5 e 13,0 mmHg no olho direito e 13,1 e 12,9 mmHg no olho esquerdo, respectivamente<br />

(p=0,38 e p=0,71). Os resultados permaneceram os mesmos após a correção<br />

pela paquimetria; 13,0 e 13,1 mmHg para o olho direito e 12,4 e 12,9 mmHg para o<br />

olho esquerdo, respectivamente (p=0,88 e p=0,41). O coeficiente de correlação entre<br />

o IMC e a pressão <strong>in</strong>traocular foi 0,070 (p=0,496).<br />

Conclusão: O índice de massa corpórea não parece apresentar correlação com a<br />

pressão <strong>in</strong>traocular em crianças. Novos estudos são necessários para esclarecer a asso ­<br />

ciação entre o IMC e a pressão <strong>in</strong>traocular.<br />

Descritores: Pressão <strong>in</strong>traocular; Tonometria; Índice de massa corpórea; Obesidade;<br />

Sobrepeso; Criança<br />

INTRODUCTION<br />

High <strong>in</strong>traocular pressure (IOP) is associated with glaucomatous<br />

optic nerve damage and its detrimental effect on vision (1,2) . IOP is<br />

currently the only modifiable risk factor for glaucoma (3) . Some epidemiological<br />

studies have described an association between obesity<br />

and IOP <strong>in</strong> adults (4,5) . A recent review concluded that there is an<br />

asso ciation between higher body mass <strong>in</strong>dex (BMI) and higher IOP<br />

<strong>in</strong> adults (6) . Although obesity is becom<strong>in</strong>g a serious health problem<br />

<strong>in</strong> children with effects later on <strong>in</strong> adult life, there is only one study<br />

that has determ<strong>in</strong>ed the IOP <strong>in</strong> obese children. Ak<strong>in</strong>ci et al. found that<br />

obesity was an <strong>in</strong>dependent risk factor for <strong>in</strong>creased IOP (7) . The aim<br />

here is to evaluate the association between BMI and IOP <strong>in</strong> children.<br />

METHODS<br />

N<strong>in</strong>ety-six children were recruited from the Department of Pediatrics<br />

of the Instituto de Medic<strong>in</strong>a Integral Prof. Fernando Figueira<br />

(IMIP), Brazil, between September, 2009 and March, 2010. The research<br />

received prior approval from the Research Ethics Committee<br />

and all parents of participants signed an <strong>in</strong>formed consent form.<br />

Weight and height were measured with the children wear<strong>in</strong>g<br />

light clothes and no shoes. Body mass <strong>in</strong>dex (BMI), weight (<strong>in</strong> kilograms)<br />

divided by height <strong>in</strong> meters squared (kg/m 2 ), was used as the<br />

<strong>in</strong>dicator of fat mass. A child with a BMI <strong>in</strong> the 95 th percentile or higher<br />

was considered to be obese, and a child with a BMI >85 th and 6D), diseases of the cornea or the presence of cardiovascular,<br />

renal, neurological, mental or metabolic disorders and<br />

genetic syndromes.<br />

All measurements were performed between 9:00 am and midday,<br />

by one of the authors (LLA).<br />

The IOP was measured us<strong>in</strong>g the Goldmann applanation tonometer.<br />

Three sequential measurements were recorded for each eye<br />

Submitted for publication: December 12, 2011<br />

Accepted for publication: December 13, 2012<br />

Study carried out at Instituto de Medic<strong>in</strong>a Integral Professor Fernando Figueira, Recife, PE, Brazil.<br />

1<br />

Physician, Serviço de Oftalmologia Pediátrica, Instituto de Medic<strong>in</strong>a Integral Professor Fernando<br />

Figueira, Recife, PE, Brazil.<br />

2<br />

Professor, Universidade Federal de Pernambuco, Recife, PE, Brazil.<br />

3<br />

Statistician, Instituto de Medic<strong>in</strong>a Integral Professor Fernando Figueira, Recife, PE, Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: L.L.de Albuquerque, None; M.I.L.Gaete, None;<br />

J.N.Figueroa, None; J.G.B.Alves, None.<br />

Correspond<strong>in</strong>g author: João Guilherme Bezerra Alves. Instituto de Medic<strong>in</strong>a Integral Prof. Fernando<br />

Figueira (IMIP). Rua dos Coelhos, 300 - Boa Vista - Recife (PE) - 50070-550 - Brazil<br />

E-mail: joaoguilherme@imip.org.br<br />

10 Arq Bras Oftalmol. 2013;76(1):10-2


Albuquerque LL, et al.<br />

and the average was recorded. Corneal thickness was determ<strong>in</strong>ed<br />

us<strong>in</strong>g a noncontact optical scann<strong>in</strong>g slit pachymeter (Orbscan II).<br />

Hertel exophthalmometry was also carried out.<br />

Blood pressure was obta<strong>in</strong>ed on the right arm, after 5 m<strong>in</strong> rest,<br />

us<strong>in</strong>g a mercury sphygmomanometer and appropriate sized cuff.<br />

After three measurements, the lowest blood pressure value was<br />

chosen. Children were classified accord<strong>in</strong>g to gender, height and<br />

age-specific charts.<br />

Student t test was used to assess mean comparisons of cont<strong>in</strong>uous<br />

variables and the chi-square test for distributions of categorical<br />

variables. The association between BMI and IOP was assessed<br />

us<strong>in</strong>g the Pearson correlation coefficient. A multiple l<strong>in</strong>ear regression<br />

model was used to analyze the possible effect of confound<strong>in</strong>g variables<br />

<strong>in</strong> the relationship between BMI and IOP. All tests used a p-value<br />

of 34 kg/m 2 ) may falsely <strong>in</strong>crease<br />

IOP (9) . Dur<strong>in</strong>g the procedure a high BMI may cause compression<br />

of the chest and hold<strong>in</strong>g of the breath, both of which give rise to an<br />

<strong>in</strong>crease <strong>in</strong> venous pressure and hence raise IOP.<br />

Some authors argue that obesity <strong>in</strong>creases IOP due to an excessive<br />

<strong>in</strong>traorbital adipose tissue deposit, lead<strong>in</strong>g to a rise <strong>in</strong> blood<br />

vis cosity and episcleral venous pressure, and a consequent decrease<br />

<strong>in</strong> the facility of aqueous outflow. For other authors, obesity only<br />

<strong>in</strong>creases IOP when it is associated with <strong>in</strong>sul<strong>in</strong>-resistance (10) . The<br />

au tonomic dysfunction and the osmotic gradient <strong>in</strong>duced by hyperglycemia<br />

with a consequent fluid shift <strong>in</strong>to the <strong>in</strong>traocular space have<br />

been proposed to expla<strong>in</strong> the association between IOP and <strong>in</strong>sul<strong>in</strong>-<br />

Table 2. Intraocular pressure (IOP), corneal thickness (COT) and<br />

exophthalmometry (exo) <strong>in</strong> normal, overweight and obese children<br />

Normal<br />

(N=63)<br />

BMI<br />

Overweight<br />

(N=21)<br />

Obese<br />

(N=12)<br />

Variable Mean (sd) Mean (sd) Mean (sd) p value<br />

IOP right eye (mmHg) 013.30 (0.3) 013.30 (00.5) 013.00 (0.3) 0.758<br />

IOP left eye (mmHg) 013.30 (0.3) 012.90 (00.5) 012.80 (0.3) 0.578<br />

COT right eye (µm) 545.20 (7.0) 549.10 (10.9) 543.20 (6.3) 0.895<br />

COP left eye (µm) 546.40 (7.0) 549.80 (10.8) 545.80 (6.3) 0.950<br />

Exo right eye (mm) 017.27 (1.7) 017.31 (01.6) 017.56 (1.8) 0.893<br />

Exo left eye (mm) 017.11 (1.9) 017.88 (01.8) 017.64 (1.7) 0.877<br />

DISCUSSION<br />

A positive correlation between IOP and obesity has been described<br />

<strong>in</strong> adults, although some studies have shown conflict<strong>in</strong>g<br />

re sults (8,9) . The relationship between IOP and obesity <strong>in</strong> children has<br />

not as yet been adequately studied. As obesity tends to cont<strong>in</strong>ue <strong>in</strong>to<br />

adulthood, a positive correlation between BMI and IOP could <strong>in</strong>dicate<br />

that obesity control <strong>in</strong> children is a crucial strategy for prevention<br />

of glaucoma. However, our results did not confirm an association<br />

between BMI and IOP. Ak<strong>in</strong>ci et al., however, <strong>in</strong> a study conducted<br />

Table 1. Biological and socio-economical characteristics of overweight/<br />

obese and non-overweight/obese children<br />

Variable<br />

Normal<br />

(N=63)<br />

Overweight<br />

(N=21)<br />

Obese<br />

(N=12)<br />

p value<br />

Age, mean (sd) 12.7 a (0.4) 12.0 a (0.7) 9.5 b (0.4) 4 years (%)<br />

Income per capita<br />

($ US ± sd)<br />

58.6 a 100.0 b 75.0 b 0.016 †<br />

095.9 (9.4) 101.9 (14.7) 106.3 (8.5) 0.713<br />

SAP (mmHg), mean (sd) 107.9 (2.4) 107.0 (3.7) 107.7 (2.1) 0.977<br />

DAP (mmHg), mean (sd) 065.8 (1.7) 061.6 (2.6) 066.6 (1.5) 0.247<br />

sd= standard deviation; $ US= US dollars; SAP= systolic arterial pres sure; DAP= diastolic<br />

arterial pressure.<br />

*= ANOVA test; † = Fisher Exact test; a,b = Pairs of different letters were statistically different.<br />

Table 3. L<strong>in</strong>ear regression model for <strong>in</strong>traocular pressure (IOP) on<br />

body mass <strong>in</strong>dex adjusted for gender, sk<strong>in</strong> color, maternal school<strong>in</strong>g,<br />

age and <strong>in</strong>come per capita<br />

Coefficient Std. err. p value<br />

IOP right eye (mmHg)<br />

Female -0.88 0.43 0.043<br />

Sk<strong>in</strong> color (not white) 0.032 0.49 0.947<br />

Maternal school<strong>in</strong>g >4 years (%) 0.28 0.49 0.563<br />

Age 0.045 0.093 0.631<br />

Income per capita 0.00011 0.0042 0.980<br />

Body mass <strong>in</strong>dex (reference: normal)<br />

Overweight -0.30 0.64 0.634<br />

Obese -0.45 0.055 0.416<br />

Constant 13.21 1.34 4 years (%) 0.31 0.49 0.528<br />

Age 0.030 0.094 0.747<br />

Income per capita -0.00028 0.0043 0.948<br />

Body mass <strong>in</strong>dex (reference: normal)<br />

Overweight -0.57 0.64 0.374<br />

Obese -0.55 0.55 0.325<br />

Constant 13.34 1.35


The correlation between body mass <strong>in</strong>dex and <strong>in</strong>traocular pressure <strong>in</strong> children<br />

-resistance. Insul<strong>in</strong>-resistance is more frequent <strong>in</strong> children with very<br />

high BMI and the present study <strong>in</strong>cluded overweight/obese children<br />

with a mean BMI of 29 kg/m 2 .<br />

All exam<strong>in</strong>ations were performed at the same time by the<br />

study’s lead author (LL). All patients underwent pachymetry and<br />

exo phthalmometry, exam<strong>in</strong>ations that <strong>in</strong>crease the reliability of IOP<br />

measurement. There is no l<strong>in</strong>ear correlation between IOP and corneal<br />

thickness, so mathematic attempts to correct the IOP for corneal<br />

thickness are not valid. However <strong>in</strong> our study corneal thickness showed<br />

no differences among overweight/obese and non-overweight/<br />

obese children which decrease the <strong>in</strong>fluence of this variable on IOP.<br />

A number of shortcom<strong>in</strong>gs of this study should be mentioned.<br />

First, the study <strong>in</strong>cluded a few number of obese children with a high<br />

BMI, as Ak<strong>in</strong>ci et al. did (7) . For this reason it is not possible to carry<br />

out a comparative analysis among the obese children. It can be hypothesized<br />

that IOP <strong>in</strong>creases only <strong>in</strong> children with extreme obesity.<br />

Another po<strong>in</strong>t is that the measurement of IOP was performed by<br />

only one ophthalmologist and it was not possible to determ<strong>in</strong>e the<br />

reliability of the test.<br />

In conclusion, no association was found between BMI and PIO <strong>in</strong><br />

this study. This f<strong>in</strong>d<strong>in</strong>g did not confirm previous results that obesity<br />

<strong>in</strong> children is an <strong>in</strong>dependent risk factor for IOP. Further studies are<br />

warranted to clarify the association between BMI and IOP <strong>in</strong> children.<br />

REFERENCES<br />

1. Mackenzie P, Cioffi G. How does lower<strong>in</strong>g of <strong>in</strong>traocular pressure protect the optic<br />

nerve? Surv Ophthalmol. 2008;53 Suppl1:S39-43.<br />

2. Harris A, Rechtman E, Siesky B, Jonescu-Cuypers C, McCranor L, Garzozi HJ. The role<br />

of optic nerve blood flow <strong>in</strong> the pathogenesis of glaucoma. Ophthalmol Cl<strong>in</strong> North<br />

Am. 2005;18(3):345-53,v.<br />

3. Coleman AL, Kodjebacheva G. Risk factors for glaucoma need<strong>in</strong>g more attention.<br />

Open Ophthalmol J. 2009;3:38-42.<br />

4. Mori K, Ando F, Nomura H, Sato Y, Shimokata H. Relationship between <strong>in</strong>traocular<br />

pressure and obesity <strong>in</strong> Japan. Int J Epidemiol. 2000;29(4):661-6.<br />

5. Lee JS, Choi YR, Lee JE, Choi HY, Lee SH, Oum BS. Relationship between <strong>in</strong>traocular<br />

pressure and systemic health parameters <strong>in</strong> the Korean population. Korean J Oph -<br />

thal mol. 2002;16(1):13-9.<br />

6. Cheung N, Wong TY. Obesity and eye diseases. Surv Ophthalmol. 2007;52(2):180-95.<br />

Review.<br />

7. Ak<strong>in</strong>ci A, Cet<strong>in</strong>kaya E, Aycan Z, Oner O. Relationship between <strong>in</strong>traocular pressure<br />

and obesity <strong>in</strong> children. J Glaucoma. 2007;16(7):627-30.<br />

8. Gasser P, Stümpfig D, Schötzau A, Ackermann-Liebrich U, Flammer J. Body mass <strong>in</strong>dex<br />

<strong>in</strong> glaucoma. J Glaucoma. 1999;8(1):8-11.<br />

9. dos Santos MG, Makk S, Berghold A, Eckhardt M, Haas A. Intraocular pressure difference<br />

<strong>in</strong> Goldmann applanation tonometry <strong>versus</strong> Perk<strong>in</strong>s hand-held applanation<br />

tonometry <strong>in</strong> overweight patients. Ophthalmology. 1998;105(12):2260-3. Comment<br />

<strong>in</strong> Ophthalmology. 1999;106(6):1041.<br />

10. Park SS, Lee EH, Jargal G, Paek D, Cho SI. The distribution of <strong>in</strong>traocular pressure and<br />

its association with metabolic syndrome <strong>in</strong> a community. J Prev Med Public Health.<br />

2010;43(2):125-30.<br />

XXXVII Congresso Brasileiro<br />

de Oftalmologia<br />

XXX Congresso Pan-Americano<br />

de Oftalmologia<br />

7 a 10 de agosto de 2013<br />

RioCentro<br />

Rio de Janeiro (RJ)<br />

Informações:<br />

Site: www.cbo2013.com.br<br />

12 Arq Bras Oftalmol. 2013;76(1):10-2


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Composition of <strong>in</strong>traocular foreign bodies: experimental study of<br />

ultrasonographic presentation<br />

Composição de corpos estranhos <strong>in</strong>traoculares: estudo experimental da apresentação ultrassonográfica<br />

Márcio Augusto Nogueira Costa 1 , Patrícia Novita Garcia 1 , Letícia Fernandes Barroso 1 , Marco Antonio Ferreira 2 , Érika Araki Okuda 1 , Norma Allemann 1<br />

ABSTRACT<br />

Purpose: To <strong>in</strong>vestigate the reliability of ultrasound <strong>in</strong> determ<strong>in</strong><strong>in</strong>g the size and<br />

identify the sonographic features and artifacts generated by <strong>in</strong>traocular foreign<br />

bodies of different materials.<br />

Methods: Experimental study us<strong>in</strong>g 36 enucleated porc<strong>in</strong>e eyes. Fragments of<br />

n<strong>in</strong>e different compositions (wood, glass, plastic, cardboard, iron, alum<strong>in</strong>um, lead,<br />

powder and concrete) and similar dimensions (4 mm) were implanted via scleral<br />

<strong>in</strong>cision <strong>in</strong>to the vitreous cavity of 36 porc<strong>in</strong>e eyes, four eyes were used for each<br />

material. Ultrasound exam<strong>in</strong>ation was performed <strong>in</strong> all eyes us<strong>in</strong>g the contact<br />

technique, conductive gel and 10-MHz transducer (EZScan, Sonomed).<br />

Results: Consider<strong>in</strong>g the material fragments of gunpowder, lead, concrete, alu -<br />

m<strong>in</strong>um, wood and glass, the size determ<strong>in</strong>ed by ultrasound was considered<br />

statistically similar to the actual size. The material iron presented ultrasound-de -<br />

term<strong>in</strong>ed dimension statistically smaller than its actual size. Cardboard and plastic<br />

materials showed ultrasound-determ<strong>in</strong>ed measurements far greater than the<br />

actual. All fragments of <strong>in</strong>traocular foreign bodies demonstrated hyper-reflective<br />

<strong>in</strong>terfaces, irrespective of their composition. Whereas the artifacts generated by<br />

different materials, it was found that the materials iron, alum<strong>in</strong>um and lead showed<br />

reverberation of great extent. The material wood showed no reverberation. The<br />

length of the reverberation artifact for the materials iron, glass, alum<strong>in</strong>um and<br />

cardboard was lower when compared to other materials. All materials presented<br />

posterior shadow<strong>in</strong>g artifact, with the exception of alum<strong>in</strong>um.<br />

Conclusion: Ultrasonography was considered a reliable technique to determ<strong>in</strong>e<br />

the size of <strong>in</strong>traocular foreign bodies <strong>in</strong> pigs, with little <strong>in</strong>fluence caused by its<br />

composition. Ultrasound artifacts generated were considered material-dependent<br />

and can assist the exam<strong>in</strong>er to identify the nature of a foreign body of unknown<br />

etiology. Ultrasonography aided the surgeon to identify, locate and measure the<br />

<strong>in</strong>traocular foreign body, direct<strong>in</strong>g appropriate surgical plann<strong>in</strong>g.<br />

Keywords: Eye foreign bodies/diagnosis; Eye foreign bodies/ultrasonography;<br />

Artifacts; Sw<strong>in</strong>e<br />

RESUMO<br />

Objetivo: Investigar a confiabilidade da ultrassonografia em determ<strong>in</strong>ar a dimensão<br />

e identificar as características ultrassonográficas e os artefatos gerados por corpos<br />

estranhos <strong>in</strong>traoculares de materiais diferentes.<br />

Métodos: Estudo experimental, utilizando 36 olhos enucleados de origem suína.<br />

Fragmentos de nove diferentes composições (madeira, vidro, plástico, papelão, ferro,<br />

alumínio, chumbo, pólvora e concreto) e de dimensões similares (4 mm) foram implantados<br />

cirurgicamente via <strong>in</strong>cisão escleral na cavidade vítrea de 36 olhos porc<strong>in</strong>os,<br />

4 olhos para cada tipo de material. O exame ultrassonográfico foi realizado em todos<br />

os olhos utilizando-se a técnica de contato, gel condutor e transdutor de 10 MHz<br />

(EZScan, Sonomed).<br />

Resultados: Considerando os fragmentos dos materiais pólvora, chumbo, concreto,<br />

alumínio, madeira e vidro, a dimensão determ<strong>in</strong>ada pela ultrassonografia foi<br />

considerada estatisticamente similar à dimensão real. O material ferro apresentou<br />

dimensão ultrassonográfica estatisticamente menor que sua dimensão real. Papelão<br />

e plástico demonstraram medida maior que o real. Todos fragmentos de corpos estranhos<br />

<strong>in</strong>traoculares demonstraram <strong>in</strong>terfaces hiper-refletivas, <strong>in</strong>dependentemente<br />

da sua composição. Considerando os artefatos gerados pelos diferentes materiais,<br />

verificou-se que os materiais ferro, alumínio e chumbo apresentaram reverberação de<br />

grande extensão. O material madeira não apresentou reverberação. O comprimento<br />

do artefato de reverberação dos materiais ferro, vidro, alumínio e papelão foi menor<br />

quando comparado aos outros materiais. Todos materiais apresentaram artefato de<br />

sombreamento posterior, com exceção do alumínio.<br />

Conclusão: A ultrassonografia foi considerada uma técnica confiável para determ<strong>in</strong>ar<br />

a dimensão de corpos estranhos <strong>in</strong>traoculares em porc<strong>in</strong>os, com pouca <strong>in</strong>fluência<br />

causada pela sua composição. Artefatos gerados à ultrassonografia foram considerados<br />

material-dependentes e podem auxiliar o exam<strong>in</strong>ador a identificar a natureza<br />

de um corpo estranho de etiologia desconhecida. O auxílio diagnóstico nestes casos<br />

permite ao cirurgião identificar, localizar e dimensionar o corpo estranho <strong>in</strong>traocular,<br />

orientando um planejamento cirúrgico adequado.<br />

Descritores: Corpo estranho <strong>in</strong>traocular/diagnóstico; Corpo estranho <strong>in</strong>traocular/<br />

ultrassonografia; Artefatos; Suínos<br />

INTRODUCTION<br />

The use of the ultrasonographic method for identification of an<br />

<strong>in</strong>traocular foreign body was reported <strong>in</strong> 1960 aim<strong>in</strong>g diagnosis and<br />

monitor<strong>in</strong>g of its surgical removal. Once <strong>in</strong> the eye, the foreign body<br />

(FB) may lodge <strong>in</strong> any of the ocular structures, which can generate<br />

important mechanical effects such as cataract formation, vitreous<br />

liquefaction, hemorrhage and ret<strong>in</strong>al breaks. Regard<strong>in</strong>g the composition<br />

of <strong>in</strong>traocular foreign bodies, the most frequent are: metal,<br />

glass, wood and plastic. The management and prognosis depends of<br />

the composition, location, size of the FB and the presence or not of<br />

<strong>in</strong>flammatory process and/or associated <strong>in</strong>traocular hemorrhage (1,2) .<br />

The ultrasonographic f<strong>in</strong>d<strong>in</strong>gs of metallic <strong>in</strong>traocular foreign<br />

bo dies (IOFBs) are similar, produc<strong>in</strong>g an echo of high density with<br />

posterior shadow<strong>in</strong>g. The spherical IOFB have specific signals due<br />

to sound reverberation produced, caus<strong>in</strong>g an acoustic artifact at<br />

B-mode, known as “comet tail”. Meanwhile, vegetal or organic nature<br />

IOFB, such as wood, may produce high reflectivity echoes although<br />

they could decrease over time due to decomposition process.<br />

Submitted for publication: August 15, 2012<br />

Accepted for publication: November 7, 2012<br />

Experiment carried out at Experimental Surgical Center and Ultrasound Service, Department of<br />

Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.<br />

1<br />

Physician, Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.<br />

2<br />

Veter<strong>in</strong>ary Physician, Department of Ophthalmology, Universidade de Franca, Franca, SP, Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: M.A.N.Costa, None; P.N.Garcia, None; L.F.Barroso,<br />

None; M.A.Ferreira, None; E.A.Okuda, None; N.Allemann, Travel/accommodations/meet<strong>in</strong>g expenses<br />

by Quantel Medical Inc.<br />

Correspondence address: Norma Allemann. Rua Olimpíadas, 134 - Conj. 51 - São Paulo (SP) -<br />

04551-000 - Brazil - E-mail: norma.allemann@pobox.com<br />

Arq Bras Oftalmol. 2013;76(1):13-7<br />

13


Composition of <strong>in</strong>traocular foreign bodies: experimental study of ultrasonographic presentation<br />

In the literature, there are few studies show<strong>in</strong>g differences of ge -<br />

nerated artifacts consider<strong>in</strong>g different materials, <strong>in</strong>clud<strong>in</strong>g analysis of<br />

its dimensions determ<strong>in</strong>ed by ultrasonography.<br />

In a study performed <strong>in</strong> 1994, <strong>in</strong> Tro<strong>in</strong>a (Italy), it was found that<br />

echographic measurements of metallic <strong>in</strong>traocular foreign bodies<br />

were overestimated when compared to actual values, especially <strong>in</strong><br />

foreign bodies of smaller diameter, with measurements of 2.0 mm<br />

and 2.2 mm (1) .<br />

The current study aims to compare the actual dimensions to<br />

those obta<strong>in</strong>ed by ultrasonography and to characterize the generated<br />

acoustic artifacts of IOFBs from various materials and of similar<br />

sizes. It aims to <strong>in</strong>vestigate the reliability of ultrasonography <strong>in</strong> determ<strong>in</strong><strong>in</strong>g<br />

the dimension and identify the artifacts generated by IOFBs<br />

from different materials.<br />

METHODS<br />

Project number and responsible <strong>in</strong>stitution for notion of the<br />

Ethics Research Committee/Investigational Review Board: Ethics Research<br />

Committee CEP - UNIFESP, Protocol approved under number:<br />

1695/11.<br />

Thirty-six enucleated porc<strong>in</strong>e eyes were used for this experimental<br />

study. The eyes were enucleated immediately after sacrifice at<br />

a local slaughterhouse and were kept <strong>in</strong> a refrigerator (1 hour) at a<br />

cons tant temperature of +5ºC until the implantation procedure of<br />

the foreign body and the ultrasonography evaluation. Fragments<br />

of 9 different materials such as wood, glass, plastic, cardboard, iron,<br />

alum<strong>in</strong>um, lead, powder and concrete, present<strong>in</strong>g similar measurements,<br />

approximately 4 mm of radial dimension, were used. In 4<br />

eyes for each material type, fragments were <strong>in</strong>serted <strong>in</strong>to the vitreous<br />

cavity through scleral <strong>in</strong>cision positioned 4 mm posteriorly to limbus,<br />

with subsequent scleral <strong>in</strong>cision sutures us<strong>in</strong>g 10-0 nylon monofilament<br />

su tures. Ultrasonography evaluation was then performed on<br />

each eye. The transducer was protected with a disposable glove du -<br />

r<strong>in</strong>g the exam, which was subsequently discarded.<br />

The ophthalmic ultrasonography device used was the A- and<br />

B-mode EZScan (Sonomed) equipped with a 10-MHz transducer.<br />

Exa m<strong>in</strong>ation was performed by one echographer us<strong>in</strong>g contact te -<br />

chnique and conductive gel.<br />

The ophthalmic ultrasonography was acquired <strong>in</strong> axial, radial and<br />

transversal scans, <strong>in</strong> order to f<strong>in</strong>d the best representation of the re -<br />

ferred foreign body. After all measurements, the images were recorded<br />

accord<strong>in</strong>g to each material used.<br />

For comparison of foreign bodies measures, an analysis of variance<br />

(ANOVA) was performed us<strong>in</strong>g the material type of FB as a<br />

factor under the measurement values made by ultrasonography<br />

(de pendent variable). For comparisons between groups, Tukey post<br />

hoc tests were used. For all tests, the alpha value considered was 0.05.<br />

The IOFBs were evaluated with the 10-MHz transducer and 60 dB<br />

ga<strong>in</strong>. Each FB was classified accord<strong>in</strong>g to its reflectivity (high, medium<br />

and low) and the presence of artifacts. The artifacts could be classified<br />

as: reverberation (or echo duplication) and acoustic shadow (shadow<strong>in</strong>g).<br />

The reverberation artifact was subjectively classified accord<strong>in</strong>g<br />

to its length (Figure 1), i.e. the maximum distance that artificial echoes<br />

(reverberation) are distant from the real object (the real fragment)<br />

and subdivided <strong>in</strong>to large, medium and small regard<strong>in</strong>g the size of<br />

the FB. It was also subjectively classified accord<strong>in</strong>g to their size, i.e.<br />

the size of the 1 st artifact <strong>in</strong>terface generated by a FB and subdivided<br />

<strong>in</strong>to larger, smaller or equal to the real object.<br />

RESULTS<br />

Measures of FBs from different materials were compared by a<br />

general l<strong>in</strong>ear model (ANOVA, one factor), followed by post hoc tests<br />

for specific comparisons. Significant differences were found among<br />

the actual measures (F=21.76, p


Costa MAN, et al.<br />

Table 1. Mean size, standard error and confidence <strong>in</strong>terval (95%) of the<br />

fragments used as <strong>in</strong>traocular foreign bodies <strong>in</strong> an experimental study<br />

<strong>in</strong> porc<strong>in</strong>e eyes, classified accord<strong>in</strong>g to the material of its composition<br />

Estimative measures of fragments used as <strong>in</strong>traocular foreign bodies (mm)<br />

Composition<br />

material<br />

Mean<br />

Standard<br />

error<br />

95% Confidence <strong>in</strong>terval<br />

Lower limit<br />

Upper limit<br />

Wood 3.925 0.145 3.617 4.216<br />

Glass 4.075 0.145 3.767 4.366<br />

Plastic 5.325 0.145 5.017 5.616<br />

Cardboard 4.950 0.145 4.642 5.241<br />

Iron 3.125 0.145 2.817 3.416<br />

Alum<strong>in</strong>um 4.150 0.145 3.842 4.441<br />

Lead 4.150 0.145 3.842 4.441<br />

Concrete 4.200 0.145 3.892 4.491<br />

Table 2. Representation of 3 subgroups considered statistically homogeneous<br />

given by Tukey b test, consider<strong>in</strong>g the mean measurements<br />

obta<strong>in</strong>ed from ultrasonography of different materials of composition<br />

from <strong>in</strong>traocular foreign bodies <strong>in</strong> an experimental study <strong>in</strong> porc<strong>in</strong>e eyes<br />

Measurements of the fragments<br />

Composition<br />

material<br />

Amount<br />

of eyes<br />

1<br />

(smaller)<br />

Subgroups<br />

2<br />

(similar)<br />

Wood 4 3.925<br />

Glass 4 4.150<br />

3<br />

(larger)<br />

Plastic 4 5.325<br />

Cardboard 4 4.950<br />

Iron 4 3.125<br />

Alum<strong>in</strong>um 4 4.150<br />

Lead 4 4.075<br />

Concrete 4 4.200<br />

th<strong>in</strong>ner portion, no artifact was identified with the 10-MHz transducer.<br />

The plastic material was hyper-reflective to ultrasonography.<br />

The cardboard material presented, at the ultrasonographic evaluation,<br />

high reflectivity and reverberation with medium length,<br />

which ended abruptly. The size of the artifact (reverberation) was<br />

slightly smaller than the real size of the object. A posterior shadow<strong>in</strong>g<br />

artifact was also observed <strong>in</strong> this type of material.<br />

The fragment of wood material presented high reflectivity and<br />

has not generated reverberation artifact, however, it caused the pos -<br />

terior shadow<strong>in</strong>g artifact.<br />

The concrete material showed high reflectivity and a slight reverberation<br />

that had already started with larger size than the actual fragment.<br />

It had a fait posterior acoustic shadow<strong>in</strong>g. The concrete foreign<br />

bodies were more concentrated <strong>in</strong> the anterior vitreous cavity.<br />

The iron material showed hyper-reflectivity and reverberation<br />

with large extent and <strong>in</strong>itial size smaller than the actual fragment<br />

(Figure 2), decreas<strong>in</strong>g progressively, recall<strong>in</strong>g the appearance of<br />

“comet tail”. There was a small acoustic shadow artifact.<br />

The alum<strong>in</strong>um material presented itself as hyper-reflective and<br />

with reverberation similar to iron (“comet tail”). No posterior shadow<strong>in</strong>g<br />

artifact was generated by alum<strong>in</strong>um material.<br />

The lead material presented itself as hyper-reflective to the ultrasonography.<br />

The <strong>in</strong>itial reverberation showed the same size of the<br />

Figure 2. A porc<strong>in</strong>e eye 10 MHz ultrasonography with iron foreign body <strong>in</strong>to the vitreous<br />

cavity, actual size of the measured object = 3.3 mm. Observe the reverberation artifact,<br />

<strong>in</strong>terfaces arranged to the right of the real object, which gradually loses strength and<br />

<strong>in</strong>tensity. Note that the size of the 1 st artifact <strong>in</strong>terface generated by iron is smaller<br />

than the real object. The correspond<strong>in</strong>g diagram represents the size of the 1 st artifact<br />

<strong>in</strong>terface generated by a foreign body <strong>in</strong> the ultrasonography exam<strong>in</strong>ation, which is<br />

smaller than real object (foreign body).<br />

actual fragment until a certa<strong>in</strong> distance and subsequently its attenuation<br />

was observed (Figure 3). Different from iron and alum<strong>in</strong>um,<br />

which generated a reverberation that <strong>in</strong>itially had already showed<br />

smaller size than the real object. The posterior shadow<strong>in</strong>g artifact<br />

was observed.<br />

The powder material presented itself as hyper-reflective to ul tra -<br />

sonography, although without posterior shadow<strong>in</strong>g and reverberation.<br />

The powder material, due to its presentation <strong>in</strong> the form of<br />

powder presented an irregular shape to ultrasonography, due to its dispersion<br />

<strong>in</strong> the vitreous. It was not possible to perform the dimension<strong>in</strong>g<br />

of foreign bodies of powder material, therefore, this material was<br />

excluded from comparative statistical evaluation of this parameter.<br />

In all the exam<strong>in</strong>ed eyes, conclusions related to ultrasonographic<br />

dimensions of the fragments and to generated artifacts were obta<strong>in</strong>ed<br />

from echograms performed with proven perpendicularity of<br />

trans ducer <strong>in</strong>cidence <strong>in</strong> relation to the tested fragment.<br />

DISCUSSION<br />

Penetrat<strong>in</strong>g <strong>in</strong>juries with retention of IOFBs are considered an<br />

important cause of ocular complications and potential risks of bl<strong>in</strong>dness<br />

(1-3) . In Brazil, among the traumatic diseases, the ocular trauma<br />

caused by FB represents the vast majority of attendances. The male<br />

gender is more affected than female, and the most affected age<br />

group corresponds to the age of greater professional productivity,<br />

i.e., from 16 to 45 years old (3) .<br />

The prognosis associated with the post-traumatic f<strong>in</strong>al visual<br />

acui ty by <strong>in</strong>traocular foreign body (IOFB) and the risk of endophthal-<br />

Arq Bras Oftalmol. 2013;76(1):13-7<br />

15


Composition of <strong>in</strong>traocular foreign bodies: experimental study of ultrasonographic presentation<br />

mitis will depend on the size and type of the foreign body, presence<br />

and location of ret<strong>in</strong>al lacerations, preoperative visual acuity and the<br />

time after trauma occurrence required to remove the IOFB. Wounds<br />

larger than 3 mm and FBs <strong>in</strong> posterior segment <strong>in</strong>crease the risk of<br />

ret<strong>in</strong>al <strong>in</strong>jury and ret<strong>in</strong>al detachment (4) . Accord<strong>in</strong>g to a study conducted<br />

<strong>in</strong> Germany (5) , the removal of IOFB <strong>in</strong> less than 24 hours from<br />

the trauma occurrence significantly decreases the risk of <strong>in</strong>fectious<br />

endophthalmitis from 13.4% to 3.5%. The same study reported that<br />

the material type is an important <strong>in</strong>dependent risk factor for complications.<br />

Fifty percent (50%) of eye <strong>in</strong>juries by foreign bodies from<br />

vegetal orig<strong>in</strong>, such as wood, had the complication of <strong>in</strong>fectious<br />

endophthalmitis. In trauma associated with foreign bodies of metallic<br />

orig<strong>in</strong>, the risk was considered low, with rates of 4.1% (3-7) .<br />

In penetrat<strong>in</strong>g trauma with foreign body, which may occur dense<br />

vitreous hemorrhage or severe anatomic disruption after trauma,<br />

there is a difficulty <strong>in</strong> identify<strong>in</strong>g an IOFB. The method of ophthalmic<br />

ultrasonography is commonly used for evaluat<strong>in</strong>g traumatized eyes<br />

<strong>in</strong> order to identify lesions associated with trauma and <strong>in</strong> search of<br />

IOFBs, may be performed by all ophthalmologists (8,9) . If a FB is identified,<br />

it is important to obta<strong>in</strong> data on this fragment: location, size<br />

and echography characteristic so that it is possible to <strong>in</strong>fer about its<br />

composition. Composition of IOFB can <strong>in</strong>fluence on the risk of endophthalmitis<br />

rate, of complications related to metallic foreign bodies<br />

and <strong>in</strong> schedul<strong>in</strong>g of surgical removal (9) .<br />

Importantly, a controlled experimental study like the present<br />

one, conta<strong>in</strong>s <strong>in</strong>formation of location, size and composition of IOFB.<br />

Moreover, as the means of implementation of FB was controlled by<br />

surgical <strong>in</strong>cision and post-mortem, the risk of associated lesions, such<br />

as hemorrhage or rupture of the lens could be elim<strong>in</strong>ated. Thus, the<br />

ultrasonography was be<strong>in</strong>g held <strong>in</strong> appropriate technical conditions<br />

to identify FB and to establish an echogenicity pattern and artifacts<br />

for each composition.<br />

The use of sw<strong>in</strong>e as experimental model is referred <strong>in</strong> Medic<strong>in</strong>e<br />

s<strong>in</strong>ce 1540 (10) . Sw<strong>in</strong>e are used <strong>in</strong> research based on application or<br />

improvement of ophthalmic surgical techniques as well as experimental<br />

models of ocular diseases. The anatomical structure and the<br />

porc<strong>in</strong>e eye dimensions differ a little <strong>in</strong> comparison to the human<br />

eye (11) , consider<strong>in</strong>g the cornea, anterior chamber, iris, ciliary body,<br />

lens, vitreous body and complex ret<strong>in</strong>a-choroid-sclera. The cornea,<br />

iris, ciliary body, anterior and posterior capsules of the lens and the<br />

posterior wall of the eye of these animals present at ultrasonography,<br />

as <strong>in</strong> human, as reflective <strong>in</strong>terfaces; and the anterior chamber and<br />

the vitreous cavity have homogeneous anechoic content free of<br />

reflective <strong>in</strong>terfaces <strong>in</strong> normal situations. The speed of sound wave<br />

propagation by aqueous humor and vitreous humor is 1,532 m/s <strong>in</strong><br />

human and 1,540 m/s <strong>in</strong> porc<strong>in</strong>e eyes. Thus, the ocular ultrasonographic<br />

sw<strong>in</strong>e evaluation has similarities to that of human, thus enabl<strong>in</strong>g<br />

the use of these animals as an experimental model (11) .<br />

The present study re<strong>in</strong>forces the importance of adequately evaluate<br />

the echographic characteristics of each material and po<strong>in</strong>ts<br />

out to what type of material <strong>in</strong> its composition could generate a<br />

sig nificant difference between its actual size and the size obta<strong>in</strong>ed<br />

by ultrasonography.<br />

The ultrasonographic measurements of fragments from iron<br />

material were significantly lower than the actual ones. Cardboard<br />

and plastic materials presented ultrasonographic measurements sig -<br />

nificantly higher than the actual ones, while for the other material<br />

differences <strong>in</strong> ultrasonographic measurements were not significantly<br />

different from the actual value (Figure 4).<br />

In the study performed <strong>in</strong> Italy (1) <strong>in</strong> 1994, different measurements<br />

and fragments were used and only 1 shape (spherical) and 1 material<br />

type (metal). The study showed that ultrasonography may overestimate<br />

the actual values, especially <strong>in</strong> smaller FBs with measurements<br />

of 2.0 mm and 2.2 mm. In the present study, the fragments used<br />

presented a measure (about 4 mm), greater than referred by Cascone<br />

et al. It was also used different materials of fragments composition<br />

with non-standardized shapes, which might have caused significant<br />

differences (Table 3). Cascone et al. (1) used only spherical shaped frag-<br />

Figure 3. A porc<strong>in</strong>e eye 10 MHz ultrasonography with lead foreign body <strong>in</strong>to the vitreous<br />

cavity, actual size of measured object = 4.1 mm. Observe the reverberation artifact,<br />

<strong>in</strong>terfaces arranged to the right of the real object, which rema<strong>in</strong> with the same size of<br />

the real object. The correspond<strong>in</strong>g diagram represents the size of artifact <strong>in</strong>terfaces<br />

caused by a foreign body <strong>in</strong> the ultrasonography, which corresponds to the same size<br />

as the real object (foreign body).<br />

Figure 4. Box plot graph of ultrasonographic measurements obta<strong>in</strong>ed (median, <strong>in</strong>terquartile<br />

range, m<strong>in</strong>imum and maximum values) of each fragment used as <strong>in</strong>traocular<br />

foreign body <strong>in</strong> the experimental study <strong>in</strong> relation to their different composition materials.<br />

16 Arq Bras Oftalmol. 2013;76(1):13-7


Costa MAN, et al.<br />

Table 3. Comparison between actual measurement and measurement obta<strong>in</strong>ed from ultrasonography of each <strong>in</strong>traocular fragment from different<br />

materials used <strong>in</strong> an experimental study <strong>in</strong> porc<strong>in</strong>e eyes<br />

Composition<br />

material<br />

Actual<br />

measurement (mm)<br />

Ultrasonographic measurement (mm)<br />

Eye 1 Eye 2 Eye 3 Eye 4<br />

Wood 4.2 4.1 4.3 4.1 4.0<br />

Glass 4.1 4.1 4.3 4.4 3.9<br />

Plastic 4.0 5.5 5.2 5.3 5.3<br />

Cardboard 4.1 5.2 4.7 5.2 5.1<br />

Iron 4.0 3.1 2.8 3.3 3.3<br />

Alum<strong>in</strong>um 4.2 4.2 4.3 4.4 4.5<br />

Lead 4.0 4.1 4.1 4.0 4.4<br />

Powder 4.2 Measurement not obta<strong>in</strong>ed Measurement not obta<strong>in</strong>ed Measurement not obta<strong>in</strong>ed Measurement not obta<strong>in</strong>ed<br />

Concrete 4.2 4.2 5.3 3.9 4.2<br />

Table 4. Ultrasonographic characteristics of fragments from different<br />

composition materials implanted <strong>in</strong>to the vitreous cavity <strong>in</strong> an<br />

experimental study, consider<strong>in</strong>g reflectivity and generated artifacts<br />

(reverberation and acoustic shadow<strong>in</strong>g)<br />

Material<br />

Reflectivity<br />

Reverberation<br />

Extent<br />

Size<br />

Acoustic shadow<strong>in</strong>g<br />

Wood High Absent Absent Present<br />

Glass High Medium Smaller Present<br />

Plastic High Small Smaller Present<br />

Cardboard High Medium Smaller Absent<br />

Iron High Large Smaller Present (discrete)<br />

Alum<strong>in</strong>um High Large Smaller Absent<br />

Lead High Large Equal Present<br />

Powder High Absent Absent Absent<br />

Concrete High Small Greater Absent (discrete)<br />

ments, but it was established that foreign bodies of different shapes<br />

could cause a variety of measures, accord<strong>in</strong>g to the object orientation<br />

<strong>in</strong> the vitreous body.<br />

In regard to echographic characteristics of various materials, we<br />

noted that they all showed hyper-reflectivity. The iron, alum<strong>in</strong>um and<br />

lead materials showed reverberation with great extent, unlike concrete<br />

material with small extent reverberation. The wood foreign bodies, however,<br />

did not present reverberation to ultrasonography. Importantly,<br />

the residence time of wood <strong>in</strong>side the eye <strong>in</strong>fluences the material consistency,<br />

as could occur fragment hydration with modification of their<br />

acoustic characteristics. Regard<strong>in</strong>g the size of the reverberation artifact,<br />

glass, alum<strong>in</strong>um, cardboard and iron materials showed reverberation<br />

with smaller size than the fragment. For lead material, reverberation<br />

showed the same size as the actual fragment. All materials generated<br />

acoustic shadow<strong>in</strong>g, except alum<strong>in</strong>um. The iron and concrete materials,<br />

however, showed a discrete acoustic shadow<strong>in</strong>g (Table 4) There<br />

is no reference to reverberation characteristics <strong>in</strong> different materials of<br />

IOFB <strong>in</strong> the literature for comparability of this study. In the literature, the<br />

echographic f<strong>in</strong>d<strong>in</strong>gs of metallic foreign bodies are similar produc<strong>in</strong>g<br />

a very dense highly reflective echo that rema<strong>in</strong>s with low ga<strong>in</strong> (6) and<br />

usually causes a posterior shadow<strong>in</strong>g (12-14) .<br />

In our study, we observed that the acoustic shadow<strong>in</strong>g is more<br />

evident <strong>in</strong> IOFB that are located closest to the wall and less evident<br />

when located further away from it. If they had been implanted closer<br />

to the ocular wall, they could have caused greater shadow<strong>in</strong>g artifact.<br />

