New trabeculectomy adjustable suture Persistent fetal

Transcription

issn 0004-2749
versão impressa
Arquivos brasileiros
publicação oficial do conselho brasileiro de oftalmologia
MAIO/JUNHO 2013
d e
76 03
New trabeculectomy adjustable
suture
Persistent fetal vasculature
Diagnosis and treatment of glaucoma
among Latin American doctors
Keratoconus and corneal stability
after radial keratectomy
Retinal vasoproliferative tumor
indexada nas bases de dados
medline | embase | isi | SciELO
© Johnson & Johnson do Brasil Indústria E Comércio de Produtos Para Saúde Ltda. MAIO/2013
1ª
Senofilcon A - 1ACUVUE® OASYS® com HYDRACLEAR® PLUS: Reg.ANVISA 80148620045, 2ACUVUE® OASYS® para ASTIGMATISMO com HYDRACLEAR® PLUS: Reg.ANVISA 80148620054, 3ACUVUE®
OASYS® com HYDRACLEAR® PLUS (Bandage): Reg.ANVISA 80148620058, Galyfilcon A - 4ACUVUE® ADVANCE® com HYDRACLEAR®: Reg.ANVISA 80148620026, Etafilcon A - 5ACUVUE® 2: Reg.
ANVISA 80148620019, 61-DAY ACUVUE® MOIST®: Reg.ANVISA 80148620052 , 71-DAY ACUVUE® MOIST® para ASTIGMATISMO: Reg.ANVISA 80148620064 , 8ACUVUE® 2 COLOURS: Reg.ANVISA
80148620013, 9ACUVUE® CLEAR: Reg.ANVISA 80148620021 e 10ACUVUE® BIFOCAL: Reg.ANVISA 80148620016. Caixas com 306,7, 61,2,3,4,5,8,9,10 ou 28 lentes de contato (LC). Indicações: LC Esféricas1,4,5,6,9:
Miopia, hipermetropia (presbiopia em regime de monovisão) afácica ou não afácica. LC Esféricas Coloridas8: Miopia, hipermetropia (presbiopia em regime de monovisão) afácica ou não afácica. LC
Bifocais10: Presbiopia afácica ou não afácica associada ou não a miopia ou hipermetropia. LC Tóricas2,7: Astigmatismo afácico ou não afácico associado ou não a miopia ou hipermetropia. LC Terapêuticas3:
As lentes de contato podem ser prescritas, em determinadas condições ou doenças oculares, como lentes de proteção para a córnea, a fim de aliviar o desconforto e servir como uma cobertura de
proteção. O médico Oftalmologista informará se o usuário apresenta essa condição, podendo prescrever medicações adicionais ou programação de substituição para a condição específica. O usuário
nunca deve tratar qualquer condição, usando lentes de contato ou medicação para os olhos, sem primeiro consultar o médico Oftalmologista. Contra-Indicações: Qualquer inflamação, infecção, doença
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
oculares ou anexas. Qualquer infecção ativa da córnea; olhos vermelhos ou irritados. Precauções e Advertências: Problemas oculares, incluindo úlceras de córnea, podem se desenvolver rapidamente
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.
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
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 incomuns
ou vermelhidão dos olhos. Acuidade visual deficiente, visão embaçada, arco-íris ou halos ao redor de
objetos, fotofobia, ou olho seco, podem ocorrer caso as LC sejam usadas continuamente ou por tempo
excessivamente longo. Se o usuário relatar algum problema, deve RETIRAR IMEDIATAMENTE AS
LENTES e contatar o Oftalmologista. Posologia: Uso prolongado1,2,3,5,8,10– Um a 7 dias/6 noites de uso
contínuo, inclusive durante o sono. Uso diário1,2,3,4,5,8,9,10 – Períodos inferiores a um dia de uso enquanto
acordado. Descartáveis diárias6,7 – uso único. VENDA SOB PRESCRIÇÃO MÉDICA REFRACIONAL
(LC com grau), VENDA SOB PRESCRIÇÃO MÉDICA (LC terapêutica plana), UTILIZAÇÃO SUJEITA À
PRESCRIÇÃO MÉDICA (LC colorida plana). Johnson & Johnson Industrial Ltda. Rod. Pres. Dutra, Km
154 - S. J. dos Campos, SP. CNPJ: 59.748.988/0001-14. Resp. Téc.: Evelise S. Godoy – CRQ No. 04345341.
Mais informações sobre uso e cuidados de manutenção e segurança, fale com seu Oftalmologista, ligue
para Central de Relacionamento com o Consumidor: 0800-7274040, acesse www.acuvue.com.br ou
consulte o Guia de Instruções ao Usuário. A PERSISTIREM OS SINTOMAS, O MÉDICO DEVERÁ SER
CONSULTADO.
1. OS BORN, K.; VEYS, J. A new silicone hydrogel lens for contact lens-related dryeness. Part 1 - Material Properties. Optician, 2005; 6004(229):
39-41.
Colocando o Futuro
em Movimento
Ū2SULPHLURSURFHGLPHQWRIHPWRVVHJXQGRGRPXQGR
Ū3UHFLV£RSHUVRQDOL]DGD
Ū3ODQHMDPHQWRJXLDGRSRULPDJHP
A avançada tecnologia
da LIO AcrySof® aliada
à plataforma LenSx®.
© 2013 Novartis 5/13
AF_AN_21x28.indd 1
LenSx®: MS - 80147540187 AcrySof®: MS - 80147540138
5/9/13 3:04 PM
3448-Hyabak Anun Med BULA NOVA_Layout 1 9/20/11 1:32 PM Page 1
Olho Seco
&
Muco-adesivo 2,4
Pós-Cirurgia
Refrativa1
Alta capacidade de retenção de água 2,3
Hidratação prolongada
Conforto prolongado
Ph e osmolaridade semelhantes às do filme lacrimal normal 2
Visco-elástico 4
Mais conforto ao paciente
Impede a visão turva
Indicado para usuários de lentes de contato 1
Melhora as propriedades de adesão intercelular 3,4
Promove rápida cicatrização pós-cirurgias
Tratamento sintomático do olho seco.
Lubrificação e hidratação de lentes de contato.
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,
Kinoshita S. Characterization of water retentive properties of hyaluronan. Cornea. 1993 Sep;12(5):433-6. 4) Gomes JA, Amankwah R, Powell-Richards A, Dua HS. Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. Br J Ophthalmol. 2004 Jun;88(6);821-5.
SE PERSISTIREM OS SINTOMAS, O MÉDICO DEVERÁ SER CONSULTADO. Informações adicionais disponíveis à classe farmacêutica mediante solicitação.
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 injetáveis q.b.p. 100 mL. NOME E
MORADA DO FABRICANTE: Laboratoires Théa, 12 rue Louis Blériot, 63017 CLERMONT-FERRAND CEDEX 2 - França. QUANDO SE DEVE UTILIZAR ESTE DISPOSITIVO: HYABAK® contém uma solução destinada a ser administrada nos olhos ou nas lentes de contato. Foi concebido: • Para
humedecimento e lubrificação dos olhos, em caso de sensações de secura ou de fadiga ocular induzidas por fatores exteriores, tais como, o vento, o fumo, a poluição, as poeiras, o calor seco, o ar condicionado, uma viagem de avião ou o trabalho prolongado à frente de uma tela de computador. • Nos
utilizadores de lentes de contato, permite a lubrificação e a hidratação da lente, com vista a facilitar a colocação e a retirada, e proporcionando um conforto imediato na utilização ao longo de todo o dia. Graças ao dispositivo ABAK®, HYABAK® permite fornecer gotas de solução sem conservantes. Pode,
assim, ser utilizado com qualquer tipo de lente de contato. A ausência de conservantes permite igualmente respeitar os tecidos oculares. ADVERTÊNCIAS E PRECAUÇÕES ESPECIAIS DE UTILIZAÇÃO: • Evitar tocar nos olhos com a ponta do frasco. • Não injetar, não engolir. Não utilize o produto caso
o invólucro de inviolabilidade esteja danificado. MANTER FORA DO ALCANCE DAS CRIANÇAS. INTERAÇÕES: É conveniente aguardar 10 minutos entre a administração de dois produtos oculares. COMO UTILIZAR ESTE DISPOSITIVO: POSOLOGIA: 1 gota em cada olho durante o dia, sempre que
necessário. Nos utilizadores de lentes: uma gota em cada lente ao colocar e retirar as lentes e também sempre que necessário ao longo do dia. MODO E VIA DE ADMINISTRAÇÃO: INSTILAÇÃO OCULAR. STERILE A - Para uma utilização correta do produto é necessário ter em conta determinadas
precauções: • Lavar cuidadosamente as mãos antes de proceder à aplicação. • Evitar o contato da extremidade do frasco com os olhos ou as pálpebras. Instilar 1 gota de produto no canto do saco lacrimal inferior, puxando ligeiramente a pálpebra inferior para baixo e dirigindo o olhar para cima. O tempo
de aparição de uma gota é mais longo do que com um frasco clássico. Tapar o frasco após a utilização. Ao colocar as lentes de contato: instilar uma gota de HYABAK® na concavidade da lente. FREQUÊNCIA E MOMENTO EM QUE O PRODUTO DEVE SER ADMINISTRADO: Distribuir as instilações
ao longo do dia, conforme necessário. CONSERVAÇÃO DE DISPOSITIVO: NÃO EXCEDER O PRAZO LIMITE DE UTILIZAÇÃO, INDICADO NA EMBALAGEM EXTERIOR. PRECAUÇÕES ESPECIAIS DE CONSERVAÇÃO: Conservar a uma temperatura inferior a 25ºC. Depois de aberto, o frasco não
deve ser conservado mais de 8 semanas.
UNIÃO QUÍMICA FARMACÊUTICA NACIONAL S/A
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Capa: Fotografia biomicroscópica de lesão de aspecto cístico da íris. Exames subsidiários foram sugestivos de lesão tumoral
irido-ciliar. Autor da Fotografia: Dra. Norma Allemann (Setor de Ultrassonografia do Departamento de Oftalmologia da
UNIFESP, Brasil).
Cover: Biomicroscopic photograph of a cystic iris lesion. Subsidiary exams were suggestive of a tumoral iridociliary lesion. Pho
tographer: Norma Allemann, MD (Ultrasound Sector, Department of Ophthalmology, UNIFESP, Brazil).
CONSELHO BRASILEIRO
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ISSN 0004-2749
(Versão impressa)
ISSN 1678-2925
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•MEDLINE
Diretoria do CBO - 2011-2013
Marco Antônio Rey de Faria (Presidente)
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Sociedades Filiadas ao Conselho Brasileiro de Oftalmologia
e seus respectivos Presidentes
Apoio:
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Sociedade Brasileira de Cirurgia Refrativa
Renato Ambrósio Júnior
Sociedade Brasileira de Ecografia em Oftalmologia
Norma Allemann
Sociedade Brasileira de Glaucoma
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Sociedade Brasileira de Laser e Cirurgia em Oftalmologia
Caio Vinicius Saito Regatieri
Sociedade Brasileira de Lentes de Contato, Córnea e Refratometria
César Lipener
Sociedade Brasileira de Oftalmologia Pediátrica
Rosa Maria Graziano
Sociedade Brasileira de Oncologia em Oftalmologia
Priscilla Luppi Ballalai Bordon
Sociedade Brasileira de Retina e Vítreo
Walter Yukihiko Takahashi
Sociedade Brasileira de Trauma Ocular
Nilva Simeren Bueno Moraes
Sociedade Brasileira de Uveítes
Wilton Feitosa de Araújo
Sociedade Brasileira de Visão Subnormal
Mayumi Sei
CONSELHO BRASILEIRO
DE OFTALMOLOGIA
ISSN 0004-2749
(Versão impressa)
ISSN 1678-2925
Periodicidade: bimestral
Arq Bras Oftalmol. São Paulo, v. 76, n. 3, p. 141-208, mai./jun. 2013
Sumário | Contents
Editorial | Editorial
As
letras pequenas no final da página
V
Fine prints at the bottom of the page
Wallace Chamon
VI
As letras pequenas no final da página
Wallace Chamon
Artigos Originais | Original Articles
141
Experimental study of new material for biocompatibility as orbital implant
Rodrigo Beraldi Kormann, Hamilton Moreira, Graziella Crescente, José Aguiomar Foggiatto
147
Posicionamento das alças de lentes intraoculares implantadas intencionalmente no sulco ciliar através
da biomicroscopia ultrassônica
Estudo experimental da biocompatibilidade de novo material para implante orbitário
Positioning of intraocular lens haptics intentionally implanted in the ciliary sulcus by ultrasound biomicroscopy
Ricardo Rau, Carmen Resende Santana, Andrea Alejandra Gonzalez Martinez, André Luiz de Freitas Silva, Norma Allemann
New adjustable suture technique for trabeculectomy
152
Nova técnica de sutura ajustável para trabeculectomia
Vespasiano Rebouças-Santos, Daniel Meira-Freitas, Angelino Júlio Cariello, Tiago dos Santos Prata, Sergio Henrique Teixeira
thickness changes during corneal collagen cross-linking with UV-A irradiation and hypo-osmolar riboflavin
155Corneal
in thin corneas
Alterações na espessura da córnea durante “cross-linking” do colágeno com irradiação UV-A e riboflavina hipo-osmolar em córneas finas
Belquiz Amaral Nassaralla, Diogo Mafia Vieira, Márcia Leite Machado, Marisa Novaes Faleiro Chaves de Figueiredo, João Jorge Nassaralla Jr.
159
Vitrectomia e troca fluido-gasosa para o tratamento do descolamento seroso da mácula por fosseta de disco óptico:
avaliação de longo prazo
Vitrectomy and gas-fluid exchange for the treatment of serous macular detachment due to optic disc pit: long-term evaluation
Carlos Augusto Moreira Neto, Carlos Augusto Moreira Junior
of agreement among Latin American glaucoma subspecialists on the diagnosis and treatment of glaucoma:
163Level
results of an online survey
Nível de concordância entre subespecialistas de glaucoma latino-americanos sobre o diagnóstico e tratamento do glaucoma:
resultados de uma pesquisa digital
Daniel E. Grigera, Paulo Augusto Arruda Mello, Wilma Lelis Barbosa, Javier Fernando Casiraghi, Rodolfo Perez Grossmann, Alejo Peyret
and specificity of machine learning classifiers for glaucoma diagnosis using Spectral Domain OCT
170Sensitivity
and standard automated perimetry
Sensibilidade e especificidade dos classificadores de aprendizagem de máquina para o diagnóstico de glaucoma usando Spectral Domain OCT
e perimetria automatizada acromática
Fabrício R. Silva, Vanessa G. Vidotti, Fernanda Cremasco, Marcelo Dias, Edson S. Gomi, Vital P. Costa
characteristics and outcomes of patients admitted with presumed microbial keratitis
175Clinical
to a tertiary medical center in Israel
Características clínicas e desfechos dos pacientes internados com diagnóstico de ceratite microbiana em um centro terciário em Israel
Fabio Lavinsky, Noah Avni-Zauberman, Irina S Barequet
bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary
180Intravitreal
to age-related macular degeneration: case report series
Administração intravítrea de bevacizumabe combinado com infliximabe no tratamento da neovascularização coroidiana secundária à degeneração macular
relacionada à idade: relato de uma série de casos
Luiz Guilherme Azevedo de Freitas, David Leonardo Cruvinel Isaac, William Thomas Tannure, Luís Alexandre Rassi Gabriel, Ricardo Gomes dos Reis, Alan Ricardo Rassi,
Clovis Arcoverde de Freitas, Marcos Pereira de Ávila
185
Persistent fetal vasculature: ocular features, management of cataract and outcomes
Marcia Beatriz Tartarella, Rodrigo Ueno Takahagi, Ana Paula Braga, João Borges Fortes Filho
Persistência da vasculatura fetal: características oftalmológicas, manuseio da catarata e resultados cirúrgicos
Relatos de Casos | Case Reports
depth imaging optical coherence tomography and fundus autofluorescence findings in
189Enhanced
bilateral choroidal osteoma: a case report
Tomografia de coerência óptica com profundidade de imagem aprimorada e resultados autofluorescência de fundo em osteoma de
coroide bilateral: relato de caso
Muhammet Kazim Erol, Deniz Turgut Coban, Basak Bostanci Ceran, Mehmet Bulut
Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome in a young man: case report
192
Oclusão unilateral da artéria central da retina como único sinal de apresentação da síndrome de Susac em jovem do sexo masculino: relato de caso
Samira Luiza dos Apóstolos-Pereira, Lúcia B. Passos Kara-José, Paulo Euripedes Marchiori, Mário Luiz Ribeiro Monteiro
195
Keratoconus and corneal stability after radial keratectomy in the fellow eye: case report
Jacqueline Martins Sousa, Flavio Eduardo Hirai, Elcio Hideo Sato
Ceratocone e estabilidade corneana após ceratectomia radial no outro olho: relato de caso
Recuo assimétrico dos músculos retos horizontais para correção de incomitância alfabética: relato de caso
197
Asymmetric recession of the horizontal rectus muscles for correction alphabetical incomitance: case report
Alyne Borges Corrêa, Tomás Fernando Scalamandré Mendonça
Artigos de Revisão | Review Articles
200
Tumor vasoproliferativo da retina
Eduardo Ferrari Marback, Ricardo Leitão Guerra, Otacilio de Oliveira Maia Junior, Roberto Lorens Marback
205 Instruções para os Autores | Instructions to Authors
Editorial |
Editorial
Wallace Chamon1
Há alguns anos o ABO mudou sua política de informações adicionais aos artigos para se adequar ao Comitê
Internacional de Editores de Periódicos Médicos (ICMJE). Todos os trabalhos submetidos à publicação nos ABO vêm
acompanhado por 3 informações adicionais importantes: Declaração de Participação dos Autores(1), Declaração de
Aprovação da Pesquisa por Comitê de Ética em Pesquisa, Declaração de Conflito de Interesse Potencial de todos os
autores envolvidos(2).