Thus, know<strong>in</strong>g the acoustic differences of each potential material<br />

component of an IOFB <strong>in</strong> order to characterize it and know what<br />

materials types are capable to generate an artifact mistaken <strong>in</strong>terpretation<br />

of its dimensions to ultrasonography will help to <strong>in</strong>terpret ultrasonographic<br />

evaluation and thus provide appropriate plann<strong>in</strong>g of<br />

surgical procedures for removal of IOFB of the human be<strong>in</strong>g, whether<br />

through limbal or pars plana <strong>in</strong>cisions, and will assist <strong>in</strong> evaluat<strong>in</strong>g<br />

the risk of endophthalmitis or associated <strong>in</strong>flammation that can be<br />

related to the nature of FB.<br />

Accurate workup <strong>in</strong> cases of trauma with retention of IOFB can<br />

help to resolve the framework sooner, aim<strong>in</strong>g to lower complication<br />

risk, identify<strong>in</strong>g best practice and establish<strong>in</strong>g a visual prognosis.<br />

REFERENCES<br />

1. Cascone G, Filipello M, Ferri R, Scimone G, Zagami A. B-scan echographic measurement<br />

of endobulbar foreign bodies. Ophthalmologica. 1994;208(4):192-4.<br />

2. Silva FM, Santos Júnior EC, Nóbrega MJ. Corpos estranhos <strong>in</strong>tra-oculares: análise de<br />

22 casos. ACM Arq Catar<strong>in</strong> Med. 2005;34(1):34-7.<br />

3. Araújo AA, Almeida DV, Araújo VM, Góes MR. Urgência oftalmológica: corpo estanho<br />

ocular a<strong>in</strong>da como pr<strong>in</strong>cipal causa. Arq Bras Oftalmol. 2002;65(2):223-7.<br />

4. Zhang Y, Zhang M, Jiang C, Qiu HY. Intraocular foreign bodies <strong>in</strong> Ch<strong>in</strong>a: cl<strong>in</strong>ical characteristics,<br />

prognostic factors, and visual outcomes <strong>in</strong> 1,421 eyes. Am J Ophthalmol.<br />

2011;152(1):66-73.e1.<br />

5. Jonas JB, Knorr HL, Budde WM. Prognostic factors <strong>in</strong> ocular <strong>in</strong>juries caused by<br />

<strong>in</strong> traocular or retrobulbar foreign bodies. Ophthalmology. 2000;107(5):823-8. Comment<br />

<strong>in</strong> Ophthalmology. 2000;107(5):821-2.<br />

6. Ehlers JP, Kunimoto DY, Ittoop S, Maguire JI, Ho AC, Regillo CD. Metallic <strong>in</strong>traocular<br />

foreign bodies: characteristics, <strong>in</strong>terventions, and prognostic factors for visual outcome<br />

and globe survival. Am J Ophthalmol. 2008;146(3):427-33.<br />

7. Greven CM, Engelbrecht NE, Slusher MM, Nagy SS. Intraocular foreign bodies: management,<br />

prognostic factors, and visual outcomes. Ophthalmology. 2000;107(3):<br />

608-12. Comment <strong>in</strong> Ophthalmology. 2001;108(1):9-10.<br />

8. Chandra A, Mastrovitch T, Ladner H, T<strong>in</strong>g V, Radeos MS, Samudre S. The utility of<br />

bedside ultrasound <strong>in</strong> the detection of a ruptured globe <strong>in</strong> a porc<strong>in</strong>e model. West J<br />

Emerg Med. 2009;10(4):263-6.<br />

9. Coleman DJ, Woods S, Rondeau MJ, Silverman RH. Ophthalmic ultrasonography.<br />

Radiol Cl<strong>in</strong> North Am. 1992;30(5):1105-14. Review.<br />

10. Mariano M. M<strong>in</strong>isuíno (m<strong>in</strong>ipig) na pesquisa biomédica experimental. O M<strong>in</strong>ipig br1.<br />

Acta Cir Bras. 2003;18(5):387-91.<br />

11. Dyce KM, Sack WO, Wes<strong>in</strong>g CJ. Os órgãos dos sentidos. In: Dyce KM, Sack WO, Wes<strong>in</strong>g<br />

CJ. Tratado de anatomia veter<strong>in</strong>ária. 2a Ed. Rio de Janeiro: Guanabara Koogan; 1997.<br />

p.258-76.<br />

12. Baillif S, Paoli V. [Open-globe <strong>in</strong>juries and <strong>in</strong>traocular foreign bodies <strong>in</strong>volv<strong>in</strong>g the<br />

posterior segment]. J Fr Ophtalmol. 2012;35(2):136-45. French.<br />

13. Obuchowska I, Sidorowicz A, Napora KJ, Mariak Z. [Cl<strong>in</strong>ical characteristics of penetrat<strong>in</strong>g<br />

ocular <strong>in</strong>juries with <strong>in</strong>traocular foreign body. Part II. Diagnostics and treatment].<br />

Kl<strong>in</strong> Oczna. 2010;112(1-3):77-81. Polish.<br />

14. Ambartsumian AR. [Potential of ultrasound biomicroscopy <strong>in</strong> diagnosis of ocular<br />

trauma with <strong>in</strong>traocular metallic foreign bodies]. Vestn Oftalmol. 2011;127(4):29-33.<br />

Russian.<br />

Arq Bras Oftalmol. 2013;76(1):13-7<br />

17


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Panret<strong>in</strong>al photocoagulation <strong>versus</strong> <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong> retreatment pa<strong>in</strong> <strong>in</strong><br />

high-risk proliferative <strong>diabetic</strong> ret<strong>in</strong>opathy<br />

Dor em panfotocogulação ret<strong>in</strong>iana <strong>versus</strong> <strong>in</strong>jeção <strong>in</strong>travítrea em pacientes com<br />

ret<strong>in</strong>opatia diabética proliferativa de alto risco<br />

Célia Reg<strong>in</strong>a Farias de Araújo Lucena 1 , José Afonso Ramos Filho 1 , André Márcio Vieira Messias 1 , José Aparecido da Silva 2 , Felipe Piacent<strong>in</strong>i Paes de Almeida 1 ,<br />

Ingrid Ursula Scott 3 , Jefferson Augusto Santana Ribeiro 1,4 , Rodrigo Jorge 1<br />

ABSTRACT<br />

Purpose: To compare pa<strong>in</strong> related to <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong> and panret<strong>in</strong>al photocoagulation<br />

<strong>in</strong> the management of patients with high-risk proliferative <strong>diabetic</strong><br />

ret<strong>in</strong>opathy.<br />

Methods: Prospective study <strong>in</strong>clud<strong>in</strong>g patients with high-risk proliferative <strong>diabetic</strong><br />

ret<strong>in</strong>opathy and no prior laser treatment randomly assigned to receive panret<strong>in</strong>al<br />

photocoagulation (PRP group) or panret<strong>in</strong>al photocoagulation plus <strong><strong>in</strong>travitreal</strong><br />

ranibizumab (PRPplus group). In all patients, panret<strong>in</strong>al photocoagulation was<br />

adm<strong>in</strong>istered <strong>in</strong> two sessions (weeks 0 and 2), and <strong><strong>in</strong>travitreal</strong> ranibizumab was<br />

adm<strong>in</strong>istered at the end of the first laser session <strong>in</strong> the PRPplus group. Retreatment<br />

was performed at weeks 16 and 32 if active new vessels were detected at fluoresce<strong>in</strong><br />

angiography. Patients <strong>in</strong> the PRPplus group received <strong><strong>in</strong>travitreal</strong> ranibizumab<br />

and patients <strong>in</strong> the PRP group received 500-μm additional spots per quadrant of<br />

active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale<br />

was used for pa<strong>in</strong> score estimation. The patient was asked about the <strong>in</strong>tensity of<br />

pa<strong>in</strong> dur<strong>in</strong>g the whole procedure (ret<strong>in</strong>al photocoagulation session or <strong><strong>in</strong>travitreal</strong><br />

ranibizumab <strong><strong>in</strong>jection</strong>). Statistics for pa<strong>in</strong> score comparison were performed us<strong>in</strong>g<br />

a non-parametric test (Wilcoxon rank sums).<br />

Results: Seventeen patients from PRPplus and 14 from PRP group were evaluated<br />

for pa<strong>in</strong> scores. There were no significant differences between both groups regard<strong>in</strong>g<br />

gender, glycosylated hemoglob<strong>in</strong> and disease duration. Mean <strong><strong>in</strong>travitreal</strong><br />

<strong><strong>in</strong>jection</strong> pa<strong>in</strong> (±SEM) was 4.7 ± 2.1 and was significantly lower (p


Almeida PP, et al.<br />

INTRODUCTION<br />

Ret<strong>in</strong>al new vessels (NV) represent an important risk factor for<br />

se vere vision loss <strong>in</strong> patients with diabetes mellitus (1) . About 60%<br />

of patients with proliferative <strong>diabetic</strong> ret<strong>in</strong>opathy (PDR) respond to<br />

panret<strong>in</strong>al photocoagulation (PRP) with regression of neovascularization<br />

with<strong>in</strong> 3 months (2) . However, many patients require additional<br />

laser treatment, and 4.5% ultimately require pars plana vitrectomy<br />

despite PRP (3) .<br />

Besides additional laser photocoagulation, <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong><br />

of anti-vascular endothelial growth factor (VEGF) agents have become<br />

an <strong>in</strong>terest<strong>in</strong>g alternative for new vessels regression (4,5) . However,<br />

both procedures (PRP and <strong><strong>in</strong>jection</strong>) may <strong>in</strong>duce discomfort and<br />

pa<strong>in</strong>. Pa<strong>in</strong> regard<strong>in</strong>g PRP treatment is a well-recognized concern and<br />

may even prevent its completion (6) , while pa<strong>in</strong> regard<strong>in</strong>g <strong><strong>in</strong>travitreal</strong><br />

<strong><strong>in</strong>jection</strong> may disturb patient compliance and peribulbar block may<br />

be necessary for uncooperative patients (7) . S<strong>in</strong>ce <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong><br />

has become a trendy alternative therapeutic strategy and PRP is<br />

the standard of care for high-risk PDR, we decided to compare pa<strong>in</strong><br />

related to both procedures <strong>in</strong> the management of patients with PDR.<br />

METHODS<br />

The study protocol adhered to the tenets of the Declaration of<br />

Hel s<strong>in</strong>ki and was approved by the local Institutional Review Board, and<br />

all patients gave written <strong>in</strong>formed consent before enter<strong>in</strong>g the study.<br />

This is a prospective, open label, randomized study <strong>in</strong> which two<br />

groups of <strong>diabetic</strong> patients were followed (5) . Between February 2009<br />

and December 2009, all patients evaluated at the Ret<strong>in</strong>a and Vitreous<br />

Section of the Department of Ophthalmology, School of Medic<strong>in</strong>e<br />

of Ribeirão Preto, who presented with high-risk PDR and had not<br />

received any prior ret<strong>in</strong>al laser treatment were <strong>in</strong>vited to participate<br />

<strong>in</strong> the study.<br />

Patients were <strong>in</strong>cluded if they had high-risk PDR, accord<strong>in</strong>g to<br />

Early Treatment Diabetic Ret<strong>in</strong>opathy Study (ETDRS) guidel<strong>in</strong>es (1,8) ,<br />

as follows: 1) presence of NV at the disc (NVD) greater than ETDRS<br />

standard photograph 10A, or; 2) presence of NVD associated with<br />

vitreous or pre-ret<strong>in</strong>al hemorrhage, or; 3) NV elsewhere (NVE) cover<strong>in</strong>g<br />

more than a half disc area associated with vitreous or pre-ret<strong>in</strong>al<br />

hemorrhage. Exclusion criteria <strong>in</strong>cluded: 1) history of prior laser<br />

treat ment or vitrectomy <strong>in</strong> the study eye; 2) history of thromboembolic<br />

event (<strong>in</strong>clud<strong>in</strong>g myocardial <strong>in</strong>farction or cerebral vascular<br />

ac cident); 3) major surgery with<strong>in</strong> the prior 6 months or planned<br />

with<strong>in</strong> the next 28 days; 4) uncontrolled hypertension (accord<strong>in</strong>g<br />

to guidel<strong>in</strong>es of the seventh report of the jo<strong>in</strong>t National Committee<br />

on Preven tion, Detection, Evaluation, and Treatment of High Blood<br />

Pressure [JNC-7]) (9) ; 5) known coagulation abnormalities or current<br />

use of anticoagulation medication other than aspir<strong>in</strong>; or 6) any<br />

condition affect<strong>in</strong>g documentation or follow-up.<br />

Dur<strong>in</strong>g the study enrollment period, high-risk PDR was identified<br />

<strong>in</strong> one eye of 5 patients and <strong>in</strong> both eyes of 35 patients based on<br />

cl<strong>in</strong>ical exam<strong>in</strong>ation and confirmed on fluoresce<strong>in</strong> angiography. At<br />

basel<strong>in</strong>e, each patient received a detailed ophthalmologic exam<strong>in</strong>ation<br />

<strong>in</strong>clud<strong>in</strong>g measurement of the logarithm of the m<strong>in</strong>imum angle<br />

of resolution (logMAR) ETDRS and best corrected visual acuity (BCVA)<br />

accord<strong>in</strong>g to a standardized refraction protocol (us<strong>in</strong>g modified<br />

ETDRS charts 1, 2, and R), as well as applanation tonometry, dilated<br />

slit lamp biomicroscopic exam<strong>in</strong>ation (<strong>in</strong>clud<strong>in</strong>g grad<strong>in</strong>g of lenticular<br />

opacities us<strong>in</strong>g the Lens Opacities Classification System III) (10) , and<br />

b<strong>in</strong>ocular <strong>in</strong>direct fundoscopic exam<strong>in</strong>ation. Digital red free fundus<br />

photography and fluoresce<strong>in</strong> angiography were performed us<strong>in</strong>g two<br />

fundus camera systems (HRA-OCT, Heidelberg, Germany/TRC-50IA/<br />

IMAGEnet; Topcon, Tokyo, Japan).<br />

All patients received PRP, which was performed <strong>in</strong> two sessions (at<br />

week 0 and week 2) accord<strong>in</strong>g to ETDRS guidel<strong>in</strong>es (11) . Six hundred to<br />

eight hundred 500µm spots were performed per session, at the discretion<br />

of the treat<strong>in</strong>g <strong>in</strong>vestigator. If patients had cl<strong>in</strong>ically significant<br />

macular edema (12) macular focal/grid laser was performed dur<strong>in</strong>g<br />

the first PRP session. Patients could be retreated with focal/grid laser<br />

at the 16 and 32-week study visits. If both eyes were eligible for the<br />

study, the eye with best visual acuity was <strong>in</strong>cluded.<br />

Patients were enrolled <strong>in</strong> groups of two. The technician was<br />

asked to pick up one of two identical opaque envelopes, one conta<strong>in</strong><strong>in</strong>g<br />

the designation for PRP, whereas the other conta<strong>in</strong>ed the designation<br />

for PRP/<strong><strong>in</strong>travitreal</strong> ranibizumab <strong><strong>in</strong>jection</strong> (IVR) treatment.<br />

The second patient was automatically assigned with the second<br />

en velope. For the 20 eyes selected to receive the comb<strong>in</strong>ed treatment<br />

(PRP plus <strong><strong>in</strong>travitreal</strong> ranibizumab), one <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong><br />

of 0.5 mg (0.05 ml) of ranibizumab was performed approximately 60<br />

m<strong>in</strong>utes after the completion of the first PRP session (week 0) by a<br />

s<strong>in</strong>gle ret<strong>in</strong>al specialist. Ranibizumab was <strong>in</strong>jected <strong>in</strong>to the vitreous<br />

cavity via a 29 gauge needle <strong>in</strong>serted through the <strong>in</strong>ferotemporal<br />

pars plana 3.0 - 3.5 mm posterior to the limbus us<strong>in</strong>g topical<br />

propa raca<strong>in</strong>e drops under sterile conditions (eyelid speculum and<br />

povidone-iod<strong>in</strong>e) (13) . Patients were <strong>in</strong>structed to <strong>in</strong>still one drop of<br />

0.3% ciprofloxac<strong>in</strong> <strong>in</strong>to the <strong>in</strong>jected eye four times daily for 1 week<br />

after the procedure.<br />

Retreatment was performed at weeks 16 and 32 if active new<br />

vessels were detected at fluoresce<strong>in</strong> angiography. Patients <strong>in</strong> the<br />

PRPplus group received IVR and patients <strong>in</strong> the PRP group received<br />

500-μm additional spots per quadrant of active new vessels.<br />

Fifteen m<strong>in</strong>utes after the end of retreatment (PRP session or retreatment<br />

IVR <strong><strong>in</strong>jection</strong>), a masked exam<strong>in</strong>er used a 100-degree Visual<br />

Analog Scale (VAS) for pa<strong>in</strong> score estimation (7) . The numbers of the<br />

scale were visible only on the exam<strong>in</strong>er’s side, so that patients could<br />

not choose the same number to guide pa<strong>in</strong> scores. Prior to rat<strong>in</strong>g<br />

level of pa<strong>in</strong>, each patient was asked to slide the marker along the<br />

entire scale, with the aid of the exam<strong>in</strong>er. At po<strong>in</strong>t 0, the exam<strong>in</strong>er<br />

clarified to the patient that this po<strong>in</strong>t of the scale represented “no<br />

pa<strong>in</strong> at all”; at po<strong>in</strong>t 100, the exam<strong>in</strong>er clarified to the patient that<br />

this po<strong>in</strong>t of the scale represented “the most <strong>in</strong>tense pa<strong>in</strong> one could<br />

ever feel”. The patient was asked about the <strong>in</strong>tensity of pa<strong>in</strong> dur<strong>in</strong>g<br />

the whole procedure (PRP session or IVR <strong><strong>in</strong>jection</strong>). Statistics for pa<strong>in</strong><br />

score comparison were performed us<strong>in</strong>g a non-parametric test (Wilcoxon<br />

rank sums).<br />

RESULTS<br />

Seventeen patients from the PRP plus patients and 16 patients<br />

from the PRP groups completed the 16-week visit, but 17 patients<br />

from PRPplus and 14 from PRP were evaluated for pa<strong>in</strong> scores. Patients’<br />

demographics are summarized <strong>in</strong> table 1. Mean age of PRP<br />

patients was significantly higher than PRPplus patients; there were<br />

no significant differences between both groups regard<strong>in</strong>g gender,<br />

glycosylated hemoglob<strong>in</strong> (HbA1c) and disease duration. Mean ± SD<br />

age (years) was 63.5 ± 8.9 and 51.1 ± 11.3 (p=0.0018); mean ± SD<br />

HbA1c (%) was 9.3 ± 1.1 and 9.1 ± 0.8 (p=0.5391); and mean ± SD di -<br />

sease duration (years) was 12.9 ± 8.8 and 14.7 ± 6.9 (p=0.5326) for PRP<br />

and PRPplus respectively. Mean IVR pa<strong>in</strong> (±SEM) was 4.7 ± 2.1 and was<br />

significantly lower (p


Panret<strong>in</strong>al photocoagulation <strong>versus</strong> <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong> retreatment pa<strong>in</strong> <strong>in</strong> high-risk proliferative <strong>diabetic</strong> ret<strong>in</strong>opathy<br />

Table 1. Patient demographics<br />

PRP PRPplus P<br />

Age (mean ± SD; <strong>in</strong> years) 63.5 ± 8.9 51.1 ± 11.3 0.0018 (t-Test)<br />

Gender (Male/Female) 9/5 10/7 0.7557<br />

(Likelihood Ratio)<br />

Race (Black/Hispanic/Caucasian) 2/7/5 2/8/7 0.9461<br />

(Likelihood Ratio)<br />

Duration of diabetes<br />

(mean ± SD; <strong>in</strong> years)<br />

12.9 ± 8.8 14.7 ± 6.9 0.5326 (t-Test)<br />

HbA1c (mean ± SD) 09.3 ± 1.1 09.1 ± 0.8 0.5391 (t-Test)<br />

HbA1c= glycosylated hemoglob<strong>in</strong>; PRP= panret<strong>in</strong>al photocoagulation; PRPplus=<br />

panret<strong>in</strong>al photocoagulation and <strong><strong>in</strong>travitreal</strong> <strong><strong>in</strong>jection</strong> of ranibizumab; SD= standard<br />

deviation.<br />

Figure 1. Intensity of pa<strong>in</strong> score distribution on PRP and PRPplus groups. Horizontal l<strong>in</strong>es<br />

represent groups’ medians and dashed l<strong>in</strong>es are the 25% and 75% quantilies. Statistically<br />

significant difference was found between groups (P


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Cl<strong>in</strong>ical trials <strong>in</strong> Brazilian journals of ophthalmology: where we are<br />

Ensaios clínicos em periódicos brasileiros de oftalmologia: onde estamos<br />

Rodrigo Pessoa Cavalcanti Lira 1,2 , Franz Schubert Leal 1 , Fauze Abdulmassih Gonçalves 1 , Fernando Henrique Ramos Amorim 1 ,<br />

João Paulo Fernandes Felix 1 , Carlos Eduardo Leite Arieta 1<br />

ABSTRACT<br />

Purpose: To compare cl<strong>in</strong>ical trials published <strong>in</strong> Brazilian journals of ophthalmology<br />

and <strong>in</strong> foreign journals of ophthalmology with respect to the number of citations<br />

and the quality of report<strong>in</strong>g [by apply<strong>in</strong>g the Consolidated Standards for Report<strong>in</strong>g<br />

Trials (CONSORT) statement writ<strong>in</strong>g standards].<br />

Methods: The sample of this systematic review comprised the two Brazilian<br />

jour nals of ophthalmology <strong>in</strong>dexed at Science Citation Index Expanded and six<br />

of the foreign journals of ophthalmology with highest Impact Factor ® accord<strong>in</strong>g<br />

ISI. All cl<strong>in</strong>ical trials (CTs) published from January 2009 to December 2010 at the<br />

Brazilians journals and a 1:1 randomized sample of the foreign journals were<br />

<strong>in</strong>cluded. The primary outcome was the number of citations through the end of<br />

2011. Subgroup analysis <strong>in</strong>cluded language. The secondary outcome <strong>in</strong>cluded<br />

likelihood of citation (cited at least once <strong>versus</strong> no citation), and presence or<br />

absence of CONSORT statement <strong>in</strong>dicators.<br />

Results: The citation counts were statistically significantly higher (P


Cl<strong>in</strong>ical trials <strong>in</strong> Brazilian journals of ophthalmology: where we are<br />

developed to assist authors <strong>in</strong> writ<strong>in</strong>g reports of cl<strong>in</strong>ical trials, editors<br />

and peer reviewers <strong>in</strong> review<strong>in</strong>g manuscripts for publication, and<br />

readers <strong>in</strong> critically apprais<strong>in</strong>g published articles. It gives guidance<br />

for report<strong>in</strong>g all cl<strong>in</strong>ical trials, but focuses on the most common design<br />

type-<strong>in</strong>dividually randomized, two group, parallel trials, which<br />

accounts for over half of trials <strong>in</strong> the literature (3) .<br />

The ma<strong>in</strong> purpose of this study is to compare cl<strong>in</strong>ical trials published<br />

<strong>in</strong> Brazilians ophthalmology journals and <strong>in</strong> foreign ophthalmology<br />

journals with respect to the number of citations and the quality<br />

of report<strong>in</strong>g (by apply<strong>in</strong>g the CONSORT statement writ<strong>in</strong>g standards).<br />

METHODS<br />

This study was a systematic review. Orig<strong>in</strong>als cl<strong>in</strong>ical trials phase<br />

III or phase IV were identified by retrospective review of articles pu -<br />

blished from January 2009 to December 2010 (2009/2010). Phase III<br />

trials compare the results of people tak<strong>in</strong>g a new treatment with the<br />

results of people tak<strong>in</strong>g the standard treatment. Phase IV trials are<br />

done us<strong>in</strong>g thousands of people after a treatment has been approved<br />

and marketed, to check for side effects that were not seen <strong>in</strong> the<br />

phase III trial.<br />

One group (Brazilian Group) <strong>in</strong>cluded the two Brazilian journals<br />

of ophthalmology <strong>in</strong>dexed at Science Citation Index Expanded (“Arquivos<br />

Brasileiros de Oftalmologia” e “Revista Brasileira de Oftalmologia”),<br />

and the other group (Foreign Group) <strong>in</strong>cluded six of the foreign<br />

journals of ophthalmology with highest Impact Factor ® accord<strong>in</strong>g<br />

ISI (Ophthalmology; American Journal of Ophthalmology; Archives<br />

of Ophthalmology; Investigative Ophthalmology and Vision Science;<br />

Journal of Cataract and Refractive Surgery; and British Journal of<br />

Oph thalmology) (4) .<br />

The Brazilian group <strong>in</strong>cluded all 20 cl<strong>in</strong>ical trials published <strong>in</strong><br />

2009/2010 (5-24) . The Foreign group <strong>in</strong>cluded a randomized (random<br />

order with a computer generated random number) sample of 20<br />

cl<strong>in</strong>ical trials among the 449 published <strong>in</strong> 2009/2010 [The Medl<strong>in</strong>e<br />

search strategies for cl<strong>in</strong>ical trial sought (publication type) was:<br />

“cl<strong>in</strong>ical trial”; or “cl<strong>in</strong>ical trial, phase III”; or “cl<strong>in</strong>ical trial, phase IV”; or<br />

“controlled cl<strong>in</strong>ical trial”] (25-44) . All articles were carefully scrut<strong>in</strong>ized to<br />

confirm the study design.<br />

The primary outcome was the number of citations through the<br />

end of 2011 (4) . Most articles are rarely cited, if at all, dur<strong>in</strong>g the same<br />

year <strong>in</strong> which they were published, but the citation count of the 2<br />

sub sequent years is representative (it forms the basis of estimat<strong>in</strong>g<br />

journal impact factors). Subgroup analysis <strong>in</strong>cluded language.<br />

The secondary outcome <strong>in</strong>cluded likelihood of citation (cited at<br />

least once <strong>versus</strong> no citation), and presence or absence of CONSORT<br />

statement <strong>in</strong>dicators (3) . Although the CONSORT checklist has 25 items,<br />

our f<strong>in</strong>al grad<strong>in</strong>g scale had a maximum of 37 possible po<strong>in</strong>ts, because<br />

there are general items divided <strong>in</strong> subparts. It was assigned 1 po<strong>in</strong>t<br />

per subpart.<br />

Descriptive statistics were calculated. Cont<strong>in</strong>uous data were ex -<br />

pres sed as mean values, standard deviation (SD) and ranges. Independent<br />

sample t-test of equality of means was used to compare the<br />

2 groups. Analyses were conducted us<strong>in</strong>g PSPP statistical software.<br />

P values are 2-tailed. Statistical significance was considered at the<br />

0.05 level.<br />

RESULTS<br />

The citation counts were statistically significantly higher (P


Lira RPC, et al.<br />

may had contributed to the low citation of papers from the Brazilian<br />

journals was its relative low IF [<strong>in</strong> 2011, the IF of ABO was 0.326, and<br />

the IF of RBO was 0.129] <strong>in</strong> comparison to the group of the foreign<br />

journals (<strong>in</strong> 2011, the average of IF was 3.692), because there is a tendency<br />

of authors to publish their best articles <strong>in</strong> journals with higher<br />

IF, perpetuat<strong>in</strong>g this situation (4) . F<strong>in</strong>ally, for the same reason above,<br />

Brazilians authors used to publish its best articles <strong>in</strong> foreign journals.<br />

Amaz<strong>in</strong>gly, <strong>in</strong> a paper apply<strong>in</strong>g the CONSORT and STROBE statements<br />

to evaluate the report<strong>in</strong>g quality of neovascular age-related macular<br />

degeneration studies the highest report<strong>in</strong>g scores were achieved by<br />

Brazilians articles published <strong>in</strong> foreign journals (48) .<br />

The boards of the Brazilians journals of ophthalmology are do<strong>in</strong>g<br />

efforts to change this current unfavorable picture because they know<br />

the editorial scenario is competitive (1,52-55) . Although the ABO and RBO<br />

have not yet officially adopted the CONSORT, neither the English<br />

lan guage, they encourage its use as well as other protocols such as<br />

STROBE and PRISMA. This attitude may contribute to the improvement<br />

of Brazilian journals global <strong>in</strong>sertion.<br />

Figure 3. Presence of CONSORT statement <strong>in</strong>dicators <strong>in</strong> the Foreign Group compared<br />

with the Brazilian Group.<br />

is possible notice that the number of citations of papers written <strong>in</strong><br />

English is higher (1) .<br />

Citation analysis of ophthalmology articles has rarely been reported.<br />

The impact of a published article can be estimated by evaluat<strong>in</strong>g<br />

how frequently the study is cited <strong>in</strong> subsequent peer-reviewed<br />

publications (45) . The number of times an article is cited over a given<br />

time period might <strong>in</strong>dicates the level of importance attributed to its<br />

f<strong>in</strong>d<strong>in</strong>gs by research medical community (46) . Researchers around the<br />

world rank their choices of journals for publication accord<strong>in</strong>g to Impact<br />

Factor ® . The Coord<strong>in</strong>ation of Improvement of Higher Education<br />

Personnel (CAPES), which is the government agency <strong>in</strong> the M<strong>in</strong>istry<br />

of Education responsible for coord<strong>in</strong>at<strong>in</strong>g the post-graduation programs<br />

<strong>in</strong> Brazil, stratified the quality of the journals based exclusively<br />

from the ISI Impact Factor ®(1) .<br />

One of the actions to reach a higher number of citations on CTs<br />

may be to embrace pr<strong>in</strong>ciples of the CONSORT (47) . The evidence-based<br />

approach that has been used for CONSORT also served as a model<br />

for development of other report<strong>in</strong>g guidel<strong>in</strong>es, such as for report<strong>in</strong>g<br />

systematic reviews and meta-analysis of studies evaluat<strong>in</strong>g <strong>in</strong>terventions<br />

(PRISMA) (48) , and Strengthen<strong>in</strong>g the Report<strong>in</strong>g of Observational<br />

Studies <strong>in</strong> Epidemiology (STROBE) (49) . However, as a potential drawback,<br />

a report<strong>in</strong>g guidel<strong>in</strong>e might encourage some authors to report fictitiously<br />

the <strong>in</strong>formation suggested by the guidance rather than what<br />

was actually done. Readers, peer reviewers, and editors should vigilantly<br />

guard aga<strong>in</strong>st that potential drawback and refer, for example,<br />

to trial protocols, to <strong>in</strong>formation on trial registers, and to regulatory<br />

agency websites. Moreover, <strong>in</strong> some cases, the CONSORT can led to<br />

improvements <strong>in</strong> report<strong>in</strong>g but not <strong>in</strong> methodological conduct (50) .<br />

Some caveats of this study should be discussed. First, we compared<br />

the national journals <strong>versus</strong> a sample of the most important<br />

foreign journals. However, the encouragement of our Brazilian<br />

scientific community toward the highest standards of study conduct<br />

and report<strong>in</strong>g is a realistic and important goal. Second, we can not<br />

generalize the results because we analyzed only CTs. But this study<br />

design, jo<strong>in</strong>tly with meta-analysis, is considered the gold standard for<br />

cl<strong>in</strong>ical research (51) . Third, a citation does not guarantee the respect<br />

of the cit<strong>in</strong>g <strong>in</strong>vestigators. Occasionally a study may be cited only to<br />

be criticized or dismissed. Nevertheless, citation still means that the<br />

study is active <strong>in</strong> the scientific debate. Moreover, we should acknowledge<br />

that number of citation does not necessarily translate <strong>in</strong>to cl<strong>in</strong>ical<br />

or scientific impact (40) . Fourth, a presumable circumstance that<br />

REFERENCES<br />

1. Chamon W, Melo Jr LA. Impact factor and <strong>in</strong>sertion of the ABO <strong>in</strong> the world scientific<br />

literature. Arq Bras Oftalmol [Internet]. 2011[cited 2012 May 21];74(4):243-4. http://<br />

www.scielo.br/pdf/abo/v74n4/v74n4a01.pdf<br />

2. Jüni P, Altman DG, Egger M. Systematic reviews <strong>in</strong> health care: assess<strong>in</strong>g the quality of<br />

controlled cl<strong>in</strong>ical trials. BMJ [Internet]. 2001[cited 2011 Jan 21];323(7303):42-6.Available<br />

from: http://www.bmj.com/content/323/7303/42?view=long&pmid=11440947<br />

3. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D,<br />

Egger M, Altman DG; Consolidated Standards of Report<strong>in</strong>g Trials Group. CONSORT<br />

2010 explanation and elaboration: updated guidel<strong>in</strong>es for report<strong>in</strong>g parallel group<br />

randomised trials. J Cl<strong>in</strong> Epidemiol [Internet]. 2010 [cited 2012 Jan 21];63(8):e1-37. Erratum<br />

<strong>in</strong>: J Cl<strong>in</strong> Epidemiol. 2012;65(3):351. Available from: http://www.sciencedirect.<br />

com/science/article/pii/S0895435610001034<br />

4. Web of Knowledge [Internet]. Philadelphia: Thomson Reuters. [cited 2012 Jun 30].<br />

Available from: http://apps.webofknowledge.com<br />

5. Fonseca Jr NL, Luci LM, Badessa MP, Rehder JR. [Comparison of two modified lidoca<strong>in</strong>e<br />

solutions for local anesthesia <strong>in</strong> blepharoplasty]. Arq Bras Oftalmol [Internet].<br />

2009[citado 2012 Jun 21];72(2):211-4. Portuguese. Dispon: http://www.scielo.br/pdf/<br />

abo/v72n2/15.pdf<br />

6. Barreiro TP, Forseto AS, P<strong>in</strong>to LF, Francesconi CM, Nosé W. [Wavefront-guided Lasik for<br />

low to moderate myopia: CustomCornea <strong>versus</strong> Zyoptix]. Arq Bras Oftalmol [Internet]<br />

2009[cited 2010 Out 21];72(4):519-25. Portuguese. Disponível em: http://www.scielo.<br />

br/pdf/abo/v72n4/a16v72n4.pdf<br />

7. Frantz KA, Moura Filho ER, Abud MB, Avila MP, Magacho L. [Comparison of the<br />

analgesic effect between 0- MG etoricoxib and dipyrone after exeresis of primary<br />

pterygium with conjunctival autograft]. Arq Bras Oftalmol [Internet]. 2009[citado<br />

2010 Jun 21];72(5):661-4. Portuguese. Disponível em: http://www.scielo.br/pdf/abo/<br />

v72n5/12.pdf<br />

8. Gonçalves RD, Cruz AA. [Oral sedation with midazolam <strong>in</strong> blepharoplasty]. Arq Bras<br />

Oftalmol [Internet]. 2009[citado 2010 Jul 21];72(5):665-8. Portuguese. Disponível em:<br />

http://www.scielo.br/pdf/abo/v72n5/13.pdf<br />

9. Hida WT, Motta AF, Kara-José Junior N, Alves E, Tadeu M, Cordeiro LN, et al. Comparison<br />

between OPD-Scan results and visual outcomes of monofocal and multifocal<br />

<strong>in</strong>traocular lenses. Arq Bras Oftalmol [Internet]. 2009[citado 2010 Mar 21];72(4):526-32.<br />

Disponível em: http://www.scielo.br/pdf/abo/v72n4/a17v72n4.pdf<br />

10. Kara-José Jr N, Santhiago MR, Parede TR, Esp<strong>in</strong>dola RF, Mazurek MG, Germano R, et al.<br />

[Influence of cataract surgical correction on work<strong>in</strong>g perception]. Arq Bras Oftalmol<br />

[Internet]. 2010 [citado 2011 Fev 21];73(6):491-3. Disponível em: http://www.scielo.<br />

br/pdf/abo/v73n6/v73n6a03.pdf<br />

11. Rask<strong>in</strong> E, Paula JS, Cruz AA, Coelho RP. Effect of bevel position on the corneal endothelium<br />

after phacoemulsification. Arq Bras Oftalmol [Internet]. 2010[citado 2012 Dez<br />

21];73(6):508-10. Disponível em: http://www.scielo.br/pdf/abo/v73n6/v73n6a08.pdf<br />

12. Rezende MP, Dias AF, Oshima A, Andrade EP, Serracarbassa PD. [Study of visual<br />

acuity and <strong>in</strong>traocular pressure <strong>in</strong> the treatment of macular <strong>diabetic</strong> edema with<br />

<strong>in</strong>travitreous triamc<strong>in</strong>olone]. Arq Bras Oftalmol [Internet]. 2010[citado 2012 Set 21];<br />

73(2):129-34. Disponível em: http://www.scielo.br/pdf/abo/v73n2/v73n2a06.pdf<br />

13. Urbano AP, Nosé W. [Correction of ocular aberrations <strong>in</strong> custom and standard LASIK<br />

retreatments]. Arq Bras Oftalmol [Internet]. 2009[citado 2010 Jul 27];72(5):687-93.<br />

Portuguese. Disponível em: http://www.scielo.br/pdf/abo/v72n5/18.pdf<br />

14. Nakano CT, Hida WT, Kara-Jose Junior N, Motta AF, Reis A, Pamplona M, et al. Comparison<br />

of central corneal edema and visual recovery between liquefaction and<br />

conventional phacoemulsification <strong>in</strong> soft cataracts. Rev Bras Oftalmol [Internet].<br />

2009[citado 2011 Jun 21];68(1):7-12. Disponível em: http://www.scielo.br/pdf/rbof/<br />

v68n1/02.pdf<br />

Arq Bras Oftalmol. 2013;76(1):21-5<br />

23


Cl<strong>in</strong>ical trials <strong>in</strong> Brazilian journals of ophthalmology: where we are<br />

15. Barreto RD, Biancardi AL, Nascimento EM, Pereira BD, de Moraes HV. Uso de ciclospor<strong>in</strong>a<br />

0,05% tópica no tratamento de olho seco de pacientes portadores do vírus<br />

HIV. Rev Bras Oftalmol [Internet]. 2009[citado 2010 Mar 19];68(2):83-9. Disponível em:<br />

http://www.scielo.br/pdf/rbof/v68n2/a04v68n2.pdf<br />

16. Mart<strong>in</strong>s FC, Miyaji ME, Lima VL, Rehder JR. Biometria ultrassônica no cálculo do poder<br />

dióptrico de lentes <strong>in</strong>traoculares: estudo comparativo dos métodos de contato e de<br />

imersão. Rev Bras Oftalmol [Internet]. 2009 [cited 2010 Aug 21];68(4):212-5. Disponível<br />

em: http://www.scielo.br/pdf/rbof/v68n4/a05v68n4.pdf<br />

17. Damasceno ED, Damasceno NA, Costa Filho AD. Ens<strong>in</strong>o de oftalmologia na graduação<br />

médica. Estudo comparativo de aprendizado na oftalmoscopia direta com<br />

oftalmoscópico convencional e de campo amplo (Panoptic), Rev Bras Oftalmol<br />

[Internet]. 2009 [cited 2010 Jan 21];68(4):231-6. Disponível em: http://www.scielo.br/<br />

pdf/rbof/v68n4/a08v68n4.pdf<br />

18. Nakano CT, Hida WT, Kara-Jose Junior N, Motta AF, Fante D, Masson VF, et al. Comparison<br />

between OPD-scan results and contrast sensitivity of three <strong>in</strong>traocular lenses:<br />

spheric AcrySof SN60AT, aspheric AcrySof SN60WF and multifocal AcrySof Restor<br />

lens. Rev Bras Oftalmol [Internet]. 2009[citado 2010 Nov 21];68(4):216-22.Disponível<br />

em: http://www.scielo.br/pdf/rbof/v68n4/a06v68n4.pdf<br />

19. Mendes MH, Bet<strong>in</strong>jane AJ, Cavalcante AF, Castanheira VR, Cheng CT, Carani JC. Estudo<br />

comparativo entre imagens ultra-sonográficas obtidas com sondas de 10MHz e 20 MHz<br />

na avaliação de anormalidades do segmento posterior do globo ocular. Rev Bras<br />

Oftalmol [Internet]. 2009[citado 2010 Jan 21];68(5):291-5.Disponível em: http://www.<br />

scielo.br/pdf/rbof/v68n5/a07v68n5.pdf<br />

20. Portes AJ, Gomes LP, Amaral BL, Massa L. Percepção da adm<strong>in</strong>istração tó pica<br />

ocular de drogas: vaporização x gotas. Rev Bras Oftalmol [Internet]. 2009 [citado<br />

2011 Jan 21];68(6):327-31.Disponível em: http://www.scielo.br/pdf/rbof/v68n6/<br />

rbofv68n06a02.pdf<br />

21. Corpa JH, Mart<strong>in</strong>elli EJ, Tarcha FA, Vitiello Neto V, Ribeiro LG, Rede JR. Estudo<br />

comparativo entre desepitelização mecânica e química na ceratectomia fotorrefrativa<br />

- s<strong>in</strong>tomatologia e re-epitelização pós operatória. Rev Bras Oftalmol [Internet].<br />

2010[citado 2012 Jun 21];69(1):23-6.Disponível em: http://www.scielo.br/pdf/rbof/<br />

v69n1/05.pdf<br />

22. Almod<strong>in</strong> EM, Almod<strong>in</strong> JM, Almod<strong>in</strong> FM. Avaliação corneana após “crossl<strong>in</strong>k” utilizando<br />

dois tipos diferentes equipamentos. Rev BrasOftalmol [Internet]. 2010 [citdo 2011 Fev<br />

21];69(3):159-64.Disponível em: http://www.scielo.br/pdf/rbof/v69n3/a04v69n3.pdf<br />

23. P<strong>in</strong>to VC, Mart<strong>in</strong>i da Costa T, Grottone GT, Schor P, Pisa IT. Avaliação de um programa<br />

para computador de mão no auxílio ao ens<strong>in</strong>o de oftalmologia para estudantes<br />

de medic<strong>in</strong>a. Rev Bras Oftalmol [Internet]. 2010[citado 2011 Jan 23];69(6):352-60.<br />

Disponível em: http://www.scielo.br/pdf/rbof/v69n6/a02v69n6.pdf<br />

24. Germano JE, Hida WT, Brasil AA, Germano RA, Yamane IS, Reis A, et al. Lente <strong>in</strong>traocular<br />

multifocal refrativa: a performance visual e qualidade de vida em implantes<br />

bilaterais <strong>versus</strong> unilaterais. Rev Bras Oftalmol [Internet]. 2010[citado 2011 Ago 25];<br />

69(6):372-7. Disponível em: http://www.scielo.br/pdf/rbof/v69n6/a05v69n6.pdf<br />

25. Bressler NM, Chang TS, Suñer IJ, F<strong>in</strong>e JT, Dolan CM, Ward J, Ianchulev T; MARINA and<br />

ANCHOR Research Groups. Vision-related function after ranibizumab treatment by<br />

better- or worse-see<strong>in</strong>g eye: cl<strong>in</strong>ical trial results from MARINA and ANCHOR. Ophthalmology.<br />

2010;117(4):747-56.e4.<br />

26. Vogel R, Crockett RS, Oden N, Laliberte TW, Mol<strong>in</strong>a L; Sodium Hyaluronate Ophthalmic<br />

Solution Study Group. Demonstration of efficacy <strong>in</strong> the treatment of dry eye<br />

disease with 0.18% sodium hyaluronate ophthalmic solution (vismed, rejena). Am J<br />

Ophthalmol. 2010;149(4):594-601. Comment <strong>in</strong>: Am J Ophthalmol. 2010;150(5):757;<br />

author reply 757.<br />

27. Pavesio C, Zierhut M, Bairi K, Comstock TL, Usner DW; Fluoc<strong>in</strong>olone Acetonide Study<br />

Group. Evaluation of an <strong><strong>in</strong>travitreal</strong> fluoc<strong>in</strong>olone acetonide implant <strong>versus</strong> standard<br />

systemic therapy <strong>in</strong> non<strong>in</strong>fectious posterior uveitis. Ophthalmology. 2010;117(3):<br />

567-75, 575.e1.<br />

28. Domalpally A, Blodi BA, Scott IU, Ip MS, Oden NL, Lauer AK, VanVeldhuisen PC; SCORE<br />

Study Investigator Group. The Standard Care vs Corticosteroid for Ret<strong>in</strong>al Ve<strong>in</strong> Occlusion<br />

(SCORE) study system for evaluation of optical coherence tomograms: SCORE<br />

study report 4. Arch Ophthalmol [Internet]. 2009 [cited 2012 Nov 21];127(11):1461-7.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788490/<br />

29. Scott IU, Oden NL, VanVeldhuisen PC, Ip MS, Blodi BA, Antoszyk AN; SCORE Study Investigator<br />

Group. SCORE Study Report 7: <strong>in</strong>cidence of <strong><strong>in</strong>travitreal</strong> silicone oil droplets<br />

associated with staked-on vs luer cone syr<strong>in</strong>ge design. Am J Ophthalmol [Internet].<br />

2009 [cited 2012 Jan 24];148(5):725-32.e7. Available from: http://www.ncbi.nlm.nih.<br />

gov/pmc/articles/PMC2780008/<br />

30. Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG. A Phase IIIb study<br />

to evaluate the safety of ranibizumab <strong>in</strong> subjects with neovascular age-related<br />

macular degeneration. Ophthalmology. 2009;116(9):1731-9. Comment <strong>in</strong>: Ophthalmology.<br />

2010;117(9):1860; author reply 1860-1. Available from: http://ac.els-cdn.com/<br />