O formulário de declaração de participação dos autores segue as diretrizes mundialmente aceitas e bem definidas
do ICMJE(3). As instruções aos autores do ABO especificam que o crédito de autoria deve ser baseado em indivíduos
que tenham contribuído de maneira concreta em todas as fases do manuscrito. O ABO requer ainda a garantia de que
todos os autores preenchem os critérios acima e que nenhuma pessoa que preencha esses critérios seja preterida
da autoria. Apenas a posição de chefia de qualquer indivíduo não atribui a este o papel de autor, o ABO não aceita a
participação de autores honorários(4).
A exigência da cópia da declaração de aprovação de comitê de ética em pesquisa é aplicada em todas as pesquisas, prospectivas ou retrospectivas, que envolvam seres humanos ou animais. A única exceção são os relatos de
caso. É necessário que o autor correspondente envie, como documento suplementar, a aprovação do comitê de ética
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a necessidade de avaliação pelo comitê. Todos os ensaios clínicos, além da aprovação do comitê, devem indicar, na
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A declaração de um potencial conflito de interesse não diminui a qualidade nem a credibilidade do trabalho,
a negação de conflito existente sim. Note que apesar da palavra conflito algumas vezes poder denotar um sentido
bélico, a presença de um conflito de interesses de maneira alguma significa que o autor com interesses distintos opte
pelo ilícito ou imoral(5). Em resumo, a declaração de potencial conflito de interesse elaborada pelo ICMJE define que o
objetivo desta é dar informações ao leitor que possam interferir na maneira com que este interpretará o artigo lido(2).
Os conflitos a serem expostos se referem à compensações financeiras ou não financeiras (equipamentos ou matérias
de consumo) que ocorreram até 36 meses antes do planejamento do trabalho até o seu envio para publicação. São
consideradas compensações aquelas que efetivamente tenham acontecido ou a expectativa de que venham a acontecer, sejam elas diretamente ligadas ao trabalho submetido ou não. Quando a compensação ocorre por meio de
bolsas ou verbas para pesquisa (sejam elas públicas ou privadas), apenas aquelas relacionadas ao trabalho submetido
devem ser declaradas, outras verbas que o autor participe não precisam ser declaradas como potencial conflito de
interesse. Também são consideradas como potenciais conflitos de interesse as participações em patentes provisórias
ou definitivas relacionadas ao trabalho submetido(2).
Todas essas informações são prestadas pelos autores de maneira eletrônica e todos os autores que não participam
diretamente do envio do trabalho devem ficar atentos para que essas informações sejam fidedignas. Não cabe à secretaria editorial do ABO o papel policialesco de confirmar as informações prestadas, mas os formulários eletrônicos
são mantidos em arquivo para qualquer questionamento futuro.
Como a transparência das informações permite aos leitores uma interpretação mais adequada dos artigos lidos,
é fundamental que estes prestem atenção no texto com letras pequenas ao final das páginas.
Referências
1.Arquivos Brasileiros de Oftalmologia. Formulário de Contribuição dos Autores [Internet].
São Paulo: Conselho Brasileiro de Oftalmologia [cited 2013 Jul 25]; Available from: http://
www.cbo.com.br/site/files/Formulario%20Contribuicao%20dos%20Autores.pdf
2. International Committee of Medical Journal Editors. ICMJE Form for Disclosure of Potential Conflicts of Interest [Internet]. British Columbia: ICMJE; 2013 [cited 2013 Jul 25].
Available from: http://www.icmje.org/coi_disclosure.pdf
3.International Committee of Medical Journal Editors. Uniform Requirements for Manus-
Submetido para publicação: 25 de julho de 2013
Aceito para publicação: 25 de julho de 2013
1
Médico, Departamento de Oftalmologia, Universidade Federal de São Paulo - UNIFESP - São Paulo
(SP), Brasil.
cripts Submitted to Biomedical Journals: ethical considerations in the conduct and
reporting of research: authorship and contributorship [Internet]. British Columbia: ICMJE;
2013 [cited 2013 Jul 25]. Available from: http://www.icmje.org/ethical_1author.html
4.Arquivos Brasileiros de Oftalmologia. Diretrizes para Autores. São Paulo: Conselho
Brasileiro de Oftalmologia [cited 2013 Jul 25]; Available from: http://submission.scielo.
br/index.php/abo/about/submissions#onlineSubmissions
5. Chamon W, Melo LA Jr, Paranhos A Jr. Declaração de conflito de interesse em apresentações e publicações científicas. Arq Bras Oftalmol. 2010;73(2):107-9.
Financiamento: Não houve financiamento para este trabalho.
Divulgação de potenciais conflitos de interesse: W.Chamon, Nenhum.
V
Editorial |
Editorial
Wallace Chamon1
Some years ago the ABO changed its policy of articles ‘additional information to suit the International Committee
of Medical Journal Editors (ICMJE). All papers submitted for publication in ABO come accompanied by three additional important information: Statement of Authors Participation(1), Statement of Approval of the Ethics on Research
Committee, Declaration of Potential Conflicts of Interest of all authors involved(2).
The form for declaration of authors’ participation follows the guidelines universally accepted and well defined
the ICMJE(3). ABO’s instructions to authors specify that authorship credits should be based on individuals who have
contributed in concrete ways at all stages of the manuscript. The ABO also requires ensuring that all authors meet the
criteria above and that no person who meets these criteria is denied authorship. The leading position alone of any
individual does not delegate authorship; the ABO does not recognizes honorary authorship(4).
A copy of the approval of the ethics committee on research is required to all studies, prospective or retrospective,
involving humans or animals. The only exceptions are case reports. It is mandatory that the corresponding author send,
as a supplementary document, the approval of the ethics committee on research or its opinion dismissing the project
evaluation by the committee. It is not up to the author to decide on the need for evaluation by the committee. All
clinical trials, in addition to the approval of the committee, shall indicate on the cover page, the registration number
on an international basis registry that allows free access to the information.