S0161642009005430/1-s2.0-S0161642009005430-ma<strong>in</strong>.pdf?_tid=c08a3786-8d8a-11e2-<br />

b888-00000aab0f26&acdnat=1363363965_5a760f5706a3fa6af5ba0a61121bdb68<br />

31. Korenfeld MS, Silverste<strong>in</strong> SM, Cooke DL, Vogel R, Crockett RS; Difluprednate<br />

Ophthalmic Emulsion 0.05% (Durezol) Study Group. Difluprednate ophthalmic<br />

emulsion 0.05% for postoperative <strong>in</strong>flammation and pa<strong>in</strong>. J Cataract Refract Surg.<br />

2009;35(1):26-34. Available from: http://onl<strong>in</strong>e.liebertpub.com/doi/pdf/10.1089/<br />

jop.2010.0059<br />

32. Ip MS, Oden NL, Scott IU, VanVeldhuisen PC, Blodi BA, Figueroa M, Antoszyk A, Elman<br />

M; SCORE Study Investigators Group. SCORE Study report 3: study design and basel<strong>in</strong>e<br />

characteristics. Ophthalmology [Internet]. 2009[cited 2011 Jun 21];116(9):1770-7.e1.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785028/<br />

33. Suñer IJ, Kokame GT, Yu E, Ward J, Dolan C, Bressler NM. Responsiveness of NEI VFQ-25<br />

to changes <strong>in</strong> visual acuity <strong>in</strong> neovascular AMD: validation studies from two phase<br />

3 cl<strong>in</strong>ical trials. Invest Ophthalmol Vis Sci [Internet]. 2009 [cited 2010 Jun 21];50(8):<br />

3629-35. Available from: http://www.iovs.org/content/50/8/3629.long<br />

34. Kohnen T, Knorz MC, Cochener B, Gerl RH, Arné JL, Col<strong>in</strong> J, et al. AcrySof phakic anglesupported<br />

<strong>in</strong>traocular lens for the correction of moderate- to-high myopia: one-year<br />

results of a multicenter European study. Ophthalmology. 2009;116(7):1314-21. Available<br />

from: http://ac.els-cdn.com/S0161642009001031/1-s2.0-S0161642009001031-ma<strong>in</strong>.<br />

pdf?_tid=308438c0-8d8b-11e2-b5d0-00000aacb362&acdnat=1363364152_64051f1<br />

a592253031533dd5c497333d1<br />

35. Friberg TR, Tolent<strong>in</strong>o M; LEVEL Study Group, Weber P, Patel S. Campbell S, Goldbaum M.<br />

Pegaptanib sodium as ma<strong>in</strong>tenance therapy <strong>in</strong> neovascular age-related macular degeneration:<br />

the LEVEL study. Br J Ophthalmol [Internet]. 2010 [cited 2012 Apr 12];94:1611-7.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991041/<br />

36. Ehrlich JS, Manche EE. Regression of effect over long-term follow-up of conductive<br />

keratoplasty to correct mild to moderate hyperopia. J Cataract Refract Surg.<br />

2009;35(9):1591-6. Available from: http://www.sciencedirect.com/science/article/pii/<br />

S0886335009005616<br />

37. Scott IU, VanVeldhuisen PC, Oden NL, Ip MS, Blodi BA, Jumper JM, Figueroa M; SCORE<br />

Study Investigator Group.SCORE Study report 1: basel<strong>in</strong>e associations between<br />

central ret<strong>in</strong>al thickness and visual acuity <strong>in</strong> patients with ret<strong>in</strong>al ve<strong>in</strong> occlusion.<br />

Ophthalmology [Internet]. 2009[cited 2010 Aug 4];116(3):504-12. Available from:<br />

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851408/<br />

38. Bressler NM, Chang TS, F<strong>in</strong>e JT, Dolan CM, Ward J; Anti-VEGF Antibody for the Treatment<br />

of Predom<strong>in</strong>antly Classic Choroidal Neovascularization <strong>in</strong> Age-Related Macular<br />

Degeneration (ANCHOR) Research Group. Improved vision-related function after<br />

ranibizumab vs photodynamic therapy: a randomized cl<strong>in</strong>ical trial. Arch Ophthalmol<br />

[Internet]. 2009[cited 2011 May 24];127(1):13-21. Available from: http://archopht.<br />

jamanetwork.com/article.aspx?articleid=420982<br />

39. Keane PA, Patel PJ, Ouyang Y, Chen FK, Ikeji F, Walsh AC, et al. Effects of ret<strong>in</strong>al<br />

morphology on contrast sensitivity and read<strong>in</strong>g ability <strong>in</strong> neovascular age-related<br />

macular degeneration. Invest Ophthalmol Vis Sci [Internet]. 2010[cited 2012 Oct<br />

21]; 51(11):5431-7. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/<br />

PMC3061494/<br />

40. Repka MX, Kraker RT, Beck RW, Atk<strong>in</strong>son CS, Bacal DA, Bremer DL, Davis PL, Gear<strong>in</strong>ger<br />

MD, Glaser SR, Hoover DL, Laby DM, Morrison DG, Rogers DL, Sala NA, Suh DW,<br />

Wheeler MB; Pediatric Eye Disease Investigator Group. Pilot study of levodopa dose as<br />

treatment for residual amblyopia <strong>in</strong> children aged 8 years to younger than 18 years.<br />

Arch Ophthalmol [Internet]. 2010 [cited 2011 Nov 24];128(9):1215-7. Available from:<br />

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137458/<br />

41. Abraham P, Yue H, Wilson L. Randomized, double-masked, sham-controlled trial of<br />

ranibizumab for neovascular age-related macular degeneration: PIER study year 2.<br />

Am J Ophthalmol. 2010;150(3):315-24.e1. Available from: http://www.sciencedirect.<br />

com/science/article/pii/S0002939410002679<br />

42. Macejko TT, Bergmann MT, Williams JI, Gow JA, Gomes PJ, McNamara TR, Abelson M;<br />

Bepotast<strong>in</strong>e Besilate Ophthalmic Solutions Cl<strong>in</strong>ical Study Group. Multicenter cl<strong>in</strong>ical<br />

evaluation of bepotast<strong>in</strong>e besilate ophthalmic solutions 1.0% and 1.5% to treat allergic<br />

conjunctivitis. Am J Ophthalmol. 2010;150(1):122-7.e5.. Available from: http://<br />

www.sciencedirect.com/science/article/pii/S0002939410002679<br />

43. Campochiaro PA, Heier JS, Fe<strong>in</strong>er L, Gray S, Saroj N, Rundle AC, Murashashi WY, Rubio<br />

RG; BRAVO Investigators. Ranibizumab for macular edema follow<strong>in</strong>g branch ret<strong>in</strong>al ve<strong>in</strong><br />

occlusion: six-month primary end po<strong>in</strong>t results of a phase III study. Oph thalmology.<br />

2010;117(6):1102-12.e1. Available from: http://ac.els-cdn.com/S0161642010001855/<br />

1-s2.0-S0161642010001855-ma<strong>in</strong>.pdf?_tid=151d2348-8d8c-11e2-a037-00000aab0f02<br />

&acdnat=1363364536_7734850870a3d0d93b75d3b4e272eec3<br />

44. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Brockhurst RJ, Hayes KC, et al.<br />

Cl<strong>in</strong>ical trial of lute<strong>in</strong> <strong>in</strong> patients with ret<strong>in</strong>itis pigmentosa receiv<strong>in</strong>g vitam<strong>in</strong> A. Arch<br />

Ophthalmol [Internet]. 2010[cited 2012 Mar 3];128(4):403-11. Available from: http://<br />

www.ncbi.nlm.nih.gov/pmc/articles/PMC2987594/<br />

45. Callaham M, Wears RL, Weber E. Journal prestige, publication bias, and other characteristics<br />

associated with citation of published studies <strong>in</strong> peer-reviewed journals. J<br />

Am Med Assoc [Internet] 2002 [cited 2012 Apr 9];287:2847-50.Available from: http://<br />

jama.jamanetwork.com/article.aspx?articleid=194972<br />

46. Patsopoulos NA, Analatos AA, Ioannidis JPA. Relative citation impact of various study<br />

designs <strong>in</strong> the health sciences. JAMA [Internet]. 2005 [cited 2009 Set 23];293(19):2362-6.<br />

Available from: http://jama.jamanetwork.com/article.aspx?articleid=200905<br />

47. Fung AE, Palanki R, Bakri SJ, Depperschmidt E, Gibson A. Apply<strong>in</strong>g the CONSORT<br />

and STROBE statements to evaluate the report<strong>in</strong>g quality of neovascular age-related<br />

macular degeneration studies. Ophthalmology. 2009;116(2):286-96. Available from:<br />

http://www.sciencedirect.com/science/article/pii/S0161642008009020<br />

48. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred report<strong>in</strong>g items<br />

for systematic reviews and meta-analyses: the PRISMA statement. BMJ [Internet].<br />

2009[cited 2012 May 9];339:b2535. Available from: http://www.ncbi.nlm.nih.gov/pmc/<br />

articles/PMC2714657/<br />

24 Arq Bras Oftalmol. 2013;76(1):21-5


Lira RPC, et al.<br />

49. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE<br />

Initiative. Strengthen<strong>in</strong>g the report<strong>in</strong>g of observational studies <strong>in</strong> epidemiology<br />

(STROBE) statement: guidel<strong>in</strong>es for report<strong>in</strong>g observational studies. BMJ [Internet].<br />

2007;335(7824):806-8. Comment <strong>in</strong>: BMJ. 2007;335(7626):900; BMJ. 2008;144(9):1200-4;<br />

BMJ. 2007;335(7624):783-4. Available from: http://www.bmj.com/content/335/7624/<br />

806?view=long&pmid=17947786<br />

50. Ivers NM, Taljaard M, Dixon S, Bennett C, McRae A, Taleban J, et al. Impact of CON-<br />

SORT extension for cluster randomised trials on quality of report<strong>in</strong>g and study<br />

methodology: review of random sample of 300 trials, 2000-8. BMJ [Internet]. 2011<br />

[cited 2009 Mar 5];343:d5886. Available from: http://www.bmj.com/content/343/<br />

bmj.d5886?view=long&pmid=21948873<br />

51. Atk<strong>in</strong>s D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour<br />

RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magr<strong>in</strong>i N, Mason J,<br />

Middle ton P, Mrukowicz J, O’Connell D, Oxman AD, Phillips B, Schünemann HJ, Edejer<br />

T, Varonen H, Vist GE, Williams JW Jr, Zaza S; GRADE Work<strong>in</strong>g Group.Grad<strong>in</strong>g quality of<br />

evidence and strength of recommendations. BMJ [Internet]. 2004 [cited 2009 Nov 10];<br />

328(7454):1490. Available from: http://www.bmj.com/content/328/7454/1490?view<br />

=long&pmid=15205295<br />

52. Rocha EM. A great season for <strong>in</strong>ternationalization of Brazilian medical research. Arq<br />

Bras Oftalmol [Internet]. 2011 [citado 2012 Jan 16];74(6):392.Disponível em: http://<br />

www.scielo.br/pdf/abo/v74n6/a01v74n6.pdf<br />

53. Lira RP, Arieta CE. Good report<strong>in</strong>g practices and the CONSORT. Arq Bras Oftalmol<br />

[Internet]. 2012 [cited 2013 Jan 15];75(2):85-6. Disponível em: http://www.scielo.br/<br />

pdf/abo/v75n2/a01v75n2.pdf<br />

54. Portes AJF. O RBO na era da <strong>in</strong>formação digital. Rev Bras Oftalmol [Internet]. 2011<br />

[citado 2012 May 18];70(1):5-6.Available from: http://www.scielo.br/pdf/rbof/<br />

v70n1/01.pdf<br />

55. Journal on Web. Onl<strong>in</strong>e manuscript submission and review system. Indian Journal of<br />

Ophthalmology. Author Instructions [Internet]. [cited 2012 Jun 30]. Available from:<br />

http://www.journalonweb.com/ijo/author/<strong>in</strong>structions.asp<br />

XXXIII Congresso do<br />

Hospital São Geraldo<br />

30 de outubro a 2 de novembro 2013<br />

Dayrell Hotel & Centro de Convenções<br />

Belo Horizonte (MG)<br />

Informações:<br />

Tel.: (31) 3342-3888<br />

E-mail: lyriumk@lyrium.com.br<br />

Site: www.hospitalsaogeraldo.com.br<br />

Arq Bras Oftalmol. 2013;76(1):21-5<br />

25


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Influence of English language <strong>in</strong> the number of citations of articles published<br />

<strong>in</strong> Brazilian journals of Ophthalmology<br />

Influência do idioma <strong>in</strong>glês no número de citações de artigos publicados em periódicos brasileiros<br />

de Oftalmologia<br />

Rodrigo Pessoa Cavalcanti Lira 1,2 , Rafael Marsicano Cezar Vieira 1 , Fauze Abdulmassih Gonçalves 1 , Maria Carol<strong>in</strong>a Alves Ferreira 1 , Diana Maziero 1 ,<br />

Thais Helena Moreira Passos 1 , Carlos Eduardo Leite Arieta 1<br />

ABSTRACT<br />

Purpose: To determ<strong>in</strong>e the association between language and number of citations<br />

of ophthalmology articles published <strong>in</strong> Brazilian journals.<br />

Methods: This study was a systematic review. Orig<strong>in</strong>al articles were identified<br />

by review of documents published at the two Brazilian ophthalmology journals<br />

<strong>in</strong>dexed at Science Citation Index Expanded - SCIE [“Arquivos Brasileiros de Oftalmologia<br />

(ABO)” and “Revista Brasileira de Oftalmologia (RBO)”]. All document types<br />

(“articles” and “reviews”) listed at SCIE <strong>in</strong> English (English Group) or <strong>in</strong> Portuguese<br />

(Portuguese Group) from January 1, 2008 to December 31, 2009 were <strong>in</strong>cluded,<br />

except: “editorial materials”; “corrections”; “letters”; and “biographical items”. The<br />

primary outcome was the number of citations through the end of second year<br />

after publication date. Subgroup analysis <strong>in</strong>cluded likelihood of citation (cited at<br />

least once <strong>versus</strong> no citation), journal, and year of publication.<br />

Results: The search at the web of science revealed 382 articles [107 (28%) <strong>in</strong> the<br />

English Group and 275 (72%) <strong>in</strong> the Portuguese Group]. Of those, 297 (77.7%)<br />

we re published at the ABO and 85 (23.3%) at the RBO. The citation counts were<br />

statistically significantly higher (P


Lira RPC, et al.<br />

committees <strong>in</strong>volved <strong>in</strong> promotions or search of new members rely<br />

heavily on impact factors, as do scientific boards of grant<strong>in</strong>g <strong>in</strong>stitutions,<br />

especially <strong>in</strong> Europe and South America. Publishers observe the<br />

impact factors of their journals (<strong>in</strong> addition to circulation numbers<br />

and <strong>in</strong>comes from advertisements) (7) . However, it is important to emphasize<br />

that the cl<strong>in</strong>ical impact of a research - how much that study<br />

has contributed to improve the cl<strong>in</strong>ical practice - may not be related<br />

to citation <strong>in</strong>dexes (8) .<br />

In Brazil, between 1986 and 2000, the most popular ophthalmology<br />

journal published only 4.6% of articles <strong>in</strong> English (9) .<br />

To the best of our knowledge, the impact of publication language<br />

on citation frequency <strong>in</strong> the ophthalmology journals has not yet<br />

been <strong>in</strong>vestigated from a Brazilian perspective. In the present study,<br />

we focused on papers published between 2008 and 2009. The ma<strong>in</strong><br />

purpose of this study was to determ<strong>in</strong>e the associations between language<br />

and number of citations of ophthalmology articles published<br />

<strong>in</strong> Brazilians journals.<br />

METHODS<br />

This study was a systematic review. Orig<strong>in</strong>al articles were identified<br />

by review of documents published at the two Brazilian ophthalmology<br />

journals <strong>in</strong>dexed at Science Citation Index Expanded - SCIE<br />

[“Ar quivos Brasileiros de Oftalmologia (ABO)” and “Revista Brasileira de<br />

Oftalmologia (RBO)”]. All document types (“articles” and “reviews”) listed<br />

at SCIE <strong>in</strong> English (English Group) or <strong>in</strong> Portuguese (Portuguese Group)<br />

from January 1, 2008 to December 31, 2009 were <strong>in</strong>cluded, except:<br />

“editorial materials”; “corrections”; “letters”; and “biographical items”.<br />

The primary outcome was the number of citations through the<br />

end of the second year after publication date. Most articles are rarely<br />

cited, if at all, dur<strong>in</strong>g the same year <strong>in</strong> which they were published,<br />

but the citation count of the 2 subsequent years is representative<br />

(it forms the basis of estimat<strong>in</strong>g journal impact factors). Subgroup<br />

analysis <strong>in</strong>cluded likelihood of citation (cited at least once <strong>versus</strong> no<br />

citation), journal, and year of publication.<br />

To estimate the citation frequency of research articles <strong>in</strong>cluded<br />

<strong>in</strong> our study, we accessed the Institute for Scientific Information (ISI)<br />

Web of Science database (10) . The Web of Science search strategies<br />

was: (publication name) “Arquivos Brasileiros de Oftalmologia OR<br />

Revista Brasileira de Oftalmologia”; (year of publication) “2008-2009”;<br />

(timespan) date range to articles published <strong>in</strong> 2008, “from 2008-01-01<br />

to 2010-12-31”, and date range to articles published <strong>in</strong> 2009, from<br />

“2009-01-01 to 2011-12-31”; and (citation database) “Science Citation<br />

Index Expanded.<br />

Descriptive statistics were calculated. Cont<strong>in</strong>uous data were ex -<br />

pressed as mean values, standard deviation (SD) and ranges. Bet -<br />

ween- group differences of cont<strong>in</strong>uous and categorical variables were<br />

com pared us<strong>in</strong>g Mann Whitney U Test or Pearson chi-square test<br />

whe re appropriate. Analyses were conducted us<strong>in</strong>g PSPP statistical<br />

software. P values are 2-tailed. Statistical significance was considered<br />

at the 0.5 level.<br />

RESULTS<br />

The search at the web of science revealed 382 articles [107 (28%)<br />

<strong>in</strong> the English Group and 275 (72%) <strong>in</strong> the Portuguese Group]. Of those,<br />

297 (77.7%) were published at the ABO and 85 (23.3%) at the RBO.<br />

The citation counts were statistically significantly higher (P


Influence of English language <strong>in</strong> the number of citations of articles published <strong>in</strong> Brazilian journals of Ophthalmology<br />

conferences, publications and communications <strong>in</strong> general (3) . It is not<br />

enough to publish abstracts and keywords <strong>in</strong> English. It is essential<br />

that the whole text to be published <strong>in</strong> English, otherwise it certa<strong>in</strong>ly<br />

should not be read or even mentioned. If we verify the references of<br />

any article we will realize that most are published <strong>in</strong> English.<br />

The results of this study suggest that the editorial boards should<br />

strongly encourage the authors to adopt English as the ma<strong>in</strong> language<br />

<strong>in</strong> their future articles. This effort may contribute to the improvement<br />

of Brazilians Ophthalmology journals impact factor.<br />

REFERENCES<br />

1. W<strong>in</strong>kmann G, Schlutius S, Schweim HG. [Publication languages of impact factor<br />

journals and of medical bibliographic databanks]. Dtsch Med Wochenschr. 2002;<br />

127(4):131-7. German. Comment <strong>in</strong> Dtsch Med Wochenschr. 2002;127(4):129-30.<br />

2. Schaffner A, Gehr P, Perruchoud A, Straub W, Suter P, von Segesser L. Welcome editorial.<br />

Swiss Med Wkly. 2001;131:3.<br />

3. Viebig RG, Pard<strong>in</strong>i F. O <strong>in</strong>glês é preciso. Arq Gastroenterol. 2009;46(3):162-3.<br />

4. W<strong>in</strong>kmann G, Schlutius S, Schweim HG. [Citation rates of medical German-language<br />

journals <strong>in</strong> English-language papers - do they correlate with the Impact Factor, and<br />

who cites?]. Dtsch Med Wochenschr. 2002;127(4):138-43. German.<br />

5. Bakewell D. Publish <strong>in</strong> english, or perish? Nature. 1992;356(6371):648.<br />

6. Borsuk RM, Budden AE, Leimu R, Aarssen LW, Lortie CJ. The <strong>in</strong>fluence of author<br />

gender, national language and number of authors on citation rate <strong>in</strong> ecology. Open<br />

Ecol J. 2009;2(1):25-8.<br />

7. Schaffner A. Journal impact factors depend on more than just publication language.<br />

Swiss Med Wkly. 2006;136(27-28):411-2.<br />

8. Campanatti-Ostiz H, Andrade CR. Periódicos nacionais em fonoaudiologia: caracterização<br />

de <strong>in</strong>dicador de impacto. Pró-Fono. 2006;18(1):99-110.<br />

9. Ventura AG, Ventura AJ, Santos SA. Características evolutivas dos artigos científicos<br />

publicados nos Arquivos Brasileiros de Oftalmologia entre os anos de 1986 e 2000.<br />

Arq Bras Oftalmol. 2008;71(5):711-6.<br />

10. Thomson Reuters. Web of Knowledge [v.5.7] - Web of Science Home [Internet].<br />

[cited 2012 Aug 28]. Available from: http://apps.webofknowledge.com/<br />

WOS_GeneralSearch_<strong>in</strong>put.do?highlighted_tab=WOS&product=WOS&last_prod=<br />

WOS&SID=4DE1fee@PiabfLlcgJc&search_mode=GeneralSearch<br />

11. Mueller PS, Murali NS, Cha SS, Erw<strong>in</strong> PF, Ghosh AK, others. The association between<br />

impact factors and language of general <strong>in</strong>ternal medic<strong>in</strong>e journals. Swiss Med Wkly.<br />

2006;136(27-28):441-3.<br />

12. Poomkottayil D, Bornste<strong>in</strong> M, Sendi P. Lost <strong>in</strong> translation: the impact of publication<br />

language on citation frequency <strong>in</strong> the scientific dental literature. Swiss Med Wkly.<br />

2011;141:w13148.<br />

13. Indian Journal of Ophthalmology. Instructions for contributors [Internet]. [cited 2012<br />

Aug 28]. Available from: http://www.ijo.<strong>in</strong>/contributors.asp<br />

14. Muccioli C, Campos M, Goldchmit M, Dantas PE, Bechara SJ, Costa VP. Artigos em<br />

<strong>in</strong>glês nos Arquivos Brasileiros de Oftalmologia: um resultado da globalização. Arq<br />

Bras Oftalmol. 2006;69(4):461.<br />

15. Chamon W, Melo Jr LA. Impact factor and <strong>in</strong>sertion of the ABO <strong>in</strong> the world scientific<br />

literature. Arq Bras Oftalmol. 2011;74(4):241-2.<br />

16. Rocha EM. Uma boa fase para a <strong>in</strong>ternacionalização da pesquisa biomédica brasileira.<br />

Arq Bras Oftalmol. 2011;74(6):391-2.<br />

17. Portes AJ. A RBO na era da <strong>in</strong>formação digital. Rev Bras Oftalmol. 2011;70(1):5-6.<br />

Encontro Anual da<br />

Academia Americana de Oftalmologia<br />

16 a 19 de novembro de 2013<br />

Nova Orleans, Louisiana (EUA)<br />

Informações:<br />

Site: www.aao.org<br />

28 Arq Bras Oftalmol. 2013;76(1):26-8


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Censo Brasileiro de Cirurgia Refrativa<br />

Brazilian Trends <strong>in</strong> Refractive Surgery<br />

Marcelo Vieira Netto 1 , Rodrigo França de Espíndola 1 , Rafael Garcia Fernandes Nogueira 2 , Mauro Campos 3 , Renato Ambrósio Jr. 4 ,<br />

Newton Leitão de Andrade 5<br />

RESUMO<br />

Objetivo: Determ<strong>in</strong>ar preferências e práticas dos cirurgiões refrativos do Brasil.<br />

Métodos: Foi realizado um estudo transversal baseado na coleta de dados de<br />

um questionário aplicado durante o VI Congresso Brasileiro de Catarata e Cirurgia<br />

Refrativa em 2011. As questões também foram enviadas por e-mail aos membros<br />

dessa sociedade. Perguntas sobre preferências de técnicas, uso de novas tecnologias,<br />

volume cirúrgico, tipo de excimer laser, microcerátomo e topógrafos mais utilizados,<br />

uso de mitomic<strong>in</strong>a C, colírios pós-operatórios, dentre outras, foram analisados.<br />

Resultados: No total, 292 cirurgiões responderam a pesquisa. A maioria possui<br />

um volume mensal entre 2 a 4 olhos por semana (57,60%). Grande parte (64,50%)<br />

realiza tomografia de córnea de rot<strong>in</strong>a e apenas 22,00% dos analisados não personalizam<br />

suas cirurgias. A técnica de ceratomileusis <strong>in</strong> situ a laser (LASIK) é a mais<br />

realizada e quando a ceratectomia fotorrefrativa (PRK) é utilizada, a maioria dos<br />

cirurgiões aplica a mitomic<strong>in</strong>a C (52,60%) nesses pacientes. A marca de excimer<br />

laser mais utilizada até o momento é a Nidek (26,12%).<br />

Conclusão: A técnica de LASIK é mais realizada pelos cirurgiões, sendo que a<br />

maioria personaliza parte de suas cirurgias e quando a ceratectomia fotorrefrativa<br />

é realizada, a mitomic<strong>in</strong>a C é empregada pela maior parte dos entrevistados. A<br />

cirurgia bilateral é rot<strong>in</strong>eiramente realizada pela maioria dos cirurgiões e o laser<br />

de femtosegundo a<strong>in</strong>da é empregado apenas por uma m<strong>in</strong>oria dos cirurgiões.<br />

Descritores: Miopia/cirurgia; Ceratomileuse assistida por excimer laser <strong>in</strong> situ; Ce -<br />

ratectomia fotorrefrativa; Mitomic<strong>in</strong>a; Censos; Brasil<br />

ABSTRACT<br />

Purpose: To determ<strong>in</strong>e preferences and practices of refractive surgeons <strong>in</strong> Brazil.<br />

Methods: A cross-sectional study was conducted based on the data collected from<br />

a questionnaire applied dur<strong>in</strong>g the VI Brazilian Congress of Cataract and Refractive<br />

Surgery and by e-mail sent to all members of that society. Refractive surgery techniques,<br />

use of emerg<strong>in</strong>g technologies, surgical volume, type of excimer laser and<br />

microkeratomes, mitomyc<strong>in</strong> C, postoperative medications were analyzed among<br />

others questions.<br />

Results: Two hundred n<strong>in</strong>ety-two surgeons replied to the questions. The majority<br />

has a surgical volume between 2 and 4 eyes per week (57.60%). Most of the surgeons<br />

(64.50%) perform corneal tomography rout<strong>in</strong>ely and 22.00% of them do never customize<br />

their surgeries. The laser <strong>in</strong> situ keratomileusis (LASIK) is the ma<strong>in</strong> technique<br />

performed and when the photorefractive keratectomy (PRK) is applied; most of the<br />

surgeons uses mitomyc<strong>in</strong> C (52.60%) <strong>in</strong> these patients. The excimer laser of choice<br />

was the Nidek (26.12%).<br />

Conclusion: LASIK is the preferred surgical procedure and the majority customizes<br />

their refractive surgeries. When photorefractive keratectomy is performed, mitomyc<strong>in</strong><br />

C is used by most of the surgeons (52.60%). Bilateral surgery is rout<strong>in</strong>ely performed and<br />

the femtosecond laser is still used by few refractive surgeons.<br />

Keywords: Myopia/surgery; Keratomileusis, laser <strong>in</strong> situ; Photorefractive keratectomy;<br />

Mitomyc<strong>in</strong>; Censuses; Brazil<br />

INTRODUÇÃO<br />

A cirurgia refrativa está presente na prática clínica de profissionais<br />

de oftalmologia há pelo menos duas décadas. O advento do excimer<br />

laser e o aumento dos níveis de segurança e eficácia da cirurgia tornaram<br />

esta técnica um procedimento cirúrgico previsível e confiável (1) .<br />

É estimado que aproximadamente 60 milhões de pessoas são<br />

candidatas à cirurgia refrativa nos Estados Unidos e que apenas 10%<br />

do mercado americano é explorado (2) .<br />

A literatura nacional é carente de <strong>in</strong>formações sobre preferências<br />

e práticas entre os cirurgiões refrativos. O presente estudo tem o objetivo<br />

de fornecer <strong>in</strong>formações importantes sobre a cirurgia refrativa<br />

no Brasil. Questões como ablação personalizada, uso de tomógrafo<br />

de córnea, volume cirúrgico, preferências de técnicas cirúrgicas,<br />

colírios pós-operatórios, leito estromal residual entre outras, foram<br />

consideradas.<br />

MÉTODOS<br />

Realizou-se um estudo transversal durante o VI Congresso Brasileiro<br />

de Catarata e Cirurgia Refrativa de 2011. A pesquisa foi baseada<br />

na coleta dos dados de um questionário aplicado aos cirurgiões de<br />

refrativa participantes do evento. Ao térm<strong>in</strong>o do congresso, o mesmo<br />

questionário foi enviado por e-mail aos membros da Sociedade Brasileira<br />

de Cirurgia Refrativa.<br />

O questionário foi composto por 31 questões de múltiplas escolha<br />

e por 1 questão aberta (“Qual porcentual de pacientes operados<br />

por você entre ceratomileusis <strong>in</strong> situ a laser (LASIK) e ceratectomia<br />

fotorrefrativa (PRK)?”). As segu<strong>in</strong>tes variáveis foram estudadas:<br />

pre ferência de técnica cirúrgica; uso de mitomic<strong>in</strong>a C; colírios pósope<br />

ratórios mais utilizados; tipo de excimer laser, microcerátomo,<br />

topógrafo e de tomógrafo de córnea; personalização de cirurgia; tipo<br />

de desepitelização usado na ceratectomia fotorrefrativa (PRK); leito<br />

Submetido para publicação: 28 de outubro de 2011<br />

Aceito para publicação: 15 de novembro de 2012<br />

Trabalho realizado pela Sociedade Brasileira de Cirurgia Refrativa.<br />

1<br />

Médico, Setor de Cirurgia Refrativa, Hospital das Clínicas, Faculdade de Medic<strong>in</strong>a, Universidade<br />

de São Paulo - USP - São Paulo (SP), Brasil.<br />

2<br />

Médico, Departamento de Oftalmologia, Faculdade de Medic<strong>in</strong>a, Universidade de São Paulo - USP -<br />

São Paulo (SP), Brasil.<br />

3<br />

Médico, Universidade Federal de São Paulo - UNIFESP - São Paulo (SP), Brasil.<br />

4<br />

Médico, Rio de Janeiro (RJ), Brasil.<br />

5<br />

Médico, Departamento de Cirurgia Refrativa do Hospital de Olhos Leiria de Andrade - Fortaleza<br />

(CE), Brasil.<br />

F<strong>in</strong>anciamento: Não houve f<strong>in</strong>anciamento para este trabalho.<br />

Divulgação de potenciais conflitos de <strong>in</strong>teresse: M.Vieira Netto, Nenhum; R.F.Espíndola, Nenhum;<br />

R.G.F.Nogueira, Nenhum; M.Campos, Nenhum; R.Ambrósio Jr., Nenhum; N.L.Andrade, Nenhum.<br />

Endereço de correspondência: Rodrigo França de Espíndola. Praça das Hortências, 70. Condomínio<br />

Portal de Itu - Itu (SP) - 13301-689 - Brasil - E-mail: rodrigo166@uol.com.br<br />

Arq Bras Oftalmol. 2013;76(1):29-32<br />

29


Censo Brasileiro de Cirurgia Refrativa<br />

estromal mínimo para ceratomileusis <strong>in</strong> situ a laser (LASIK); paquimetria<br />

mínima necessária para PRK e LASIK; medida <strong>in</strong>traoperatória do<br />

“flap” corneano; volume cirúrgico mensal, valor médio cobrado por<br />

cirurgia, bilateralidade, dentre outras.<br />

A amostragem foi por conveniência (não probabilística), e o nú -<br />

mero de cirurgiões analisados foi estabelecido arbitrariamente de<br />

acordo com o número de voluntários participantes. A análise estatística<br />

baseou-se em dados descritivos da amostra, sendo as variáveis<br />

descritas por meio de médias ou proporções.<br />

Durante o congresso, os questionários foram entregues aos participantes<br />

na entrada das sessões e recolhidos ao térm<strong>in</strong>o da mesma.<br />

Os entrevistados foram orientados a não mudarem ou rasurarem suas<br />

respostas. Questões deixadas em branco, rasuradas e/ou ass<strong>in</strong>aladas<br />

mais de uma vez foram desconsideradas para a análise estatística.<br />

O mesmo questionário foi também enviado por e-mail a todos os<br />

membros da Sociedade Brasileira de Cirurgia Refrativa. As respostas<br />

foram enviados para o e-mail da mesma Sociedade.<br />

Os questionários foram respondidos de forma anônima pelos<br />

cirurgiões participantes.<br />

RESULTADOS<br />

Responderam ao questionário 292 cirurgiões refrativos. Durante<br />

o VI Congresso Brasileiro de Cirurgia Refrativa foram analisadas as<br />

respostas de 245 oftalmologistas (83,90%) e 47 (16,10%) por e-mail<br />

enviados aos membros da Sociedade.<br />

A maioria dos entrevistados realizam suas próprias cirurgias<br />

(89,70%), possuem um volume cirúrgico mensal de 2 a 4 olhos por<br />

semana (61,53%) e esse volume não vem aumentando nos últimos<br />

anos (52,30%). O valor médio cobrado por olho está entre R$ 1.000 e<br />

R$ 2.000 (54,05%) e entre R$ 2.500 e R$ 3.000 (28,85%).<br />

Técnica cirúrgica<br />

Com relação à preferência de técnica cirúrgica utilizada em pacientes<br />

com 30 anos de idade, com miopia de -10,00 D; espessura<br />

corneana maior que 550 micra e sem alterações topográficas, 42,47%<br />

optam pela lente fácica, seguidos de LASIK (30,97%) e PRK (13,27%).<br />

Apenas 3,56% dos entrevistados optaram pela extração do cristal<strong>in</strong>o<br />

transparente e 9,73% aguardariam melhores técnicas.<br />

Quando o paciente é hipermétrope de +3,00 D com 45 anos<br />

de idade e curvatura e espessura coreanas normais, a maioria realizaria<br />

LASIK (70,64%), seguido por extração do cristal<strong>in</strong>o transparente<br />

(16,51%), PRK (9,17%) e 3,68% aguardariam melhores técnicas. Se esse<br />

mesmo paciente hipermétrope possuísse +5,00 D a técnica preferida<br />

seria realizar a extração do cristal<strong>in</strong>o transparente (39,47%), seguido<br />

por LASIK (35,96%), PRK (5,26%) e apenas 2,63% optariam pela lente<br />

fácica. Alguns dos analisados (16,68%) nesta questão aguardariam<br />

melhores técnicas.<br />

Dentre os questionários analisados, a técnica preferida para a<br />

cor reção de presbiopia em pacientes com cristal<strong>in</strong>o transparente é<br />

a monovisão (53,33%). Grande parte (25,73%) não realiza cirurgias<br />

para a correção da pesbiopia, enquanto 18,09% prefere a cirurgia da<br />

extração do cristal<strong>in</strong>o transparente com implante de lente multifocal<br />

e apenas 2,95% realizam a ablação multifocal com excimer laser.<br />

Nas ablações de superfície, a técnica de rot<strong>in</strong>a empregada por<br />

58,00% dos cirurgiões é realizar o debridamento epitelial manual,<br />

se guido de debridamento com motor (22,40%), debridamento por<br />

álcool (16,80%) e Epi-LASIK (2,80%).<br />

Com relação ao uso da mitomic<strong>in</strong>a C no PRK, a maioria dos cirurgiões<br />

utiliza em todos os pacientes (52,60%). Os demais utilizam<br />

a mitomic<strong>in</strong>a desta maneira: 22,80% usam em 2/3 de seus pacientes;<br />

9,60% em metade dos casos; 8,70% usam apenas para tratar “haze”<br />

pré-existente; 4,30% utilizam em 1/4 dos pacientes e apenas 1,70%<br />

dos analisados nunca utilizam a mitomic<strong>in</strong>a C.<br />

Quanto à personalização da cirurgia refrativa, o maior porcentual<br />

de entrevistados (48%) a realiza em 1/4 de seus pacientes, enquanto<br />

que 22% nunca personalizam suas cirurgias. Apenas 10% dos entrevistados<br />

realizam a personalização em todos os casos, seguidos por<br />

5% dos cirurgiões em 2/3 de seus casos e 15% dos analisados em<br />

metade de seus pacientes.<br />

O LASIK cont<strong>in</strong>ua a ser a técnica cirúrgica de escolha dos cirurgiões<br />

refrativos. O gráfico 1 demonstra a distribuição de preferência<br />

entre LASIK e PRK.<br />

A maioria dos analisados não realiza cirurgia refrativa em portadores<br />

de olho único (56,70%). Sobre a lateralidade da cirurgia, a<br />

grande maioria prefere realizar o procedimento nos dois olhos si -<br />

multaneamente tanto no LASIK (82,00%), quanto no PRK (70,70%).<br />

Com relação à espessura corneana, 43,20% cirurgiões ass<strong>in</strong>ala -<br />

ram que o leito estromal residual na técnica de LASIK deve ser de 300<br />

micra, seguido por 250 micra (32,40%), 350 micra (23,40%) e apenas<br />

1,00% dos entrevistados não consideram leito estromal residual<br />

mínimo.<br />

No LASIK, 60,20% dos cirurgiões consideraram que a paquimetria<br />

mínima necessária para sua realização (considerando todos os<br />

demais parâmetros como normais) é de 500 micra, seguido por<br />

520 micra (20,30%), 490 micra (7,50%), 480 micra (7,00%), 450 micra<br />

(3,00%) e apenas 2,00% dos analisados não utilizam limite mínimo. No<br />

caso do PRK, o maior porcentual dos respondentes considera o limi -<br />

te mínimo de 480 micra (30,60%), seguido de 450 micra (23,40%), 500<br />

micra (20,00%), 490 micra (19,00%) e apenas 7,00% não consideram<br />

nenhum limite mínimo.<br />

A maioria não realiza a paquimetria <strong>in</strong>traoperatória (85,30%) para<br />

medir a lamela corneana.<br />

Com relação ao número de pacientes que evoluíram para ectasia<br />

após a cirurgia refrativa, a maioria dos entrevistados relataram não ter<br />

ciência de nenhum caso (58,30%). O restante dos cirurgiões relataram<br />

ter ciência de caso(s) de ectasia(s) distribuídos da segu<strong>in</strong>te forma: 1<br />

caso (18,00%); 2 casos (9,00%); 6 casos (4,60%); 3 casos (3,70%); mais<br />

de 10 casos (3,70%); 4 casos (2,70%).<br />

Exames pré-operatórios e equipamentos cirúrgicos<br />

De acordo com os cirurgiões participantes, os microcerátomos<br />

mais utilizados foram o Hansatome/XP (55,88%) e o Moria (21,58%).<br />

Apenas 4,98% dos entrevistados realizam a confecção da lame la<br />

cor neana com o laser de femtosegundo como demonstrado no<br />

gráfico 2.<br />

Com relação às marcas de excimer laser mais utilizadas o Nidek<br />

(26,14%), o Baush & Lomb Z100 (22,53%) e o Schw<strong>in</strong>d Amaris (18,02%)<br />

foram os mais citados. A distribuição das marcas de excimer laser<br />

citados no questionário está demonstrada no gráfico 3.<br />

O modelo de topógrafo de córnea mais utilizado foi o EyeSys<br />

(34,69%), seguido pelo Tomey (15,30%) e Alcon Eye Map (9,18%). O<br />

gráfico 4 demonstra a relação dos topógrafos mais citados.<br />

Gráfico 1. Procedimento refrativo de escolha para paciente de 30 anos, míope (-10,00 DE)<br />

com córnea >550 micra e sem s<strong>in</strong>ais de ceratocone.<br />

30 Arq Bras Oftalmol. 2013;76(1):29-32


Vieira Netto M, et al.<br />

O anti-<strong>in</strong>flamatório mais usado foi o acetato de prednisolona<br />

(61,53%) seguido pela dexametasona (37,50%) e loteprolol (0,97%). A<br />

maioria dos entrevistados prescreve como anti-<strong>in</strong>flamatório não hormonal<br />

o cetorolac de trometam<strong>in</strong>a (64,76%), seguido pelo nepafenaco<br />

(26,66%) e diclofenaco (0,95%). Não utilizam esse medicamento<br />

7,63% dos analisados.<br />

Gráfico 2. Distribuição dos microcerátomos mais utilizados entre os cirurgiões.<br />

Gráfico 3. Distribuição dos excimer lasers mais utilizados entre os cirurgiões.<br />

Gráfico 4. Distribuição dos topógrafos corneanos mais utilizados entre os cirurgiões.<br />

A maioria dos entrevistados (64,50%) utiliza tomógrafo de córnea<br />

rot<strong>in</strong>eiramente, 32,00% apenas em casos selecionados e 3,5% nunca<br />

utilizam esse exame. O tomógrafo mais usado foi o Orbscan (60,00%),<br />

seguidos pelo Pentacam (33,40%) e o Galilei (6,60%).<br />

Os cirurgiões analisados não pretendem trocar ou adquirir um<br />

excimer laser nos próximos 12 meses (71,68%) e a grande maioria<br />

(75,67%) não pretende trocar ou comprar um laser de femtosegundo<br />

nos próximos 12 meses.<br />

Colírios pós-operatórios<br />

O antibiótico mais prescrito foi o moxifloxac<strong>in</strong>o (46,82%) seguidos<br />

pelo gatifloxac<strong>in</strong>o (45,68%), ciprofloxac<strong>in</strong>o (3,00%), ofloxac<strong>in</strong>o<br />

(2,25%) e tobramic<strong>in</strong>a (2,25%).<br />

DISCUSSÃO<br />

O objetivo pr<strong>in</strong>cipal deste estudo é compartilhar e tornar disponíveis<br />

<strong>in</strong>formações sobre as preferências e práticas em cirurgia<br />

refrativa no Brasil para todos os oftalmologistas, bem como identificar<br />

tendências entre os cirurgiões refrativos.<br />

O LASIK é a técnica mais utilizada pelos cirurgiões entrevistados.<br />

A cirurgia bilateral simultânea é rot<strong>in</strong>eiramente realizada pelos ci -<br />

rurgiões tanto nas técnicas de LASIK ou PRK. Esses resultados asse -<br />

melham-se aos últimos levantamentos da Sociedade Americana de<br />

Catarata e Cirurgia Refrativa (ASCRS) (3,4) .<br />

O último censo brasileiro de cirurgia refrativa realizado no Brasil<br />

em 2005 (5) , aponta resultados semelhantes ao presente estudo. A<br />

maioria dos cirurgiões realizavam como técnica de escolha o LASIK,<br />

operavam os dois olhos simultaneamente, usavam o excimer laser da<br />

Nidek (42,60% <strong>versus</strong> 26,14% em 2011) e o Hansatome era o microcerátomo<br />

mais utilizado (57,70% <strong>versus</strong> 55,88% em 2011).<br />

Porém algumas diferenças entre os dois censos foram notadas.<br />

Em 2005 (5) , 62,00% não usavam anti-<strong>in</strong>flamatórios não hormonais<br />

con tra apenas 7,63% em 2011. Quarenta por cento dos entrevistados<br />

não realizavam a monovisão e no presente estudo, pouco mais de<br />

50,00% preferiam esta técnica para a correção da presbiopia. O custo<br />

por cirurgia refrativa também variou entre os dois levantamentos,<br />

em 2005 a maioria cobrava até US$ 500/olho (67,40%) e hoje o valor<br />

cobrado (em dólares) por 54,05% dos entrevistados varia entre<br />

US$ 535 - US$ 1070/olho.<br />

Com relação à cirurgia personalizada, apenas 22% dos analisados<br />

nunca realizaram essa modalidade em seus pacientes. Somente 10%<br />

dos cirurgiões utiliza a cirurgia personalizada em todos os pa cientes.<br />

Alguns autores (3) relataram que os cirurgiões americanos <strong>in</strong> dicam<br />

a cirurgia personalizada com maior frequência e cobram em média<br />

US$ 300 a mais por olho com essa modalidade técnica, Em 2005,<br />

apenas 4,50% dos cirurgiões brasileiros realizavam “wavefront” (5) .<br />

Apesar da cirurgia de retirada do cristal<strong>in</strong>o transparente não ser<br />

regulamentada pelo Conselho Federal de Medic<strong>in</strong>a no Brasil, ela foi<br />

considerada para correção de altas ametropias por boa parte dos<br />

entrevistados, tanto para correção de presbiopia como para hipermetropia<br />

de +5,00 D. E o número de cirurgiões que consideram esta<br />

técnica parece estar crescendo no Brasil, em 2005, a grande maioria<br />

dos cirurgiões (61,50%) não realiza esse procedimento (5) .<br />

Outra tendência que pode ser notada ao compararmos o censo<br />

anterior com os dados deste estudo é um aumento da <strong>in</strong>dicação<br />

do PRK. Em 2005, praticamente 64% dos cirurgiões não faziam ou<br />

realizavam até 10% de PRK considerando o volume cirúrgico total (5) .<br />

Os dados deste estudo mostram que esse número caiu para aproximadamente<br />

36% em 2011. Esse aumento da frequência do PRK pode<br />

ser atribuído a uma maior preocupação com a ectasia pós-operatória,<br />

avanços na tecnologia dos lasers, uso da mitomic<strong>in</strong>a C e dim<strong>in</strong>uição<br />

da dor no pós-operatório com melhores anti-<strong>in</strong>flamatórias não hormonais.<br />