The declaration of a possible conflict of interest does not diminish the quality or credibility of the work, the
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immoral(5). In short, the declaration of potential conflict of interest established by the ICMJE defines that its purpose
is to give the reader information that may interfere with the way that he or she interprets the article read(2). Conflicts
to be acknowledged refer to financial or non-financial compensation (equipment or material) that occurred within
36 months before the planning of the research until its submission for publication. Compensation are considered
those that have actually happened or the expectation that may happen, whether directly related to the submitted
paper or not. When compensation occurs through grants or research funding (public or private), only those related
to the submitted paper must be declared, other funds which the author participates do not have to be declared as
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The authors to provide all information electronically and all authors who do not participate directly in the submission must be sure that this information is trustworthy. It is not up to the editorial office of ABO to confirm the
information provided, but the electronic forms are kept on file for any future questioning.
As the transparency of information allows readers a more adequate interpretation of articles read, it is essential
that these pay attention to the fine prints at the bottom of the page.
ReferEncEs
1.Arquivos Brasileiros de Oftalmologia. Formulário de Contribuição dos Autores [Internet].
São Paulo: Conselho Brasileiro de Oftalmologia [cited 2013 Jul 25]; Available from: http://
www.cbo.com.br/site/files/Formulario%20Contribuicao%20dos%20Autores.pdf
2. International Committee of Medical Journal Editors. ICMJE Form for Disclosure of Potential Conflicts of Interest [Internet]. British Columbia: ICMJE; 2013 [cited 2013 Jul 25].
Available from: http://www.icmje.org/coi_disclosure.pdf
3.International Committee of Medical Journal Editors. Uniform Requirements for Manus-
Submitted for publication: July 25, 2013
Accepted for publication: July 25, 2013
1
Physician, Department of Ophthalmology, Federal University of São Paulo - UNIFESP - São Paulo
(SP), Brazil.
VI
cripts Submitted to Biomedical Journals: ethical considerations in the conduct and
reporting of research: authorship and contributorship [Internet]. British Columbia: ICMJE;
2013 [cited 2013 Jul 25]. Available from: http://www.icmje.org/ethical_1author.html
4.Arquivos Brasileiros de Oftalmologia. Diretrizes para Autores. São Paulo: Conselho
Brasileiro de Oftalmologia [cited 2013 Jul 25]; Available from: http://submission.scielo.
br/index.php/abo/about/submissions#onlineSubmissions
5. Chamon W, Melo LA Jr, Paranhos A Jr. Declaração de conflito de interesse em apresentações e publicações científicas. Arq Bras Oftalmol. 2010;73(2):107-9.
Funding: No specific financial support was available for this study.
Disclosure of potencial of interest: W.Chamon, None.
Artigo Original | Original Article
Experimental study of new material for biocompatibility as orbital implant
Rodrigo Beraldi Kormann1, Hamilton Moreira2, Graziella Crescente3, José Aguiomar Foggiatto4
RESUMO
ABSTRACT
Objetivo: Avaliar a biocompatibilidade de material FullCure 720®, que é uma resina, na confecção de implante orbitário. Avaliou-se a resposta clínica dos animais,
toxicidade sistêmica e a resposta inflamatória crônica. Os animais foram pesados,
exames bioquímicos e resposta inflamatória foram avaliados. Foi efetuada evisceração e colocado implante esférico orbitário. Os animais foram acompanhados
durante o período de 60 dias, onde se avaliou o comportamento clínico e sinais
locais. Após este período, procedeu-se a eutanásia seguida da enucleação. Foi
realizada análise macroscópica e histomorfométrica. Os resultados revelaram
comportamento normal dos animais, com ausência de exposição ou extrusão
dos implantes, morte de algum animal e ausência de toxicidade sistêmica. Houve
formação de uma cápsula fibrosa entre a capa escleral e o implante orbitário,
resposta inflamatória considerada normal quando em contato com o tecido do
coelho. A resina FullCure 720® utilizada como implante orbitário, mostrou-se
biocompatível neste estudo.
Purpose: To evaluate the resin FullCure 720® biocompatibility as orbital implant.
Clinical response and signs of systemic toxicity to the resin were evaluated, local
biocompatibility and microscopic analysis regarding chronic local inflammatory
response to the implant. The animals were weighted, biochemical exams and
inflammatory response were evaluated. All animals were eviscerated and implan
tation of the spheres was carried out. Animals were followed for 60 days. Clinical
behavior of animals and local signals of inflammation had been observed. After this
period animals underwent euthanasia followed by enucleation. Macroscopic and
histomorphometric analysis were performed. The results showed normal behavior
of the animals, without implant exposure, extrusion, death or systemic toxicity.
Capsule tissue formation was observed between the sclera and the implant. Normal
inflammatory response to the foreign material in contact with the rabbit soft tissue
was observed. The resin FullCure 720®, demonstrated to be biocompatible as an
orbital implant in this study.
Descritores: Materiais biocompatíveis; Resinas compostas; Teste de materiais;
Próteses e implantes; Implantes orbitários; Animais; Coelhos
Keywords: Biocompatible materials; Composite resins; Materials testing; Prostheses
and implants; Orbital implants; Animals; Rabbits
INTRODUÇÃO
Cavidade anoftálmica é definida como a órbita desprovida do
bulbo ocular, podendo ser congênita ou adquirida. Quando congênita, podemos subdividir em: anoftalmia, microftalmia e nanoftalmia.
As cavidades anoftálmicas adquiridas são deformidades causadas
pela remoção do bulbo ocular ou de seu conteúdo, cirurgicamente
ou após um trauma óculo-orbitário(1).
A evisceração (remoção do conteúdo intraocular) e a enucleação
(remoção do globo ocular) são procedimentos cirúrgicos inevitáveis
em algumas doenças oculares. Tanto na evisceração, quanto na enucleação, ocorre redução do conteúdo da cavidade orbitária, necessitando reposição de volume orbitário o mais precoce possível, com
implante e técnica cirúrgica adequada, a fim de proporcionar um aspecto estético aceitável, evitando deformidades orbitopalpebrais(2).
Normalmente utilizam-se enxertos autógenos (ex.: enxerto dermogorduroso) ou materiais aloplásticos (biomateriais), estes conhecidos como implantes orbitários, para a reconstituição das cavidades
anoftálmicas. A vantagem do enxerto autógeno é a compatibilidade
tecidual, porém pode haver certa absorção do enxerto ao longo do
tempo, com consequente perda de resultado, assim como o uso
destes tecidos (autógenos) está relacionado à necessidade de áreas
doadoras de enxerto, aumentando a morbidade do ato cirúrgico. Os
biomateriais simplificam o ato cirúrgico, mas necessitam de algumas
propriedades essenciais, entre elas de serem biocompatíveis(3).
A descoberta de novos biomateriais, mudanças no formato e
dimensões dos implantes orbitários, tem ajudado na melhora da
reconstituição das cavidades orbitárias. Apesar destes fatos, as com
plicações precoces e tardias ainda existem, como: exposições, infecções e extrusões dos implantes orbitários. Estas complicações estão
principalmente relacionadas com o tipo de material implantado,
além da técnica cirúrgica utilizada, sendo um dos motivos da procura
de novos materiais(4).
O implante orbitário ideal seria aquele que pudesse proporcionar a melhor estética, fosse biocompatível, não alergênico e não
cancerígeno, tivesse baixos índices de exposição, extrusão, infecção
ou migração, e fossem leves, passíveis de esterilização e de baixo
custo de fabricação. Entretanto, ainda não existe este implante ideal,
motivando-nos a pesquisa de um novo material para implante orbitário que pudesse proporcionar bons resultados, contando com as
características supracitadas e custo aceitável à realidade da população do nosso país.
O objetivo deste estudo é avaliar se os implantes orbitários esféricos de resina FullCure 720® são biocompatíveis e podem ser utilizados
para reparo de cavidades anoftálmicas, usando modelo experimental.
Submetido para publicação: 10 de outubro de 2012
Aceito para publicação: 25 de janeiro 2013
Trabalho realizado na Faculdade Evangélica do Paraná - FEPAR - Curitiba (PR), Brasil.
Médico, Setor de Oftalmologia, Faculdade Evangélica do Paraná - FEPAR - Curitiba (PR), Brasil.
Médico, Setor de Oftalmologia, Universidade Federal do Paraná - UFPR - Curitiba (PR), Brasil.
Médica, Setor de Patologia, Universidade Católica do Paraná - PUCPR - Curitiba (PR), Brasil.
4
Engenheiro Mecânico, Núcleo de Prototipagem e Ferramental, Universidade Tecnologia Federal do
Paraná - UTFPR - Curitiba (PR), Brasil.
1
2
3
Divulgação de potenciais Conflitos de Interesse: R.B.Kormann, Nenhum; H.Moreira, Nenhum;
G.Crescente, Nenhum; J.A.Foggiatto, Nenhum.
Endereço para correspondência: Rodrigo Beraldi Kormann. Rua Deputado Emílio Carlos, 50 Curitiba (PR) - 80540-080 - Brasil - E-mail: [email protected]
Comitê de Ética em Pesquisa da Sociedade Evangélica Beneficente de Curitiba N. 3336/11.
Arq Bras Oftalmol. 2013;76(3):141-6
141
MÉTODOS
Para a confecção deste novo implante foi utilizada uma máquina
de prototipagem rápida (Eden 250®), no Núcleo de Prototipagem e
Ferramental (NUFER) da Universidade Tecnológica Federal do Paraná
(UTFPR). A resina denominada FullCure 720® é um monômero acrílico, translúcida, resistente, sem propriedades de hipersensibilidade(5),
que pode ser utilizada pela Tecnologia Polyjet® para prototipagem de
biomodelos com muita precisão e confecção de finos detalhes. O implante foi confeccionado com duas superfícies distintas, uma rugosa
e outra lisa (Figura 1), com o intuito de analisar por exame histológico
as possíveis diferenças de reação inflamatória na porção interna da
capa escleral em cada uma das situações e, posteriormente, através
da avaliação histomorfométrica mensurar essa diferença. Ao término
da confecção, os implantes orbitários de resina FullCure 720® foram
enviados a Sterilab® para esterilização a gás, em óxido de etileno.
Foi desenhado um estudo experimental, prospectivo e com
intervenção. Foram utilizados 16 coelhos (Oryctolagus cuniculus)
machos, albinos, da espécie Nova Zelândia, com peso variando entre
2.400 e 3.100 g e idade superior a 120 dias. Houve dois momentos
experimentais (M1 e M2), no momento 1 os animais foram anestesiados, pesados e procedeu-se a coleta de sangue para os exames
bioquímicos (alanina transaminase (TGP), aspartato aminotransferase (TGO), albumina, ureia, creatinina, FA, CPK e proteína C reativa),
então realizou-se a evisceração do olho direito de cada animal e foi
colocado um implante esférico de resina FullCure 720® de 10 mm de
diâmetro. O implante orbitário foi posicionado adequadamente no
interior da cavidade escleral, permanecendo 50% da superfície rugosa e 50% da superfície lisa do implante na porção posterior da capa
escleral. Depois de operados, os animais permaneceram 60 dias com
os implantes esféricos na cavidade eviscerada e foram clinicamente
acompanhados a cada cinco dias, de acordo com a ficha clínica
elaborada, onde consta: peso, dados bioquímicos pré-operatórios,
eventual intercorrência per-operatória (evisceração), avaliação ectoscópica dos animais. O exame avaliou alterações da saúde geral dos
animais, estimada pela atividade, apetite e postura em suas gaiolas
(mímica de dor ocular - “coçar” a face contra a gaiola), eventuais sinais
presentes na cavidade orbitária (presença de sinais inflamatórios,
infecciosos, deiscência de sutura, exposição ou extrusão do implante
orbitário) e morte de algum animal.
Após os 60 dias de acompanhamento iniciou-se o momento 2,
onde foi mensurado novamente o peso e os exames bioquímicos,
então procedeu-se a enucleação e eutanásia dos animais.
Os olhos enucleados foram colocados isoladamente em recipientes com formaldeído tamponado a 10%, identificados e encaminhados para exame histopatológico. Após sete dias de fixado o material,
realizou-se o exame macroscópico de cada olho enucleado dos 16
animais, avaliando a linha de sutura na porção anterior, aspecto geral
A
B
Figura 1. Superfícies: rugosa (A) e lisa (B) do implante orbitário FullCure 720®.
142
da esclera, coto do nervo óptico na porção posterior. A área escleral
(interface) onde estava a porção rugosa e lisa do implante em cada
animal foi marcada com tinta azul, certificando-se do adequado
posicionamento do implante dentro da cavidade escleral. Remo
veu-se as esferas de resina acrílica FullCure 720® do interior de cada
esclera e apenas a capa escleral de cada olho enucleado foi enviada
para análise morfológica (qualitativa) e o estudo histomorfométrico
(quantitativo).
As lâminas coradas pelo método HE e para fibra elástica pelo mé
todo Verhoeff-Van Gieson (VVG), foram analisadas visando avaliação
histológica da reparação tecidual inflamatória (cápsula fibrosa), encontrada nos tecidos ao redor do implante orbitário de resina acrílica
FullCure 720®. O exame morfométrico fez uma avaliação quantitativa
da cápsula formada ao redor dos implantes, empregando-se um
sistema com pontos fixos e sistematicamente equidistantes. As avaliações foram realizadas, adotando-se a padronização de análise de
cortes em quatro posições (pontos), todos na porção posterior da
esclera, a fim de evitar a área de sutura anterior e o processo inflamatório gerado durante o procedimento cirúrgico. Conforme a disposição do corte sobre a lâmina histológica, a capa escleral posterior
em contato com o implante foi analisada em dois pontos na porção
rugosa e dois pontos na porção lisa (Figura 2). Sob microscopia óptica
em aumento de 10 vezes, obtiveram-se duas imagens da porção da
interface lisa (área da esclera em íntimo contato com a superfície lisa
do implante) e duas imagens da porção da interface rugosa (área
da esclera em íntimo contato com a superfície rugosa do implante),
totalizando quatro imagens em cada um dos 16 olhos enucleados.
Em cada uma destas imagens, foram realizadas 10 medidas morfométricas lineares da espessura da esclera-cápsula fibrosa, obtendo-se
ao total 40 medidas de cada coelho (Figura 3). Finalmente, foram
feitas as médias da espessura esclera-cápsula fibrosa das 20 medidas
obtidas da interface lisa (ECL) e das 20 medidas obtidas da interface
rugosa (ECR) de cada coelho (unidade utilizada = micrômetros - µm).
Como apenas enucleou-se o olho onde foi implantada a esfera
de resina, não havia maneira de medir a espessura da esclera normal
destes coelhos para compará-las. Visto que o intuito era de analisar e
Figura 2. Foto de lâmina mostrando corte histológico. Com objetiva de 4 x, evidencia-se
capa escleral anterior (área sutura), capa escleral posterior (nervo óptico) e as porções
esclerais que estavam em contato com superfície rugosa (ECR) e lisa (ECL) do implante
FullCure 720®. Foram feitas duas fotos em cada uma destas porções (área marcada com
ponto preto) e estas analisadas sob microscopia óptica em aumento de 10x.
Kormann RB, et al.
discutir as alterações encontradas na espessura destas escleras com
implante (Figura 3), comparando com escleras normais (sem implante orbitário), avaliou-se a medida da esclera normal (EC) através da
mesma metodologia descrita, utilizando os blocos de parafina do
grupo controle(6), os quais se encontravam arquivados no Laboratório
do Departamento de Patologia da Pontifícia Universidade Católica
do Paraná (PUCPR), uma vez que neste grupo controle os animais
apresentavam os mesmos padrões deste estudo (espécie, raça, sexo,
idade, peso). As imagens e medidas obtidas destes blocos de parafina
foram realizadas pela mesma pessoa, especializada em informática,
que fez as medidas de nossas lâminas.