Outros estudos também tem demonstrado um aumento na <strong>in</strong> -<br />

dicação do PRK, já que essa técnica não apresenta complicações na<br />

confecção da lamela corneana, possuí menor risco de ectasia pósope<br />

ratória e resultados comparáveis ao LASIK (6-9) .<br />

Apenas 1,70% dos cirurgiões nunca utilizam a mitomic<strong>in</strong>a C após<br />

o PRK, porém a maioria a utiliza rot<strong>in</strong>eiramente, sendo que 52,60%<br />

dos cirurgiões a utilizam em todos os seus pacientes. Dados americanos<br />

apontam também para um crescente aumento no uso da<br />

mitomic<strong>in</strong>a C (58,4% em 2004 contra 49,50% em 2002) (4) .<br />

Arq Bras Oftalmol. 2013;76(1):29-32<br />

31


Censo Brasileiro de Cirurgia Refrativa<br />

Com relação ao laser de femtosegundo, somente uma pequena<br />

parte dos entrevistados (4,90%) utiliza essa tecnologia e a grande<br />

maioria dos cirurgiões (75,67%) não pretende trocar ou adquirir<br />

um laser de femtosegundo nos próximos 12 meses. O uso do IntraLase<br />

® para a confeção da lamela aumenta ao redor do mundo<br />

e segundo Sandoval e colaboradores 5,10% dos cirurgiões utilizam<br />

essa tecnologia (4) .<br />

Apesar da importância epidemiológica, o presente estudo apresenta<br />

algumas limitações. A opção por questões de múltipla escolha<br />

facilita a análise, porém não leva em consideração outros tipos de<br />

respostas não listadas nas alternativas. Devido ao caráter anônimo<br />

e voluntário da pesquisa, é impossível compararmos as respostas<br />

daqueles que não enviaram o questionário para a análise. E por fim,<br />

o questionário foi enviado somente aos membros da Sociedade e<br />

aos participantes do VI Congresso Brasileiro de Catarata e Cirurgia<br />

Refrativa, e não para todos os cirurgiões que realizam cirurgia refrativa<br />

no Brasil. De uma forma geral, a análise fica restrita aos cirurgiões<br />

refrativos que participam dos congressos ou que fazem parte da<br />

Sociedade Brasileira de Cirurgia Refrativa.<br />

Sabemos que os resultados apontados por esta pesquisa representam<br />

apenas as práticas de um determ<strong>in</strong>ado grupo de oftalmologistas<br />

em um determ<strong>in</strong>ado período de tempo. Práticas e tendências<br />

mudam com o passar dos anos, novas tecnologias e novas pesquisas<br />

são <strong>in</strong>corporadas rapidamente na prática diária dos cirurgiões ao redor<br />

do mundo. Por isso, levantamentos como este devem ser sempre<br />

estimulados e repetidos ao longo dos anos, abrangendo um número<br />

cada vez maior de cirurgiões.<br />

CONCLUSÃO<br />

O LASIK cont<strong>in</strong>ua sendo a técnica mais utilizada pelos cirurgiões<br />

refrativos, apesar do aumento do emprego da técnica de PRK nos<br />

últimos c<strong>in</strong>co anos. A cirurgia bilateral é realizada rot<strong>in</strong>eiramente pela<br />

maioria dos cirurgiões tanto nas técnicas de LASIK ou PRK.<br />

A tomografia de córnea vem sento utilizada de forma rot<strong>in</strong>eira<br />

pela maioria dos cirurgiões refrativos. Porém, o laser de femtosegundo<br />

a<strong>in</strong>da é empregado pela menor parte dos cirurgiões. O volume<br />

de cirurgias refrativas realizadas no Brasil não aumentou nos últimos<br />

anos, segundo os cirurgiões participantes.<br />

REFERÊNCIAS<br />

1. Bechara SJ, Garcia R, Medeiros FW, Barreto-Junior J, Netto MV. Cirurgia Refrativa. São<br />

Paulo: Artmed; 2009.<br />

2. Kuo IC. Trends <strong>in</strong> refractive surgery at an academic center: 2007-2009. BMC Ophthalmol<br />

[Internet]. 2011[cited 2012 Jun 21];11:11. Available from: http://www.ncbi.nlm.<br />

nih.gov/pmc/articles/PMC3115925/<br />

3. Duffey RJ, Leam<strong>in</strong>g D. Trends <strong>in</strong> refractive surgery <strong>in</strong> the United States. J Cataract<br />

Refract Surg [Internet]. 2004[cited 2010 Mar 19];30(8):1781-5. Available from: http://<br />

www.sciencedirect.com/science/article/pii/S0886335004005784<br />

4. Sandoval HP, Castro LE, Vroman DT, Solomon KD. Refractive Surgery Survey 2004. J<br />

Cataract Refract Surg [Internet]. 2005[cited 2010 Jan 21];31(1):221-33. Available from:<br />

http://www.sciencedirect.com/science/article/pii/S0886335004010958<br />

5. Victor G, Urbano A, Marçal S, Porto R, Francesconi CM, Forseto AS, et al. Primeiro censo<br />

brasileiro em cirurgia refrativa. Arq Bras Oftalmol [Internet]. 2005 [cited 2010 Oct<br />

15];68(6):727-33.Available from: http://www.scielo.br/pdf/abo/v68n6/a05v68n6.pdf<br />

6. Moshirfar M, Schliesser JA, Chang JC, Oberg TJ, Miffl<strong>in</strong> MD, Townley R, et al. Visual outcomes<br />

after wavefront guided photorefractive keratectomy and wavefront guided<br />

laser <strong>in</strong> situ keratomileusis: Prospective comparison. J Cataract Refract Surg [Internet].<br />

2010 [cited 2012 Nov 21];36(8):1336-43. Available from: http://www.sciencedirect.<br />

com/science/article/pii/S0886335010006930<br />

7. Shortt AJ, Allan BD. Photorefractive keratectomy (PRK) <strong>versus</strong> laser-assisted <strong>in</strong>-situ keratomileusis<br />

(LASIK) for myopia. Cochrane Database Syst Rev. 2006;19(2):CD005135.<br />

Update <strong>in</strong>: Cochrane Database Syst Rev. 2013;1:CD005135.<br />

8. Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA, Agapitos PJ, et al. Laser <strong>in</strong><br />

situ keratomileusis for myopia and astigmatism: safety and efficacy: a report by the<br />

American Academy of Ophthalmology. Ophthalmology [Internet]. 2002 [cited 2012<br />

Set 12];109(1):175-87. Available from: http://www.sciencedirect.com/science/article/<br />

pii/S0161642001009666<br />

9. Forseto AS, Nosé RA, Nosé W. PRK <strong>versus</strong> LASIK para correção de miopia baixa e<br />

moderada. Arq Bras Oftalmol [Internet]. 2000[citado 2010 Dez 21];63(4):257-62. Dis -<br />

ponível em: http://www.scielo.br/pdf/abo/v63n4/12327.pdf<br />

32 Arq Bras Oftalmol. 2013;76(1):29-32


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Lentes progressivas - análise dos campos <strong>in</strong>termediário e de perto por deflexometria<br />

Progressive addition lenses - analysis of <strong>in</strong>termediate and near vision zones by deflectometry<br />

Celso Marcelo Cunha 1 , Renato José Bett Correia 2 , Antonio Augusto Sard<strong>in</strong>ha Neto 3<br />

RESUMO<br />

Objetivo: Avaliar por deflexometria as diferentes regiões das lentes progressivas<br />

e determ<strong>in</strong>ar as áreas dos campos de visão <strong>in</strong>termediário e de perto.<br />

Métodos: Foram <strong>in</strong>cluídas v<strong>in</strong>te e duas lentes progressivas com poder +1,00 DE<br />

para longe e duas adições diferentes (adição 1,00 e 2,00, 11 de cada). Mediram-se<br />

as áreas dos campos <strong>in</strong>termediário e de perto entre as isoastigmáticas de 0,5 DC.<br />

Resultados: Encontraram-se diferenças significativas entre as áreas dos campos<br />

<strong>in</strong>termediário e de perto das lentes estudadas. Entre a área do campo <strong>in</strong>termediário<br />

e a adição observou-se correlação <strong>in</strong>versa; entre a área do campo <strong>in</strong>termediário e<br />

a extensão vertical do corredor encontrou-se correlação direta.<br />

Conclusão: Com esses dados permitem-se recomendar as lentes de acordo com<br />

o campo de maior necessidade visual de cada usuário.<br />

Descritores: Presbiopia/terapia; Lentes; Refração; Óptica e fotônica<br />

ABSTRACT<br />

Purpose: To determ<strong>in</strong>e near and <strong>in</strong>termediate vision areas of progressive addition<br />

lenses by means of a deflectometer.<br />

Methods: Twenty-two progressive addition lenses with +1.00 SD far power and two<br />

different additions (add 1.00 and 2.00; eleven subjects <strong>in</strong> each addition) were studied.<br />

Near and <strong>in</strong>termediate vision areas with<strong>in</strong> 0.50 CD isoastigmatic l<strong>in</strong>es were determ<strong>in</strong>ed.<br />

Results: There are significant differences between near and <strong>in</strong>termediate vision<br />

areas of the studied lenses. There is also an <strong>in</strong>verse correlation between the addition<br />

and <strong>in</strong>termediate areas as well as direct relation between the vertical length of the<br />

corridor and its area.<br />

Conclusion: Based on those f<strong>in</strong>d<strong>in</strong>gs, progressive addition lenses can be selected to<br />

suit the wearer’s visual requirements.<br />

Keywords: Presbyopia/therapy; Lenses; Refraction; Optics and photonics<br />

INTRODUÇÃO<br />

O Instituto Brasileiro de Geografia e Estatística no Censo 2010 es -<br />

tima que no Brasil existam cerca de 63 milhões (34% da população)<br />

de pessoas acima de 40 anos (1) . A presbiopia, sendo uma redução<br />

natural da capacidade acomodativa, está presente na maioria dos<br />

pacientes a partir da qu<strong>in</strong>ta década de vida (2) .<br />

As lentes progressivas (LP), sem l<strong>in</strong>ha divisória entre os campos<br />

de visão de longe, <strong>in</strong>termediária e de perto, são largamente utilizadas<br />

para os présbitas amétropes (3) .<br />

As LP têm passado por diversas etapas de evolução nos últimos<br />

50 anos, porém, para ter os poderes dióptricos diferentes em cada<br />

campo, a<strong>in</strong>da mantêm áreas ao lado do corredor progressivo com<br />

aberrações em todas elas, chamadas de astigmatismo <strong>in</strong>duzido (AI),<br />

ou também de astigmatismo irregular ou áreas de aberrações, em<br />

variáveis quantidades e distribuições (2,4) .<br />

Existem vários fabricantes de LP, e mais de 150 modelos estão<br />

disponíveis no Brasil, no entanto, poucas <strong>in</strong>formações técnicas sobre<br />

os AI são fornecidas aos oftalmologistas e ópticos. Existem poucos estudos<br />

sobre estas <strong>in</strong>formações na literatura mundial, sendo a maioria<br />

estudos subjetivos baseados na satisfação dos pacientes (5) .<br />

O objetivo deste estudo foi determ<strong>in</strong>ar as áreas da visão <strong>in</strong>termediária<br />

e de perto nas LP em duas adições dist<strong>in</strong>tas, por meio de<br />

um deflexômetro. A <strong>in</strong>adequação das áreas de perto e <strong>in</strong>termediária<br />

às necessidades visuais do portador poderia levar a não adaptação<br />

a lente escolhida.<br />

MÉTODOS<br />

Foram selecionadas 22 lentes progressivas das empresas Essilor®,<br />

Multivis, Segment e Zeiss (Tabela 1). Todas com poder dióptrico de<br />

+1,00 esférico para longe; 11 com adição 1,00 (gru po 1) e 11 com<br />

adição 2,00 (grupo 2). Outras empresas do setor foram procuradas,<br />

mas não manifestaram <strong>in</strong>teresse em <strong>in</strong>cluir suas LP neste estudo<br />

(Lista das LP em anexo).<br />

Foram solicitadas LP em res<strong>in</strong>a surfaçadas para o olho direito, e<br />

selecionadas pela frequência que são encontradas em clínica privada<br />

e em hospital universitário de Cuiabá - MT, e por variedade de altura<br />

mínima de montagem. As LP foram nomeadas por letras de A a L,<br />

sendo que as com adição 1,00 são acompanhadas do número 1, e as<br />

de adição 2,00 do número 2.<br />

As LP foram analisadas no deflexômetro de <strong>in</strong>terferência de<br />

franjas “Rotlex Class Plus ® ” da Empresa Rotlex (1994) de Israel. Este<br />

<strong>in</strong>strumento detecta em segundos todas as medições dióptricas de<br />

uma lente em uma única medida. O aparelho utiliza uma fonte de<br />

“laser” puntiforme que <strong>in</strong>cide diretamente sobre a lente exam<strong>in</strong>ada.<br />

Os raios refratados pela lente em avaliação passam por duas grades<br />

Submetido para publicação: 24 de outubro de 2011<br />

Aceito para publicação: 23 de novembro de 2012<br />

Trabalho realizado no Hospital Geral Universitário, Cuiabá (MT), Brasil.<br />

1<br />

Médico, Oftalmocenter Santa Rosa, Cuiabá (MT), Brasil.<br />

2<br />

Médico, Hospital Geral Universitário, Cuiabá (MT), Brasil.<br />

3<br />

Acadêmico de Medic<strong>in</strong>a, Universidade Gama Filho, Rio de Janeiro (RJ), Brasil.<br />

F<strong>in</strong>anciamento: Não houve f<strong>in</strong>anciamento para este trabalho.<br />

Divulgação de potenciais conflitos de <strong>in</strong>teresse: C.M.Cunha, Nenhum; R.J.B.Correia, Nenhum;<br />

A.A.Sard<strong>in</strong>ha Neto, Nenhum.<br />

Endereço para correspondência: Renato José Bett Correia. Hospital Universitário Geral de Cuiabá.<br />

Rua 13 de junho, 2101 - Cuiabá (MT) - 78025-000<br />

E-mail: celsomcunha@terra.com.br; renatobett@bol.com.br; sard<strong>in</strong>ha_dm@hotmail.com<br />

Comitê de Ética: UNIC - 2011/048.<br />

Arq Bras Oftalmol. 2013;76(1):33-7<br />

33


Lentes progressivas - análise dos campos <strong>in</strong>termediário e de perto por deflexometria<br />

Tabela 1. Dimensões de alguns parâmetros estudados nas lentes progressivas<br />

Lentes<br />

estudadas<br />

Comprimento do<br />

corredor progressivo<br />

Distância da cruz de<br />

montagem a 0,25 DE da adição<br />

Distância da cruz de montagem à l<strong>in</strong>ha<br />

horizontal entre as marcas de remarcações<br />

Altura mínima de montagem<br />

<strong>in</strong>dicado pelo fabricante<br />

A1 8 -6,0 3,8 18<br />

B1 9 -4,5 5,5 18<br />

C1 7 -2,5 2,7 16<br />

D1 9 -3,0 2,9 18<br />

E1 8 -2,5 3,7 20<br />

F1 6 -2,5 3,7 17<br />

G1 7 -3,5 3,7 18<br />

H1 8 -3,5 3,7 18<br />

I1 8 -4,0 4,0 17<br />

J1 6 -1,5 3,6 14<br />

L1 8 -4,0 4,0 17<br />

A2 6 -1,5 3,6 18<br />

B2 6 -1,5 5,5 18<br />

C2 5 -1,0 2,7 16<br />

D2 6 -1,0 3,0 18<br />

E2 6 -1,0 4,0 20<br />

F2 6 -0,5 3,7 17<br />

G2 6 -0,5 3,7 18<br />

H2 6 -1,0 3,7 18<br />

I2 6 -1,8 3,8 17<br />

J2 5 0 3,6 14<br />

L2 6 -2,0 4,0 17<br />

Notas: Todas as medidas estão em milímetros.<br />

Nas LP de adição 1,00 (A1 a L1) o corredor é da progressão de 0,25 a 0,75 DE. De adição 2,00 (A2 a L2) o corredor é da progressão de 0,75 a 1,50 DE.<br />

Na coluna 3 o valor negativo representa o <strong>in</strong>ício de 0,25 DE da adição acima da cruz de montagem.<br />

Altura mínima é a menor distância permitida pelo fabricante entre a cruz de montagem e a borda <strong>in</strong>ferior da armação.<br />

e formam um padrão tipo “moiré” em uma tela difusora. Destes se<br />

fazem mapas que representam o poder esférico, cilíndrico e eixo em<br />

cada milímetro da lente (Figura 1).<br />

Os arquivos das 22 LP foram avaliados no “software” de análise<br />

do aparelho e registrados milimetricamente: na vertical da cruz de<br />

montagem a 22 mm abaixo; e, no sentido horizontal, 17 mm em cada<br />

lado da cruz de montagem.<br />

Admitiram-se como limites superior e <strong>in</strong>ferior do corredor progressivo:<br />

• Nas lentes do grupo 1, poderes dióptricos esféricos entre +1,25<br />

e +1,75 (valores compreendidos entre 0,25 e 0,75 da progressão<br />

desta adição).<br />

• Nas lentes do grupo 2, poderes dióptricos esféricos entre +1,75<br />

e +2,50 (valores compreendidos entre 0,75 e 1,50 da progressão<br />

desta adição).<br />

Assim se procedeu pela necessidade de contar com 50% a 75%<br />

da adição para visão nítida na distância do campo de visão <strong>in</strong>termediária,<br />

pois alguma acomodação residual se observa nos usuários que<br />

necessitam das adições abaixo de 2,00.<br />

Admitiu-se como limite superior da área de perto:<br />

• Nas lentes do grupo 1, poderes dióptricos esféricos a partir de<br />

+1,76.<br />

• Nas lentes do grupo 2, poderes dióptricos esféricos a partir de<br />

+2,76.<br />

Admitiram-se como limites laterais do campo <strong>in</strong>termediário e<br />

de perto, em todas as lentes, as l<strong>in</strong>has isoastigmáticas de 0,50 DC<br />

(li mite de AI).<br />

As áreas de perto e <strong>in</strong>termediária foram calculadas em mm² no<br />

“software” do deflexômetro.<br />

Para avaliar a extensão horizontal mediu-se a largura do campo<br />

em três posições entre as isoastigmáticas de 0,50 DC no <strong>in</strong>ício, meio<br />

e fim do campo <strong>in</strong>termediário.<br />

Para análise dos resultados adotou-se nível de significância de 5%<br />

(α=0,05), correspondente a probabilidade de erro (p)


Cunha CM, et al.<br />

No campo de perto, quando se utiliza a altura mínima de montagem<br />

autorizada pelos fabricantes para cada uma das LP como limite<br />

<strong>in</strong>ferior, encontra-se a mediana das áreas de 51,4 e 22,7 mm², e um<br />

Anexo 1. Relação das lentes progressivas estudadas e seus fabricantes<br />

Lentes<br />

estudadas<br />

Nome das<br />

lentes progressivas<br />

Fabricante das<br />

lentes progressivas<br />

A1 Espace Selective Brasilor<br />

A2 Espace Selective Brasilor<br />

B1 Gradal Top Zeiss<br />

B2 Gradal Top Zeiss<br />

C1 Multivis Ampla Multivis<br />

C2 Multivis Ampla Multivis<br />

D1 Multivis Extra Multivis<br />

D2 Multivis Extra Multivis<br />

E1 Sapphire LP Segment<br />

E2 Sapphire LP Segment<br />

F1 Sola Elan Zeiss<br />

F2 Sola Elan Zeiss<br />

G1 Solamax Zeiss<br />

G2 Solamax Zeiss<br />

H1 Varilux Comfort Essilor<br />

H2 Varilux Comfort Essilor<br />

I1 Varilux Physio Essilor<br />

I2 Varilux Physio Essilor<br />

J1 Varilux Pix Essilor<br />

J2 Varilux Pix Essilor<br />

L1 Zeiss GT2 Zeiss<br />

L2 Zeiss GT2 Zeiss<br />

Obs.: As lentes progressivas 1 são adições 1,00 D e as lentes progressivas 2 são adições 2,00 D.<br />

alto CV de 32,45 e 47,45% para os grupos 1 e 2 respectivamente,<br />

conforme as tabelas 2 e 3. Utilizando a altura de 22 mm como limite<br />

<strong>in</strong>ferior fixo, encontra- se a mediana das áreas de 114,3 e 53,3 mm²,<br />

e um alto CV de 21,5 e 26,7% para os grupos 1 e 2 respectivamente,<br />

conforme as tabelas 2 e 3.<br />

Existe correlação positiva forte entre a altura do corredor progressivo<br />

e a área do campo <strong>in</strong>termediário nas LP do grupo 1 (coeficiente<br />

de Pearson=0,92), e correlação positiva moderada nas LP do grupo 2<br />

(coeficiente de Pearson=0,69).<br />

DISCUSSÃO<br />

Existem <strong>in</strong>úmeras comb<strong>in</strong>ações possíveis de curva base e desenho<br />

de LP. Alguns desenhos resultam em maior campo de longe,<br />

<strong>in</strong>termediário ou de perto. A presença concomitante dos três campos<br />

com grandes áreas e sem AI maior que 0,50 DC nas adições além de<br />

1,50 parece não ser possível (6) .<br />

Neste estudo de LP com adições diferentes demonstrou-se relação<br />

diretamente proporcional entre o aumento do valor da adição<br />

e os AI, bem como relação <strong>in</strong>versa entre a altura do corredor e os AI,<br />

como relatado na literatura (7,8) . No entanto, no grupo 2, existe uma<br />

correlação l<strong>in</strong>ear moderada para esta segunda afirmativa, pois se<br />

considerou altura do corredor somente a porção de adição útil para<br />

a visão <strong>in</strong>termediária (entre 0,75 e 1,50 do total da adição). Encontrou-<br />

-se a maioria dos corredores com 6 mm de altura. Acharam-se somente<br />

dois com 5 mm, mas com um CV de 16,5%, o que demonstra<br />

o empenho dos fabricantes no aumento da área <strong>in</strong>termediária, mas<br />

sem aumentar muito a altura do corredor.<br />

Ressalta-se que os modelos mais atuais de LP são oferecidos<br />

com desenhos dist<strong>in</strong>tos pela variação das adições e mostram alturas<br />

verticais totais dos corredores (desde 0,25 até 1,75 da adição 2,00)<br />

maiores com o aumento da adição, deixando as LP de adição 2,00<br />

com AI mais reduzido do que se fosse mantida a altura dos corredores<br />

das adições 1,00.<br />

O limite do AI tolerável pelos pacientes tem sido estudado na<br />

literatura. Alguns autores, em estudos clínicos, encontraram 0,50 DC<br />

e outros até 1,00 DC sem alterar a AV ou aumentar significativamente<br />

as aberrações de maior ordem. Como a maioria dos estudos objetivos<br />

utilizou 0,50 DC, manteve-se este parâmetro para poder comparar as<br />

A<br />

B<br />

Figura 1. Mapas de contornos por deflexometria vistos de frente. Áreas isoesféricas e l<strong>in</strong>has isoastigmáticas de 0,50 DC. A) LP D1; B) LP D2.<br />

Arq Bras Oftalmol. 2013;76(1):33-7<br />

35


Lentes progressivas - análise dos campos <strong>in</strong>termediário e de perto por deflexometria<br />

Tabela 2. Áreas dos campos <strong>in</strong>termediário e de perto e altura do campo de perto nas LP do grupo 1<br />

Lentes<br />

estudadas<br />

Área do campo<br />

<strong>in</strong>termediário com<br />

progressão da adição<br />

de 0,25 a 0,75 DE<br />

com isoastigmática<br />

limite de 0,50 DC<br />

Soma das<br />

extensões laterais<br />

das três barras<br />

horizontais<br />

do campo<br />

<strong>in</strong>termediário<br />

Área do campo<br />

de perto com progressão<br />

de 0,76 da adição e<br />

com limite <strong>in</strong>ferior<br />

de 22 mm de altura<br />

de montagem<br />

Área do campo perto<br />

com progressão de 0,76<br />

da adição e com limite<br />

<strong>in</strong>ferior na altura mínima<br />

de montagem de cada<br />

LP (fabricante)<br />

Altura da cruz de<br />

montagem ao<br />

<strong>in</strong>ício do campo<br />

de perto<br />

(0,76 DE da<br />

adição)<br />

Altura da área<br />

do campo de<br />

perto com a<br />

altura mínima<br />

de montagem<br />

de cada LP<br />

A1 076,9% 29,9% 082,6% 31,9% 15,0% 04<br />

B1 094,1% 36,0% 072,4% 39,1% 14,5% 04<br />

C1 063,0% 27,9% 104,1% 45,8% 10,7% 06<br />

D1 119,6% 42,6% 116,1% 54,9% 13,0% 06<br />

E1 065,1% 25,7% 094,8% 80,0% 10,7% 10<br />

F1 043,4% 22,2% 124,6% 70,3% 09,7% 08<br />

G1 056,7% 25,1% 141,6% 89,3% 11,7% 07<br />

H1 080,3% 32,2% 124,1% 73,8% 12,7% 06<br />

I1 081,7% 32,9% 114,3% 46,4% 13,0% 05<br />

J1 045,2% 23,6% 152,5% 51,4% 08,6% 06<br />

L1 077,1% 30,0% 101,6% 44,1% 13,0% 05<br />

Mediana 076,9% 29,9% 114,3% 51,4% 12,7% 06<br />

Coeficiente de<br />

variação (CV)<br />

030,2% 20,0% 021,5% 32,5% 16,4% 28,9%<br />

Notas: áreas medidas em mm². Extensão horizontal e altura em mm.<br />

Tabela 3. Áreas dos campos <strong>in</strong>termediário e de perto e altura do campo de perto nas LP do grupo 2<br />

Lentes<br />

estudadas<br />

Área do campo<br />

<strong>in</strong>termediário com<br />

progressão da adição<br />

de 0,75 a 1,50 DE com<br />

isoastigmática limite<br />

de 0,50 DC<br />

Soma das<br />

extensões laterais<br />

das três barras<br />

horizontais<br />

do campo<br />

<strong>in</strong>termediário<br />

Área do campo<br />

de perto com<br />

progressão de 1,75 da<br />

adição e com limite<br />

<strong>in</strong>ferior de 22 mm de<br />

altura de montagem<br />

Área do campo perto<br />

com progressão de<br />

1,75 da adição e com<br />

limite <strong>in</strong>ferior na altura<br />

mínima de montagem<br />

de cada LP (fabricante)<br />

Altura da cruz de<br />

montagem ao<br />

<strong>in</strong>ício do campo<br />

de perto<br />

(1,75 DE da<br />

adição)<br />

Altura da área<br />

do campo de<br />

perto com a<br />

altura mínima de<br />

montagem<br />

de cada LP<br />

A2 24,3% 17,8% 53,0% 22,7% 15,6% 3<br />

B2 22,8% 15,7% 47,0% 25,7% 15,5% 4<br />

C2 18,2% 14,8% 53,3% 21,8% 10,7% 6<br />

D2 23,6% 18,5% 41,3% 12,2% 16,0% 3<br />

E2 18,5% 13,7% 54,7% 41,0% 15,0% 6<br />

F2 19,5% 14,5% 63,9% 28,9% 13,7% 4<br />

G2 18,4% 15,4% 93,3% 45,8% 13,0% 6<br />

H2 20,7% 14,7% 75,0% 37,2% 13,7% 5<br />

I2 24,6% 16,9% 52,6% 17,0% 14,8% 3<br />

J2 13,2% 10,4% 70,8% 16,7% 11,6% 3<br />

L2 24,2% 14,1% 42,2% 08,6% 16,0% 2<br />

Mediana 20,7% 14,8% 53,3% 22,7% 14,8% 4<br />

Coeficiente de<br />

variação (CV)<br />

17,1% 14,5% 26,7% 47,4% 12,7% 35,3%<br />

Notas: áreas medidas em mm². Extensão horizontal e altura em mm.<br />

LP (4,7,9) . Este limite de 0,50 DC é uma das l<strong>in</strong>has isoastigmáticas que<br />

compõe o mapa de contornos cilíndricos das LP (Figura 1).<br />

A evolução das LP, nos últimos anos, tem se concentrado no aumento<br />

lateral da área do corredor com AI mínimo para facilitar o uso<br />

do computador, uma das atividades que mais necessitam da visão<br />

no campo <strong>in</strong>termediário. O monitor é focalizado com 50% e 75% do<br />

valor total da adição (0,50 e 0,75 DE para adição 1,00; e entre 1,00 e<br />

1,50 DE para adição 2,00) (10,11) . Admite-se que o tamanho da área <strong>in</strong>termediária<br />

por si só não garanta o melhor desempenho destas lentes,<br />

pois, por exemplo, pode-se ter um mesmo tamanho de área em duas<br />

LP: uma com altura de 10 mm e 4 mm de largura; e outra de 4 mm<br />

de altura e 10 mm de largura. No entanto, é bem provável que a LP<br />

com maior largura de corredor facilite o desempenho da leitura, pois,<br />

para esta tarefa, deve-se ter mais campo horizontal do que vertical.<br />

36 Arq Bras Oftalmol. 2013;76(1):33-7


Cunha CM, et al.<br />

Para comparar a extensão horizontal das áreas dos campos <strong>in</strong>termediários<br />

utilizou-se a soma da largura de três posições horizontais<br />

neste estudo (Tabelas 2 e 3), mostrando um CV moderado de 20,2<br />

e 14,5% para o grupo 1 e 2 respectivamente, o que demonstra a<br />

dificuldade dos fabricantes do setor em manter um campo maior, de<br />

pouco AI, nas adições acima de 2,00.<br />

Estudo semelhante na literatura americana (7) utilizou 28 LP, três<br />

delas <strong>in</strong>cluídas neste estudo (as LP B 2, G 2 e H 2). Observa-se que<br />

estas LP mantêm as proporções dos tamanhos entre as áreas dos<br />

campos <strong>in</strong>termediário e de perto. No entanto, o estudo citado considerou<br />

somente uma largura horizontal para comparar a extensão<br />

lateral do campo <strong>in</strong>termediário e, para área considerou duas vezes o<br />

componente horizontal por uma vez do vertical.<br />

Por sua vez, a tendência dos fabricantes ao aumento do campo<br />

<strong>in</strong>termediário (lentes progressivas A2, C2, D2, I2 e L2), vem reduz<strong>in</strong>do<br />

o campo de perto, quando estas lentes são montadas com a altura<br />

mínima sugerida pelos fabricantes, pr<strong>in</strong>cipalmente nas lentes com<br />

adições maiores (Tabela 3).<br />

Na literatura, encontra-se comparação da área do campo de perto<br />

entre algumas lentes em alturas fixas (16, 18, 22 mm) para todas<br />

elas, de forma justa a compará-las (4,7) . No entanto, isto não ocorre na<br />

prática, em razão da variação da altura mínima sugerida para cada<br />

tipo de LP pelos fabricantes. Neste estudo, verificaram-se também<br />

as alturas variáveis para compará-las na forma que se encontram<br />

dis poníveis aos usuários.<br />

Dentre as lentes do grupo 1, as c<strong>in</strong>co com maiores áreas em<br />

ordem decrescente são:<br />

Área <strong>in</strong>termediária: D1, B1, I1, H1 e L1.<br />

Área de perto (aplicando-se como limite <strong>in</strong>ferior a altura mínima<br />

de montagem sugerida pelo fabricante): G1, E1, H1, F1 e D1.<br />

Dentre as lentes do grupo 2, as c<strong>in</strong>co com maiores áreas em<br />

ordem decrescente são:<br />

Área <strong>in</strong>termediária: I2, A2, L2, D2 e B2.<br />

Área de perto (aplicando como limite <strong>in</strong>ferior a altura mínima de<br />

montagem sugerida pelo fabricante): G2, E2, H2, F2 e B2.<br />

Os achados sugerem a conveniência de se basear a recomendação<br />

das LP com base nos tamanhos das áreas de visão <strong>in</strong>termediária<br />

e de perto as relacionando à necessidade visual do paciente. Alguns<br />

estudos têm se ocupado deste aspecto (4,7) , no entanto, necessitam-se<br />

ensaios clínicos para sua melhor compreensão. O presente estudo<br />

tratou apenas de um dos aspectos relacionados às LP. Outros fatores<br />

importantes, tais como simetria dos desenhos, poder total do<br />

AI, aberrações de segunda ordem, equilíbrio b<strong>in</strong>ocular e <strong>in</strong>dução<br />

prismática podem <strong>in</strong>fluir sobre a adaptação e desempenho visual<br />

do portador.<br />

Nas tabelas 2 e 3, constata-se a <strong>in</strong>dependência entre o tamanho<br />

da área de perto e o AI, dessa maneira, corroborando os achados da literatura<br />

(7) . Por outro lado, observa-se a correlação positiva forte entre<br />

altura do corredor e área do campo <strong>in</strong>termediário no grupo 1 (r: 0,92)<br />

e correlação positiva moderada no grupo 2 (r: 0,69), demonstrando<br />

os esforços dos fabricantes para desenvolverem as LP, como já citado<br />

anteriormente. Por este fato, o surgimento de LP com corredor mais<br />

curto para armações pequenas, com altura mínima de montagem<br />

de 14 mm, não é considerado, pelos autores, como evolução das LP,<br />

e sim adaptação dos fabricantes a tais armações. Isto, talvez, até não<br />

seja um problema nas LP de adição 1,00, porém, naquelas do grupo 2<br />

(LP J2=área <strong>in</strong>termediária de 13,2 mm² - mediana deste grupo=20,7),<br />

deve levar a menor rendimento visual neste campo.<br />

CONCLUSÃO<br />

Encontraram-se diferenças estatisticamente significativas entre<br />

as áreas dos campos <strong>in</strong>termediário e de perto das diferentes lentes<br />

progressivas. Seu conhecimento oferece subsídios aos oftalmologistas<br />

para orientarem os pacientes na escolha de lentes adequadas a<br />

suas necessidades visuais. Porém, novos estudos são necessários para<br />

comprovar esta hipótese clínica.<br />

AGRADECIMENTOS<br />

Agradecemos ao Sr. Gilmar Oliveira Júnior pelo apoio estatístico.<br />

REFERÊNCIAS<br />

1. Instituto Brasileiro de Geografia e Estatística - IBGE. Censo Demográfico 2010. Disponível:<br />

. Acesso em 04 de<br />

maio de 2011.<br />

2. Lui Netto A, Alves MR, Lui AC, Lui GA, Giovedi Filho R, Lui TA, et al. Avaliação clínica<br />

comparativa de lentes progressivas na correção da presbiopia. Rev Bras Oftalmol.<br />

2009;68(3):129-33.<br />

3. Karp A. Lenses by the numbers. Lenses Technol. 2004;50-4.<br />

4. Sheedy J, Hardy RF, Hayes JR. Progressive addition lenses--measurements and rat<strong>in</strong>gs.<br />

Optometry. 2006;77(1):23-39.<br />

5. Monte FQ, Carvalho Filho CJ. Proposta para uma visão clínica das lentes progressivas.<br />

Rev Bras Oftalmol. 2008;67(2):69-81.<br />

6. M<strong>in</strong>kwitz G. [On the surface astigmatism of a fixed symmetrical aspheric surface].<br />

Opt Acta (Lond). 1963;10:223-7. German.<br />

7. Sheedy JE. Correlation analysis of the optics of progressive addition lenses. Optom<br />

Vis Sci. 2004;81(5):350-61.<br />

8. Bell GR. Verify<strong>in</strong>g and evaluat<strong>in</strong>g progressive addition lenses <strong>in</strong> cl<strong>in</strong>ical practice. Optometry.<br />

2001;72(4):239-46.<br />

9. Selenow A, Bauer EA, Ali SR, Spencer LW, Ciuffreda KJ. Assess<strong>in</strong>g visual performance<br />

with progressive addition lenses. Optom Vis Sci. 2002;79(8):502-5.<br />

10. Sheedy JE, Shaw-McM<strong>in</strong>n PG. Diagnos<strong>in</strong>g and treat<strong>in</strong>g computer-related vision pro -<br />

blems. Woburn, Mass: Butterworth-He<strong>in</strong>emann; 2002.<br />

11. Pedrono C, Obrecht G, Stark L. Eye-head coord<strong>in</strong>ation with laterally “modulated” gaze<br />

field. Am J Optom Physiol Opt. 1987;64(11):853-60.<br />

Arq Bras Oftalmol. 2013;76(1):33-7<br />

37


Artigo Orig<strong>in</strong>al | Orig<strong>in</strong>al Article<br />

Assessment of ocular surface toxicity after topical <strong>in</strong>stillation of nitric oxide donors<br />

Avaliação da toxicidade na superfície ocular após <strong>in</strong>stilação tópica de doadores de óxido nítrico<br />

Angel<strong>in</strong>o Julio Cariello 1 , Gabriela Freitas Pereira de Souza 2 , Márcia Serva Lowen 3 , Marcelo Ganzarolli de Oliveira 2 , Ana Luisa Höfl<strong>in</strong>g-Lima 1<br />

ABSTRACT<br />

Purpose: To evaluate the ocular surface toxicity of two nitric oxide donors <strong>in</strong> ex<br />

vivo and <strong>in</strong> vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-Nace<br />

tylcyste<strong>in</strong>e (SNAC) <strong>in</strong> a hydroxypropyl methylcellulose (HPMC) matrix at f<strong>in</strong>al<br />

concentrations 1.0 and 10.0 mM.<br />

Methods: Ex vivo GSNO and SNAC toxicities were cl<strong>in</strong>ically and histologically<br />

ana lyzed us<strong>in</strong>g freshly excised pig eyeballs. In vivo experiments were performed<br />

with 20 alb<strong>in</strong>o rabbits which were randomized <strong>in</strong>to 4 groups (5 animals each):<br />

Groups 1 and 2 received <strong>in</strong>stillations of 150 µL of aqueous HPMC solution conta<strong>in</strong><strong>in</strong>g<br />

GSNO 1.0 and 10.0 mM, respectively, <strong>in</strong> one of the eyes; Groups 3 and 4<br />

received <strong>in</strong>stillations of 150 µL of aqueous HPMC solution-conta<strong>in</strong><strong>in</strong>g SNAC 1.0 and<br />

10.0 mM, respectively, <strong>in</strong> one of the eyes. The contralateral eyes <strong>in</strong> each group<br />

received aqueous HPMC as a control. All animals underwent cl<strong>in</strong>ical evaluation<br />

on a slit lamp and the eyes were scored accord<strong>in</strong>g to a modified Draize eye test<br />

and were histologically analyzed.<br />

Results: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or<br />

other gross damage. These f<strong>in</strong>d<strong>in</strong>gs were confirmed by histological analysis. The re<br />

was no difference between control and treated rabbit eyes accord<strong>in</strong>g to the Draize<br />

eye test score <strong>in</strong> all groups (p>0.05). All formulations showed a mean score under<br />

1 and were classified as “non-irritat<strong>in</strong>g”. There was no evidence of tissue toxicity<br />

<strong>in</strong> the histological analysis <strong>in</strong> all animals.<br />

Conclusion: Aqueous HPMC solutions conta<strong>in</strong><strong>in</strong>g GSNO and SNAC at concentrations<br />

up to 10.0 mM do not <strong>in</strong>duce ocular irritation.<br />

Keywords: Drug toxicity; S-nitrosothiols; S-nitrosoglutathione; Methylcellulose;<br />

Ni tric oxide donors<br />

RESUMO<br />

Objetivo: Avaliar a toxidade na superfície ocular de dois compostos doadores de<br />

óxido nítrico em modelos ex vivo e <strong>in</strong> vivo: S-nitrosoglutationa (GSNO) e S-nitroso-<br />

N-acetilcisteína (SNAC), em uma matriz de hidroxipropil metilcelulose (HPMC) nas<br />

concentrações f<strong>in</strong>ais de 1,0 and 10,0 mM.<br />

Métodos: As toxicidades de GSNO e SNAC foram avaliadas cl<strong>in</strong>icamente e histologicamente<br />

em modelo ex vivo usando globos oculares porc<strong>in</strong>os recém excisados.<br />

Experimentos <strong>in</strong> vivo foram realizados com 20 coelhos alb<strong>in</strong>os que foram randomiza ­<br />

dos em 4 grupos (5 animais em cada): Os grupos 1 e 2 receberam <strong>in</strong>stilações de 150 µL<br />

de solução aquosa de HPMC contendo GSNO 1,0 e 10,0 mM, respectivamente, em<br />

um dos olhos; Os grupos 3 e 4 receberam <strong>in</strong>stilações de 150 µL de solução aquosa de<br />

HPMC contendo SNAC 1,0 and 10,0 mM, respectivamente, em um dos olhos. Os olhos<br />

contralaterias em cada grupo receberam solução aquosa de HPMC como controle.<br />

Todos os animais foram cl<strong>in</strong>icamente avaliados em lâmpada de fenda e os olhos foram<br />

pontuados de acordo com o teste de Draize modificado e analisados histologicamente.<br />

Resultados: Os globos oculares porc<strong>in</strong>os não apresentaram s<strong>in</strong>ais de perfuração,<br />

erosão, opacidade da córnea ou outros danos graves. Esses resultados foram confirmados<br />

pela análise histológica. Não houve diferença entre os olhos dos coelhos<br />

tratados e controles de acordo com a pontuação do teste de Draize em todos os<br />

grupos (p>0,05). Todas as formulações apresentaram um escore médio menor do<br />

que 1 e foram classificadas como “não-irritantes”. Não houve evidência de toxicidade<br />

tecidual nas análises histológicas em todos os animais.<br />

Conclusão: Soluções aquosas de HPMC contendo GSNO e SNAC em concentrações<br />

até 10,0 mM não <strong>in</strong>duzem irritação ocular.<br />

Descritores: Toxicidade de drogas; S-nitrosotióis; S-nitrosoglutationa, Metilcelulose;<br />

Doadores de óxido nítrico<br />

INTRODUCTION<br />

Nitric Oxide (NO) is a signal<strong>in</strong>g molecule responsible for several<br />

physiological and pathophysiological actions throughout the human<br />

body, <strong>in</strong>clud<strong>in</strong>g blood flow control and modulation of immune<br />

res ponse (1,2) . In mammals, NO is considered to circulate as S-nitrosothiols,<br />

ma<strong>in</strong>ly S-nitrosoglutathione (GSNO), S-nitrosoalbum<strong>in</strong> and<br />

pos sibly S-nitrosohemoglob<strong>in</strong> (3,4) . Synthetic GSNO and S-nitroso-Nace<br />

tylcyste<strong>in</strong>e (SNAC) were already used as exogenous NO donors <strong>in</strong><br />

different experimental sett<strong>in</strong>gs (5,6) .<br />

In the eye, NO has been shown to be a key regulator of vascular<br />

tone <strong>in</strong> ophthalmic arteries (7,8) and animal and human studies have<br />

demonstrated reduction <strong>in</strong> the choroidal blood flow with systemic<br />

<strong>in</strong>fusion of NO <strong>in</strong>hibitors (9-11) . NO donors were also shown to <strong>in</strong>crease<br />

blood flow <strong>in</strong> the ret<strong>in</strong>a, choroid and the optic nerve head (12,13) .<br />

Additionally, some studies have addressed the beneficial effect of<br />

S-nitrosothiols on the reduction of <strong>in</strong>traocular pressure (14-17) , and suggest<br />

that S-nitrosothiols are potential new drugs for the treatment of<br />

glaucoma and other ocular ischemic diseases (13) .<br />

Nitric oxide-mediated antimicrobial activity has also been the focus<br />

of recent research (18,19) . GSNO and SNAC displayed bactericidal and<br />

bac teriostatic activities aga<strong>in</strong>st several Gram-positive and Gram-ne -<br />

gative cl<strong>in</strong>ical isolates from patients with bacterial <strong>in</strong>fectious keratitis<br />

(20) . In addition, GSNO and SNAC were also shown to exert potent<br />

antimicrobial actions aga<strong>in</strong>st trophozoites of Acanthamoeba castellanii,<br />

the etiological agent responsible for a devastat<strong>in</strong>g si ght-threaten<strong>in</strong>g<br />

keratitis (21) . These data suggest that NO donors are important candidates<br />

for treat<strong>in</strong>g <strong>in</strong>fectious eye diseases. Other possible therapeutic<br />

applications of S-nitrosothiols <strong>in</strong> ophthalmology <strong>in</strong>clude corneal<br />

wound heal<strong>in</strong>g (22) , antifibrotic effect <strong>in</strong> glaucoma filter<strong>in</strong>g surgery (23)<br />

and anti-<strong>in</strong>flammatory action <strong>in</strong> autoimmune uveitis (24) .<br />

Submitted for publication: August 16, 2012<br />

Accepted for publication: November 20, 2012<br />

Study carried out at Universidade Federal de São Paulo, São Paulo, SP, Brazil.<br />

1<br />

Physician, Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.<br />

2<br />

Chemistry, Institute of Chemistry, Universidade Estadual de Camp<strong>in</strong>as, Camp<strong>in</strong>as, SP, Brazil.<br />

3<br />

Physician, Department of Pathology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.<br />

Fund<strong>in</strong>g: This study was supported by GFPS received a studentship from FAPESP, (grant<br />

#07/55877-3). MGO ack nowledges support from CNPq (grant #309390/2011-7) and FAPESP<br />

(grant #2011/18334-7).<br />

Disclosure of potential conflicts of <strong>in</strong>terest: A.J.Cariello, None; G.F.P.de Souza, received a studentship<br />

from FAPESP, Proj.07/55877-3; M.S.Lowen, None; M.G.de Oliveira, None; A.L.Höfl<strong>in</strong>g-Lima, None.<br />

Correspondence address: Angel<strong>in</strong>o Julio Cariello. Sadalla Am<strong>in</strong> Ghanem Eye Hospital. Rua Abdon<br />

Batista, 146 - Jo<strong>in</strong>ville (SC) - 89201-010 - Brazil - E-mail: angel<strong>in</strong>o@sadalla.com.br<br />

Ethic committee from UNIFESP: number 1573/08.<br />

38 Arq Bras Oftalmol. 2013;76(1):38-41


Cariello AJ, et al.<br />

Despite these potential cl<strong>in</strong>ical applications of S-nitrosothiols <strong>in</strong><br />

ophthalmology, the ocular toxicity of these compounds is not yet<br />

known. The purpose of the present study was to evaluate the ocular<br />

surface toxicity of GSNO and SNAC after topical <strong>in</strong>stallations <strong>in</strong> ex vivo<br />

and <strong>in</strong> vivo animal models.<br />

METHODS<br />

Materials<br />

Glutathione (g-Glu-Cys-Glu, GSH), N-acetyl-cyste<strong>in</strong>e (NAC), sodium<br />

nitrite (NaNO2), hydrochloric acid (HCl), phosphate buffer sal<strong>in</strong>e so -<br />

lution, pH 7.4 (PBS) and acetone were purchased from Sigma (St.<br />

Louis, MO, USA) and used as received. Ketam<strong>in</strong>e and xylaz<strong>in</strong>e hydrochlorides<br />

were purchased from Phoenix Scientific Inc. (St. Joseph, MO,<br />

USA). Hydroxypropyl methylcellulose (HPMC) was manufactured by<br />

Dow Chemical Company (Midland, MI, USA).<br />

Synthesis of GSNO and SNAC<br />

GSNO and SNAC were synthesized as previously described (25) .<br />

SNAC solutions were prepared from a freshly made stock solution<br />

40.0 mM and further diluted <strong>in</strong> PBS to 2.0 and 20.0 mM with a f<strong>in</strong>al<br />

pH 7.0. GSNO solutions 2.0 and 20.0 mM, pH 7.0, were prepared immediately<br />

before use from solid GSNO.<br />

Preparation of S-nitrosothiols-conta<strong>in</strong><strong>in</strong>g HPMC formulations<br />

SNAC and GSNO concentrations 1.0 and 10.0 mM <strong>in</strong> HPMC solution<br />

2% (w/v) were prepared by mix<strong>in</strong>g equal volumes of aqueous<br />

HPMC solution 4% (w/v) and SNAC or GSNO solutions 2.0 or 20.0 mM,<br />

prepared as above, under stirr<strong>in</strong>g. These formulations were designated<br />

as SNAC 1, SNAC 10, GSNO 1 and GSNO 10, respectively.<br />

Stability of the HPMC-conta<strong>in</strong><strong>in</strong>g S-nitrosothiols formulations<br />

The concentrations of SNAC and GSNO <strong>in</strong> the HPMC formulations<br />

were spectrophotometrically monitored dur<strong>in</strong>g their storage <strong>in</strong> the<br />

dark at 37ºC for 1 h, based on their characteristic optical absorption<br />

bands at 336 nm, assigned to the -SNO moiety. A Diode-array spectrophotometer<br />

(HP-8453, Hewlett-Packard, Palo Alto, CA, USA) was<br />

used for this purpose. GSNO and SNAC solutions 10 mmol L -1 were<br />

monitored over 1 h <strong>in</strong> a 1 cm optical path quartz cuvette. Concentration<br />

changes <strong>in</strong> the solutions were calculated based on the molar absorption<br />

coefficient of GSNO and SNAC (900.0 mol -1 L cm -1 at 336 nm).<br />

Animals<br />

Male New Zealand healthy alb<strong>in</strong>o rabbits (1.8 to 2.2 kg) were pur -<br />

chased from the Center of Development of Experimental Models for<br />

Medic<strong>in</strong>e and Biology (CEDEME, São Paulo, Brazil). All animals were<br />

handled <strong>in</strong> accordance with the NIH Pr<strong>in</strong>ciples of laboratory animal<br />

care and the ARVO statement for the use of animals <strong>in</strong> ophthalmic<br />

and vision research. The experimental protocol was previously approved<br />

by the Research Ethics Committee from Federal University of São<br />

Paulo. All animals were acclimated and housed <strong>in</strong> <strong>in</strong>dividual cages<br />

(designed to avoid accidental <strong>in</strong>jury) and kept <strong>in</strong> a room with 12-h<br />

light-dark diurnal cycle, adequate air turnover and constant temperature<br />

(22°C), receiv<strong>in</strong>g standard rabbit chow (Pur<strong>in</strong>a, São Paulo, Brazil)<br />

and water ad libitum. All procedures were performed under systemic<br />

anesthesia with <strong>in</strong>tramuscular <strong><strong>in</strong>jection</strong> of 30 mg/kg of ketam<strong>in</strong>e hy -<br />

drochloride and 5 mg/kg of xylaz<strong>in</strong>e hydrochloride.<br />

Ex vivo evaluation<br />

For ethical reasons, the toxicities of the S-nitrosothiols formulations<br />

were previously evaluated <strong>in</strong> an ex vivo model to lessen the<br />

likelihood of any non-selective effects <strong>in</strong> rabbit eyes dur<strong>in</strong>g the <strong>in</strong><br />

vivo tests. Twenty-five freshly excised pig eyeballs were obta<strong>in</strong>ed<br />

from a local slaughterhouse immediately after slaughter, washed<br />

thoroughly with PBS and divided <strong>in</strong>to five groups. The eyeballs of<br />

each of four experimental groups were <strong>in</strong>stilled with 500 μL of SNAC<br />

1, SNAC 10, GSNO 1 or GSNO 10 formulations onto the cornea and<br />

conjunctiva.<br />

The fifth group received the same volume of pure HPMC solution<br />

2% (w/v) and served as a control. The eyeballs were cl<strong>in</strong>ically analyzed<br />

under a surgical microscope before <strong>in</strong>stillation and 30 m<strong>in</strong> and 1 h<br />

after <strong>in</strong>stillation. The eyeballs were fixed <strong>in</strong> 10% formal<strong>in</strong> solution for<br />

48 h, sta<strong>in</strong>ed with hematoxyl<strong>in</strong>-eos<strong>in</strong> and subjected to histological<br />

analysis.<br />

Ocular tolerability<br />

Twenty rabbits were randomized <strong>in</strong>to 4 groups with 5 animals<br />

each: groups 1 and 2 received <strong>in</strong>stillations of 150 mL of GSNO 1 and<br />

GSNO 10, respectively, <strong>in</strong> one eye (randomly chosen by co<strong>in</strong> toss bet -<br />

ween right or left side); groups 3 and 4 received 150 mL of SNAC 1 and<br />

SNAC 10, respectively, <strong>in</strong> one eye (randomly chosen as above). The<br />

contralateral eye of each animal received aqueous HPMC as a control.<br />

A sent<strong>in</strong>el study with a s<strong>in</strong>gle animal per group was performed<br />

before the entire experiment and showed no cl<strong>in</strong>ical and histological<br />

damage up to 72 h. Based on this result, the evaluation of toxicity<br />

was limited to 24 h.<br />

A modified Draize test was used to access potential ocular irritancy<br />

(26) . Slit lamp exam<strong>in</strong>ation was performed before drug exposure<br />

to ensure normal ocular surface <strong>in</strong>tegrity and repeated 1 and 24 h<br />

after drug <strong>in</strong>stillation. The score system evaluated the corneal opacity<br />

(scored from 0 to 4), iritis (from 0 to 2) and conjunctival redness (from<br />

0 to 3) (26) . The f<strong>in</strong>al score was calculated by summ<strong>in</strong>g the cornea, iris<br />

and conjunctiva scores, which ranged from 0 to 9. The score criteria<br />

were def<strong>in</strong>ed accord<strong>in</strong>g to the follow<strong>in</strong>g cutoffs: under 1: non-ir ri -<br />

tat<strong>in</strong>g; 1 to 4: mildly irritat<strong>in</strong>g; 5 to 7: moderately irritat<strong>in</strong>g; over 7:<br />

severely irritat<strong>in</strong>g.<br />

After 24 h all animals were sacrificed with <strong>in</strong>travenous pentobar -<br />

bital sodium <strong><strong>in</strong>jection</strong> under anesthesia, the eyes were enucleated,<br />

fixed <strong>in</strong> 10% formal<strong>in</strong> solution for 48 h and then histologically ana -<br />

lyzed (hematoxyl<strong>in</strong>-eos<strong>in</strong> sta<strong>in</strong>). All the slit lamp evaluations were<br />

performed under double bl<strong>in</strong>d conditions (i.e. both the <strong>in</strong>vestigator<br />

who performed the <strong>in</strong>stillations and the <strong>in</strong>vestigator who performed<br />

the histological analysis did not know the formulation identity).<br />

Statistical analyses<br />

Data were expressed as mean ± standard deviation. The comparisons<br />

between Draize score of control and treated eyes were done<br />

us<strong>in</strong>g the non-parametric Mann-Whitney U test. P values 0.05) (Table 1). The animal<br />

bl<strong>in</strong>k rate or eye wip<strong>in</strong>g 5 m<strong>in</strong> <strong>in</strong>to the recovery period after anesthesia<br />

were unaffected by drug treatment.<br />

The palpebral, cul-de-sac and bulbar conjunctival histologies<br />

of all control and treated animals were unchanged. No vessel proliferation<br />

or immune cell <strong>in</strong>filtration was detected. The Goblet-cells<br />

were present throughout the entire conjunctival surface with no<br />

Arq Bras Oftalmol. 2013;76(1):38-41<br />

39


Assessment of ocular surface toxicity after topical <strong>in</strong>stillation of nitric oxide donors<br />

Table 1. Draize eye test score<br />

Compounds<br />

Interval of<br />

exposure<br />

Treatment<br />

mean ± SD<br />

Control<br />

mean ± SD<br />

p value*<br />

SNAC 1 After 1 hour 0.2 ± 0.45 0.2 ± 0.45 1.00<br />

After 24 hour 0 0 -<br />

SNAC10 After 1 hour 0.4 ± 0.55 0.2 ± 0.45 0.69<br />

After 24 hour 0.2 ± 0.45 0.2 ± 0.45 1.00<br />

GSNO1 After 1 hour 0 0 -<br />

After 24 hour 0 0 -<br />

GSNO10 After 1 hour 0.4 ± 0.55 0.2 ± 0.45 0.69<br />

After 24 hour 0.2 ± 0.45 0.2 ± 0.45 1.00<br />

SNAC= S-nitroso-N-acetylcyste<strong>in</strong>e; GSNO= S-nitrosoglutathione; SD= standard deviation.<br />

*= Mann-Whitney U test.<br />

A<br />

cytoarchitectural modifications. The limbus was preserved and no<br />

<strong>in</strong>flammatory cell <strong>in</strong>filtration was noted. The cornea also had an unchanged<br />

appearance <strong>in</strong> all its layers with no angiogenesis or <strong>in</strong>flammatory<br />

signs (Figure 1). No histological modifications were noted <strong>in</strong><br />

the sclera, iris, lens, choroid and ret<strong>in</strong>a.<br />

Evaluation of the stability of the SNAC 10 and GSNO 10 formulations<br />

at 37ºC showed that less than 2% of the SNAC or GSNO decompose<br />

under this condition after 1 h.<br />

DISCUSSION<br />

In spite of their potential therapeutic applications, the ocular to -<br />

xicity of GSNO and SNAC had not been characterized yet. Previous<br />

studies performed to evaluate the ocular hypotensive effect of other<br />

topical NO donors, like sodium nitroprusside and S-nitroso-N-acetyl-<br />

DL-penicillam<strong>in</strong>e reported no adverse effects <strong>in</strong> the concentration<br />

range 1-2 mM (14,15) . Equimolar concentrations of different NO donors<br />

lead to variable levels of detectable NO metabolites <strong>in</strong> vitro and <strong>in</strong> vivo<br />

and differences <strong>in</strong> pharmacological and pharmacok<strong>in</strong>etic properties<br />

of these compounds can lead to different cl<strong>in</strong>ical effects <strong>in</strong> ocular<br />

tissues (15) . Thus, results obta<strong>in</strong>ed with a specific nitric oxide donor<br />

cannot always be extended to S-nitrosothiols such as GSNO and<br />

SNAC. This was the first standardized study to evaluate the potential<br />

toxic effects of topical <strong>in</strong>stillation of aqueous HPMC formulations<br />

conta<strong>in</strong><strong>in</strong>g GSNO and SNAC on the surface of the eye. We chose the<br />

concentration 1 mM, which was previously shown to have <strong>in</strong> vitro microbicidal<br />

effects aga<strong>in</strong>st trophozoites of Acanthamoeba castellanii (21)<br />

and a concentration ten times higher than this <strong>in</strong> order to explore the<br />

toxicity level of these RSNOs.<br />

The Draize rabbit eye test used <strong>in</strong> the present study has been<br />

globally accepted s<strong>in</strong>ce 1944 as the standard regulatory method for<br />

determ<strong>in</strong><strong>in</strong>g the ocular irritation potential of chemical products (27-30) .<br />

However, its use has been criticized on the bases of ethical considerations<br />

s<strong>in</strong>ce it is employed on live animals. Alternative methods<br />

have been discussed for ocular toxicity assessment (30) . Many tests<br />

have been published us<strong>in</strong>g ex vivo tissue and cell culture of animal<br />

and human tissue (27,30,31) . Despite good reproducibility and sensitivity<br />

of several <strong>in</strong> vitro alternative model assays for ocular irritation, their<br />

predictive power was not as reliable as the rabbit Draize eye test (30) .<br />

Moreover, the majority of these tests do not address the issue of ocular<br />

irritation reversibility (32) . Ex vivo assays are accepted by regulatory<br />

authorities for specific and limited purposes (30) . As recommended<br />

by regulatory agencies (27,30) , <strong>in</strong> the present study a tiered test<strong>in</strong>g<br />

stra tegy was performed to m<strong>in</strong>imize consequential animal distress.<br />

It <strong>in</strong>cluded concerns about the use of neutral formulations and the<br />

use of similar NO donors <strong>in</strong> animal eyes and ocular tissue described<br />

<strong>in</strong> the literature (14,15) .<br />

B<br />

C<br />

Figure 1. Representative histological images of rabbit eyes after <strong>in</strong>stillation of HPMC formulations<br />

conta<strong>in</strong><strong>in</strong>g 10.0 mM S-nitrosogluthatione (GSNO) or S-nitroso-N-acetilcyste<strong>in</strong>e<br />

(SNAC). (A) Conjunctival cul-de-sac (arrow) (100x). (B) Conjunctival bulbar epithelium<br />

(arrow shows a globetcell) (200x). (C) Cornea with normal aspect of epithelium (thick<br />

arrow) and endothelium (th<strong>in</strong> arrow) (200x). Hematoxyl<strong>in</strong>-eos<strong>in</strong> sta<strong>in</strong> <strong>in</strong> all pictures.<br />

Consider<strong>in</strong>g that the cornea is an avascular tissue, topical adm<strong>in</strong>istration<br />

is a first choice approach for treat<strong>in</strong>g diseases of the anterior<br />

segment of the eye such as glaucoma and keratitis (33) . In addition,<br />

topical application may allow the use of locally high concentrations<br />

of active pr<strong>in</strong>ciples, with m<strong>in</strong>or or non-significant side effects (33) . The<br />

HPMC used for the topical <strong>in</strong>stillations of aqueous SNAC and GSNO<br />

solutions <strong>in</strong> this work is a non-toxic hydrophilic mucoadhesive po -<br />

lymer with film form<strong>in</strong>g properties, commonly used <strong>in</strong> <strong>in</strong>traocular<br />

sur gery, topical adm<strong>in</strong>istrations, artificial tears and drug vehicle (34,35) .<br />

It is known that tear dra<strong>in</strong>age and bl<strong>in</strong>k<strong>in</strong>g action may result <strong>in</strong> low<br />

40 Arq Bras Oftalmol. 2013;76(1):38-41


Cariello AJ, et al.<br />

drug absorption follow<strong>in</strong>g topical ocular application. This consideration<br />

accounts for why HPMC solution was used as a vehicle. It acts as<br />

a viscosity enhancer and is expected to <strong>in</strong>crease both the residence<br />

time of the S-nitrosothiols <strong>in</strong> the cul-de-sac and their bioavailability<br />

on the pre corneal tear film (36-38) . Moreover, the low amount of S-ni -<br />

trosothiols decomposition <strong>in</strong> the HPMC matrix <strong>in</strong>dicates that this<br />

vehicle is appropriate for ocular drug delivery.<br />

Generally, topical drug <strong>in</strong>stillation does not result <strong>in</strong> the diffusion<br />

of the drugs <strong>in</strong>to the vitreous chamber and their pharmacological<br />

actions are limited to the anterior ocular surfaces not affect<strong>in</strong>g the<br />

ret<strong>in</strong>a and the choroid. In fact, Behar-Cohen et al. (14) showed that<br />

nitrite levels were undetectable <strong>in</strong> the rabbit vitreous humor after an<br />

NO donor <strong><strong>in</strong>jection</strong> <strong>in</strong>to the anterior chamber. The absence of histological<br />

alterations and of <strong>in</strong>flammatory <strong>in</strong>filtrates observed <strong>in</strong> our <strong>in</strong><br />

vivo results is, therefore, consistent with the ex vivo results.<br />

CONCLUSIONS<br />

Aqueous HPMC formulations conta<strong>in</strong><strong>in</strong>g SNAC or GSNO up to<br />

10 mM display low ocular surface toxicity <strong>in</strong> topical applications<br />

and might be a promis<strong>in</strong>g option for treat<strong>in</strong>g ocular diseases where<br />

nitric oxide may have microbicidal or other beneficial pharmaceutical<br />

actions.<br />

ACKNOWLEDGEMENTS<br />

GFPS received a fellowship from Fundação de Amparo à Pesquisa<br />

do Estado de São Paulo, FAPESP (grant # 07/55877). MGO received<br />

a f<strong>in</strong>ancial support from Conselho Nacional de desenvolvimento<br />

científico e tecnológico, CNPq (grant # 309390/2011-7) and FAPESP,<br />

(grant # 2011/18334-7).<br />

References<br />

1. Wanstall JC, Jeffery TK, Gamb<strong>in</strong>o A, Lovren F, Triggle CR. Vascular smooth muscle<br />

relaxation mediated by nitric oxide donors: a comparison with acetylchol<strong>in</strong>e, nitric<br />

oxide and nitroxyl ion. Br J Pharmacol. 2001;134(3):463-72.<br />

2. Bogdan C. Nitric oxide and the immune response. Nat Immunol. 2001;2(10):907-16.<br />

Review.<br />

3. Gladw<strong>in</strong> MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA, et<br />

al. Role of circulat<strong>in</strong>g nitrite and S-nitrosohemoglob<strong>in</strong> <strong>in</strong> the regulation of regional<br />

blood flow <strong>in</strong> humans. Proc Natl Acad Sci U S A. 2000;97(21):11482-7.<br />

4. MacArthur PH, Shiva S, Gladw<strong>in</strong> MT. Measurement of circulat<strong>in</strong>g nitrite and S-nitrosothiols<br />

by reductive chemilum<strong>in</strong>escence. J Chromatogr B Analyt Technol Biomed<br />

Life Sci. 2007;851(1-2):93-105.<br />

5. Ricardo KF, Shishido SM, de Oliveira MG, Krieger MH. Characterization of the hypotensive<br />

effect of S-nitroso-N-acetylcyste<strong>in</strong>e <strong>in</strong> normotensive and hypertensive conscious<br />

rats. Nitric Oxide. 2002;7(1):57-66.<br />

6. Seabra AB, Pankotai E, Fehér M, Somlai A, Kiss L, Bíró L, et al. S-nitrosoglutathionecon<br />

ta<strong>in</strong><strong>in</strong>g hydrogel <strong>in</strong>creases dermal blood flow <strong>in</strong> streptozotoc<strong>in</strong>-<strong>in</strong>duced <strong>diabetic</strong><br />

rats. Br J Dermatol. 2007;156(5):814-8.<br />

7. Yao K, Tschudi M, Flammer J, Lüscher TF. Endothelium-dependent regulation of<br />

vascular tone of the porc<strong>in</strong>e ophthalmic artery. Invest Ophthalmol Vis Sci. 1991;<br />

32(6):1791-8.<br />

8. Lockhart CJ, Gamble AJ, Rea D, Hughes S, McGivern RC, Wolsley C, et al. Nitric oxide<br />

modulation of ophthalmic artery blood flow velocity waveform morphology <strong>in</strong><br />

healthy volunteers. Cl<strong>in</strong> Sci (Lond). 2006;111(1):47-52.<br />

9. Luksch A, Polak K, Beier C, Polska E, Wolzt M, Dorner GT, et al. Effects of systemic NO<br />

synthase <strong>in</strong>hibition on choroidal and optic nerve head blood flow <strong>in</strong> healthy subjects.<br />

Invest Ophthalmol Vis Sci. 2000;41(10):3080-4.<br />

10. Dorner GT, Garhofer G, Kiss B, Polska E, Polak K, Riva CE, et al. Nitric oxide regulates<br />

ret<strong>in</strong>al vascular tone <strong>in</strong> humans. Am J Physiol Heart Circ Physiol. 2003;285(2):H631-6.<br />

11. Simader C, Lung S, Weigert G, Kolodjaschna J, Fuchsjäger-Mayrl G, Schmetterer L,<br />

et al. Role of NO <strong>in</strong> the control of choroidal blood flow dur<strong>in</strong>g a decrease <strong>in</strong> ocular<br />

perfusion pressure. Invest Ophthalmol Vis Sci. 2009;50(1):372-7.<br />

12. Grunwald JE, Iannaccone A, DuPont J. Effect of isosorbide mononitrate on the human<br />

optic nerve and choroidal circulations. Br J Ophthalmol. 1999;83(2):162-7.<br />

13. Schmetterer L, Polak K. Role of nitric oxide <strong>in</strong> the control of ocular blood flow. Prog<br />

Ret<strong>in</strong> Eye Res. 2001;20(6):823-47.<br />

14. Behar-Cohen FF, Goureau O, D’Hermies F, Courtois Y. Decreased <strong>in</strong>traocular pressure<br />

<strong>in</strong>duced by nitric oxide donors is correlated to nitrite production <strong>in</strong> the rabbit eye.<br />

Invest Ophthalmol Vis Sci. 1996;37(8):1711-5.<br />

15. Carreiro S, Anderson S, Gukasyan HJ, Krauss A, Prasanna G. Correlation of <strong>in</strong> vitro and<br />

<strong>in</strong> vivo k<strong>in</strong>etics of nitric oxide donors <strong>in</strong> ocular tissues. J Ocul Pharmacol Ther. 2009;<br />

25(2):105-12.<br />

16. Chuman H, Chuman T, Nao-i N, Sawada A. The effect of L-arg<strong>in</strong><strong>in</strong>e on <strong>in</strong>traocular<br />

pressure <strong>in</strong> the human eye. Curr Eye Res. 2000;20(6):511-6.<br />

17. Kotikoski H, Alajuuma P, Moilanen E, Salmenperä P, Oksala O, Laippala P, et al. Comparison<br />

of nitric oxide donors <strong>in</strong> lower<strong>in</strong>g <strong>in</strong>traocular pressure <strong>in</strong> rabbits: role of cyclic<br />

GMP. J Ocul Pharmacol Ther. 2002;18(1):11-23. Erratum <strong>in</strong> J Ocul Pharmacol Ther.<br />

2002;18(4):389.<br />

18. Kaplan SS, Lancaster JR Jr, Basford RE, Simmons RL. Effect of nitric oxide on staphylococcal<br />

kill<strong>in</strong>g and <strong>in</strong>teractive effect with superoxide. Infect Immun. 1996;64(1):69-76.<br />

19. Stroeher UH, Kidd SP, Stafford SL, Jenn<strong>in</strong>gs MP, Paton JC, McEwan AG. A pneumococcal<br />

MerR-like regulator and S-nitrosoglutathione reductase are required for systemic<br />

virulence. J Infect Dis. 2007;196(12):1820-6.<br />

20. Cariello AJ, Bispo PJ, de Souza GF, Pignatari AC, de Oliveira MG, Hofl<strong>in</strong>g-Lima AL.<br />

Bactericidal effect of S-nitrosothiols aga<strong>in</strong>st cl<strong>in</strong>ical isolates from keratitis. Cl<strong>in</strong> Oph -<br />

thalmol. 2012;6:1907-14.<br />

21. Cariello AJ, de Souza GF, Foronda AS, Yu MC, Höfl<strong>in</strong>g-Lima AL, de Oliveira MG. In vitro<br />

amoebicidal activity of S-nitrosoglutathione and S-nitroso-N-acetylcyste<strong>in</strong>e aga<strong>in</strong>st<br />

trophozoites of Acanthamoeba castellanii. J Antimicrob Chemother. 2010;65(3):588-91.<br />

22. Bonfiglio V, Camillieri G, Avitabile T, Leggio GM, Drago F. Effects of the COOH-term<strong>in</strong>al<br />

tripeptide alpha-MSH(11-13) on corneal epithelial wound heal<strong>in</strong>g: role of nitric oxide.<br />

Exp Eye Res. 2006;83(6):1366-72.<br />

23. Tannous M, Hutnik CM, T<strong>in</strong>gey DP, Mutus B. S-nitrosoglutathione photolysis as a novel<br />

therapy for antifibrosis <strong>in</strong> filtration surgery. Invest Ophthalmol Vis Sci. 2000;41(3):<br />

749-55.<br />

24. Haq E, Rohrer B, Nath N, Crosson CE, S<strong>in</strong>gh I. S-nitrosoglutathione prevents <strong>in</strong>ter -<br />

photoreceptor ret<strong>in</strong>oid-b<strong>in</strong>d<strong>in</strong>g prote<strong>in</strong> (IRBP(161-180))-<strong>in</strong>duced experimental<br />

au toimmune uveitis. J Ocul Pharmacol Ther. 2007;23(3):221-31.<br />

25. de Souza GF, Yokoyama-Yasunaka JK, Seabra AB, Miguel DC, de Oliveira MG, Uliana<br />

SR. Leishmanicidal activity of primary S-nitrosothiols aga<strong>in</strong>st Leishmania major and<br />

Leishmania amazonensis: implications for the treatment of cutaneous leishmaniasis.<br />

Nitric Oxide. 2006;15(3):209-16.<br />

26. Chambers WA, Green S, Gupta KC, Hill RN, Huntley K, Hurley PM, et al. Scor<strong>in</strong>g for eye<br />

irritation tests. Food Chem Toxicol. 1993;31(2):111-5.<br />

27. Wilhelmus KR. The Draize eye test. Surv Ophthalmol. 2001;45(6):493-515.<br />

28. Liang H, Baudou<strong>in</strong> C, Faure MO, Lambert G, Brignole-Baudou<strong>in</strong> F. Comparison of the<br />

ocular tolerability of a latanoprost cationic emulsion <strong>versus</strong> conventional formulations<br />

of prostagland<strong>in</strong>s: an <strong>in</strong> vivo toxicity assay. Mol Vis. 2009;15:1690-9.<br />

29. Liang H, Baudou<strong>in</strong> C, Pauly A, Brignole-Baudou<strong>in</strong> F. Conjunctival and corneal<br />

reactions <strong>in</strong> rabbits follow<strong>in</strong>g short- and repeated exposure to preservative-free<br />

tafluprost, commercially available latanoprost and 0.02% benzalkonium chloride. Br<br />

J Ophthalmol. 2008;92(9):1275-82.<br />

30. McNamee P, Hibatallah J, Costabel-Farkas M, Goebel C, Araki D, Dufour E, et al. A tiered<br />

approach to the use of alternatives to animal test<strong>in</strong>g for the safety assessment of<br />

cosmetics: eye irritation. Regul Toxicol Pharmacol. 2009;54(2):197-209.<br />

31. V<strong>in</strong>ardell MP, Mitjans M. Alternative methods for eye and sk<strong>in</strong> irritation tests: an over -<br />

view. J Pharm Sci. 2008;97(1):46-59.<br />

32. Piehl M, Gilotti A, Donovan A, DeGeorge G, Cerven D. Novel cultured porc<strong>in</strong>e corneal<br />

irritancy assay with reversibility endpo<strong>in</strong>t. Toxicol In Vitro. 2010;24(1):231-9.<br />

33. Burste<strong>in</strong> NL, Anderson JA. Corneal penetration and ocular bioavailability of drugs. J<br />

Ocul Pharmacol. 1985;1(3):309-26.<br />

34. Waseem M, Rustam N, Qamar ul Islam. Intraocular pressure after phacoemulsification<br />

us<strong>in</strong>g hydroxypropyl methylcellulose and sodium hyaluronate as viscoelastics. J Ayub<br />

Med Coll Abbottabad. 2007;19(1):42-5.<br />

35. Lozano JS, Chay EY, Healey J, Sullenberger R, Klarlund JK. Activation of the epidermal<br />

growth factor receptor by hydrogels <strong>in</strong> artificial tears. Exp Eye Res. 2008;86(3):500-5.<br />

36. Srividya B, Cardoza RM, Am<strong>in</strong> PD. Susta<strong>in</strong>ed ophthalmic delivery of ofloxac<strong>in</strong> from a<br />

pH triggered <strong>in</strong> situ gell<strong>in</strong>g system. J Control Release. 2001;73(2-3):205-11.<br />

37. Liu Z, Li J, Nie S, Liu H, D<strong>in</strong>g P, Pan W. Study of an alg<strong>in</strong>ate/HPMC-based <strong>in</strong> situ gell<strong>in</strong>g<br />

ophthalmic delivery system for gatifloxac<strong>in</strong>. Int J Pharm. 2006;315(1-2):12-7.<br />

38. Al-Kassas RS, El-Khatib MM. Ophthalmic controlled release <strong>in</strong> situ gell<strong>in</strong>g systems for<br />

ciprofloxac<strong>in</strong> based on polymeric carriers. Drug Deliv. 2009;16(3):145-52.<br />

Arq Bras Oftalmol. 2013;76(1):38-41<br />

41


Relato de Caso | Case Report<br />

Bilateral acute depigmentation of the iris (BADI): first reported case <strong>in</strong> Brazil<br />

Despigmentação aguda bilateral da íris (BADI): primeiro relato de caso no Brasil<br />

Heloisa Andrade Maestr<strong>in</strong>i 1 , Angela Andrade Maestr<strong>in</strong>i 2 , Danuza de Oliveira Machado 3 , Daniel Vitor Vasconcelos Santos 4 , Homero Gusmão de Almeida 4<br />

ABSTRACT<br />

Bilateral acute depigmentation of the iris (BADI) is a recently described entity<br />

cha racterized by acute onset of pigment dispersion <strong>in</strong> the anterior chamber, depigmentation<br />

of the iris, and heavy pigment deposition <strong>in</strong> the anterior chamber<br />

angle. Involvement is always bilateral, simultaneous, and symmetrical. We report<br />

the case of a 61-year-old man who presented with bilateral ocular pa<strong>in</strong>, red eyes,<br />

and severe photophobia. Exam<strong>in</strong>ation revealed a dense Krukenberg sp<strong>in</strong>dle, heavy<br />

pigment dispersion <strong>in</strong> the anterior chamber, extensive transillum<strong>in</strong>ation iris<br />

defects, and a heavy pigment deposition <strong>in</strong> the trabecular meshwork bilaterally.<br />

Intraocular pressure <strong>in</strong>creased to 48 mmHg <strong>in</strong> both eyes. The patient received<br />

topical steroids, maximum hypotensive treatment and oral valacyclovir. Intraocular<br />

pressure gradually decreased throughout the second and third months, and<br />

medications were gradually tapered. The time to complete resolution of pigment<br />

dispersion was 18 weeks. Visual acuity and visual fields rema<strong>in</strong>ed normal, but the<br />

photophobia was permanent.<br />

Keywords: Iris diseases; Acute disease, Transillum<strong>in</strong>ation; Intraocular pressure;<br />

Go nioscopy; Pigment epithelium of eye; Case reports; Humans; Male; Middle age<br />

RESUMO<br />

Despigmentação aguda bilateral da íris (BADI) é uma nova doença caracterizada<br />

pela despigmentação aguda da íris, dispersão de pigmentos na câmara anterior e<br />

<strong>in</strong>tensa deposição de pigmentos no seio camerular. O acometimento é sempre bilateral,<br />

simultâneo e simétrico. Relatamos o caso de um paciente de 61 anos, com dor<br />

ocular bilateral aguda, hiperemia e <strong>in</strong>tensa fotofobia. Ao exame, apresentava denso<br />

fuso de Krukenberg, importante dispersão de pigmentos na câmara anterior, extensos<br />

defeitos à transilum<strong>in</strong>ação iriana e densa deposição de pigmentos no seio camerular<br />

em ambos os olhos. O paciente recebeu corticoide tópico, terapia hipotensora máxima<br />

e valacyclovir oral. A pressão <strong>in</strong>traocular chegou a 48 mmHg em ambos os olhos mas<br />

foi reduz<strong>in</strong>do gradativamente ao longo do segundo e terceiro meses, permit<strong>in</strong>do a<br />

suspensão gradativa da medicação. A resolução completa da dispersão pigmentar<br />

demorou 18 semanas. A acuidade e os campos visuais permaneceram normais, mas<br />

o paciente manteve a fotofobia.<br />

Descritores: Doenças da íris, Doença aguda; Transilum<strong>in</strong>ação; Pressão <strong>in</strong>traocular;<br />

Gonioscopia; Epitélio pigmentado ocular; Relatos de casos; Humanos; Mascul<strong>in</strong>o;<br />

Meia-idade<br />

INTRODUCTION<br />

Bilateral acute depigmentation of the iris (BADI) is a recently<br />

des cribed cl<strong>in</strong>ical entity (1) characterized by acute onset of pigment<br />

dispersion <strong>in</strong> the anterior chamber, depigmentation of the iris, and<br />

heavy pigment deposition <strong>in</strong> the anterior chamber angle. Involvement<br />

is always bilateral, simultaneous, and symmetrical. Clogg<strong>in</strong>g of<br />

the trabecular meshwork with pigment may cause an acute rise of<br />

<strong>in</strong>traocular pressure (IOP). Patients typically present with acute and<br />

usually severe photophobia, red eye, and ocular discomfort or pa<strong>in</strong>,<br />

which sometimes simulates acute bilateral iridocyclitis. Cases often<br />

occur after a flulike illness or upper respiratory tract <strong>in</strong>fection, some<br />

of them after the use of oral moxifloxac<strong>in</strong> (2-4) . Middle-aged women are<br />

most commonly affected.<br />

Two cl<strong>in</strong>ical sub-types have been described. In the first (1,5) , pig -<br />

ment discharge orig<strong>in</strong>ates <strong>in</strong> the iris stroma. Patients show a geographic<br />

or diffuse depigmentation of the iris and a change <strong>in</strong> iris texture<br />

and color without transillum<strong>in</strong>ation defects or pupil distortion. It<br />

often has a benign and short course. Increase <strong>in</strong> IOP is uncommon,<br />

and iris changes may be reversible. In the second and more severe<br />

sub-type, described as bilateral acute iris transillum<strong>in</strong>ation (6) , pigment<br />

discharge orig<strong>in</strong>ates <strong>in</strong> the iris pigment epithelium caus<strong>in</strong>g<br />

extensive and diffuse iris transillum<strong>in</strong>ation. Patients typically show<br />

an atonic, mydriatic, or distorted pupil and occasional posterior synechiae.<br />

An early and severe rise <strong>in</strong> IOP is common. Both sub-types<br />

have a self-limited course and a good prognosis. In the first sub-type,<br />

complete resolution of pigment discharge occurs after 8 to 16 weeks.<br />

In the second sub-type, complete resolution may take months or<br />

more than 1 year. The etiopathogenesis is unknown, but might be<br />

related to a viral <strong>in</strong>fection.<br />

Previous cases have been reported <strong>in</strong> Turkey (5,6) (51 cases), Netherlands<br />

(3,7) (4 cases), Belgium (3,4,6) (4 cases), Spa<strong>in</strong> (2) (one case) and France<br />

(8) (one case). We describe the first reported case <strong>in</strong> the Southern<br />

Hemisphere. Informed consent was obta<strong>in</strong>ed from the patient. This<br />

case report was approved by the Ethical Committee/Investigational<br />

Review Board of the Federal University of M<strong>in</strong>as Gerais.<br />

CASE REPORT<br />

A 61-year-old man presented <strong>in</strong> July 2011 with acute onset of<br />

bilateral and simultaneous ocular pa<strong>in</strong>, red eye, and severe photophobia.<br />

Visual acuity was 20/20 OU. Exam<strong>in</strong>ation revealed 2+<br />

pigmented cells <strong>in</strong> the anterior chamber and a slight deposition<br />

Submitted for publication: December 7, 2012<br />

Accepted for publication: January 31, 2013<br />

Study carried out at Clínica Oculare, Belo Horizonte (MG).<br />

1<br />

Physician, Glaucoma Service, Oculare Ophthalmology Center, Belo Horizonte, Brazil.<br />

2<br />

Physician, Ret<strong>in</strong>a and Cataract Services, Oculare Ophthtalmology Center, Belo Horizonte (MG), Brazil.<br />

3<br />

Physician, Uveitis Service, Department of Ophthalmology, Universidade Federal de M<strong>in</strong>as Gerais<br />

- UFMG - Belo Horizonte (MG), Brazil.<br />

4<br />

Physician, Department of Ophthalmology, Universidade Federal de M<strong>in</strong>as Gerais - UFMG - Belo<br />

Horizonte (MG), Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: H.A.Maestr<strong>in</strong>i, None; A.A.Maestr<strong>in</strong>i, None; D.O.Machado,<br />

None; D.V.V.Santos, None; H.G.de Almeida, None.<br />

Correspond<strong>in</strong>g author: Heloisa Andrade Maestr<strong>in</strong>i. Rua Maranhão, 65 - Belo Horizonte (MG) -<br />

30150-330 - Brazil - E-mail: heloisa.maestr<strong>in</strong>i@gmail.com<br />

42 Arq Bras Oftalmol. 2013;76(1):42-4


Maestr<strong>in</strong>i HA, et al.<br />

of pigment on the corneal endothelium. IOP was low (6/9 mmHg<br />

OD/OS). The <strong>in</strong>itial diagnosis was bilateral anterior uveitis, and the<br />

patient was treated us<strong>in</strong>g a topical steroid (1% prednisolone every<br />

3 hours) with marked relief of symptoms. However, on the fourth<br />

day, while play<strong>in</strong>g “foot volley”, his vision suddenly blurred. The next<br />

day, slit-lamp evaluation revealed a dense Krukenberg sp<strong>in</strong>dle bilaterally.<br />

The aqueous humor was turbid with heavy pigment dispersion<br />

<strong>in</strong> the anterior chamber. Pigment granules were deposited on<br />

the anterior surface of the iris and posterior lens surface (Figure 1).<br />

Transillum<strong>in</strong>ation showed extensive bilateral iris defects (Figure 2).<br />

IOP was 36/40 mmHg OD/OS. Gonioscopy revealed a wide open angle,<br />

a dark trabecular meshwork 360 degrees, and a heavy pigment<br />

deposition, particularly <strong>in</strong> the <strong>in</strong>ferior sector (Figure 3). The vitreous<br />

was clear, the fundus was normal, and the optic nerve head cupdisc<br />

ratio was 0.1 bilaterally. Over the follow<strong>in</strong>g days, IOP <strong>in</strong>creased<br />

to 48 mmHg <strong>in</strong> both eyes. The pupil be came progressively irregular<br />

with small posterior synechiae (Figure 4) and iris transillum<strong>in</strong>ation<br />

gradually <strong>in</strong>creased. Corneal endothelial cell density was normal<br />

(2,877 cells/mm 2 OD and 2,984 cells/mm 2 OS).<br />

Previous cl<strong>in</strong>ical and ocular histories were unremarkable, with<br />

the exception of a previous laser photocoagulation <strong>in</strong> the right eye<br />

to treat a peripheral ret<strong>in</strong>al tear 1 year prior to BADI onset. IOP was<br />

normal at that time (10 mmHg bilaterally).<br />

The patient underwent a complete laboratory evaluation, <strong>in</strong>clud<strong>in</strong>g<br />

complete blood count, erythrocyte sedimentation rate, liver en -<br />

zymes, chest X-ray, anti-nuclear factor, rheumatoid factor, C-reactive<br />

prote<strong>in</strong>, tubercul<strong>in</strong> sk<strong>in</strong> test, blood and ur<strong>in</strong>ary calcium, angiotens<strong>in</strong><br />

convert<strong>in</strong>g enzyme, and lysozyme. The results were unremarkable.<br />

Serological tests for toxoplasmosis, syphilis, herpes simplex virus (HSV)<br />

I and II, varicella-zoster virus, and cytomegalovirus (CMV) were performed.<br />

All IgM antibodies were negative. IgG antibodies were positive<br />

aga<strong>in</strong>st toxoplasmosis, HSV I and II, varicella-zoster virus and CMV.<br />

Prednisolone eye drops were adm<strong>in</strong>istered every 3 hours and the<br />

maximum tolerated hypotensive treatment was <strong>in</strong>stituted (timolol,<br />

brimonid<strong>in</strong>e, and oral acetazolamide 750 mg/day), which lowered<br />

IOP to 25-30 mmHg bilaterally. Mydriasis always caused an acute rise<br />

<strong>in</strong> IOP up to 42 mmHg because of an <strong>in</strong>crease <strong>in</strong> pigment discharge.<br />

Abrupt discont<strong>in</strong>uation of prednisolone resulted <strong>in</strong> immediate relapse.<br />

On day 28, empirical treatment with oral valacyclovir 3 g/day was<br />

<strong>in</strong>troduced result<strong>in</strong>g <strong>in</strong> a significant reduction <strong>in</strong> pigment dispersion<br />

<strong>in</strong> a few days. After 3 weeks, the dose was reduced to 1,500 mg/day<br />

for 3 more weeks, and then to 500 mg/day for 8 weeks. Prednisolone<br />

was gradually tapered and completely discont<strong>in</strong>ued after 18 weeks.<br />

IOP gradually decreased throughout the second and third months,<br />

and hypotensive medications were gradually tapered until discont<strong>in</strong>uation<br />

after 24 weeks. The time to complete resolution of pigment<br />

dispersion was 18 weeks. No cupp<strong>in</strong>g of the optic discs was observed;<br />

however, <strong>in</strong> the seventh week, a small disc hemorrhage appeared <strong>in</strong><br />

the left eye. Visual acuity and visual fields rema<strong>in</strong>ed normal; however,<br />

the photophobia was permanent. Six months after complete<br />

resolution, we performed a water dr<strong>in</strong>k<strong>in</strong>g test and IOP rema<strong>in</strong>ed at<br />

normal levels (IOP rose from 13 to 19 mmHg bilaterally). After 1 year,<br />

the patient developed bilateral cataracts, which were removed uneventfully.<br />

IOP was high on the first postoperative day (34/26 mmHg<br />

OD/OS), but returned to12 mmHg after 1 week.<br />

Figure 1. Heavy pigment deposit on the posterior lens surface <strong>in</strong> the left eye.<br />

Figure 3. Gonioscopic view of the <strong>in</strong>ferior sector of the anterior chamber angle (right<br />

eye). Heavy pigment deposit <strong>in</strong> the trabecular meshwork. The aspect is identical <strong>in</strong><br />

the left eye.<br />

A<br />

Figure 2. Diffuse and severe iris defects seen on retroillum<strong>in</strong>ation <strong>in</strong> the right (A) and<br />

left (B) eyes.<br />

B<br />

A<br />

Figure 4. Iris aspect 1 month after presentation <strong>in</strong> the right (A) and left (B) eyes. Areas<br />

of discrete atrophy are apparent <strong>in</strong> the midstroma, particularly <strong>in</strong> the <strong>in</strong>ferior half. Small<br />

pigmented granules deposited on the anterior surface of the iris. Pupils are distorted<br />

and unresponsive to light.<br />

B<br />

Arq Bras Oftalmol. 2013;76(1):42-4<br />

43


Bilateral acute depigmentation of the iris (BADI): first reported case <strong>in</strong> Brazil<br />

DISCUSSION<br />

BADI is a recently described and rare entity. Our patient presented<br />

with the more severe BADI sub-type show<strong>in</strong>g a severe rise <strong>in</strong> IOP, extensive<br />

areas of iris transillum<strong>in</strong>ation, distorted pupils, and posterior<br />

synechiae, but no change <strong>in</strong> iris color.<br />

Differential diagnosis <strong>in</strong>cludes herpetic iridocyclitis (9) (tipically<br />

uni lateral), Fuchs’ uveitis (bilateral <strong>in</strong> only 5-10% of cases), pigment<br />

dis persion syndrome, and pseudoexfoliation syndrome (do not have<br />

an acute onset).<br />

Although the cause is not known, BADI shares some features of<br />

viral herpetic iridocyclitis. The marked improvement <strong>in</strong> our patient<br />

follow<strong>in</strong>g valacyclovir treatment suggests a possible viral etiology.<br />