Para análise estatística as variáveis qualitativas (hiperemia conjuntival e secreção ocular) foram efetuadas pelo teste binominal e para
as variáveis quantitativas (peso, exames bioquímicos e espessura
esclera entre os grupos), foi avaliada a condição de normalidade
pelo teste de Kolmogorov-Smirnov, e os momentos (M1 e M2) foram
comparados pelo teste t de Student para amostras pareadas ou pelo
teste não paramétrico de Wilcoxon. Valores de p<0,05 indicaram
significância estatística.
RESULTADOS
Durante todo o seguimento, os coelhos não apresentaram mu
danças significativas de comportamento, como: irritabilidade, estresse, entre outros. Nenhum animal apresentou sinais infecciosos,
deiscência de sutura, exposição ou extrusão do implante orbitário;
também não houve morte de nenhum animal durante o estudo.
Em relação à hiperemia conjuntival e secreção ocular, estas foram
encontradas somente até o 10o dia da avaliação clínica, sendo que
apenas 6,3% dos coelhos não apresentaram hiperemia conjuntival.
Nas avaliações de 15 a 60 dias não foram verificados casos com a
presença de hiperemia conjuntival e secreção ocular (Gráfico 1).
Em relação às outras variáveis analisadas, como: exposição ou
extrusão do implante esférico de resina FullCure 720®, ou morte, não
foram observadas em nenhum dos animais durante todo o período
de observação (60 dias pós-operatório).
Observamos um ganho médio de 475 gramas de peso em cada
animal durante os 60 dias do estudo.
Para avaliação da toxicidade renal, analisou-se o valor da ureia e
da creatinina entre os momentos M1 e M2, onde houve um aumento
da ureia de 33,8 mg/dL (M1) para 34,1 mg/dL (M2) e a creatinina
aumento de 0,92 mg/dL (M1) para 1,23 mg/dL (M2). Para avaliação
hepática coletou-se: aspartato aminotransferase (TGO) que apresentou diminuição entre os momentos M1 e M2 (26,3 U/L para 20,7 U/L),
Figura 3. Morfometria: realizadas dez medidas verticais lineares da espessura esclera
até o término da cápsula fibrosa (grupo experimento).
alanina aminotransferase (TGP) que aumentou de 38,9 U/L para
49,2 U/L, albumina que aumentou de 3,70 g/dL para 3,86 g/dL e a
fosfatase alcalina que apresentou uma diminuição entre M1 e M2
(186,6 g/dL para 134,9 g/dL). A avaliação cardíaca foi realizada através
da creatinofosfoquinase (CPK), que se apresentou bem elevada no
momento M1 (2.245,4 U/L) e diminuiu no M2 (602,4 U/L) e a reação
inflamatória pela proteína C reativa (PCR) que diminuiu de 1,67 mg/L
para 0,57 mg/L.
Neste estudo observamos a formação de uma cápsula fibrosa entre a esclera dos animais e o implante orbitário, sendo esta
constituída por tecido conjuntivo fibroso e componentes celulares
inflamatórios em quantidades variáveis. Em todos os animais estes
componentes foram discretos (linfócitos, macrófagos, células gigantes e raros neutrófilos e eosinófilos), no entanto a espessura da
cápsula fibrosa formada diferiu significativamente (p<0,001) quando
a esclera estava em contato com a área lisa (814,3 µm) ou a área
rugosa (1.177,4 µm) do implante orbitário, sendo mais espessa nesta
(Figuras 4 e 5). Utilizando a coloração para fibra elástica (VVG), no
grupo experimento, é possível diferenciar melhor a esclera normal
em relação à cápula fibrosa, pois esta não possui fibras elásticas, não
corando (Figura 6). No grupo controle observamos a esclera normal,
com ausência da cápsula fibrosa. A espessura da esclera normal (grupo controle) foi de 642,9 µm.
Gráfico 1. Presença de hiperemia e secreção de acordo com os momentos de avaliação.
Figura 4. Foto de lâmina mostrando esclera-cápsula lisa (coloração HE).
143
Figura 5. Foto de lâmina mostrando esclera-cápsula rugosa (coloração HE).
Figura 6. Foto de lâmina coelho 6 mostrando a esclera-cápsula fibrosa em área de
esfera rugosa. Observe a ausência de fibras elásticas na porção cápsula fibrosa (própria
de processo inflamatório) e a presença das fibras elásticas na esclera (com distribuição
habitual) - coloração para fibra elástica (VVG).
DISCUSSÃO
Procurou-se, por meio deste estudo, analisar a biocompatibilida
de de um novo material, para a confecção de implante orbitário es
férico composto por resina FullCure 720®, utilizados em cavidades
orbitárias evisceradas de coelhos. É de extrema importância na
escolha de um biomaterial, fatores como tecnologia envolvida na
produção da matéria prima e do componente, disponibilidade e
custo dos insumos, entre outros, que influenciam no preço final da
peça. A resina FullCure 720® é um material de base acrílica fotocurável, que pode ser facilmente obtida em nosso país, com um custo
acessível à nossa população. O implante orbitário de FullCure 720®
foi fácil e rapidamente confeccionado em local apropriado (UTFPR),
por pessoal treinado, utilizando a prototipagem rápida, que é uma
forma de tecnologia que fabrica modelos ou materiais a partir de
informação eletrônica (CAD). Após modelado o material no programa
CAD-3D, ele precisa ser convertido para o formato STL para possibilitar a prototipagem rápida pela tecnologia Polyjet, onde encontramos
alta qualidade e resolução para obtenção de partes lisas, precisas e
altamente detalhadas, sendo um processo rápido por não necessitar
de “cura” do material.
Após a cirurgia de evisceração e a devida recuperação pós-operatória dos animais, estes foram colocados em condições ambientais
144
estáveis (ruído, temperatura, gaiolas padronizadas, entre outros) para
assegurar a reprodução dos resultados experimentais.
Não houve qualquer sinal de irritabilidade dos animais e o ganho
de peso ficou dentro do esperado no curso normal do estudo. Em
relação à hiperemia conjuntival e à secreção ocular (consistência
mucoide e cor esbranquiçada) observadas durante o estudo, podem
ser considerado como dentro da normalidade. Em relação às outras
variáveis analisadas: quemose, deiscência de sutura, exposição do
implante, extrusão do implante orbitário e eventuais sinais de debilidade ou morte de algum animal, nenhuma esteve presente neste
estudo, revelando uma tolerância clínica do material.
Para verificar possíveis efeitos tóxicos da resina FullCure 720®
ao organismo, caso esta fosse absorvida sistemicamente causando
danos aos tecidos: hepáticos, renais, cardíacos e sinais inflamatórios,
foram realizados exames bioquímicos (TGP, TGO, albumina, ureia,
creatinina, fosfatase alcalina, CPK, e PCR), logo antes do procedimento cirúrgico de evisceração (M1) e antes da enucleação (M2).
Considerou-se o momento M1 como o padrão de normalidade para
o estudo bioquímico, comparando com o momento M2. Procurouse dar maior valor a esta diferença (entre os momentos M1 e M2),
do que para os valores citados na literatura(7-8), pois existem poucas
informações disponíveis sobre o efeito da doença clínica nos parâmetros sanguíneos de coelhos, ou sobre exames bioquímicos como
indicadores de diagnóstico(7). Durante a avaliação dos parâmetros
bioquímicos estudados, observou-se que a ureia teve aumento não
significativo (p=0,912), sendo que ela altera com o ritmo circadiano,
quantidade e qualidade de proteínas na dieta, absorção intestinal
e hidratação. A creatinina apresentou um aumento significativo
(p<0,001), mas mesmo assim permanecendo dentro dos padrões de
normalidade (0,5-2,5 mg/dL) para os valores de referência da literatura. O estresse é um fator que poderia causar diminuição da perfusão
renal, provocando aumento da creatinina(8). Com estes resultados,
pode-se considerar que a resina FullCure 720® não causou danos
renais aos animais deste estudo.