REFERENCES<br />

1. Tugal-Tutkun I, Urgancioglu M. Bilateral acute depigmentation of the iris. Graefes Arch<br />

Cl<strong>in</strong> Exp Ophthalmol [Internet]. 2006[cited 2010 Jun 23];244(6):742-6. Available from:<br />

http://download.spr<strong>in</strong>ger.com/static/pdf/167/art%253A10.1007%252Fs00417-005-<br />

0137-x.pdf?auth66=1365100095_059b651a5046293dc04e84295d29658b&ext=.pdf<br />

2. Br<strong>in</strong>gas Calvo R, Iglesias Cortiñas D. [Acute and bilateral uveitis secondary to moxifloxac<strong>in</strong>].<br />

Arch Soc Esp Oftalmol [Internet]. 2004 [cited 2011 Mar 19];79(7):357-9.<br />

Spanish. Available from: http://www.oftalmo.com/seo/archivos/articulo.php?idSolici<br />

tud=1358&numR=7&mesR=7&anioR=2004&idR=84<br />

3. Wefers Bett<strong>in</strong>k-Remeijer M, Brouwers K, van Langenhove L, De Waard PW, Missotten<br />

TO, Mart<strong>in</strong>ez Ciriano JP, et al. Uveitis-like syndrome and iris transillum<strong>in</strong>ation after the<br />

use of oral moxifloxac<strong>in</strong>. Eye (Lond) [Internet]. 2009 [cited 2011 Jul 21];23(12):2260-2.<br />

Comment <strong>in</strong>: Eye (Lond). 2010;24(8):1419; author reply 1419-20. Available from: http://<br />

www.nature.com/eye/journal/v23/n12/full/eye2009234a.html<br />

4. Willerma<strong>in</strong> F, Deflorenne C, Bouffioux C, Janssens X, Koch P, Caspers L. Uveitis-like<br />

syndrome and iris transillum<strong>in</strong>ation after the use of oral moxifloxac<strong>in</strong>. Eye (Lond)<br />

[Internet]. 2010 [cited 2011 Mar 19];24(8):1419; author reply -20. Comment on: Eye<br />

(Lond). 2009;23(12):2260-2. Available from: http://www.nature.com/eye/journal/v24/<br />

n8/full/eye201019a.html<br />

5. Tugal-Tutkun I, Araz B, Taskapili M, Akova YA, Yalniz-Akkaya Z, Berker N, et al.<br />

Bilateral acute depigmentation of the iris: report of 26 new cases and four-year<br />

follow-up of two patients. Ophthalmology [Internet]. 2009 [cited 2012 Oct 12];116(8):<br />

1552-7, 7 e1. Available from: http://www.sciencedirect.com/science/article/pii/S016<br />

1642009001791#<br />

6. Tugal-Tutkun I, Onal S, Garip A, Taskapili M, Kazokoglu H, Kadayifcilar S, et al. Bilateral<br />

acute iris transillum<strong>in</strong>ation. Arch Ophthalmol [Internet]. 2011[cited 2012<br />

Jan 4];129(10):1312-9. Available from: http://archopht.jamanetwork.com/article.<br />

aspx?articleid=1106464<br />

7. Goktas A, Goktas S. Bilateral acute depigmentation of the iris first misdiagnosed as<br />

acute iridocyclitis. Int Ophthalmol [Internet]. 2011[cited 2012 Nov 21];31(4):337-9.<br />

Available from: http://download.spr<strong>in</strong>ger.com/static/pdf/837/art%253A10.1007%<br />

252Fs10792-011-9452-x.pdf?auth66=1365100875_cc2c3b75db0d3efc4911fa04f5cf1<br />

332&ext=.pdf<br />

8. Portmann A, Gueudry J, Siahmed K, Mura<strong>in</strong>e M. [Bilateral acute depigmentation of<br />

the iris syndrome]. J Fr Ophtalmol. 2011;34(5):309-12. French.<br />

9. Dastrup BT, Cantor L, Moorthy RS, Vasconcelos-Santos D, Rao N. An unusual manifestation<br />

of herpes simplex virus-associated acute iris depigmentation and pigmentary<br />

glaucoma. Arch Ophthalmol [Internet]. 2011[cited 2012 Dec 21];129(2):253-4. Available<br />

from: http://archopht.jamanetwork.com/article.aspx?articleid=426961<br />

VII Congresso Internacional da<br />

Asociación Lat<strong>in</strong>oamericana de Cirujanos de<br />

Catarata, Segmento Anterior y Refractiva -<br />

ALAccsA-R<br />

21 a 23 de novembro de 2013<br />

Cidade do México - México<br />

Informações:<br />

Site: www.alaccsa-rmexico2013.com<br />

44 Arq Bras Oftalmol. 2013;76(1):42-4


Relato de Caso | Case Report<br />

Idiopathic dilated episcleral vessels (Radius-Maumenee syndrome): case report<br />

Dilatação idiopática dos vasos episclerais (síndrome de Radius-Maumenee): relato de caso<br />

Ricardo Alexandre Stock 1 , Natalie Lucas Fernandes 2 , Nathan Lopes Pastro 2 , Rafaela Sant<strong>in</strong>i de Oliveira 2 , Elcio Luiz Bonamigo 3<br />

ABSTRACT<br />

Radius-Maumenee syndrome comprises idiopathic dilated episcleral vessels that<br />

are usually associated with glaucoma. The case described here<strong>in</strong> is of a male<br />

patient, 69 years old, with chronic dilation of the episcleral vessels and glaucoma<br />

<strong>in</strong> his left eye, with no history of systemic disease. Visual acuity and fundoscopy<br />

were normal <strong>in</strong> both eyes. Tonometry measured 14 mmHg <strong>in</strong> the right eye and<br />

25 mmHg <strong>in</strong> the left. Computed tomography angiography (CTA) was negative for<br />

carotid-cavernous fistula. The <strong>in</strong>traocular pressure of the left eye decreased to<br />

20 mmHg with cl<strong>in</strong>ical treatment without regression of episcleral venous dilation.<br />

Trabeculectomy normalized the <strong>in</strong>traocular pressure and reduced the vessels.<br />

There was choroidal effusion on day 16 of the postoperative period, which resolved<br />

with corticosteroids. Although choroidal effusion can occur, the efficacy of<br />

trabeculectomy <strong>in</strong> controll<strong>in</strong>g glaucoma and the reduction of episcleral vessels<br />

are clearly demonstrated.<br />

Keywords: Eye abnormalities/diagnosis; Glaucoma open-angle/surgery; Eye health;<br />

Sclera/blood supply; Venous pressure; Ve<strong>in</strong>s/pathology; Syndrome; Varicose ve<strong>in</strong>s;<br />

Angiography; Ocular physiological processes; Humans; Male; Aged; Case report<br />

RESUMO<br />

A síndrome de Radius-Maumenee consiste na dilatação idiopática dos vasos episclerais<br />

geralmente associada ao glaucoma. Descreve-se o caso de paciente mascul<strong>in</strong>o,<br />

69 anos, portador de dilatação crônica dos vasos episclerais e glaucoma do<br />

olho esquerdo, sem histórico de doença sistêmica. A acuidade visual e fundoscopia<br />

apresentaram-se normais em ambos os olhos. A tonometria mediu 14 mmHg no olho<br />

direito e 25 mmHg no esquerdo. A angiotomografia foi negativa para fístula carotí ­<br />

deo-cavernosa. A pressão <strong>in</strong>traocular do olho esquerdo dim<strong>in</strong>uiu para 20 mmHg com<br />

tratamento clínico, sem regressão da dilatação venosa episcleral. A trabeculectomia<br />

normalizou a pressão <strong>in</strong>traocular e reduziu os vasos. Houve efusão coroidiana no 16 o<br />

dia de pós-operatório que regrediu com corticoterapia. Embora possa ocorrer efusão<br />

coroidiana, destaca-se a eficácia da trabeculectomia no controle do glaucoma e na<br />

redução dos vasos episclerais.<br />

Descritores: Anormalidades do olho/diagnóstico; Glaucoma de ângulo aberto/<br />

ci rurgia; Saúde ocular; Esclera/irrigação sanguínea; Pressão venosa; Síndrome;<br />

Va rizes; Angiografia; Processos fisiológicos oculares; Humanos; Mascul<strong>in</strong>o; Idoso;<br />

Relato de caso<br />

INTRODUCTION<br />

Radius-Maumenee syndrome was identified for the first time <strong>in</strong><br />

1978 by the two ophthalmologists who gave their names to the<br />

di sease (1) . The characteristic cl<strong>in</strong>ical picture of this syndrome is idiopathic<br />

dilated episcleral vessels associated with <strong>in</strong>creased <strong>in</strong>traocular<br />

pressure.<br />

The authors (1) presented a report of four cases of idiopathic dilated<br />

episcleral vessels <strong>in</strong> the absence of carotid-cavernous fistulas,<br />

obstructive orbital lesions or hemangiomatosis, which at the time<br />

were the diseases that expla<strong>in</strong>ed such occurrences. Three of the four<br />

patients presented with <strong>in</strong>creased unilateral <strong>in</strong>traocular pressure,<br />

correspond<strong>in</strong>g to unilateral open-angle glaucoma. In these patients,<br />

<strong>in</strong>traocular pressure was controlled by surgery. The authors hypothesized<br />

that a congenital vascular anomaly was the cause of this ocular<br />

manifestation. Subsequently, other cases have been published, with<br />

several theories seek<strong>in</strong>g to expla<strong>in</strong> the occurrence of the syndrome.<br />

This manuscript describes the case of a patient with Radius-Mau -<br />

menee syndrome whose glaucoma and episcleral dilation were con -<br />

trolled by trabeculectomy.<br />

CASE REPORT<br />

A male patient, aged 69 years old, was admitted to the ophthalmology<br />

service with chronic hyperemia of the left eye, which was<br />

unresponsive to medical treatment, without other ocular symptoms<br />

(Figure 1). He had normal cranial tomography. In his first assessment<br />

<strong>in</strong> 2008, the patient presented with 20/20 visual acuity bilaterally and<br />

with normal fundoscopy, without dilation or <strong>in</strong>creased tortuosity of<br />

the ret<strong>in</strong>al vessels, as demonstrated by ret<strong>in</strong>ography (Figure 2). The<br />

<strong>in</strong>traocular pressure measurement was 14 mmHg <strong>in</strong> the right eye<br />

and 25 mmHg <strong>in</strong> the left eye, which had dilated episcleral vessels.<br />

Bio microscopy of the left eye showed <strong>in</strong>creased tortuosity and venous<br />

engorgement of the conjunctiva and episclera. The patient was<br />

treated with antiglaucoma eye drops, which reduced the <strong>in</strong>traocular<br />

pressure to 20 mmHg. The episcleral vessel dilation persisted, and CT<br />

angiography, obta<strong>in</strong>ed to <strong>in</strong>vestigate the possibility of arteriovenous<br />

fistula, was negative (Figure 3).<br />

Due to the presence of glaucoma, tortuosity, episcleral venous<br />

engorgement and negative tests for other possible diseases, the<br />

cl<strong>in</strong>ical diagnosis of idiopathic dilated episcleral vessels (Radius-Mau -<br />

Submitted for publication: February 1, 2013<br />

Accepted for publication: May 8, 2013<br />

Work conducted at the University of West Santa Catar<strong>in</strong>a, Universidade do Oeste de Santa Catar<strong>in</strong>a -<br />

UNOESC - Joaçaba campus (SC), Brazil<br />

1<br />

Professor of Ophthalmology at Universidade do Oeste de Santa Catar<strong>in</strong>a - UNOESC - Joaçaba<br />

campus (SC), Brazil.<br />

2<br />

Academic, Course of Medic<strong>in</strong>e, Universidade do Oeste de Santa Catar<strong>in</strong>a - UNOESC - Joaçaba<br />

campus (SC), Brazil.<br />

3<br />

Ophthalmologist and professor at Universidade do Oeste de Santa Catar<strong>in</strong>a - UNOESC - Joaçaba<br />

campus (SC), Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: R.A.Stock, None; N.L.Fernandes, None; N.L.Pastro,<br />

None; R.S.Oliveira, None; E.L.Bonamigo, None.<br />

Correspondence address: Elcio Luiz Bonamigo. Rua Francisco L<strong>in</strong>dner, 310 - Joaçaba (SC) -<br />

89600-000 - Brazil - E-mail: elcio.bonamigo@unoesc.edu.br<br />

Study approved by Research Ethics Committee/Investigational Review Board of the University of<br />

the West of Santa Catar<strong>in</strong>a, under the number 40191.<br />

Arq Bras Oftalmol. 2013;76(1):45-7<br />

45


Idiopathic dilated episcleral vessels (Radius-Maumenee syndrome): case report<br />

menee syndrome) was confirmed <strong>in</strong> the left eye, and as a treatment<br />

option, a trabeculectomy was performed. On the first day of the pos -<br />

toperative period, the <strong>in</strong>traocular pressure decreased to 9 mmHg.<br />

Episcleral vessels showed gradual regression <strong>in</strong> the days that followed.<br />

However, on the 16 th day after surgery, choroidal detachment<br />

occurred, which was completely reversed us<strong>in</strong>g systemic and topi cal<br />

steroids. After stabilization, the <strong>in</strong>traocular pressure rema<strong>in</strong>ed at<br />

12 mmHg and the visual acuity at 20/20, with complete regression<br />

A<br />

Figure 1. Cl<strong>in</strong>ical appearance of the eyes <strong>in</strong> the preoperative show<strong>in</strong>g episcleral dilated<br />

ve<strong>in</strong>s of the left eye (B).<br />

Figure 2. Ret<strong>in</strong>ography of the left eye show<strong>in</strong>g uremarkable fundoscopy of the left eye.<br />

B<br />

of the signs and symptoms caused by the dilated episcleral vessels<br />

(Figure 4).<br />

DISCUSSION<br />

Increased <strong>in</strong>traocular pressure, which is often associated with<br />

ocular <strong><strong>in</strong>jection</strong>s and dilated episcleral vessels, can occur for several<br />

reasons, arteriovenous fistulas be<strong>in</strong>g the most common. However,<br />

the discovery of Radius-Maumenee syndrome, an unusual cl<strong>in</strong>ical<br />

picture that presents identical symptoms, means that its <strong>in</strong>clusion<br />

among differential diagnoses should always be considered.<br />

The diagnosis of Radius-Maumenee syndrome is based on cl<strong>in</strong>ical<br />

f<strong>in</strong>d<strong>in</strong>gs characteristic of episcleral vessel dilation and <strong>in</strong>creased<br />

<strong>in</strong>traocular pressure, correspond<strong>in</strong>g to a picture of open-angle glaucoma.<br />

In this case, arteriography was used to detect the presence of<br />

arteriovenous fistulas, which are the most common cause of dilated<br />

episcleral vessels (2) , but the result was normal. Other tests, <strong>in</strong>clud<strong>in</strong>g<br />

neuro-imag<strong>in</strong>g exam<strong>in</strong>ation, orbital venography and angiography,<br />

were also negative. Although the pathogenesis of this condition rema<strong>in</strong>s<br />

obscure, it is believed that the presence of abnormal pressure<br />

<strong>in</strong> blood dra<strong>in</strong>age could expla<strong>in</strong> the emergence of the condition (3) .<br />

One hypothesis to expla<strong>in</strong> the difficulty of venous return <strong>in</strong>volves the<br />

hyal<strong>in</strong>ization of Schlemm’s canal, which causes distal obstruction of<br />

the anterior chamber (4) .<br />

Radius-Maumenee syndrome thus occurs due to a poor venous<br />

dra<strong>in</strong>age of ocular episcleral vessels. The difficulty <strong>in</strong> establish<strong>in</strong>g an<br />

early diagnosis can cause negative effects on visual function <strong>in</strong> the<br />

affected eye due to an <strong>in</strong>crease <strong>in</strong> secondary <strong>in</strong>traocular pressure and<br />

its consequent damage to the optic nerve (5) .<br />

Intraocular pressure is dependent on the rate of aqueous humor<br />

production and dra<strong>in</strong>age of the episcleral ve<strong>in</strong>s. Increased <strong>in</strong>traocular<br />

pressure and visual field loss due to optical impairment can be the<br />

result of the <strong>in</strong>creased pressure of these vessels (6) . Possible causes<br />

<strong>in</strong>clude venous obstructions (venous s<strong>in</strong>us thrombosis and superior<br />

vena cava syndrome), arteriovenous shunts or fistulas, Sturge-Weber<br />

syndrome, scleritis, orbital diseases related to thyroidopathy and<br />

or bital tumors. Radius-Maumenee syndrome presents as an uncommon<br />

entity with a characteristic cl<strong>in</strong>ical presentation, and therefore,<br />

it should be <strong>in</strong>cluded among diagnostic possibilities. The f<strong>in</strong>d<strong>in</strong>g of<br />

episcleral vessel dilation <strong>in</strong> non-<strong>in</strong>flamed eyes constitutes a warn<strong>in</strong>g<br />

to the ophthalmologist of possible glaucoma (4) .<br />

Glaucoma surgeries, such as trabeculectomy, sclerectomy and<br />

s<strong>in</strong>usotomy, performed at the appropriate time, can provide good<br />

treatment results, although they do not always result <strong>in</strong> the reduction<br />

of episcleral vessels (7) . Dur<strong>in</strong>g the postoperative period, as <strong>in</strong> this<br />

case, there can be more frequent choroidal effusion than normal (8) .<br />

S<strong>in</strong>usotomy is a surgical procedure effective <strong>in</strong> treat<strong>in</strong>g Radius-Maumenee<br />

syndrome, and its early realization prevents damage to the<br />

optic nerve (9,10) .<br />

This report highlights the need to <strong>in</strong>vestigate the diagnosis of<br />

Radius-Maumenee syndrome <strong>in</strong> patients with glaucoma and epis-<br />

A<br />

B<br />

Figure 3. CT Angiography with<strong>in</strong> the normality.<br />

Figure 4. Cl<strong>in</strong>ical appearance of the preoperative (A) and eight months after surgery (B)<br />

show<strong>in</strong>g the reduction of the episcleral ve<strong>in</strong>s.<br />

46 Arq Bras Oftalmol. 2013;76(1):45-7


Stock RA, et al.<br />

cleral vessel dilation, as well as the benefits of glaucoma surgery <strong>in</strong><br />

the resolution of cl<strong>in</strong>ical symptoms, although choroidal effusion can<br />

occur <strong>in</strong> the postoperative period.<br />

REFERENCES<br />

1. Radius RL, Maumenee E. Dilated episcleral vessels and open-angle glaucoma. Am J<br />

Ophthalmol. 1978;86(1):31-5.<br />

2. Foroozan R, Buono LM, Sav<strong>in</strong>o PJ, Sergott RC. Idiopathic dilated episcleral ve<strong>in</strong>s and<br />

<strong>in</strong>creased <strong>in</strong>traocular pressure. Br J Ophthalmol. 2003;87(5):652-3.<br />

3. Grieshaber MC, Dubler B, Knodel C, Killer HE, Flammer J, Orgül S. Retrobulbar blood<br />

flow <strong>in</strong> idiopathic dilated episcleral ve<strong>in</strong>s and glaucoma. Kl<strong>in</strong> Monbl Augenheilkd<br />

[Internet] 2007[cited 2012 Jan 2];224(4):320-3. Available from: https://www.thiemecon<br />

nect.com/ejournals/html/10.1055/s-2007-962946<br />

4. Lanzl IM, Welge-Luessen U, Spaeth GL. Unilateral open-angle glaucoma secondary<br />

to idiopathic episcleral ve<strong>in</strong>s dilated. Am J Ophthalmol. 1996;121(5):587-9.<br />

5. Acaroglu G, Eranil S, Ozdamar Y, Ural F, Teke Y. Idiopathic episcleral venous engorgement.<br />

Cl<strong>in</strong> Exp Optom. 2009;92(6):507-10.<br />

6. Jyothi PT, B<strong>in</strong>dus S, Shimna I. Radius-Maumenee Syndrome - a case report. Kerala J<br />

Ophthalmol [Internet]. 2011[cited 2012 Nov 21];23(2):152-4. Available from: http://<br />

ksos.<strong>in</strong>/ksosjournal/journalsub/Journal_Article_24_415.pdf<br />

7. Otulana TO, Onabolu OO, Fafiolu VO. Unilateral idiopathic dilated episcleral ve<strong>in</strong> with<br />

secondary open angle glaucoma (Radius-Maumenee Syndrome) <strong>in</strong> an African - a<br />

case report and literature review. Niger J Ophthalmol. 2008;16(1):20-2.<br />

8. Parikh R, Desai S, Kothari K. Dilated episcleral ve<strong>in</strong>s with secondary open angle glau -<br />

coma. Indian J Ophthalmol. 2011;59(2):153-5.<br />

9. Groh MJ, Kuchle M. [Idiopathic episcleral venous stasis with secondary open-angle<br />

glaucoma (Radius-Maumenee-Syndrom). Kl<strong>in</strong> Monatsbl Augenheilkd. 1997;211(2):<br />

131-2. German.<br />

10. Lämmer R. [Secundary open angle glaucoma with idiopathic episcleral venous pressure<br />

(Radius-Maumenee syndrome). S<strong>in</strong>us-otomy as operative preocedure of choice].<br />

Ophthalmologe. 2007;104(6):515-6. Comment on: Ophthalmologe. 2007;104(6):<br />

513-4. German.<br />

16 o Congresso de Oftalmologia USP e<br />

15 o Congresso de Auxiliar de Oftalmologia<br />

29 e 30 de novembro de 2013<br />

Centro de Convenções Rebouças<br />

São Paulo (SP)<br />

Informações:<br />

Tels.: (11) 5082-3030 / 5084-9174<br />

Site: www.oftalmologiausp.com.br<br />

Arq Bras Oftalmol. 2013;76(1):45-7<br />

47


Relato de Caso | Case Report<br />

Topiramate-associated acute, bilateral, angle-closure glaucoma: case report<br />

Glaucoma agudo de ângulo fechado, bilateral, desencadeado pelo topiramato: relato de caso<br />

Lucas Barasnevicius Quagliato 1 , Kleyton Barella 1 , José Maria Abreu Neto 1 , Elizabeth Maria Aparecida Barasnevicius Quagliato 2<br />

ABSTRACT<br />

This paper describes a topiramate <strong>in</strong>duced acute bilateral angle-closure glaucoma.<br />

This rare adverse effect is an idiosyncratic reaction characterized by uveal effusion<br />

and lens forward displacement, lead<strong>in</strong>g to <strong>in</strong>creased <strong>in</strong>traocular pressure and<br />

vision loss. We describe a 55 year-old white woman with migra<strong>in</strong>e, spasmodic<br />

torticollis and essential tremor, who developed bilateral acute angle-closure<br />

glaucoma, one week after start<strong>in</strong>g topiramate 25 mg/day. She was seen at the<br />

Ophthalmology Emergency Department of the Fundação João Penido Burnier<br />

(Camp<strong>in</strong>as, SP, Brazil) with a 4 hours history of blurry vision, ocular pa<strong>in</strong> and bright<br />

flashes vision. Slit lamp exam<strong>in</strong>ation revealed moderate conjunctival <strong><strong>in</strong>jection</strong><br />

and corneal edema, and shallow anterior chambers. Intraocular pressure was<br />

48 mmHg <strong>in</strong> both eyes. Fundoscopic exam<strong>in</strong>ation f<strong>in</strong>d<strong>in</strong>gs were normal. She<br />

was treated with timolol, brimonid<strong>in</strong>e, dorzolamide, pilocarp<strong>in</strong>e, prednisone<br />

acetate eye drops and acetazolamide. One hour after those measures, as the<br />

<strong>in</strong>traocular pressure was 30 mmHg, she received a manitol <strong>in</strong>travenous <strong><strong>in</strong>jection</strong><br />

and the <strong>in</strong>traocular pressure normalized. After 24 hours an iridotomy with Yag<br />

laser was performed. Topiramate was discont<strong>in</strong>ued and she was totally recovered<br />

after one week.<br />

Keywords: Glaucoma, angle closure/diagnosis; Glaucoma, angle closure/chemically<br />

<strong>in</strong>duced; Anticonvulsants/adverse effects; Intraocular pressure; Uveal diseases/<br />

chemically <strong>in</strong>duced; Case report<br />

RESUMO<br />

Relato de um caso de glaucoma bilateral de ângulo fechado <strong>in</strong>duzido pelo topira ­<br />

mato. Este raro efeito colateral é uma idios<strong>in</strong>crasia causada por efusão uveal e<br />

deslocamento do cristal<strong>in</strong>o para frente, causando aumento da pressão <strong>in</strong>traocular<br />

e perda visual. Descrevemos o caso de uma paciente de 55 anos com migrânea,<br />

torcicolo espasmódico e tremor essencial, que desenvolveu glaucoma bilateral<br />

de ângulo fechado uma semana após <strong>in</strong>iciar o uso de topiramato, 25 mg/dia. A<br />

paciente foi atendida no setor de Emergências Oftalmológicas da Fundação Penido<br />

Burnier (Camp<strong>in</strong>as, SP, Brasil), com história de 4 horas de embaçamento visual, dor<br />

ocular e visão de flashes brilhantes. O exame com lâmpada de fenda revelou <strong>in</strong>jeção<br />

conjuntival moderada, edema corneano e câmara anterior rasa em ambos os<br />

olhos. A pressão <strong>in</strong>traocular era de 48 mmHg bilateralmente e a fundoscopia era<br />

normal. Foi tratada com colírios de timolol, brimonid<strong>in</strong>a, dorzolamida, pilocarp<strong>in</strong>a<br />

e acetato de prednisona e acetazolamida via oral. Uma hora após essas medidas, a<br />

pressão <strong>in</strong>traocular era 30 mmHg, e a paciente recebeu uma <strong>in</strong>jeção <strong>in</strong>travenosa de<br />

manitol, ocorrendo normalização da pressão <strong>in</strong>traocular após essa medida. Após<br />

24 horas foi realizada iridectomia com Yag laser. O topiramato foi <strong>in</strong>terrompido e<br />

ela se recuperou totalmente após uma semana.<br />

Descritores: Glaucoma, ângulo-fechado/diagnóstico; Glaucoma, ângulo-fechado/<br />

quimicamente <strong>in</strong>duzido; Anticonvulsivantes/efeitos adversos; Pressão <strong>in</strong>traocular; Doen ­<br />

ças uveais/<strong>in</strong>duzidas quimicamente; Relato de caso<br />

INTRODUTION<br />

Many systemic action drugs can cause acute glaucoma, but si -<br />

mul taneous bilateral acute angle-closure glaucoma (BAACG) is rare.<br />

Topiramate is a sulpha-derivative monosaccharide that is used for<br />

treat<strong>in</strong>g epilepsy (1996) and migra<strong>in</strong>e (2004), but other <strong>in</strong>dications<br />

<strong>in</strong>cludes <strong>in</strong>fantile spasms, psychiatric disorders, neuropathic pa<strong>in</strong>,<br />

weight reduction, tobacco dependence, essential tremor, and<br />

post-herpetic neuralgia (1) . Topiramate blocks voltage-gated sodium<br />

channels, hyperpolarizes potassium currents, enhances postsynaptic<br />

gamma-am<strong>in</strong>obutyric acid receptor activity, suppresses the α-ami -<br />

no-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ka<strong>in</strong>ate<br />

re ceptor, reduces glutamate excitatory activity and <strong>in</strong>hibits some<br />

carbonic anhydrase isoenzimes (2) . This drug is rapidly absorbed<br />

after oral <strong>in</strong>take and is excreted <strong>in</strong> ur<strong>in</strong>e with a half-life of almost<br />

24 hours (1) . Adverse ophthalmologic events topiramate-related are<br />

rare, and they generally occur dur<strong>in</strong>g the first treatment month (3) .<br />

Besides BAACG, other ocular side effects related to topiramate are<br />

massive choroidal effusion, ocular <strong>in</strong>flammatory reactions, unilateral<br />

hemianopsia, neuro-ophthalmologic complications and irreversible<br />

maculopathy (1,2) . The first description of BAACG related to topiramate<br />

was published <strong>in</strong> 2001 (4) and a systematic 2012 review described 75<br />

relevant studies concern<strong>in</strong>g topiramate effects on vision. Sixty-five<br />

small observational studies described the ophthalmologic side<br />

effects <strong>in</strong> 84 patients (1) .<br />

The putative mechanism of acute glaucoma and myopia are related<br />

to uveal effusion, that leads to zonula relaxation, caus<strong>in</strong>g anterior<br />

displacement of the lens-iris diaphragm. As consequence, occurs<br />

miopization and reduction of anterior camera deepness. Choroidal<br />

detachment is frequently associated. Some authors suggest that<br />

acu te myopia is due to the anhydrase carbonic <strong>in</strong>hibition, lens edema<br />

and accommodation spasm (5,6) .<br />

Topiramate is the lead<strong>in</strong>g cause of BAACG <strong>in</strong> patients under<br />

the forties and is a potentially bl<strong>in</strong>d<strong>in</strong>g disease. The cl<strong>in</strong>ical picture<br />

is reversible if diagnosed and treated precociously and the drug is<br />

immediately discont<strong>in</strong>ued (4,7-10) . The <strong>in</strong>cidence of permanent vision<br />

loss <strong>in</strong> topiramate-associated BAACG is 8.1% (6) .<br />

CASE PRESENTATION<br />

A 55-year-old white woman presented with BAACG, one week<br />

after start<strong>in</strong>g topiramate, 25 mg/day, <strong>in</strong>dicated to migra<strong>in</strong>e prevention.<br />

She also had spasmodic torticollis and essential tremor. She<br />

presented a 4 hours history of sudden blurr<strong>in</strong>g of vision, feel<strong>in</strong>g of<br />

Submitted for publication: January 16, 2013<br />

Accepted for publication: February 4, 2013<br />

Study carried out at Fundação João Penido Burnier, Camp<strong>in</strong>as (SP) - Brazil<br />

1<br />

Physician, Fundação João Penido Burnier, Camp<strong>in</strong>as (SP) - Brazil<br />

2<br />

Physician, Neurology Departament, Universidade Estadual de Camp<strong>in</strong>as, Camp<strong>in</strong>as (SP) - Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: L.B.Quagliato, None; K.Barella, None; J.M.Abreu<br />

Neto, None; E.M.A.B.Quagliato, None.<br />

Correspond<strong>in</strong>g author: Lucas Barasnevicius Quagliato. Rua Alfredo Calil, 187 - Camp<strong>in</strong>as (SP) -<br />

13101-507 - Brazil - E-mail- lucasquagliato@yahoo.com.br<br />

48 Arq Bras Oftalmol. 2013;76(1):48-9


Quagliato LB, et al.<br />

pressure over the eyes and visual flashes perception. On the <strong>in</strong>itial<br />

exam<strong>in</strong>ation, the best corrected visual acuities were 0.8 and 0.5 on<br />

the right eye (OD) and left eye (OS) respectively, with -2.00 <strong>in</strong> both<br />

eyes (BE). The biomicroscopy showed shallow anterior chambers,<br />

moderate corneal edema and moderate conjunctival <strong><strong>in</strong>jection</strong> (Figure<br />

1). The IOPs were 48 mmHg OU. The gonioscopy with and without<br />

compression revealed a 360 o bilateral closed angle and a superior<br />

180 o synechiae <strong>in</strong>dentation. Fundoscopic exam<strong>in</strong>ation was normal.<br />

After the diagnosis of BAACG topiramate was immediately discont<strong>in</strong>ued.<br />

She was treated with topical 0.5% timolol maleate, 0.15%<br />

brimonid<strong>in</strong>e tartrate, 2% dorzolamide hydrochloride, 1% prednisolo -<br />

ne acetate, 1% pilocarp<strong>in</strong>e and 500 mg acetazolamide orally. After<br />

one hour, the IOP was 30 mmHg OU and <strong>in</strong>travenous 20% mannitol<br />

(50 g) was adm<strong>in</strong>istered. After two hours, the IOP was 18 mmHg <strong>in</strong><br />

both eyes, the symptoms improved and she was discharged home<br />

with prednisolone acetate, pilocarp<strong>in</strong>e, brimonid<strong>in</strong>e tartrate and<br />

timolol maleate. By the next morn<strong>in</strong>g the patient cont<strong>in</strong>ued asymptomatic<br />

and the visual acuities were 0.8 on the OD and 0.66 on the<br />

OS. Biomicroscopy showed shallow anterior chambers and there was<br />

no corneal edema. Gonioscopy revealed s<strong>in</strong>echiae and a superior<br />

180 o closed angle and IOP was 16 mmHg. An Yag laser iridotomy<br />

was performed OU because there was risk of total angle closure. She<br />

was sent home with prednisolone acetate, brimonid<strong>in</strong>e tartrate and<br />

timolol maleate. After 48 hours, she returned asymptomatic, and<br />

the best corrected visual acuities were 0.8 OU, without myopic shift.<br />

The corneal edema disappeared and there was a lens <strong>in</strong>tumescence.<br />

Gonioscopy revealed synechiae on 180 o <strong>in</strong>ferior OU. Fundoscopy<br />

showed a 0.6 X 0.6 excavation bilaterally. Visual fields were full OU.<br />

The pachymetry results were 473 µm on the RE and 475 µm on the<br />

LE. The optical coherence tomography showed a 0.6 x 0.7 excavation<br />

and there was no optical nerve fiber loss OU. The IOP was 12 mmHg<br />

<strong>in</strong> BE, and the iridotomy was patent. The patient was discharged with<br />

a brimonid<strong>in</strong>e tartrate and timolol maleate prescription. One month<br />

after, she had no symptoms, the visual acuity returned to normal, and<br />

the pattern shift visual evoked potentials results were normal.<br />

DISCUSSION<br />

We report the third Brazilian case of BAACG related to topiramate,<br />

with a favorable outcome (2,10) . Our patient symptoms began<br />

one week after <strong>in</strong>itiat<strong>in</strong>g topiramate, accord<strong>in</strong>gly to other previous<br />

published cases, which visual symptoms <strong>in</strong>itiated dur<strong>in</strong>g the two<br />

<strong>in</strong>itial treatment weeks (6,8) . Topiramate dosis related to BAACG was<br />

up to 50 mg <strong>in</strong> almost 50% of the yet described cases, as occurred<br />

with this patient (6) .<br />

Ophthalmologic evaluation showed <strong>in</strong>creased IOP, shallow anterior<br />

chambers, moderate corneal edema and moderate conjunctival<br />

<strong><strong>in</strong>jection</strong>, signs frequently described <strong>in</strong> the literature (1,6) . This cl<strong>in</strong>ical<br />

picture was acute and bilateral, as commonly seen <strong>in</strong> other topiramate-<strong>in</strong>duced<br />

glaucoma reports, and can occur at any age (1,2,10) . This<br />

patient <strong>in</strong>itial treatment was a conventional one for glaucoma, but<br />

there was no complete IOP normalization until mannitol <strong>in</strong>travenous<br />

adm<strong>in</strong>istration. On the next day, the biomicroscopy showed s<strong>in</strong>echiae<br />

and she was treated with a bilateral Yag laser iridotomy because<br />

those s<strong>in</strong>echiae could be present previously and then predispose to a<br />

total angle closure recurrence. Laser or surgical peripheral iridotomy<br />

was performed on 38% of the BAACG described <strong>in</strong> the literature,<br />

but generally this procedure is not <strong>in</strong>dicated, because as the acute<br />

glaucoma is caused by uveal effusion without pupillary block, a<br />

pe ripheral iridotomy can aggravate the glaucoma, putt<strong>in</strong>g forward<br />

iris and lens (6) . An <strong>in</strong>creased IOP, if ma<strong>in</strong>ta<strong>in</strong>ed for long periods, can<br />

damage severely the optic nerve and is of paramount importance<br />

that the glaucoma etiology could be removed. This case illustrates<br />

the importance of recogniz<strong>in</strong>g this entity <strong>in</strong> a non-ophthalmic sett<strong>in</strong>g<br />

and that <strong>in</strong>travenous mannitol may be useful <strong>in</strong> the treatment of the<br />

condition when it is not responsive to conventional treatment. Thus,<br />

it was possible a complete visual symptoms normalization, lead<strong>in</strong>g to<br />

recovery of the deepness of the anterior chamber and normalization<br />

of IOP.<br />

Figure 1. Biomicroscopy demonstrat<strong>in</strong>g a shallow anterior chamber.<br />

REFERENCES<br />

1. Abtahi MA, Abtahi SH, Fazei F, Roomizadeh P, Etemadifar M, Jenab K, et al. Topiramate<br />

and the vision: a systematic review. Cl<strong>in</strong> Ophthalmol. 2012;6:117-31.<br />

2. Brandão MN, Fernandes IC, Barradas FF, Machado JF, Oliveira MT. Miopia aguda e<br />

glaucoma de ângulo fechado associados ao uso de topiramato em paciente jovem:<br />

relato de caso. Arq Bras Oftalmol. 2009;72(1):103-5.<br />

3. Cereza G, Pedrós C, Garcia N, Laporte JR. Topiramate <strong>in</strong> non-approved <strong>in</strong>dications and<br />

acute myopia or angle closure glaucoma. Br J Cl<strong>in</strong> Pharmacol. 2005;60(5):578-9.<br />

4. Banta JT, Hoffman K, Budenz DL, Ceballos E, Greenfield DS. Presumed topiramate-<strong>in</strong>duced<br />

bilateral acute angle-closure glaucoma. Am J Ophthalmol. 2001;132(1):112-4.<br />

5. Lee GC, Tam CP, Danesh-Meyer HV, Myers JS, Katz LJ. Bilateral angle closure glaucoma<br />

<strong>in</strong>duced by sulphonamide-derived medications. Cl<strong>in</strong> Experiment Ophthalmol. 2007;<br />

35(1):55-8.<br />

6. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramate-associated acute, bilateral,<br />

secondary angle-closure glaucoma. Ophthalmology. 2004;111(1):109-11.<br />

7. Medeiros FA, Zhang XY, Bernd AS, We<strong>in</strong>reb RN. Angle-closure glaucoma associated<br />

with ciliary body detachment <strong>in</strong> patients us<strong>in</strong>g topiramate. Arch Ophthalmol. 2003;<br />

121(2):282-5.<br />

8. Sankar PS, Pasquale LR, Grosskreutz CL. Uveal effusion and secondary angle-closure<br />

glaucoma associated with topiramate use. Arch Ophthalmol. 2001;119(8):1210-1. Com -<br />

ment <strong>in</strong> Arch Ophthalmol. 2002;120(8):1108.<br />

9. L<strong>in</strong> J, Fosnot J, Edmond J. Bilateral angle closure glaucoma <strong>in</strong> a child receiv<strong>in</strong>g oral<br />

topiramate. J AAPOS. 2003;7(1):66-8.<br />

10. Stangler F, Prietsch RF, Fortes Filho JB. Glaucoma agudo bilateral em paciente jovem<br />

secundário ao uso de topiramato: relato de caso. Arq Bras Oftalmol. 2007;70(1):133-6.<br />

Arq Bras Oftalmol. 2013;76(1):48-9<br />

49


Relatos de Casos | Case Reports<br />

Essential trichomegaly: case report<br />

Tricomegalia essencial: relato de caso<br />

Julia Dutra Rossetto 1 , Heloisa Nascimento 1 , Crist<strong>in</strong>a Muccioli 2 , Rubens Belfort Jr. 2<br />

ABSTRACT<br />

The present study reports two cases of symptomatic essential trichomegaly.<br />

Tri chomegaly may develop <strong>in</strong> various diseases, <strong>in</strong>clud<strong>in</strong>g anorexia nervosa, hypothyroidism,<br />

pregnancy, pretibial myxedema, systemic lupus erythematosus, vernal<br />

keratoconjunctivitis, and uveitis. The exact <strong>in</strong>cidence trichomegaly is unknown,<br />

and the condition rema<strong>in</strong>s sporadically reported. Two cases of symptomatic trichomegaly<br />

without any associated systemic disorder are presented <strong>in</strong> this paper.<br />

Keywords: Visual acuity/etiology; Hypertrichosis/complications; Eyelashes/pa -<br />

thology; Case reports<br />

RESUMO<br />

O presente estudo tem por objetivo relatar dois casos de tricomegalia essencial com<br />

dim<strong>in</strong>uição da acuidade visual. A tricomegalia pode se desenvolver em várias doenças,<br />

<strong>in</strong>clu<strong>in</strong>do anorexia nervosa, hipotireoidismo, gravidez, mixedema pré-tibial,<br />

lúpus eritematoso sistêmico, ceratoconjuntivite primaveril, e uveíte. A <strong>in</strong>cidência da<br />

tricomegalia essencial é desconhecida e a condição permanece esporadicamente<br />

relatada. São apresentados dois casos de tricomegalia s<strong>in</strong>tomática em pacientes sem<br />

distúrbios sistêmicos associados.<br />

Descritores: Acuidade visual/etiologia; Hipertricose/complicações; Pestanas/pa tolo ­<br />

gia; Relatos de casos<br />

INTRODUCTION<br />

The periocular hair holds special significance given its central<br />

lo cation. Eyelash dysfunction may have significant effects, rang<strong>in</strong>g<br />

from ocular discomfort to visual acuity decrease. The hair’s unique importance<br />

and location often results <strong>in</strong> early detection of pathology (1) .<br />

Beyond vanity, periocular hair disease may <strong>in</strong>dicate a wide spectrum<br />

of systemic or localized pathology. Trichomegaly or hypertrichosis is<br />

def<strong>in</strong>ed as an <strong>in</strong>crease <strong>in</strong> the length, thickness, stiffness, curl<strong>in</strong>g, and<br />

pigmentation of exist<strong>in</strong>g eyelashes beyond normal variation for a<br />

patient’s ethnicity, age, and/or gender (2) .<br />

Usually trichomegaly is an isolated f<strong>in</strong>d<strong>in</strong>g, although it can be<br />

en countered <strong>in</strong> the context of generalized acquired hypertrichosis<br />

or secondary to irritation or <strong>in</strong>flammation.<br />

The purpose of this paper is to present two cases of patients with<br />

symptomatic essential trichomegaly.<br />

CASE REPORT<br />

Patient 1. A 63 year-old male patient with medical history of treated<br />

prostate cancer five years ago and considered cured and with an<br />

unremarkable past ocular history. His compla<strong>in</strong>t was decreased visual<br />

acuity <strong>in</strong> both eyes. The ophthalmological exam disclosed trichomegaly,<br />

as seen below (Figure 1).<br />

Patient 2. A 72 year-old female patient with medical history of<br />

diabetes, systemic hypertension and hypercholesterolemia and with<br />

an unremarkable past ocular history. Her compla<strong>in</strong>ts comprised decrease<br />

of visual acuity and burn<strong>in</strong>g sensation. Ocular exam revealed<br />

hypertrichosis <strong>in</strong> both eyes, as seen below (Figure 2).<br />

Both patients were seen at the Department of Ophthalmology<br />

of Escola Paulista de Medic<strong>in</strong>a (Hospital São Paulo/UNIFESP) and the<br />

systemic and ophthalmologic work-up excluded <strong>in</strong>fection as well as<br />

other diseases. Both denied use of systemic medication.<br />

Both patients were submited to eyelash trimm<strong>in</strong>g with improvement<br />

of their visual quality.<br />

DISCUSSION<br />

Trichomegaly is a rare condition that may develop <strong>in</strong> various<br />

di seases, <strong>in</strong>clud<strong>in</strong>g anorexia nervosa, acrodynia, dermatomyositis, hy -<br />

pothyroidism, pregnancy, pretibial myxedema, porphyria, metastatic<br />

renal cell adenocarc<strong>in</strong>oma, systemic lupus erythematosus, vernal<br />

ke ratoconjunctivitis, and uveitis (3,4) , as well as l<strong>in</strong>ear scleroderma, he -<br />

patopathy (5,6) , and leishmania/Kala-azar (4,5,7) . Congenital conditions such<br />

as Oliver-McFarlane syndrome (8) , oculocutaneous alb<strong>in</strong>ism type I (9) ,<br />

or familial hypertrichosis (10) are also associated with hypertrichosis.<br />

AIDS is among the well-studied systemic causes of trichomegaly (1) , although<br />

primarily described dur<strong>in</strong>g later disease stages.<br />

Submitted for publication: January 11, 2013<br />

Accepted for publication: January 31, 2013<br />

Study carried out at Hospital São Paulo, Ophthalmology Department, Universidade Federal de São<br />

Paulo - São Paulo (SP) - Brazil.<br />

1<br />

Physician, Department of Ophthalmology, Universidade Federal de São Paulo - São Paulo (SP), Brazil.<br />

2<br />

Professor, Department of Ophthalmology, Universidade Federal de São Paulo - São Paulo (SP), Brazil.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: J.D.Rossetto, None; H.Nascimento, None; C.Muccioli,<br />

None; R.Belfort Jr, None.<br />

Correspond<strong>in</strong>g author: Júlia Rossetto. Rua Botucatu, 821 - São Paulo (SP) - 04023-062 - Brazil -<br />

E-mail: Julia_rossetto@hotmail.com<br />

50 Arq Bras Oftalmol. 2013;76(1):50-1


Rossetto JD, et al.<br />

Nazareth et al. (11) documented 23 medications associated with<br />

tri chomegaly. The most common were prostagland<strong>in</strong> analogs, cy -<br />

clospor<strong>in</strong>e, <strong>in</strong>terferon, topiramate and cetuximab.<br />

cOnclusion<br />

Trimm<strong>in</strong>g and epilation have been found to be satisfactory and<br />

safe therapeutic options. The exact <strong>in</strong>cidence of eyelash trichomegaly<br />

is unknown, and the condition is rare and sporadically reported.<br />

Figure 1. Trichomegaly on the right eye (Patient 1).<br />

Figure 2. Trichomegaly on the right eye (Patient 2).<br />

REFERENCES<br />

1. Modjtahedi BS, Alikhan A, Maibach HI, Schwab IR. Diseases of periocular hair. Surv<br />

Ophthalmol. 2011;56(5):416-32.<br />

2. Braiteh F, Kurzrock R, Johnson FM. Trichomegaly of the eyelashes after lung cancer<br />

treatment with the epidermal growth factor receptor <strong>in</strong>hibitor erlot<strong>in</strong>ib. J Cl<strong>in</strong> Oncol.<br />

2008;26(20):3460-2.<br />

3. Wendel<strong>in</strong> DS, Pope DN, Mallory SB. Hypertrichosis. J Am Acad Dermatol. 2003;48(2):<br />

161-79; quiz 180-1. Review.<br />

4. Schneiderman PI, Grossman ME. A cl<strong>in</strong>ician’s guide to dermatologic differential diag -<br />

nosis. Boca Raton: Informa Healthcare; 2006.<br />

5. Almagro M, del Pozo J, García-Silva J, Martínez W, Castro A, Fonseca E. Eyelash length<br />

<strong>in</strong> HIV-<strong>in</strong>fected patients. AIDS. 2003;17(11):1695-6.<br />

6. Kaplan MH, Sadick NS, Talmor M. Acquired trichomegaly of the eyelashes: a cutaneous<br />

marker of acquired immunodeficiency syndrome. J Am Acad Dermatol. 1991;<br />

25(5 Pt 1):801-4. Comment <strong>in</strong> J Am Acad Dermatol. 1993;28(3):513.<br />

7. Ward KM, Barnett C, Fox LP, Grossman ME. Eyelash trichomegaly associated with<br />

sys temic tacrolimus. Arch Dermatol. 2006;142(2):248.<br />

8. Oliver GL, McFarlane DC. Congenital trichomegaly: with associated pigmentary degeneration<br />

of the ret<strong>in</strong>a, dwarfism, and mental retardation. Arch Ophthalmol. 1965;<br />

74:169-71.<br />

9. Ziakas NG, Jogiya A, Michaelides M. A case of familial trichomegaly <strong>in</strong> association<br />

with oculocutaneous alb<strong>in</strong>ism type 1. Eye (Lond). 2004;18(8):863-4.<br />

10. Harrison DA, Mullaney PB. Familial trichomegaly. Arch Ophthalmol. 1997;115(12):1602-3.<br />

11. Nazareth MR, Bunimovich O, Rothman IL. Trichomegaly <strong>in</strong> a 3-year-old girl with alo -<br />

pecia areata. Pediatr Dermatol. 2009;26(2):188-93.<br />

XX Congresso Norte-Nordeste<br />

de Oftalmologia<br />

27 a 29 de março de 2014<br />

Fortaleza (CE)<br />

Informações:<br />

E-mail: secretaria@snno.com.br<br />

Arq Bras Oftalmol. 2013;76(1):50-1<br />

51


Artigo de Revisão | Review Article<br />

Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento<br />

Fungal keratitis: review of diagnosis and treament<br />

Felipe Mellado 1 , Tomás Rojas 1 , Cristián Cumsille 1<br />

RESUMEN<br />

La queratitis fúngica es una <strong>in</strong>fección característica de zonas tropicales, asociada<br />

a trauma vegetal. Existen dudas respecto al método diagnóstico óptimo y la efec -<br />

tividad de los tratamientos disponibles. ¿Cuál es el manejo más apropiado en<br />

queratitis fúngica? y ¿Cuál es la mejor forma de establecer el diagnóstico? El cultivo<br />

para hongos es el gold standard diagnóstico de elementos fúngicos. Respecto al<br />

tratamiento, natamic<strong>in</strong>a y anfoteric<strong>in</strong>a B fueron los más utilizados y no demostraron<br />

efectividad en estudios prospectivos. Voriconazol demostró efectividad en múlti ples<br />

<strong>in</strong>fecciones fúngicas. Pudiera ser la droga de elección en condiciones óptimas, dado<br />

su mejor penetración <strong>in</strong>traocular. Se ha reconocido su elevado costo dificultando<br />

su aplicación generalizada. Esta revisión entrega recomendaciones para el manejo<br />

y establece la necesidad de realizar estudios que evalúen la costo-efectividad de<br />

voriconazol para la queratitis fúngica.<br />

Descriptores: Queratitis/diagnóstico; Queratitis/microbiologia; Queratitis/quimioterapia;<br />

Cornea/microbiologia; Infecciones fúngicas del ojo; Itraconazol/uso<br />

terapéutico; Anfoteric<strong>in</strong>a B/uso terapéutico; Antifúngicos<br />

ABSTRACT<br />

Fungal keratitis is a characteristic <strong>in</strong>fection upon tropical zones, associated with<br />

ve getal trauma. Doubt exists about the best diagnostic test and the effectiveness<br />

of available treatment. Which is the best diagnostic method for fungal keratitis?<br />

And, which is the best management? Fungal culture rema<strong>in</strong>s as diagnostic gold<br />

standard of fungal elements. As of treatment, natamyc<strong>in</strong> and amphoteric<strong>in</strong> B are<br />

the most popular drugs for fungal keratitis and they have not shown effectiveness <strong>in</strong><br />

randomized controlled trials or systematic reviews. Voriconazole showed effectiveness<br />

and security <strong>in</strong> multiple fungal <strong>in</strong>fections. It may be the drug of choice <strong>in</strong> optimal<br />

conditions, because of its better ocular penetration and wider coverage. However,<br />

its high price difficult general application. This review establishes management<br />

recommendations and the need to perform studies that address cost-effectiveness<br />

analysis of voriconazole for fungal keratitis.<br />

Keywords: Keratitis/diagnosis; Keratitis/microbiology; Keratitis/drug therapy; Cornea/<br />

microbiology; Eye <strong>in</strong>fections, fungal; Itraconazole/therapeutic use; Amphoteric<strong>in</strong> B/<br />

therapeutic use; Antifungal agents<br />

INTRODUCCIÓN<br />

Actualmente la queratitis <strong>in</strong>fecciosa se mantiene como una de<br />

las causas más prevalentes de ceguera no reversible a nivel mundial,<br />

según datos de la OMS (1) . Las pr<strong>in</strong>cipales causas de la queratitis <strong>in</strong>fecciosa<br />

varían enormemente según la región geográfica, el nivel socioeconómico,<br />

la presencia de factores de riesgo como el uso de lentes<br />

de contacto, historia de trauma ocular, comorbilidades y edad del<br />

paciente (2) . Dentro de la etiología de la queratitis <strong>in</strong>fecciosa, la <strong>in</strong>fección<br />

corneal por hongos varía entre un 6 y un 60% dependiendo de la<br />

región geográfica que se exponga (3-6) . Tradicionalmente se describe a<br />

esta entidad como una afección oportunista de zonas tropicales y rurales,<br />

causada mayoritariamente por trauma con exposición vegetal.<br />

S<strong>in</strong> embargo, en países desarrollados su causa sería pr<strong>in</strong>cipalmente<br />

secundaria al uso de lentes de contacto (7) . Los estudios microbiológicos<br />

exponen que la queratitis fúngica es producida fundamentalmente<br />

por hongos filamentosos y levaduras (8) . Los estudios realizados<br />

en Sudamérica muestran que los hongos filamentosos afectarían<br />

con mayor frecuencia, siendo Fusarium y Aspergillus las pr<strong>in</strong>cipales<br />

etiologías (2,9,10) . El pr<strong>in</strong>cipal factor de riesgo asociado a <strong>in</strong>fecciones por<br />

hongos filamentosos es el trauma vegetal. Respecto a las levaduras,<br />

Candida es la que afecta con mayor frecuencia y se presenta mayormente<br />

cuando existe compromiso de la superficie corneal como en<br />

córneas neurotróficas, usuarios de corticoides tópicos crónicos o<br />

luego de procedimientos quirúrgicos (11) . El diagnóstico de la queratitis<br />

fúngica es difícil y debe estar basado en la clínica y el laboratorio.<br />

Los hallazgos oculares más frecuentes al examen oftalmológico son<br />

compromiso epitelial y estromal, s<strong>in</strong> embargo se documentan casos<br />

de compromiso endotelial y de cámara anterior s<strong>in</strong> daño corneal<br />

previo (12) . La queratitis fúngica es una entidad de tratamiento complejo,<br />

requiere antifúngicos por tiempo prolongado y debridaciones<br />

frecuentes (13) . Presenta un peor pronóstico visual que las queratitis<br />

bacterianas, probablemente explicado por la carencia de tratamientos<br />

efectivos, requiriendo más <strong>in</strong>jertos corneales y enucleaciones (14) .<br />

Clásicamente los tratamientos más utilizados han sido natamic<strong>in</strong>a<br />

tópica para hongos filamentosos y anfoteric<strong>in</strong>a B para levaduras (15) .<br />

S<strong>in</strong> embargo persisten dudas respecto al mejor esquema de tratamiento<br />

actual, pr<strong>in</strong>cipalmente dado la escasa penetración <strong>in</strong>traocular<br />

de los antifúngicos mencionados (14) . La rareza de esta patología, la<br />

falta de terapias efectivas que se encuentren disponibles para países<br />

en vías de desarrollo, sumado a la escasez de estudios locales de esta<br />

condición, generan un gran desafío para el médico oftalmólogo y<br />

dan cuenta de la necesidad de realizar una revisión actualizada de<br />

las terapias disponibles, basado en evidencia y con recomendaciones<br />

claras para un mejor enfrentamiento de esta afección.<br />

Esta revisión pretende contestar las dos siguientes preguntas:<br />

¿Cuál es el manejo más apropiado para la queratitis por hongos?<br />

y ¿Cuál es la mejor forma de realizar el diagnóstico?, entregando<br />

recomendaciones claras y adaptadas a nuestro medio para el enfrentamiento<br />

en la práctica clínica.<br />

Submitted for publication: August 17, 2012<br />

Accepted for publication: December 7, 2012<br />

Study carried out at Department of Ophthalmology, Facultad de Medic<strong>in</strong>a, Universidad de Chile.<br />

1<br />

Department of Ophthalmology, Facultad de Medic<strong>in</strong>a, Universidad de Chile, Santiago, Chile.<br />

Fund<strong>in</strong>g: No specific f<strong>in</strong>ancial support was available for this study.<br />

Disclosure of potential conflicts of <strong>in</strong>terest: F.Mellado, None; T.Rojas,None; C.Cumsille, None.<br />

Correspondence address: Felipe Mellado. Julia Berste<strong>in</strong> 0607-H - Santiago, Chile - 8320000 -<br />

E-mail: felipemc85@gmail.com<br />

52 Arq Bras Oftalmol. 2013;76(1):52-6


Mellado F, et al.<br />

MÉTODOS<br />

Se realizó una búsqueda acabada en las pr<strong>in</strong>cipales bases de<br />

datos MEDLINE, Cochrane Library, EMBASE, CINAHL, SCISEARCH,<br />

EPISTEMONIKOS, LILACS, con térm<strong>in</strong>os específicos “microbiology”<br />

[MeSH Terms] OR “fungi” [MeSH Terms] OR fungal[Text Word] and “keratitis”<br />

[MeSH Terms] OR keratomycosis [Text Word] and “Antifungal<br />

Medication” [MeSH Terms]. Se seleccionaron 15 artículos, prefiriéndose<br />

los ensayos clínicos randomizados (ECR) y revisiones sistemáticas<br />

de ECR, además se <strong>in</strong>cluyeron estudios retrospectivos y cohortes<br />

his tóricas. Los artículos fueron seleccionados por dos revisores en<br />

forma <strong>in</strong>dependiente. Todos los artículos fueron revisados en idioma<br />

<strong>in</strong>glés y español.<br />

Diagnóstico<br />

Como se describió anteriormente, el manejo de la queratitis<br />

fúngica ofrece múltiples dificultades. Siempre debiera sospecharse<br />

una queratitis mediada por hongos en casos de queratitis que no<br />

res pondan a terapia antibacteriana y que tengan como factores<br />

de riesgo un trauma con exposición vegetal o el uso extendido de<br />

lentes de contacto (14) . Existe amplia evidencia de la necesidad de<br />

un diagnóstico precoz para impartir tratamiento lo antes posible y<br />

así evitar las complicaciones que amenacen la <strong>in</strong>tegridad visual (2) . Si<br />

bien se han descrito ciertos elementos al examen físico que pudieran<br />

orientar a la queratitis por hongos, como un cuadro de curso <strong>in</strong>doloro<br />

en presencia de lesión corneal de márgenes irregulares en forma<br />

de pluma, asociado a lesiones satélites, de textura seca, con placas<br />

endoteliales, etc., (Figura 1) éstos no se han demostrado suficientes<br />

para establecer el diagnóstico por sí solos (16) . En la serie de Ibrahim et<br />

al. (17) , se demostró que solo el 48% de los casos de queratitis fúngica<br />

fueron correctamente identificados mediante el examen clínico.<br />

Tradicionalmente el diagnóstico se establece con una visualización<br />

directa de muestra corneal en conjunto de cultivos para hongo. En<br />

otras ocasiones se puede requerir <strong>in</strong>cluso de biopsia corneal o paracentesis<br />

de cámara anterior.<br />

Visualización directa<br />

El frotis busca la visualización directa de formas fúngicas usando<br />

t<strong>in</strong>ciones. La t<strong>in</strong>ción de KOH al 10% ha demostrado la mayor sensibilidad<br />

y especificidad para el diagnóstico de hongos alcanzando cifras<br />

entre 50 y 99% para ambas medidas según la serie. Tiene como ventajas<br />

el fácil acceso y la disponibilidad en países en vías de desarrollo<br />

que a su vez son los que han reportado mayor prevalencia de queratitis<br />

fúngica. A su vez, se han buscado asociaciones con otras t<strong>in</strong>ciones<br />

como Calco Flúor y Giemsa para aumentar el rendimiento (18) .<br />

Cultivos para hongo<br />

En general se ha mantenido el cultivo para hongos como el Gold<br />

Standard para el diagnóstico de la queratitis fúngica (Figura 2). Su<br />

utilidad para identificar el microorganismo y la susceptibilidad antibiótica<br />

de éste, ha sido ampliamente reconocida (19,20) . S<strong>in</strong> embargo,<br />

tiene como desventajas el tiempo que requiere para encontrar hallazgos,<br />

ya que hasta un 25% de los cultivos podrían hacerse positivos<br />

recién a las 3 semanas del cuadro (18) , lo que retrasaría el tratamiento<br />

pudiendo otorgar un peor pronóstico. Los medios de cultivos para<br />

hongos con mejor rendimiento y más utilizados son agar sangre y<br />

Sabouraud. En un estudio de 28 ojos que fueron positivos para diagnóstico<br />

de queratitis fúngica mediante frotis directo y PCR, sólo un<br />

68% de los cultivos resultaron positivos, lo que pudiera ser explicado<br />

dado la alta tasa de falsos negativos que se producen producto de<br />

los tratamientos previos a la toma de muestras (19) .<br />

Técnicas moleculares<br />

Durante los últimos años han surgido nuevas técnicas basadas<br />

en la biología molecular, como la reacción de polimerasa en cadena<br />

Figura 1. Cuadro clínico típico de queratitis fúngica al examen oftalmológico. Se presenta<br />

como un cuadro no doloroso de afección corneal, de bordes irregulares y lesiones<br />

sa télite asociadas.<br />

Figura 2. Cultivo para hongos (agar Saboraud) revela crecimiento de Fusarium al 5to día.<br />

(PCR) para detección precoz de <strong>in</strong>fección fúngica. Su ventaja pr<strong>in</strong>cipal<br />

es que sólo requiere una pequeña muestra para la detección tanto<br />

de organismos viables como no viables. (19) A su vez la PCR entrega<br />

resultados en menos de 24 horas, lo que es una ventaja respecto al<br />

cultivo en cuanto al tiempo de diagnóstico. En una evaluación prospectiva<br />

de PCR, utilizada para casos sugerentes de queratitis fúngica<br />

mediante clínica, se observó que un 50% de los casos resultaron<br />

positivos con PCR, mientras que sólo un 25% de los cultivos mostró<br />

desarrollo fúngico. Es de notar en este estudio, que los ojos tratados<br />

previamente a la toma de muestras dieron 50% de positividad para<br />

PCR, comparado con sólo un 30% de positividad para los cultivos (21) .<br />

Este estudio también reportó algunos casos de cultivo positivo con<br />

resultado negativo al utilizar PCR, por lo que esta prometedora técnica<br />

molecular, sólo debiera ser utilizada de manera s<strong>in</strong>érgica al cultivo<br />

y frotis, no así como único método diagnóstico.<br />

Imágenes<br />

Lo más novedoso respecto al diagnóstico de la queratitis fúngica,<br />

son las nuevas técnicas imagenológicas mediante microscopía confocal<br />

<strong>in</strong> vivo (IVCM) (22,23) . Este sistema permite la visualización de todas<br />

las capas corneales y a su vez de componentes microbianos que<br />

pudieran estar presentes entre ellas, de manera rápida y no <strong>in</strong>vasiva.<br />

Vadavalli et al. (23) , presentaron 146 casos de queratitis <strong>in</strong>fecciosa (de<br />

las cuales el 98 fueron mediadas por hongos). En esta serie la IVCM<br />

tuvo una sensibilidad de 89% y una especificidad de 93% para la de-<br />

Arq Bras Oftalmol. 2013;76(1):52-6<br />

53


Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento<br />

tección de elementos fúngicos. Todavía se requiere de mayor evidencia<br />

sistematizada para poner en práctica este método diagnóstico<br />

pero se empieza a observar una tendencia en esta dirección (Tabla 1).<br />

Tratamiento<br />

En el caso de diagnóstico de elementos fúngicos corneales con<br />

las técnicas recién descritas, se debe establecer terapia antifúngica<br />

lo más pronto posible. El objetivo de la terapia es evitar las complicaciones<br />

visuales de la queratitis y lograr la erradicación de la <strong>in</strong>fección<br />

al examen clínico, que se demuestra al lograr la desaparición de los<br />

bordes irregulares en pluma de la lesión corneal, la dism<strong>in</strong>ución de<br />

reacción de cámara anterior y reepitelización corneal (18) . S<strong>in</strong> embargo,<br />

lograr lo anterior ofrece muchas dificultades. La <strong>in</strong>efectividad de los<br />

antifúngicos disponibles y la mínima penetración ocular de las terapias<br />

tópicas sumado a la capacidad de los hongos para penetrar de<br />

manera profunda en el estroma, membrana de Descemet y cámara<br />

anterior s<strong>in</strong> requerir de una irrupción previa en la superficie epitelial<br />

corneal, dificultan la resolución clínica de la <strong>in</strong>fección (12).<br />

Polienos<br />

Tratamiento clásico de la queratitis fúngica, primer antifúngico<br />

aceptado por la Food and Drug Adm<strong>in</strong>istration (FDA) fue la natamic<strong>in</strong>a<br />

tópica al 5% (24) . Este polieno, cuyo mecanismo de acción es la unión<br />

al ergosterol de la pared celular del hongo, impide su homeostasis<br />

y provoca muerte celular por esta causa. Desde su aprobación, la<br />

natamic<strong>in</strong>a se volvió el fármaco más popular para el tratamiento de<br />

hongos filamentosos. Dado su mala penetración ocular y baja tasa de<br />

tratamiento exitoso, la mayoría de los <strong>in</strong>vestigadores recomiendan<br />

debridaciones corneales seguidas para una mejor penetración ocular<br />

del fármaco (13) . Por su parte, la anfoteric<strong>in</strong>a B al 0,15%, ha sido utilizada<br />

ampliamente para el tratamiento de <strong>in</strong>fecciones por levaduras siendo<br />

fármaco de primera línea para queratitis por Candida (15) , y al igual que<br />

la natamic<strong>in</strong>a, presenta problemas para atravesar la superficie corneal<br />

a través de un epitelio <strong>in</strong>tacto (18) .<br />

Azoles<br />

La familia antifúngica de los azoles, tanto imidazoles como triazoles<br />

(diferenciados en su vida media) logran su efecto <strong>in</strong>hibiendo<br />

la síntesis de ergoesterol, esencial para la pared celular y mediante<br />

este mecanismo lograrían su efecto manteniéndose clásicamente<br />

como fármacos de segunda línea en el tratamiento de la queratitis<br />

fúngica. S<strong>in</strong> embargo, durante los últimos años el voriconazol, un<br />

derivado s<strong>in</strong>tético del fluconazol, se ha convertido en una alternativa<br />

prometedora de tratamiento para esta entidad, dado su excelente<br />

penetrancia ocular y su gran espectro de cobertura fúngica (25) .<br />

Equ<strong>in</strong>ocand<strong>in</strong>as<br />

Caspofung<strong>in</strong>a y micafung<strong>in</strong>a son los pr<strong>in</strong>cipales representantes.<br />

Actúan <strong>in</strong>hibiendo enzimas de síntesis de membrana celular. No han<br />

demostrado efectividad sobre los tratamientos anteriores ni evidencia<br />

para su aplicación de elección en queratitis fúngica (18) .<br />

Tabla 1. Alternativas diagnósticas y sus características<br />

Métodos diagnósticos<br />

Visualización directa<br />

Cultivos para hongos<br />

Técnicas moleculares<br />

Imágenes<br />

Componentes<br />

Frotis con t<strong>in</strong>ción de KOH, Giemsa o Blanco de Calco<br />

flúor<br />

Cultivo para hongo en agar Sabouraud o agar sangre<br />

Resultados desde 24-36 horas hasta 3 semanas<br />

PCR para detección precoz. Resultados en menos<br />

de 24 horas<br />

Microscopia confocal <strong>in</strong> vivo<br />

Terapia antifúngica sistémica<br />

En aquellos casos de queratitis fúngica más severos, que se<br />

presentan o evolucionan con úlceras grandes, hipopion y/o compromiso<br />

de cámara anterior, se recomienda utilizar terapia antifúngica<br />

sistémica adyuvante, aún cuando no ha demostrado un claro<br />

beneficio en ensayos clínicos randomizados llevados a cabo (26) . La<br />

anfoteric<strong>in</strong>a B se ha usado ampliamente para el tratamiento de<br />

endoftalmitis fúngica, tanto EV como con <strong>in</strong>yecciones <strong>in</strong>travítreas,<br />

con limitación de cobertura micótica y conocidos efectos adversos<br />

de toxicidad ret<strong>in</strong>al e <strong>in</strong>flamación ocular (14,27) . Por su parte, el fluconazol<br />

vía oral tiene claro efecto en la <strong>in</strong>fección por Candida, no así<br />

en hongos filamentosos que se describen como pr<strong>in</strong>cipal causa de<br />

queratitis fúngica (28) , limitando así su uso como primera línea. Itraconazol<br />

oral ha sido poco utilizado en <strong>in</strong>fecciones fúngicas oculares<br />

dado su pobre espectro de acción, especialmente contra Fusarium,<br />

s<strong>in</strong> embargo se ha reportado útil para <strong>in</strong>fecciones por Aspergillus y<br />

ha sido considerado recientemente terapia convencional (27) . Durante<br />

los últimos años, voriconazol oral ha demostrado efectividad y<br />

seguridad en múltiples <strong>in</strong>fecciones por hongos. Presenta un mayor<br />

espectro de acción, mejor susceptibilidad <strong>in</strong> vitro y menores concentraciones<br />

<strong>in</strong>hibitorias mínimas (CIM) para Candida y Aspergillus,<br />

que los antifúngicos previamente mencionados (29) . Sólo se ha realizado<br />

un ECR comparando voriconazol tópico y oral <strong>versus</strong> terapia<br />

antifúngica convencional (natamic<strong>in</strong>a 5% + itraconazol oral). Este<br />

estudio concluye que voriconazol podría ofrecer mayor eficacia<br />

sobre el tratamiento convencional, especialmente en queratitis por<br />

Aspergillus (27) . En casos de compromiso de cámara anterior secundario<br />

a queratitis por Candida, se ha recomendado <strong>in</strong>iciar terapia<br />

antifúngica <strong>in</strong>tracameral con anfoteric<strong>in</strong>a B o voriconazol como primera<br />

línea (30,31) . Se han explorado otras formas de tratamiento como<br />

<strong>in</strong>yecciones <strong>in</strong>tracorneales o subconjuntivales, las que se reportan<br />

dolorosas y susceptibles de efectos adversos severos como la necrosis<br />

epitelial conjuntival (32) . La carencia de evidencia de calidad no<br />

permite recomendarlas como tratamiento actualmente (33) .<br />

Cirugía<br />

Cuando el tratamiento médico máximo no obtiene resultados<br />

o la <strong>in</strong>fección clínica es muy grave, se debe realizar manejo quirúrgico.<br />

Entre las técnicas utilizadas encontramos el flap conjuntival, la<br />

adhesión de superficie ocular y la queratoplastia lamelar. Si bien el<br />

flap conjuntival aumentaría la llegada de células <strong>in</strong>munocompetentes<br />

para la reparación del tejido corneal, podría actuar como barrera<br />

para los antifúngicos tópicos sumado a la <strong>in</strong>capacidad de observar<br />

la evolución de la lesión (34) . A su vez la queratoplastía lamelar no<br />

sería útil dado la capacidad de los hongos de penetrar en capas<br />

profundas lo que explicaría la falla terapéutica de abordaje quirúrgico<br />

(35) . S<strong>in</strong> embargo la técnica de excelencia es la queratoplastia<br />

terapéutica penetrante, que corresponde a la extracción del tejido<br />

corneal <strong>in</strong>fectado y reemplazado mediante un transplante de córnea<br />

(33) . Se ha reportado que hasta un 30% de las queratitis fúngicas<br />

se resuelven mediante queratoplastia penetrante (36) . Cabe desta car<br />

que aun cuando los casos de queratitis fúngicas documentadas<br />

son poco comunes, dan cuenta de la mitad de las queratoplastías<br />

penetrantes que se realizan por queratitis <strong>in</strong>fecciosas (37) . A su vez se<br />

ha descrito que la tasa de éxito quirúrgico es peor en pacientes con<br />

queratitis fúngica, <strong>in</strong>dependiente de la tasa de erradicación, el éxito<br />

anatómico o la claridad del <strong>in</strong>jerto, y que pesar de este tratamiento<br />

quirúrgico, cerca de un 7% de los casos presentan recurrencia de la<br />

<strong>in</strong>fección (33) . Es por esto que en los últimos años se han proyectado<br />

nuevas formas de abordaje quirúrgico basadas en UV-A uniones de<br />

colágeno y riboflav<strong>in</strong>a (38) , que representan alternativas de <strong>in</strong>vestigación<br />

novedosas para el tratamiento de esta patología, pero que<br />

carecen de evidencia sistematizada que las soporte actualmente<br />

(Tabla 2).<br />

54 Arq Bras Oftalmol. 2013;76(1):52-6


Mellado F, et al.<br />

DISCUSIÓN<br />

En esta revisión se encontraron 3 revisiones sistemáticas que<br />

abordaron el tratamiento médico antibiótico para esta patología. En<br />

la Revisión Cochrane 2008 (39) , se concluyó que tanto la natamic<strong>in</strong>a al<br />

5% como todos los medicamentos evaluados fueron <strong>in</strong>efectivos en el<br />

tratamiento de la queratitis fúngica, evidenciándose la necesidad de<br />

realizar nuevos estudios clínicos aleatorizados de terapia. S<strong>in</strong> embargo,<br />

n<strong>in</strong>guno de los estudios evaluados en dicha revisión sistemática<br />

utilizó anfoteric<strong>in</strong>a B ni voriconazol. A su vez se han realizado múltiples<br />

ensayos clínicos aleatorizados que compararon anfoteric<strong>in</strong>a B<br />

y voriconazol, que no pudieron demostrar diferencias significativas<br />

entre ambos fármacos (40-42) . En la serie publicada por Hariprasad et<br />

al. (25) , se evaluaron cerca de 40 casos clínicos de queratitis fúngica<br />

en los que se adm<strong>in</strong>istró voriconazol oral y tópico, concluyéndose<br />

que es un medicamento que podría usarse de manera segura y<br />

efectiva para múltiples <strong>in</strong>fecciones por hongos. En una encuesta de<br />

práctica clínica realizada por The Cornea Society a nivel mundial, los<br />

oftalmólogos entrevistados eligieron voriconazol, sobre natamic<strong>in</strong>a,<br />

como terapia de elección para la queratitis fúngica en un mundo<br />

ideal (15) . Cabe recordar que el voriconazol oral es muy costoso, lo que<br />

es una desventaja en su implementación, a pesar de su efectividad.<br />

A su vez, este medicamento es metabolizado a través del sistema de<br />

citocromos p450, por lo que se debiera tener precaución especial con<br />

pacientes bajo terapia anticoagulante.<br />

cOnclusión y recomendaciones<br />

La queratitis fúngica es una entidad poco común dentro de las<br />

queratitis <strong>in</strong>fecciosas. Los estudios han señalado que su manejo es<br />

complejo. Una vez confirmado el diagnóstico, o teniendo sugerencia<br />

del éste, debe <strong>in</strong>staurarse tratamiento antibiótico <strong>in</strong>mediato cubriendo<br />

al microorganismo de sospecha. En esta revisión se ha planteado<br />

que la sospecha diagnóstica es em<strong>in</strong>entemente clínica, sugerida por<br />

las lesiones características de la queratomicosis al examen clínico.<br />

S<strong>in</strong> embargo dado la baja sensibilidad del examen clínico como<br />

único elemento diagnóstico, deben realizarse estudios de laboratorio<br />

complementarios que identifiquen el tipo de hongo y def<strong>in</strong>an su<br />

susceptibilidad frente al antifúngico. Los estudios diagnósticos a realizar<br />

debieran <strong>in</strong>cluir un frotis de KOH junto a cultivo para hongos en<br />

agar Sabouraud, en todo paciente en que se sospeche una queratitis<br />

fúngica al examen con lámpara de hendidura. Luego de la toma de<br />

muestras, se debe comenzar con un régimen antifúngico precoz. Si<br />

bien la natamic<strong>in</strong>a tópica al 0,5% es el fármaco más disponible, no<br />

Tabla 2. Alternativas terapéuticas y objetivos<br />

Tratamiento<br />

Polienos tópicos<br />

(Natamic<strong>in</strong>a y anfoteric<strong>in</strong>a B)<br />

Azoles tópicos<br />

(Voriconazol, itraconazol)<br />

Terapia sistémica<br />

(Oral, E.V., <strong>in</strong>tracameral,<br />

subconjuntival)<br />

Cirugía<br />

Objetivo<br />

-Natamic<strong>in</strong>a en caso de aislar hongos filamentosos<br />

-Anfoteric<strong>in</strong>a en caso de aislar levaduras<br />

-Voriconazol tópico de elección tanto para hongos<br />

filamentosos o levaduras y en caso de agente<br />

desconocido dado su amplio espectro<br />

-Itraconazol tópico s<strong>in</strong> evidencia que lo sustente<br />

-Voriconazol oral es de elección, <strong>in</strong>dicado en<br />

falla a tratamiento tópico, en caso de úlceras<br />

corneales centrales y profundas al diagnóstico y en<br />

compromiso de cámara anterior. Es primera línea<br />

para hongos filamentosos y levaduras<br />

-Inyeccion <strong>in</strong>tracamerales en caso de levaduras<br />

aisladas y como segunda línea<br />

-Itraconazol oral segunda línea para hongos<br />

filamentosos<br />

-Queratoplastía penetrante es de elección en caso<br />

de falla a tratamiento médico máximo y en casos<br />

de perforación corneal <strong>in</strong>m<strong>in</strong>ente<br />

ha sido capaz de demostrar su efectividad para el tratamiento de la<br />

queratomicosis en ensayos clínicos aleatorizados ni revisiones sistemáticas<br />

llevadas a cabo. Por esta razón, en casos sugerentes de queratitis<br />

fúngica en los que el microorganismo no ha sido identificado,<br />

la literatura actual recomienda <strong>in</strong>iciar terapia antimicótica biasociada,<br />

con un régimen basado en anfoteric<strong>in</strong>a B al 0,15% y/o voriconazol<br />

tópico 1% dado su mejor espectro de cobertura. En países en vías de<br />

desarrollo, la disponibilidad de voriconazol tópico u oral es mínima,<br />

por lo que debieran buscarse alternativas basadas en anfoteric<strong>in</strong>a B<br />

tópica al 0,15% como fármaco de elección. S<strong>in</strong> embargo, al no comercializarse<br />

preparado, se debe solicitar su composición al laboratorio<br />

lo que pudiera resultar engorroso para su aplicación generalizada.<br />

Inicialmente, e <strong>in</strong>dependiente del fármaco utilizado, se recomienda<br />

adm<strong>in</strong>istrar el antifúngico cada 1 hora acompañado de debridaciones<br />

cada 3 días (Tabla 3). El tiempo de tratamiento no está claro, se ha<br />

descrito que en promedio se requiere de 80 días para la erradicación<br />

de la <strong>in</strong>fección al examen clínico. Cuando el paciente se presenta con<br />

úlceras grandes, centrales, profundas, con placas endoteliales, compromiso<br />

de cámara anterior y/o hipopion, se recomienda establecer<br />

terapia antifúngica sistémica de manera coadyuvante al tratamiento<br />

tópico y derivación a oftalmólogo especialista en córnea durante el<br />

mismo día (Tabla 4). Si la <strong>in</strong>fección no responde al tratamiento médico<br />

máximo, con aumento de reacción en cámara anterior, sospecha<br />

de perforación corneal o compromiso de segmento posterior, el tratamiento<br />

quirúrgico estaría <strong>in</strong>dicado. El procedimiento de elección es<br />

la queratoplastia terapéutica penetrante, s<strong>in</strong> embargo puede llegar a<br />

realizarse enucleación en los casos más severos. Debido a que la queratomicosis<br />

puede tener como secuela la pérdida de agudeza visual o<br />

<strong>in</strong>cluso pérdida del globo ocular, se debe establecer un diagnóstico<br />

oportuno y un tratamiento adecuado para dism<strong>in</strong>uir el riesgo de<br />

desenlaces graves e irreversibles. Es imperativo la realización de más<br />

estudios que evalúen la implementación y aplicabilidad de los tratamientos<br />

descritos, especialmente de voriconazol dado su espectro<br />

de acción, seguridad y preferencia por parte de médicos oftalmólo-<br />

Tabla 3. Terapia médica recomendada para la queratitis fúngica<br />

Microorganismo<br />

Hongos filamentosos 1 o Voriconazol 1%<br />

2 o Natamic<strong>in</strong>a 5%<br />

Tratamiento médico tópico<br />

recomendado según acceso*<br />

Levaduras 1 o Voriconazol 1%<br />

2 o Anfoteric<strong>in</strong>a 0,15% (1,5 mg/1 mL)<br />

Desconocido 1 o Voriconazol 1% + Anfoteric<strong>in</strong>a 0,15%<br />

2 o Anfoteric<strong>in</strong>a 0,15% + Natamic<strong>in</strong>a 5%<br />

*= se recomienda la adm<strong>in</strong>istración antibiótica cada 1 hora <strong>in</strong>icialmente, acompañada<br />

de debridaciones cada 3 días. La aplicación tópica se distanciará según mejoría clínica.<br />

Si no se logra mejoría típica temprana debe derivarse a especialista en córnea para<br />

eventual resolución quirúrgica.<br />

Tabla 4. Terapia médica sistémica coadyuvante en casos de queratitis<br />

fúngica severa*<br />

Microorganismo<br />

Hongos filamentosos<br />

Levaduras<br />

Tratamiento médico sistémico<br />

recomendado según acceso*<br />

1 o Voriconazol oral 400 mg/d<br />

2 o Itraconazol oral 100-200 mg cada 12 hrs<br />

1 o Voriconazol oral 400 mg/d<br />

2 o Anfoteric<strong>in</strong>a <strong>in</strong>tracameral (5 mcg/0,05 mL agua estéril)<br />

Voriconazol <strong>in</strong>tracameral (50 mcg/0,05 mL agua estéril)<br />

3 o Fluconazol oral 400 mg/d<br />

*= se recomienda la adm<strong>in</strong>istración antibiótica sistémica coadyuvante al tratamiento<br />

tópico, en casos de compromiso de cámara anterior, úlceras grandes y profundas, compromiso<br />

de cámara anterior y falla a tratamiento tópico <strong>in</strong>icial con germen identificado.<br />

Arq Bras Oftalmol. 2013;76(1):52-6<br />

55


Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento<br />

gos a nivel mundial. Se debe evaluar el costo-beneficio terapéutico,<br />

para que <strong>in</strong>dependiente de los recursos económicos de un sistema<br />

de salud, éstos apunten a garantizar la terapia de mejor efectividad<br />

demostrada y que mayor beneficio reporte para el paciente.<br />

REFERENCIAS<br />

1. Whitcher JP, Sr<strong>in</strong>ivasan M, Upadhyay MP. Corneal bl<strong>in</strong>dness: a global perspective. Bull<br />

World Health Organ [Internet]. 2001[cited 2012 Feb 21];79(3):214-21. Available from:<br />

http://www.scielosp.org/pdf/bwho/v79n3/v79n3a09.pdf<br />

2. Passos RM, Cariello AJ, Yu MC, Höfl<strong>in</strong>g-Lima AL. Microbial keratitis <strong>in</strong> the elderly: a 32-year<br />

review. Arq Bras Oftalmol [Internet] 2010[cited 2011 Oct 21];73:315-9. Available from:<br />

http://www.scielo.br/pdf/abo/v73n4/v73n4a02.pdf<br />

3. Liesegang TJ, Forster RK. Spectrum of microbial keratitis <strong>in</strong> South Florida. Am J Oph -<br />

thalmol 1980;90(1):38-47.<br />

4. Gop<strong>in</strong>athan U, Sharma S, Garg P, Rao GN. Review of epidemiological features, microbiological<br />

diagnosis and treatment outcome of microbial keratitis: experience of<br />

over a decade. Indian J Ophthalmol [Internet]. 2009[cited 2010 Nov 7];57(4):273-9.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712695/<br />

5. Furlanetto RL, Andreo EG, F<strong>in</strong>otti IG, Arcieri ES, Ferreira MA, Rocha FJ. Epidemiology<br />

and etiologic diagnosis of <strong>in</strong>fectious keratitis <strong>in</strong> Uberlandia, Brazil. Eur J Ophthalmol.<br />

2010;20(3):498-503.<br />

6. Ibrahim MM, Van<strong>in</strong>i R, Ibrahim FM, Fioriti LS, Furlan EM, Prov<strong>in</strong>zano LM, De Castro RS,<br />

Sousa SJ, Rocha EM. Epidemiologic aspects and cl<strong>in</strong>ical outcome of fungal keratitis<br />

<strong>in</strong> southeastern Brazil. Eur J Ophthalmol. 2009;19:355-61.<br />

7. Iyer SA, Tuli SS, Wagoner RC. Fungal keratitis: emerg<strong>in</strong>g trends and treatment outcomes.<br />

Eye Contact Lens. 2006;32(6):267-71.<br />

8. Gower EW, Keay LJ, Oechsler RA, Iovieno A, Alfonso EC, Jones CD, et al. Trends <strong>in</strong> fungal<br />

keratitis <strong>in</strong> the United States, 2001 to 2007. Ophthalmology [Internet]. 2010[cited 2012<br />

Jun 21];117(12):2263-7. Available from: http://ac.els-cdn.com/S0161642010003271/<br />

1-s2.0-S0161642010003271-ma<strong>in</strong>.pdf?_tid=4862006e-8be0-11e2-a772-00000aab0f6c<br />

&acdnat=1363180797_2793943d9323cfa131ce51f00ce4a86d<br />

9. Nicola F. [Non-viral <strong>in</strong>fectious keratitis: predispos<strong>in</strong>g factors, etiologic agents and<br />

laboratory diagnosis]. Rev Argent Microbiol. 2005;37(4):229-39. Spanish.<br />

10. Miño de Kaspar H, Zoulek G, Paredes ME, Alborno R, Med<strong>in</strong>a D, Centurion de Mor<strong>in</strong>igo<br />

M, et al. Mycotic keratitis <strong>in</strong> Paraguay. Mycoses. 1991;34:251-4.<br />

11. Jurkunas U, Behlau I, Colby K. Fungal keratitis: chang<strong>in</strong>g pathogens and risk factors.<br />

Cornea. 2009;28(6):638-43.<br />

12. Yildiz EH, Abdalla YF, Elsahn AF, Rapuano CJ, Hammersmith KM, Laibson PR, et al.<br />

Update on fungal keratitis from 1999 to 2008. Cornea. 2010;29(12):1406-11.<br />

13. O’Day DM, Head WS, Rob<strong>in</strong>son RD, Clanton JA. Corneal penetration of topical amphoteric<strong>in</strong><br />

B and natamyc<strong>in</strong>. Curr Eye Res. 1986;5(11):877-82.<br />

14. Tuli SS. Fungal keratitis. Cl<strong>in</strong> Ophthalmol[Internet]. 2011[cited 2012 Aug 25];5:275-9.<br />

Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065567/<br />

15. Loh AR, Hong K, Lee S, Mannis M, Acharya NR. Practice patterns <strong>in</strong> the management<br />

of fungal corneal ulcers. Cornea. 2009;28:856-9.<br />

16. Thomas PA, Leck AK, Myatt M. Characteristic cl<strong>in</strong>ical features as an aid to the diagnosis<br />

of suppurative keratitis caused by filamentous fungi. Br J Ophthalmol [Internet.<br />

2005[cited 2011 Oct 23];89:1554-8. Available from: http://www.ncbi.nlm.nih.gov/<br />

pmc/articles/PMC1772991/<br />

17. Ibrahim MM, Van<strong>in</strong>i R, Ibrahim FM, Fioriti LS, Furlan EM, Prov<strong>in</strong>zano LM, et al. Epidemiologic<br />

aspects and cl<strong>in</strong>ical outcome of fungal keratitis <strong>in</strong> southeastern Brazil. Eur<br />

J Ophthalmol. 2009;19(3):355-61.<br />

18. Chang HY, Chodosh J. Diagnostic and therapeutic considerations <strong>in</strong> fungal keratitis.<br />

Int Ophthalmol Cl<strong>in</strong>. 2011;51(4):33-42.<br />

19. Badiee P, Nejabat M, Alborzi A, Keshavarz F, Shakiba E. Comparative study of gram<br />

sta<strong>in</strong>, potassium hydroxide smear, culture and nested PCR <strong>in</strong> the diagnosis of fungal<br />

keratitis. Ophthalmic Res [Internet]. 2010[cited 2012 May 21];44(4):251-6. Available<br />

from: http://www.karger.com/Article/FullText/313988<br />

20. Bharathi MJ, Ramakrishnan R, Meenakshi R, Mittal S, Shivakumar C, Sr<strong>in</strong>ivasan M.<br />

Microbiological diagnosis of <strong>in</strong>fective keratitis: comparative evaluation of direct<br />

microscopy and culture results. Br J Ophthalmol [Internet]. 2006[cited 2010 Aug<br />

21];90:1271-6. Available from: http://bjo.bmj.com/content/90/10/1271.long<br />

21. Vengayil S, Panda A, Satpathy G, Nayak N, Ghose S, Patanaik D, et al. Polymerase<br />

cha<strong>in</strong> reaction-guided diagnosis of mycotic keratitis: a prospective evaluation of its<br />

efficacy and limitations. Invest Ophthalmol Vis Sci [Internet]. 2009 [cited 2012 Dec<br />

21];50(1):152-6. Available from: http://www.iovs.org/content/50/1/152.long<br />

22. Victor G, Alves MR, Nosé W. Microscopia confocal <strong>in</strong> vivo no diagnóstico de ceratite<br />

fúngica: relato de caso. Arq Bras Oftalmol [Internet]. 2006[citado 2011 Fev 12];<br />

69;399-402. Disponível em: http://www.scielo.br/pdf/abo/v69n3/30794.pdf<br />

23. Vaddavalli PK, Garg P, Sharma S, Sangwan VS, Rao GN, Thomas R. Role of confocal<br />

microscopy <strong>in</strong> the diagnosis of fungal and acanthamoeba keratitis. Ophthalmology<br />

[Internet]. 2011[cited 2012 May 24];118(1):29-35. Comment <strong>in</strong>: Ophthalmology.<br />

2012;119(2):428-9; author reply 429-30. Available from: http://l<strong>in</strong>k<strong>in</strong>ghub.elsevier.<br />

com/retrieve/pii/S0161-6420(10)00560-9<br />

24. Natamyc<strong>in</strong> approved-first US drug for fungal keratitis. FDA Drug Bull. 1978;8(6):37-8.<br />

25. Hariprasad SM, Mieler WF, L<strong>in</strong> TK, Sponsel WE, Graybill JR. Voriconazole <strong>in</strong> the treatment<br />

of fungal eye <strong>in</strong>fections: a review of current literature. Br J Ophthalmol. 2008;<br />

92(7):871-8.<br />

26. Agarwal PK, Roy P, Das A, Banerjee A, Maity PK, Banerjee AR. Efficacy of topical and<br />

systemic itraconazole as a broad-spectrum antifungal agent <strong>in</strong> mycotic corneal<br />

ulcer. A prelim<strong>in</strong>ary study. Indian J Ophthalmol [Internet]. 2001[cited 2010 Mar<br />