A avaliação hepática foi realizada através de indicadores apropriados, sendo que a enzima TGO teve diminuição não significativa
em seus níveis sanguíneos (p=0,148), a TGP teve um aumento, mas
não foi significativo (p=0,134). Em dano hepatocelular leve, a forma
predominante no soro é a citoplasmática (TGP), enquanto em lesões
graves há liberação da enzima mitocondrial (TGO), elevando a relação TGO/TGP(9). Considerando que neste estudo esta relação diminuiu (TGO/TGP M1=0,68 TGO/TGP M2=0,42), evidencia-se ausência
de lesão hepática.
A fosfatase alcalina teve uma diminuição significativa (p<0,001)
em seus parâmetros, situação esta que não se conseguiu esclarecer
o(s) motivo(s), sendo que a média no momento M2 ficou mais próxima aos valores da normalidade na literatura (12-96 U/L). A albumina
apresentou um aumento dos seus níveis séricos, mas não significativo (p=0,007), permanecendo dentro de seus limites de normalidade
diante da literatura (2,7-5,0 g/dL), sendo a desidratação a principal
causa de hiperproteinemia em coelhos(8). A hipoalbuminemia poderia ser consequência de defeito da sua síntese, ocasionada por um
dano hepatocelular(9). Neste estudo, houve um aumento da albumina
sérica entre os momentos M1 e M2, observando-se que não existiram
efeitos adversos significativos no metabolismo hepático dos coelhos.
Para avaliação cardíaca, a CPK foi analisada no sangue dos animais. Inicialmente, chamou-se a atenção pelo fato de os níveis desta
enzima se encontrarem bem acima dos considerados normais pela
literatura(7) no momento M1, levando a acreditar que o estresse dos
animais pela mudança de ambiente tenha provocado este aumento
exagerado da CPK sanguínea, sendo que houve diminuição signifi
cativa em seus valores (p<0,001) até o momento M2, chegando
próximo dos níveis normais (140-372 U/L), podendo assim considerar
a ausência de lesões cardíacas.
Como uma das intenções deste estudo seria avaliar a resposta
inflamatória sistêmica e local causada pela resina FullCure 720®,
Kormann RB, et al.
optou-se pela análise da PCR, sendo um bom parâmetro para esta
avaliação. Esperava-se encontrar níveis menores no momento M1
(antes da evisceração) e mais elevados no momento M2 (60 dias
após a evisceração), resposta normal do organismo agredido, mes
mo sabendo que neste momento (M2) a resposta inflamatória era
crônica e os níveis de PCR são mais elevados nos primeiros dias
após um procedimento cirúrgico, pois medem a reação inflamatória
aguda. No entanto, os níveis de PCR apresentaram uma diminuição
significativa (p<0,001) entre os momentos M1 e M2 deste estudo.
Apesar de não haver uma justificativa para a diminuição dos níveis
de PCR, demonstrou-se que a resposta inflamatória era baixa ao fim
do experimento. O valor da proteína C reativa e da CPK elevado no
momento M1, pode estar relacionado com a miosite de transporte e
aclimatação ambiental (estresse).
A partir do momento compreendido, que qualquer tipo de
material estranho sempre desencadeia uma resposta do tecido hos
pedeiro, representada inicialmente por um processo inflamatório
agudo e após crônico granulomatoso do tipo corpo estranho, com
formação de tecido de reparo e cápsula fibrosa ao redor do implante,
reconsiderou-se o conceito de que biocompatível era aquele material totalmente inerte ao organismo. Quando um material estranho
é introduzido nos tecidos, comumente induz a uma reação inflamatória crônica, mediada predominantemente por macrófagos, já que
os neutrófilos são incapazes de fagocitar e destruir o material. Ao
redor deste material, forma-se um agregado granulomatoso, que tem
como característica apresentar macrófagos com ocasional formação
de células gigantes entre outras, que podemos chamar de cápsula
fibrosa(10). A matriz fibrosa tenta deter a inflamação pela presença de
uma lesão ou corpo estranho, isolando-o do ambiente biológico para
minimizar os efeitos adversos.
Neste estudo, evidenciou-se a formação de uma cápsula fibrosa
entre a esclera e o implante orbitário de resina FullCure 720® em
todos os animais, corroborando com outros estudos que também
evidenciaram a formação de uma cápsula fibrosa entre o tecido
hospedeiro e o implante(4-11-13). A cápsula fibrosa é constituída por
tecido conjuntivo fibroso e componentes celulares inflamatórios em
quantidades variáveis, sendo que neste estudo todos os componentes celulares eram discretos: linfócitos, macrófagos, ocasionais
células gigantes, inclusive englobando partículas inertes do implante
orbitário. Observou-se que estas células estavam presentes em quantidades diversas em cada área examinada (interface lisa e interface
rugosa), sendo mais discretas na área em contato com a interface
lisa do implante orbitário, que permitia assim, constituições de espessuras diferentes.
Durante o exame histológico, a coloração inicial e universal é a
hematoxilina-eosina (HE), mas com frequência há necessidade de se
evidenciar algum constituinte específico. Assim, usam-se colorações
especiais, específicas para determinada substância ou constituinte
do tecido. Sabe-se que nos processos cicatriciais não há formação
de fibra elástica, mas apenas depósito de colágeno, então para evidenciar a presença de cápsula fibrosa e delimitar o início da esclera,
utilizou-se da coloração especial para fibra elástica (Verhoeff-Van
Gieson), pois histologicamente os tecidos são semelhantes, ficando
difícil diferenciar tecido escleral normal e cápsula fibrosa, sendo assim
na porção da lâmina onde não se evidenciou a presença das fibras
elásticas (VVG), trata-se da área de fibrose (cápsula fibrosa).
A espessura desta cápsula fibrosa não é homogênea, podendo
diferenciar dependendo do local mensurado(4-11), então, procurou-se
neste estudo estabelecer locais fixos para avaliação destas medidas
em todos os animais, tanto do grupo experimento, quanto do grupo
controle. Todas as medidas foram mensuradas na região posterior da
esclera, evitando a área de sutura, onde a reação inflamatória seria
maior, como já evidenciado no estudo de Brandão, podendo haver
interferência nos resultados(4).
Foi observado que a cápsula fibrosa formada entre a esclera e
a porção lisa (ECL) do implante orbitário de resina FullCure 720®,
obteve uma espessura média de 814,3 µm, diferença esta estatisticamente significativa (p<0,001) quando comparada com a cápsula
fibrosa formada entre a esclera e a porção rugosa (ECR) do implante
orbitário FullCure 720®, que apresentou valor médio de 1.177,4 µm.
Verificou-se que quando comparada a espessura média da esclera
normal de coelhos do grupo controle (EC), com a espessura média
da esclera-cápsula do grupo experimento (ECL e ECR), a diferença da
EC (642,9 µm) versus a ECL (814,3 µm), assim como a diferença da EC
(642,9 µm) versus a ECR (1.177,4 µm), foram estatisticamente significativas (p=0,019/p<0,001), permitindo concluir que este aumento significativo de espessura da esclera no grupo experimento, deve-se ao
fato da formação de uma cápsula fibrosa entre a esclera e o implante
orbitário, independente da interface deste implante (lisa ou rugosa),
no entanto esta cápsula fibrosa seria menos espessa na interface lisa
do implante orbitário de FullCure 720®. Como existe a possibilidade
de um polimento da superfície destes implantes orbitários, a ideia
seria deixar esta superfície mais lisa (polida) possível, resultando em
menos reação inflamatória, consequentemente na formação de uma
cápsula fibrosa menos espessa. Este modelo está em fase inicial de
patenteação no Brasil, pela UTFPR.
CONCLUSÃO
Conclui-se que a resina FullCure 720® é biocompatível quando
confeccionada em forma de implante orbitário esférico para ser uti
lizada em cavidades anoftálmicas de coelhos.
O comportamento clínico dos animais durante todo o seguimen
to do estudo foi normal e não houve exposições, extrusões dos im
plantes orbitários ou morte de algum animal.
Os exames bioquímicos não evidenciaram alterações significativas, confirmando a ausência de toxicidade sistêmica da resina
FullCure 720® para implante orbitário.