19]; 49(3):173-6. Comment <strong>in</strong>: Indian J Opthalmol. 2002;50(1):71-2; author reply 72.<br />

Available from: http://www.ijo.<strong>in</strong>/article.asp?issn=0301-4738;year=2001;volume=49;<br />

issue=3;spage=173;epage=176;aulast=Agarwal<br />

27. Parchand S, Gupta A, Ram J, Gupta N, Chakrabarty A. Voriconazole for fungal corneal<br />

ulcers. Ophthalmology [Internet]. 2012[cited 2012 Dec 21];119(5):1083. Available<br />

from: http://www.sciencedirect.com/science/article/pii/S0161642011011407<br />

28. Bennett JE. Diagnosis and treatment of fungal <strong>in</strong>fections. In: Fauci AS, Braunwald E,<br />

Isselbacher KJ, Wilson JD, Mart<strong>in</strong> IB, Kasper DL, et al, editors. Harrison’s pr<strong>in</strong>ciples of<br />

Internal Medic<strong>in</strong>e. 14th ed. New York: McGraw - Hill; 1998. v. 1, p.1148-54.<br />

29. Marangon FB, Miller D, Giaconi JA, et al. In vitro <strong>in</strong>vestigation of voriconazole susceptibility<br />

for keratitis and endophthalmitis fungal pathogens. Am J ophthalmol [Internet].<br />

2004 [cited 2011 Aug 4];137(5):820-5. Available from: http://www.sciencedirect.com/<br />

science/article/pii/S0002939403015265<br />

30. Shen YC, Wang CY, Tsai HY, Lee HN, Intracameral voriconazole <strong><strong>in</strong>jection</strong> <strong>in</strong> the treatment<br />

of fungal endophtalmitis result<strong>in</strong>g from keratitis. Am J Ophthalmol [Internet]. 2010<br />

[cited 2012 Oct 21];149(6);916-21. Comment <strong>in</strong>: Am J Ophthalmol. 2010;150(6):939;<br />

author reply 939-40; Am J Ophthalmol. 2011;151(1):185-6; author reply 186. Available<br />

from: http://www.sciencedirect.com/science/article/pii/S0002939410000668<br />

31. L<strong>in</strong> RC, Sanduja N, Hariprasad SM. Succesful treatment of postoperative fungal<br />

endophthalmitis us<strong>in</strong>g <strong><strong>in</strong>travitreal</strong> and <strong>in</strong>tracameral voriconazole. J Ocul Pharmacol<br />

Ther [Internet]. 2008[cited 2010 Apr 21];24(2):245-8. Available from: http://onl<strong>in</strong>e.<br />

liebertpub.com/doi/pdf/10.1089/jop.2007.0105<br />

32. Carrasco MA, Genesoni G. Treatment of severe fungal keratitis with subconjunctival<br />

amphoteric<strong>in</strong> B. Cornea. 2011;30(5);608-11.<br />

33. Chen WL, Wu CY, Hu FR, Wang IJ. Therapeutic penetrat<strong>in</strong>g keratoplasty for microbial<br />

keratitis <strong>in</strong> Taiwan from 1987-2001. Am. J Ophthalmol [Internet] 2004[cited 2010 Mar<br />

23];137(4):736-43.Available from: http://www.sciencedirect.com/science/article/pii/<br />

S000293940301417X<br />

34. Foster CS, Lass JH, Moran-Wallace K, Giovanoni R. Ocular toxicity of topical antifungal<br />

agents. Arch Ophthalmol.1981;99(6):1081-4.<br />

35. Oliveira PR de, Resende SM, Oliveira FC de, Oliveira AC de. Ceratite fúngica. Arq Bras<br />

Oftalmol [Internet]. 2001[citado 2010 Jan 21];64(1);75-9. Disponível em: http://www.<br />

scielo.br/pdf/abo/v64n1/9130.pdf<br />

36. Forster RK, Rebell G. Therapeutic surgery <strong>in</strong> failures of medical treatment for fungal<br />

keratitis. Br J Ophthalmol [Internet]. 1975[cited 2010 Jun 21];59(7):366-71.Available<br />

from: http://bjo.bmj.com/content/59/7/366.long<br />

37. Shi W, Wang T, Xie L, Li S, Gao H, Liu J, al. Risk factors, cl<strong>in</strong>ical features, and outcomes<br />

of recurrent fungal keratitis after corneal transplantation. Ophthalmology [Internet].<br />

2010[cited 2011 Jun 12];117(5);890-6. Available from: http://www.sciencedirect.com/<br />

science/article/pii/S0161642009011750<br />

38. Galper<strong>in</strong> G, Berra M, Tau J, Boscaro G, Zarate J, Berra A. Treatment of fungal keratitis<br />

from Fusarium <strong>in</strong>fection by corneal cross-l<strong>in</strong>k<strong>in</strong>g. Cornea. 2012;31(2);176-80. Comment<br />

<strong>in</strong>: Cornea. 2013;32(2):218; Cornea. 2013;32(2):217-8.<br />

39. Florcruz NV, Peczon I Jr. Medical <strong>in</strong>terventions for fungal keratitis. Cochrane Database<br />

Syst Rev 2008:23(1):CD004241.<br />

40. Mahdy RA, Nada WM, Wageh MM. Topical amphoteric<strong>in</strong> B and subconjunctival<br />

<strong><strong>in</strong>jection</strong> of fluconazole (comb<strong>in</strong>ation therapy) <strong>versus</strong> topical amphoteric<strong>in</strong> B<br />

(monotherapy) <strong>in</strong> treatment of keratomycosis. J Ocul Pharmacol Ther [Internet].<br />

2010[cited 2012 Jul 21];26(3):281-5. Available from: http://onl<strong>in</strong>e.liebertpub.com/doi/<br />

pdf/10.1089/jop.2010.0005<br />

41. Prajna NV, Mascarenhas J, Krishnan T, Reddy PR, Prajna L, Sr<strong>in</strong>ivasan M, et al.<br />

Comparison of natamyc<strong>in</strong> and voriconazole for the treatment of fungal keratitis.<br />

Arch Ophthalmol [Internet]. 2010[cited 2012 Apr 21];128:672-8. Comment <strong>in</strong>: Arch<br />

Ophthalmol. 2011;129(6):814; author reply 814-5. Available from: http://archopht.<br />

jamanetwork.com/article.aspx?articleid=425787<br />

42. Arora R, Gupta D, Goyal J, Kaur R. Voriconazole <strong>versus</strong> natamyc<strong>in</strong> as primary treatment<br />

<strong>in</strong> fungal corneal ulcers. Cl<strong>in</strong> Experiment Ophthalmol [Internet]. 2011[cited 2012<br />

Jul 27];39(5):434-40. Available from: http://onl<strong>in</strong>elibrary.wiley.com/doi/10.1111/j.<br />

1442-9071.2010.02473.x/full<br />

56 Arq Bras Oftalmol. 2013;76(1):52-6


Cartas ao Editor | Letters to the Editor<br />

Abnormal vascular regulation <strong>in</strong> the ophthalmic artery of chronic heart failure patients<br />

Alteração na regulação vascular da artéria oftálmica em pacientes com <strong>in</strong>suficiência cardíaca crônica<br />

Daniel Meira-Freitas 1 , Daniela B. Almeida-Freitas 2 , Augusto Paranhos Jr. 1<br />

In a previous article we described f<strong>in</strong>d<strong>in</strong>gs of color Doppler imag<strong>in</strong>g<br />

of ophthalmic artery <strong>in</strong> chronic heart failure (CHF) patients (1) .<br />

CHF patients presented lower blood flow velocities and higher<br />

resistance <strong>in</strong>dex <strong>in</strong> ophthalmic artery when compared to control<br />

group. Our research group also reported that CHF is associated with<br />

glaucomatous optic nerve head changes that correlate with ocular<br />

perfusion pressure (OPP) and echocardiographic parameters (2) .<br />

Here<strong>in</strong>, we expand on these f<strong>in</strong>d<strong>in</strong>gs and show the relationship<br />

between OPP and blood flow parameters of ophthalmic artery <strong>in</strong><br />

CHF patients.<br />

METHODS<br />

A cross-sectional study was performed. Patients with CHF symptoms<br />

and left ventricle ejection fractions below 55% documented by<br />

echocardiography were recruited from the outpatient heart failure<br />

cl<strong>in</strong>ic of the Federal University of São Paulo, Brazil. Noncardiopathic<br />

volunteers were <strong>in</strong>cluded as a control group.<br />

Doppler parameters of ophthalmic artery of 18 patients with CHF<br />

<strong>in</strong> different stages of disease were compared with 18 healthy volunteers<br />

(control group). Ophthalmic artery blood flow velocities<br />

were measured by transpalpebral Doppler ultrasound (EnVisor -<br />

Philips, Bothell, WA, USA), with a l<strong>in</strong>ear high frequency transducer<br />

(10MHz). Participants also underwent a standardized exam<strong>in</strong>ation<br />

that <strong>in</strong>cluded slit-lamp biomicroscopy, gonioscopy, Goldmann applanation<br />

to nometry, and systemic blood pressure measurement.<br />

CHF patients and control subjects under 18 years of age, patients<br />

with a prior history of significant ocular disease, ocular trauma or<br />

ocular surgery, spherical equivalent greater than ±4.0 D, chronic<br />

corticosteroid usage (topical or systemic), angle closure suspect,<br />

secondary glaucoma, dense media opacities, ret<strong>in</strong>al disease, heart<br />

trans plantation, stroke or any other neurological diseases were not<br />

<strong>in</strong>cluded <strong>in</strong> the study.<br />

Systolic and diastolic blood pressure read<strong>in</strong>gs were obta<strong>in</strong>ed and<br />

used to calculate the mean arterial blood pressure (MAP) accord<strong>in</strong>g<br />

to the follow<strong>in</strong>g formula: MAP=2/3* diastolic blood pressure +1/3*<br />

systolic blood pressure. The mean OPP was calculated us<strong>in</strong>g the<br />

follow<strong>in</strong>g formula: OPP=2/3 * MAP - IOP.<br />

To take <strong>in</strong>to account the correlation between both eyes of the<br />

same <strong>in</strong>dividual, generalized estimat<strong>in</strong>g equation regression was used<br />

to evaluate the relationship between the Doppler parameters of<br />

ophthalmic artery and mean OPP.<br />

RESULTS<br />

No age or gender differences were observed between CHF patients<br />

and controls. Mean OPP was significantly lower <strong>in</strong> CHF group<br />

than <strong>in</strong> control group (p


Abnormal vascular regulation <strong>in</strong> the ophthalmic artery of chronic heart failure patients<br />

that <strong>in</strong>clude peripheral vasoconstriction <strong>in</strong> an attempt to ma<strong>in</strong>ta<strong>in</strong><br />

satisfactory blood pressure and perfusion to essential tissues such<br />

as the heart and bra<strong>in</strong>. In CHF patients, the sympathetic and ren<strong>in</strong>an<br />

giotens<strong>in</strong> systems are activated as a neurohormonal response<br />

to ma<strong>in</strong>ta<strong>in</strong> cardiac output and hemodynamic balance (3) . However,<br />

excessive neurohormonal activity dur<strong>in</strong>g CHF causes an <strong>in</strong>creased<br />

cerebral vascular resistance, which is often accompanied by symptoms,<br />

such as cognitive dysfunction (4) . In the retrobulbar circulation,<br />

vasoconstriction may cause <strong>in</strong>stability <strong>in</strong> blood flow to the optic<br />

nerve head. Ischemia followed by reperfusion is a known cause of<br />

oxidative stress and cell death by apoptosis (5) . Accord<strong>in</strong>g to this pa -<br />

thophysiology, patients with CHF could theoretically be exposed<br />

to hemodynamic changes <strong>in</strong> ocular microcirculation and have an<br />

<strong>in</strong>creased risk for develop<strong>in</strong>g glaucoma. In fact, previous study have<br />

shown an association between CHF and glaucomatous optic nerve<br />

head alterations (2) .<br />

In conclusion, the abnormal relationship between resistance <strong>in</strong> -<br />

dex of ophthalmic artery and OPP corroborates to the hypothesized<br />

vascular mechanism of the reported glaucomatous optic nerve<br />

head alterations <strong>in</strong> CHF patients. Prospective longitud<strong>in</strong>al studies<br />

are required to confirm the causal relationship between abnormal<br />

ocular blood flow and optic nerve head alterations <strong>in</strong> patients with<br />

heart failure.<br />

AcknowledgEments<br />

The project number and <strong>in</strong>stitution responsible for the approval<br />

of the Research Ethics Committee is 0812/07 - UNIFESP. The authors<br />

are grateful for the f<strong>in</strong>ancial support provided by CAPES (Coordenação<br />

de Aperfeiçoamento de Pessoal de Nível Superior) for PhD<br />

stu dent scholarship.<br />

References<br />

1. Almeida-Freitas DB, Meira-Freitas D, Melo Jr LA, Paranhos Jr A, Iared W, Ajzen S. Color<br />

Doppler imag<strong>in</strong>g of the ophthalmic artery <strong>in</strong> patients with chronic heart failure. Arq<br />

Bras Oftalmol [Internet]. 2011[cited 2012 Dec 21];74(5):326-9. Available from: http://<br />

www.scielo.br/pdf/abo/v74n5/v74n5a03.pdf<br />

2. Meira-Freitas D, Melo LA, Jr., Almeida-Freitas DB, Paranhos A, Jr. Glaucomatous<br />

optic nerve head alterations <strong>in</strong> patients with chronic heart failure. Cl<strong>in</strong> Ophthalmol.<br />

2012;6:623-9.<br />

3. Choi BR, Kim JS, Yang YJ, Park KM, Lee CW, Kim YH, et al. Factors associated with<br />

decreased cerebral blood flow <strong>in</strong> congestive heart failure secondary to idiopathic<br />

dilated cardiomyopathy. Am J Cardiol. 2006;97(9):1365-9.<br />

4. Zuccala G, Pedone C, Cesari M, Onder G, Pahor M, Marzetti E, et al. The effects of<br />

cognitive impairment on mortality among hospitalized patients with heart failure.<br />

Am J Med. 2003;115(2):97-103. Comment <strong>in</strong>: Am J Med. 2004;116(2):137-8; author<br />

reply 138.<br />

5. Harris A, Rechtman E, Siesky B, Jonescu-Cuypers C, McCranor L, Garzozi HJ. The role<br />

of optic nerve blood flow <strong>in</strong> the pathogenesis of glaucoma. Ophthalmol Cl<strong>in</strong> North<br />

Am. 2005;18(3):345-53, v.<br />

58 Arq Bras Oftalmol. 2013;76(1):57-8


Instruções para Autores | Instructions to Authors<br />

O ARQUIVOS BRASILEIROS DE OFTALMOLOGIA (ABO, ISSN 0004-<br />

2749 - versão impressa e ISSN 1678-2925 - versão eletrônica), publicação<br />

bimestral oficial do Conselho Brasileiro de Oftalmologia, obje -<br />

tiva divulgar estudos científicos em Oftalmologia, Ciências Visuais e<br />

Saúde Pública, fomentando a pesquisa, o aperfeiçoamento e a atualização<br />

dos profissionais relacionados à área.<br />

Metodologia<br />

São aceitos manuscritos orig<strong>in</strong>ais, em português, <strong>in</strong>glês ou<br />

espanhol que, de acordo com a metodologia empregada, deverão<br />

ser caracterizados em uma das segu<strong>in</strong>tes modalidades:<br />

Estudos Clínicos<br />

Estudos descritivos ou analíticos que envolvam análises em<br />

seres humanos ou avaliem a literatura pert<strong>in</strong>ente a seres humanos.<br />

Estudos Epidemiológicos<br />

Estudos analíticos que envolvam resultados populacionais.<br />

Estudos de Experimentação Laboratorial<br />

Estudos descritivos ou analíticos que envolvam modelos ani -<br />

mais ou outras técnicas biológicas, físicas ou químicas.<br />

Estudos Teóricos<br />

Estudos descritivos que se refiram à descrição e análise teórica<br />

de novas hipóteses propostas com base no conhecimento existente<br />

na literatura.<br />

Tipos de Manuscritos<br />

A forma do manuscrito enviado deve enquadrar-se em uma das<br />

categorias a seguir. Os limites para cada tipo de manuscrito estão<br />

entre parênteses ao f<strong>in</strong>al das descrições das categorias. A contagem<br />

de palavras do manuscrito refere-se do <strong>in</strong>ício da <strong>in</strong>trodução ao f<strong>in</strong>al<br />

da discussão, portanto, não participam da contagem a pág<strong>in</strong>a de<br />

rosto, abstract, resumo, referências, agradecimentos, tabelas e figu -<br />

ras <strong>in</strong>clu<strong>in</strong>do legendas.<br />

Editoriais<br />

Os editoriais são feitos a convite e devem ser referentes a<br />

assuntos de <strong>in</strong>teresse atual, preferencialmente relacionados a arti -<br />

gos publicados no mesmo fascículo do ABO (limites máximos: 1.000<br />

palavras, título, 2 figuras ou tabelas no total e 10 referências).<br />

Artigos Orig<strong>in</strong>ais<br />

Artigos orig<strong>in</strong>ais apresentam experimentos completos com<br />

resultados nunca publicados (limites máximos: 3.000 palavras, tí -<br />

tulo, resumo estruturado, 7 figuras ou tabelas no total e 30 referências).<br />

A avaliação dos manuscritos enviados seguirá as prioridades<br />

abaixo:<br />

1. Informação nova e relevante comprovada em estudo com<br />

metodologia adequada.<br />

2. Repetição de <strong>in</strong>formação existente na literatura a<strong>in</strong>da não<br />

comprovada regionalmente baseada em estudo com metodologia<br />

adequada.<br />

3. Repetição de <strong>in</strong>formação existente na literatura e já compro vada<br />

regionalmente, desde que baseada em estudo com me todologia<br />

adequada.<br />

* Não serão aceitos manuscritos com conclusões especulativas, não<br />

comprovadas pelos resultados ou baseadas em estudo com metodologia<br />

<strong>in</strong>adequada.<br />

Relatos de Casos ou Série de Casos<br />

Relatos de casos ou série de casos serão considerados para<br />

publicação se descreverem achados com raridade e orig<strong>in</strong>alidade<br />

a<strong>in</strong>da não comprovadas <strong>in</strong>ternacionalmente, ou quando o relato<br />

apresentar respostas clínicas ou cirúrgicas que auxiliem na elu -<br />

cidação fisiopatológica de alguma doença (limites máximos: 1.000<br />

pa lavras, título, resumo não estruturado, 4 figuras ou tabelas no<br />

total e 10 referências).<br />

Cartas ao Editor<br />

As cartas ao editor serão consideradas para publicação se <strong>in</strong>cluírem<br />

comentários pert<strong>in</strong>entes a manuscritos publicados anteriormente<br />

no ABO ou, excepcionalmente, resultados de estudos origi -<br />

nais com conteúdo <strong>in</strong>suficiente para serem enviados como Artigo<br />

Orig<strong>in</strong>al. Elas devem <strong>in</strong>troduzir nova <strong>in</strong>formação ou nova <strong>in</strong>terpre -<br />

tação de <strong>in</strong>formação já existente. Quando seu conteúdo fizer referência<br />

a algum artigo publicado no ABO, este deve estar citado no<br />

primeiro parágrafo e constar das referências. Nestes casos, as cartas<br />

estarão associadas ao artigo em questão, e o direito de réplica dos<br />

autores será garantido na mesma edição. Não serão publicadas cartas<br />

de congratulações (limites máximos: 700 palavras, título, 2 figuras<br />

ou tabelas no total e 5 referências).<br />

Manuscritos de Revisão<br />

Manuscritos de revisão seguem a l<strong>in</strong>ha editorial da revista e são<br />

aceitos apenas por convite do editor. Sugestões de assuntos para<br />

artigos de revisão podem ser feitas diretamente ao editor, mas os<br />

manuscritos não podem ser enviados sem um convite prévio (limi-<br />

tes máximos: 4.000 palavras, título, resumo não estruturado, 8 figuras<br />

ou tabelas no total e 100 referências).<br />

Processo Editorial<br />

Para que o manuscrito <strong>in</strong>gresse no processo editorial, é fundamental<br />

que todas as regras tenham sido cumpridas. A secretaria<br />

editorial comunicará <strong>in</strong>adequações no envio do manuscrito. Após<br />

a notificação, o autor correspondente terá o prazo de 30 dias para<br />

adequação do seu manuscrito. Se o prazo não for cumprido, o ma -<br />

nuscrito será excluído.<br />

Os manuscritos enviados ao ABO são avaliados <strong>in</strong>icialmente<br />

pelos editores quanto à adequação do seu conteúdo à l<strong>in</strong>ha edito -<br />

rial do periódico. Após essa avaliação, todos os manuscritos são<br />

encam<strong>in</strong>hados para análise e avaliação por pares, sendo o anonima -<br />

to dos avaliadores garantido em todo o processo de julgamento. O<br />

anonimato dos autores não é implementado.<br />

Após a avaliação editorial <strong>in</strong>icial, os comentários dos avaliado -<br />

res podem ser encam<strong>in</strong>hados aos autores como orientação para as<br />

mo dificações que devam ser realizadas no texto. Após a implemen<br />

ta ção das modificações sugeridas pelos avaliadores, o manuscrito<br />

re visado deverá ser encam<strong>in</strong>hado, acompanhado de carta<br />

(enviada como documento suplementar) <strong>in</strong>dicando pon tual mente<br />

todas as modificações realizadas no manuscrito ou os motivos<br />

pelos quais as modificações sugeridas não foram efetuadas. Manuscritos<br />

que não vierem acompanhados da carta <strong>in</strong>dicando as<br />

modificações ficarão retidos aguardando o recebimento da mesma.<br />

O prazo para envio da nova versão do manuscrito é de 90 dias<br />

após a comunicação da necessidade de modificações, sendo<br />

ex cluído após esse prazo. A publicação dependerá da aprovação<br />

f<strong>in</strong>al dos editores.<br />

Os trabalhos devem dest<strong>in</strong>ar-se exclusivamente ao Arquivos<br />

Brasileiros de Oftalmologia, não sendo permitido envio simultâneo<br />

a outro periódico, nem sua reprodução total ou parcial, ou<br />

tradução para publicação em outro idioma, sem autorização dos<br />

editores.<br />

Arq Bras Oftalmol. 2013;76(1):59-62<br />

59


Autoria<br />

Os critérios para autoria de manuscritos em periódicos médi -<br />

cos está bem estabelecido. O crédito de autoria deve ser baseado<br />

em <strong>in</strong>divíduos que tenham contribuído de maneira concreta nas<br />

segu<strong>in</strong>tes três fases do manuscrito:<br />

I. Concepção e del<strong>in</strong>eamento do estudo, coleta dos dados ou<br />

análise e <strong>in</strong>terpretação dos dados.<br />

II. Redação do manuscrito ou revisão crítica do manuscrito com<br />

relação ao seu conteúdo <strong>in</strong>telectual.<br />

III. Aprovação f<strong>in</strong>al da versão do manuscrito a ser publicada.<br />

O ABO requer que os autores garantam que todos os autores<br />

preenchem os critérios acima e que nenhuma pessoa que preencha<br />

esses critérios seja preterida da autoria. Apenas a posição de chefia<br />

de qualquer <strong>in</strong>divíduo não atribui a este o papel de autor, o ABO não<br />

aceita a participação de autores honorários.<br />

É necessário que o autor correspondente preencha e envie o<br />

formulário de Declaração de Contribuição dos Autores como docu -<br />

mento suplementar.<br />

Preparação do Artigo<br />

Os artigos devem ser enviados exclusivamente de forma eletrônica,<br />

pela Internet, na <strong>in</strong>terface apropriada do ABO. As normas que se<br />

seguem foram baseadas no formato proposto pelo Inter na tional<br />

Com mittee of Medical Journal Editors (ICMJE) e publicadas no artigo:<br />

Uniform Requirements for Manuscripts Submitted to Bio medical Journals.<br />

O respeito às <strong>in</strong>struções é condição obrigatória para que o tra -<br />

balho seja considerado para análise.<br />

O texto deve ser enviado em formato digital, sendo aceitos<br />

apenas os formatos .doc. ou .rtf. O corpo do texto deve ser digitado<br />

em espaço duplo, fonte tamanho 12, com pág<strong>in</strong>as numeradas em<br />

al garismos arábicos, <strong>in</strong>iciando-se cada seção em uma nova pági na.<br />

As seções devem se apresentar na sequência: Pág<strong>in</strong>a de Rosto,<br />

Abstract e Keywords, Resumo e Descritores, Introdução, Métodos,<br />

Resultados, Discussão Agradecimentos (eventuais), Referências, Tabelas<br />

(opcionais) e Figuras (opcionais) com legenda.<br />

1. Pág<strong>in</strong>a de Rosto. Deve conter: a) título em <strong>in</strong>glês (máximo<br />

de 135 caracteres, <strong>in</strong>clu<strong>in</strong>do espaços); b) título em português ou<br />

es panhol (máximo de 135 caracteres, <strong>in</strong>clu<strong>in</strong>do espaços); c) tí tulo<br />

resumido para cabeçalho (máximo 60 caracteres, <strong>in</strong>clu<strong>in</strong>do os<br />

es paços); d) nome científico de cada autor; e) titulação de cada<br />

autor (área de atuação profissional*, cidade, estado, país e, quando<br />

houver, depar tamento, escola, Universidade); f ) nome, endereço,<br />

telefone e e-mail do autor correspondente; g) fontes de auxilio<br />

à pesquisa (se hou ver); h) número do projeto e <strong>in</strong>stituição responsável<br />

pelo parecer do Co mitê de Ética em Pesquisa; i) declaração dos<br />

conflitos de <strong>in</strong> teresses de todos os autores; j) número do registro<br />

dos ensaios clí nicos em uma base de acesso público.<br />

*Médico, estatístico, enfermeiro, ortoptista, fisioterapeuta, estudante etc.<br />

Aprovação do Comitê de Ética em Pesquisa. Todos os estudos<br />

que envolvam coleta de dados primários ou relatos clínico-cirúrgicos,<br />

sejam retrospectivos, transversais ou prospectivos, de vem<br />

<strong>in</strong>dicar, na pág<strong>in</strong>a de rosto, o número do projeto e nome da Instituição<br />

que forneceu o parecer do Comitê de Ética em Pes quisa.<br />

As pesquisas em seres humanos devem seguir a Declaração de<br />

Hels<strong>in</strong>que, enquanto as pesquisas envolvendo animais devem<br />

seguir os pr<strong>in</strong>cí pios propostos pela Association for Research <strong>in</strong> Vision<br />

and Oph thal mo logy (ARVO).<br />

É necessário que o autor correspondente envie, como documento<br />

suplementar, a aprovação do Comitê de Ética em Pesquisa ou seu<br />

parecer dispensando da avaliação do projeto pelo Comitê. Não cabe<br />

ao autor a decisão sobre a necessidade de avaliação pelo Comitê de<br />

Ética em Pesquisa.<br />

Declaração de Conflito de Interesses. A pág<strong>in</strong>a de rosto deve<br />

conter a declaração de conflitos de <strong>in</strong>teresse de todos os autores<br />

(mesmo que esta seja <strong>in</strong>existente). Para maiores <strong>in</strong>formações sobre<br />

os potenciais conflitos de <strong>in</strong>teresse acesse: Chamon W, Melo LA Jr,<br />

Paranhos A Jr. Declaração de conflito de <strong>in</strong>teresse em apresentações<br />

e publicações científicas. Arq Bras Oftalmol. 2010;73(2):107-9.<br />

É necessário que todos os autores enviem os Formulários para Declaração<br />

de Conflitos de Interesse como documentos suplementares.<br />

Ensaios Clínicos. Todos os Ensaios Clínicos devem <strong>in</strong>dicar, na pá g<strong>in</strong>a<br />

de rosto, número de registro em uma base <strong>in</strong>ternacional de re gis -<br />

tro que permita o acesso livre a consulta (exemplos: U.S. Na tional<br />

Ins ti tutes of Health, Australian and New Zealand Cl<strong>in</strong>ical Trials<br />

Registry, Inter national Standard Randomised Controlled Trial Num ber<br />

- ISRCTN, University Hos pital Medical Information Net work Cl<strong>in</strong>ical Trials<br />

Registry - UMIN CTR, Ne derlands Trial Register).<br />

2. Abstract e Keywords. Resumo estruturado (Purpose, Methods,<br />

Re sults, Conclusions) com, no máximo, 300 palavras. Resumo não<br />

estruturado com, no máximo, 150 palavras. Citar c<strong>in</strong>co descritores<br />

em <strong>in</strong>glês, listados pela National Library of Medic<strong>in</strong>e (MeSH - Medical<br />

Subject Head<strong>in</strong>gs).<br />

3. Resumo e Descritores. Resumo estruturado (Objetivos, Méto -<br />

dos, Resultados, Conclusões) com, no máximo 300 palavras. Resumo<br />

não estruturado com, no máximo, 150 palavras. Citar c<strong>in</strong>co descritores,<br />

em português listados pela BIREME (DeCS - Descritores<br />

em Ciências da Saúde).<br />

4. Introdução, Métodos, Resultados e Discussão. As citações no<br />

texto devem ser numeradas sequencialmente, em números arábi -<br />

cos sobrescritos e entre parênteses. É desaconselhada a citação<br />

no m<strong>in</strong>al dos autores.<br />

5. Agradecimentos. Colaborações de pessoas que mereçam<br />

re conhecimento, mas que não justificam suas <strong>in</strong>clusões como<br />

auto res, devem ser citadas nessa seção. Estatísticos e editores médicos<br />

po dem preencher os critérios de autoria e, neste caso, de vem<br />

ser reconhecidos como tal. Quando não preencherem os critérios<br />

de autoria, eles deverão, obrigatoriamente, ser citados nesta<br />

seção. Não são aceitos escritores não identificados no manus -<br />

crito, portanto, escritores profissionais devem ser reconhecidos<br />

nes ta seção.<br />

6. Referências. A citação (referência) dos autores no texto deve<br />

ser numérica e sequencial, na mesma ordem que foram citadas<br />

e identificadas por algarismos arábicos sobrescritos. A apresen tação<br />

deve estar baseada no formato proposto pelo International<br />

Com mittee of Medical Journal Editors (ICMJE), conforme os exem -<br />

plos que se seguem.<br />

Os títulos de periódicos devem ser abreviados de acordo com o<br />

estilo apresentado pela List of Journal Indexed <strong>in</strong> Index Medicus, da<br />

National Library of Medic<strong>in</strong>e.<br />

Para todas as referências, cite todos os autores, até seis. Nos traba -<br />

lhos com sete ou mais autores, cite apenas os seis primeiros,<br />

seguidos da expressão et al.<br />

Exemplos de referências:<br />

Artigos de Periódicos<br />

Costa VP, Vasconcellos JP, Comegno PEC, José NK. O uso da mitomic<strong>in</strong>a<br />

C em cirurgia comb<strong>in</strong>ada. Arq Bras Oftalmol. 1999; 62(5):577-80.<br />

Livros<br />

Bicas HEA. Oftalmologia: fundamentos. São Paulo: Contexto; 1991.<br />

60 Arq Bras Oftalmol. 2013;76(1):59-62


Capítulos de livros<br />

Gómez de Liaño F, Gómez de Liaño P, Gómez de Liaño R. Exploración<br />

del niño estrábico. In: Horta-Barbosa P, editor. Estrabismo. Rio de<br />

Ja neiro: Cultura Médica; 1997. p. 47-72.<br />

Anais<br />

Höfl<strong>in</strong>g-Lima AL, Belfort R Jr. Infecção herpética do recém-nascido.<br />

In: IV Congresso Brasileiro de Prevenção da Cegueira; 1980 Jul 28-30,<br />

Belo Horizonte, Brasil. Anais. Belo Horizonte; 1980. v.2. p. 205-12.<br />

Teses<br />

Schor P. Idealização, desenho, construção e teste de um cera tô -<br />

metro cirúrgico quantitativo [tese]. São Paulo: Universidade Federal<br />

de São Paulo; 1997.<br />

Documentos Eletrônicos<br />

Monteiro MLR, Scapolan HB. Constrição campimétrica causada por<br />

vigabatr<strong>in</strong>. Arq Bras Oftalmol. [periódico na Internet]. 2000 [citado<br />

2005 Jan 31]; 63(5): [cerca de 4 p.]. Disponível em:http://www.scielo.<br />

br/scielo.php?script=sci_arttext&pid=S0004-274920000005000<br />

12&lng=pt&nrm=iso<br />

7. Tabelas. A numeração das tabelas deve ser sequencial, em algarismos<br />

arábicos, na ordem em que foram citadas no texto. Todas<br />

as tabelas devem ter título e cabeçalho para todas as colunas<br />

e se rem apresentadas em formatação simples, sem l<strong>in</strong>has verticais<br />

ou preen chimentos de fundo. No rodapé da tabela deve constar<br />

legenda para todas as abreviaturas (mesmo que def<strong>in</strong>idas previamente<br />

no texto) e testes estatísticos utilizados, além da fonte<br />

bi bliográfica quando extraída de outro trabalho. Todas as tabelas<br />

devem estar contidas no documento pr<strong>in</strong>cipal do manuscrito após<br />

as referências bibliográficas, além de serem enviadas como documento<br />

suplementar.<br />

8. Figuras (gráficos, fotografias, ilustrações, quadros). A nu -<br />

meração das figuras deve ser sequencial, em algarismos arábi -<br />

cos, na ordem em que foram citadas no texto. O ABO publicará as<br />

figuras em preto e branco sem custos para os autores. Os manus -<br />

critos com figuras coloridas apenas serão publicados após o<br />

pagamento da respectiva taxa de publicação de R$ 500,00 por<br />

manuscrito.<br />

Os gráficos devem ser, preferencialmente, em tons de c<strong>in</strong>za, com<br />

fundo branco e sem recursos que simulem 3 dimensões ou profundidade.<br />

Gráficos do tipo torta são dispensáveis e devem ser substituídos<br />

por tabelas ou as <strong>in</strong>formações serem descritas no texto.<br />

Fotografias e ilustrações devem ter resolução mínima de 300 DPI<br />

para o tamanho f<strong>in</strong>al da publicação (cerca de 2.500 x 3.300 pixels,<br />

para pág<strong>in</strong>a <strong>in</strong>teira). A qualidade das imagens é considerada na<br />

avaliação do manuscrito.<br />

Todas as figuras devem estar contidas no documento pr<strong>in</strong>cipal do<br />

manuscrito após as tabelas (se houver) ou após as referências bibliográficas,<br />

além de serem enviadas como documento suplementar.<br />

No documento pr<strong>in</strong>cipal, cada figura deve vir acompanhada de sua<br />

respectiva legenda em espaço duplo e numerada em algarismo<br />

arábico.<br />

Os arquivos suplementares enviados podem ter as segu<strong>in</strong>tes extensões:<br />

JPG, BMP, TIF, GIF, EPS, PSD, WMF, EMF ou PDF, e devem<br />

ser nomeados conforme a identificação das figuras, por exemplo:<br />

“grafico_1.jpg” ou “figura_1A.bmp”.<br />

9. Abreviaturas e Siglas. Quando presentes, devem ser precedidas<br />

do nome correspondente completo ao qual se referem, quando<br />

ci tadas pela primeira vez, e nas legendas das tabelas e figuras<br />

(mesmo que tenham citadas abreviadas anteriormente no texto).<br />

Não devem ser usadas no título e no resumo.<br />

10. Unidades: Valores de grandezas físicas devem ser referidos de<br />

acordo com os padrões do Sistema Internacional de Unidades.<br />

11. L<strong>in</strong>guagem. A clareza do texto deve ser adequada a uma<br />

pu blicação científica. Opte por sentenças curtas na forma direta e<br />

ati va. Quando o uso de uma palavra estrangeira for absolutamente<br />

ne cessário, ela deve aparecer com formatação itálica. Agentes<br />

te ra pêuticos devem ser <strong>in</strong>dicados pelos seus nomes genéricos<br />

seguidos, entre parênteses, pelo nome comercial, fabricante, cidade,<br />

es tado e país de origem. Todos os <strong>in</strong>strumentos ou apare -<br />

lhos de fabricação utilizados devem ser citados com o seu nome<br />

comercial, fabricante, cidade, estado e país de origem. É necessária<br />

a colocação do símbolo (sobrescrito) de marca registrada ® ou <br />

em todos os nomes de <strong>in</strong>strumentos ou apresentações comerciais<br />

de drogas. Em situações de dúvidas em relação a estilo, term<strong>in</strong>ologia,<br />

medidas e assuntos correlatos, o AMA Manual of Style 10th<br />

edition deverá ser consultado.<br />

12. Documentos Orig<strong>in</strong>ais. Os autores correspondentes devem ter<br />

sob sua guarda os documentos orig<strong>in</strong>ais como a carta de aprovação<br />

do comitê de ética <strong>in</strong>stitucional para estudos com humanos ou<br />

animais; o termo de consentimento <strong>in</strong>formado ass<strong>in</strong>ado por todos<br />

os pacientes envolvidos, a declaração de concordância com o conteúdo<br />

completo do trabalho ass<strong>in</strong>ada por todos os autores e declaração<br />

de conflito de <strong>in</strong>teresse de todos os autores, além dos re gistros<br />

dos dados colhidos para os resultados do trabalho.<br />

13. Correções e Retratações. Erros podem ser percebidos após a<br />

publicação de um manuscrito que requeiram a publicação de<br />

uma correção. No entanto, alguns erros, apontados por qualquer<br />

leitor, podem <strong>in</strong>validar os resultados ou a autoria do manuscrito.<br />

Se al guma dúvida concreta a respeito da honestidade ou fidedignidade<br />

de um manuscrito enviado para publicação for levantada,<br />

é obri gação do editor excluir a possibilidade de fraude. Nestas<br />

si tuações o editor comunicará as <strong>in</strong>stituições envolvidas e as agências<br />

f<strong>in</strong>anciadoras a respeito da suspeita e aguardará a decisão<br />

f<strong>in</strong>al desses órgãos. Se houver a confirmação de uma publicação<br />

frau dulenta no ABO, o editor seguirá os protocolos sugeridos pela<br />

In ter na tional Committee of Medical Journal Editors (ICMJE) e pelo<br />

Com mittee on Publication Ethics (COPE).<br />

Lista de Pendências<br />

Antes de <strong>in</strong>iciar o envio do seu manuscrito o autor deve confir -<br />

mar que todos os itens abaixo estão disponíveis:<br />

□ Manuscrito formatado de acordo com as <strong>in</strong>struções aos autores.<br />

□ Limites de palavras, tabelas, figuras e referências adequados<br />

para o tipo de manuscrito.<br />

□ Todas as figuras e tabelas <strong>in</strong>seridas no documento pr<strong>in</strong>cipal<br />

do manuscrito.<br />

□ Todas as figuras e tabelas na sua forma digital para serem<br />

enviadas separadamente como documentos suplementares.<br />

□ Formulário de Declaração da Participação dos Autores<br />

preen chido e salvo digitalmente, para ser enviado como<br />

do cumento suplementar.<br />

□ Formulários de Declarações de Conflitos de Interesses de<br />

todos os autores preenchidos e salvos digitalmente, para<br />

serem enviados como documentos suplementares.<br />

□ Número do registro na base de dados que contem o proto -<br />

colo do ensaio clínico constando na folha de rosto.<br />

□ Versão digital do parecer do Comitê de Ética em Pesquisa<br />

com a aprovação do projeto, para ser enviado como documento<br />

suplementar.<br />

Arq Bras Oftalmol. 2013;76(1):59-62<br />

61


Lista de Sítios da Internet<br />

Interface de envio de artigos do ABO<br />

http://www.scielo.br/ABO<br />

Formulário de Declaração de Contribuição dos Autores<br />

http://www.cbo.com.br/site/files/Formulario Contribuicao dos Autores.pdf<br />

International Committee of Medical Journal Editors (ICMJE)<br />

http://www.icmje.org/<br />

Uniform requirements for manuscripts submitted<br />

to biomedical journals<br />

http://www.icmje.org/urm_full.pdf<br />

Declaração de Hels<strong>in</strong>que<br />

http://www.wma.net/en/30publications/10policies/b3/<strong>in</strong>dex.html<br />

Pr<strong>in</strong>cípios da Association for Research <strong>in</strong><br />

Vision and Ophthal mo logy (ARVO)<br />

http://www.arvo.org/eweb/dynamicpage.aspx?site=arvo2&<br />

webcode=AnimalsResearch<br />

Chamon W, Melo LA Jr, Paranhos A Jr. Declaração de conflito de<br />

<strong>in</strong>teresse em apresentações e publicações científicas.<br />

Arq Bras Oftalmol. 2010;73(2):107-9.<br />

http://www.scielo.br/pdf/abo/v73n2/v73n2a01.pdf<br />

Pr<strong>in</strong>cípios de Autoria segundo ICMJE<br />

http://www.icmje.org/ethical_1author.html<br />

Formulários para Declaração de Conflitos de Interesse<br />

http://www.icmje.org/coi_disclosure.pdf<br />

U.S. National Institutes of Health<br />

http://www.cl<strong>in</strong>icaltrials.gov<br />

Australian and New Zealand Cl<strong>in</strong>ical Trials Registry<br />

http://www.anzctr.org.au<br />

International Standard Randomised Controlled<br />

Trial Number - ISRCTN<br />

http://isrctn.org/<br />

University Hospital Medical Information Network<br />

Cl<strong>in</strong>ical Trials Registry - UMIN CTR<br />

http://www.um<strong>in</strong>.ac.jp/ctr/<strong>in</strong>dex/htm<br />

Nederlands Trial Register<br />

http://www.trialregister.nl/trialreg/<strong>in</strong>dex.asp<br />

MeSH - Medical Subject Head<strong>in</strong>gs<br />

http://www.ncbi.nlm.nih.gov/sites/entrez?db=mesh&term=<br />

DeCS - Descritores em Ciências da Saúde<br />

http://decs.bvs.br/<br />

Formatação proposta pela International Committee<br />

of Medical Journal Editors (ICMJE)<br />

http://www.nlm.nih.gov/bsd/uniform_requirements.html<br />

List of Journal Indexed <strong>in</strong> Index Medicus<br />

http://www.ncbi.nlm.nih.gov/journals<br />

ama Manual of Style 10th edition<br />

http://www.amamanualofstyle.com/<br />

Protocolos da International Committee of<br />

Medical Journal Editors (ICMJE)<br />

http://www.icmje.org/publish<strong>in</strong>g_2corrections.html<br />

Protocolos da Committee on Publication Ethics (COPE)<br />

http://publicationethics.org/flowcharts<br />

Editada por<br />

Ipsis Gráfica e Editora S.A.<br />

Rua Vereador José Nanci, 151 - Parque Jaçatuba<br />

CEP 09290-415 - Santo André - SP<br />

Fone: (0xx11) 2172-0511 - Fax (0xx11) 2273-1557<br />

Diretor-Presidente: Fernando Steven Ullmann;<br />

Diretora Comercial: Helen Suzana Perlmann; Diretora de Arte: Elza Rudolf;<br />

Editoração Eletrônica, CTP e Impressão: Ipsis Gráfica e Editora S.A.<br />

Periodicidade: Bimestral; Tiragem: 7.200 exemplares<br />

Publicidade<br />

conselho brasileiro de<br />

oftalmologia<br />

R. Casa do Ator, 1.117 - 2º andar - Vila Olímpia -<br />

São Paulo - SP - CEP 04546-004<br />

Contato: Fabrício Lacerda<br />

Fone: (5511) 3266-4000 - Fax: (5511) 3171-0953<br />

E-mail: assessoria@cbo.com.br<br />

62 Arq Bras Oftalmol. 2013;76(1):59-62


Ronda Propaganda<br />

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O cuidado com<br />

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TUDO<br />

Gel hipoalergênico:<br />

• Cuida suavemente da limpeza<br />

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• Demaquilante. 1<br />

Não deixa resíduos. 1<br />

Apresentação:<br />

Tubo com 40g<br />

e 100 compressas. 1<br />

Adequado para usuários<br />

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Referência Bibliográfica: 1) Bula do produto: Blephagel ® . Registro MS nº2.5203.0006.001-4.<br />

BLEPHAGEL ® Gel hipoalergênico. Higiene diária das pálpebras e dos cílios. Tubo de 40 g. Conteúdo: Gel para a higiene das pálpebras e dos cílios. Tubo de 40 g e 100 compressas. Composição: Aqua, poloxamer 188, PEG-90, sodium borate, carbomer,<br />

methylparaben. Indicações: BLEPHAGEL ® , gel hipoalergênico, demaquilante, cuida suavemente da limpeza da área dos olhos. Pode ser recomendado aos utilizadores de lentes de contato. Propriedades: BLEPHAGEL ® , hipoalergênico (formulado para<br />

m<strong>in</strong>imizar os riscos de reação alérgica), sem perfume, não é gorduroso, limpa de forma adequada as pálpebras. A sua fórmula: • Facilita a aderência do produto; • Produz uma agradável sensação de frescor, descongestionando as pálpebras e respeitando<br />

o pH da pele; • Não deixa resíduos. Precauções de utilização: • Produto dest<strong>in</strong>ado a aplicação sobre as pálpebras e cílios, não aplicar no olho; • Não utilizar em crianças. NÃO USAR EM PELE LESIONADA OU IRRITADA. Modo de usar: Em média duas<br />

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