As análises histológicas e morfométricas foram consideradas normais para este tipo de experimento, com formação de uma cápsula
fibrosa entre a capa escleral e o implante orbitário.
Ao implantar um material com uma interface mais homogênea
em sua superfície, o organismo formou uma barreira (cápsula fibrosa)
menos espessa.
AGRADECIMENTOS
Aos amigos Drª. Renata Lopes e Dr. Tiago Moraes, médicos oftalmologistas, pela ajuda com os materiais, documentação fotográfica
e auxílio nos procedimentos cirúrgicos.
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uso de implantes de compósito bioativo de biocerâmica em matriz polimérica na
reconstrução do complexo zigomático orbitário: novas perspectivas em biomateriais.
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em cavidade eviscerada de coelho [tese]. Botucatu: Universidade Estadual Paulista
“Julio de Mesquita Filho”; 2010.
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and sclera early alterations in hypercholestrerolemic rabbits: histologic and histo
morphometric study]. Arq Bras Oftalmol. 2009;72(1):68-74. Portuguese.
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com antocianina e antocianina + naringenina. Rev Bras Anal Clin [Internet]. 2006
[citado 2010 Jun 21];38(1):23-7. Disponível em: http://www.sbac.org.br/pt/pdfs/rbac/
rbac_38_01/rbac3801_07.pdf
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Portuguese.
XXXIII Congresso do
Hospital São Geraldo
30 de outubro a 2 de novembro 2013
Dayrell Hotel & Centro de Convenções
Belo Horizonte (MG)
Informações:
Tel.: (31) 3342-3888
E-mail: [email protected]
Site: www.hospitalsaogeraldo.com.br
146
Posicionamento das alças de lentes intraoculares implantadas intencionalmente
no sulco ciliar através da biomicroscopia ultrassônica
Positioning of intraocular lens haptics intentionally implanted in the ciliary sulcus
by ultrasound biomicroscopy
Ricardo Rau1, Carmen Resende Santana1, Andrea Alejandra Gonzalez Martinez1, André Luiz de Freitas Silva1, Norma Allemann1
RESUMO
ABSTRACT
Objetivos: Avaliar a posição das alças das lentes intraoculares implantadas intencionalmente no sulco ciliar, em olhos submetidos à cirurgia de catarata com
complicação de ruptura de cápsula posterior, e correlacionar os achados com
alterações clínicas observadas no exame oftalmológico, utilizando a biomicroscopia
ultrassônica.
Métodos: Onze olhos (11 pacientes) que apresentaram ruptura de cápsula posterior
durante a cirurgia de catarata com implantação intencional das alças no sulco
ciliar foram submetidos ao exame oftalmológico e biomicroscopia ultrassônica.
Biomicroscopia ultrassônica avaliou os seguintes parâmetros: posicionamento da
porção distal das alças, inclinação e descentração da lente intraocular. O exame
oftalmológico foi focalizado para avaliar a presença de “flare” e células na câmara
anterior, depósitos na lente e defeitos de transiluminação de íris. A pressão in
traocular foi medida, a pigmentação do trabeculado foi determinada, e a avaliação
fundoscópica foi necessária para afastar a presença de ruptura retiniana periférica
e edema de mácula.
Resultados: Tempo pós-operatório médio para os exames: 103,09 ± 32,93 dias.
Assimetria da posição foi observada em 3 olhos (27,2%), que tinham alça no sulco
ciliar e a segunda alça localizada na pars plana em 2 olhos, associada à inclinação
e descentração da lente intraocular; ou no corpo ciliar (1 olho). O exame oftalmológico observou: 5 (45,5%) olhos com defeitos de transiluminação de íris, 2
(18,1%) olhos com descentração da lente intraocular; 1 olho (9%) apresentou
hipertensão intraocular. Em todos os casos observou-se hiperpigmentação do
trabeculado à gonioscopia. Nenhum caso de rotura periférica de retina e/ou ede
ma de mácula foi relatado.
Conclusões: A biomicroscopia ultrassônica foi capaz de localizar as alças das
lentes intraoculares implantadas intencionalmente no sulco ciliar durante cirurgia
complicada de catarata, e pôde demonstrar a relação da descentração da lente
intraocular com a implantação assimétrica das alças.
Purpose: To evaluate the position of haptics of intraocular lens intentionally
implanted in the ciliary sulcus in eyes undergoing cataract surgery complication
associated with intraoperative posterior capsule rupture, as well as to correlate the
findings with clinical changes observed in ophthalmic examination, utilizing ul
trasound biomicroscopy.
Methods: Eleven eyes (11 patients) who had posterior capsule rupture during cataract
surgery with intentional implantation of the haptics in the ciliary sulcus, underwent
complete ophthalmic examination and ultrasound biomicroscopy. Ultrasound biomi
croscopy evaluated the parameters: positioning of the distal portion of the haptics,
tilt and decentration of the intraocular lens. Ophthalmic examination was aimed to
evaluate the presence of flare and cells in the anterior chamber, deposits on the lens
and iris transillumination defects. Intraocular pressure was measured, pigmentation of
the trabecular meshwork was determined, and a fundoscopic evaluation was needed
to rule out peripheral retinal rupture and macular edema.
Results: Mean postoperative time for the examinations: 103.09 ± 32.93 days. Asymmetry
of the haptics positioning was observed in 3 eyes (27.2%) that had one haptic in the
ciliary sulcus, the second haptic was placed in the pars plana in 2 eyes, associated to
intraocular lens tilt and decentration; or in the ciliary body (1 eye). Ophthalmic exa
mination observed: 5 (45.5%) eyes with iris transillumination defects, 2 (18.1%) with
intraocular lens decentration; 1 eye (9%) presented ocular hypertension. In all cases
trabecular hyperpigmentation was observed at gonioscopy. No cases of peripheral
retinal rupture and/or macular edema were reported.
Conclusions: Ultrasound biomicroscopy was able to locate the intraocular lens haptics
intentionally implanted in the ciliary sulcus during complicated cataract surgery, and
could demonstrate the relation of intraocular lens decentration to assymetric haptic
implantation.
Descritores: Implante de lente intraocular; Extração de catarata; Catarata; Ultras
sonografia
Keywords: Lens, implantation, intraocular; Cataract extraction; Cataract; Ultraso
nography
INTRODUÇÃO
A rotura de cápsula posterior (RCP) é uma complicação intraoperatória importante na cirurgia de catarata, principalmente entre
os cirurgiões iniciantes. O implante primário da lente intraocular
(LIO) de câmara posterior no sulco ciliar continua sendo uma opção
para reabilitação visual em olhos com suporte capsular periférico
adequado(1-3).
Estudos já descreveram complicações associadas ao implante da
LIO no sulco ciliar, sendo a dispersão de pigmento iriano, associada
com defeitos de transiluminação da íris, a mais comum(4). A elevação
da pressão intraocular (PIO) e sintomas causados pela borda da LIO,
secundários à descentração da mesma, também foram observados
em vários pacientes. Outros achados, como hemorragia intraocular e
edema macular cistoide, já foram relatados com menor frequência(5).
Em muitos casos, para se resolver a complicação, faz-se necessário
um procedimento cirúrgico. No estudo de Chang et al., relativo ao
implante de LIO acrílica peça única no sulco, a intervenção cirúrgica
para reposicionamento ou troca de LIO foi necessária em 93,0% dos
olhos, que apresentaram complicações como sintomas causados
pela borda da LIO, aumento da PIO e hemorragia intraocular(5).
Submetido para publicação: 21 de junho de 2012
Aceito para publicação: 10 de março de 2013
Trabalho realizado no Departamento de Oftalmologia, Universidade Federal de São Paulo - UNIFESP.
Declaração de Conflitos de interesses: R.Rau, Nenhum; C.R.Santana, Nenhum; A.A.G.Martinez,
Nenhum; A.L.F.Silva, Nenhum; N.Allemann, Nenhum.
Médico, Departamento de Oftalmologia, Universidade Federal de São Paulo - UNIFESP - São Paulo
(SP), Brasil.
Endereço para correspondência: Norma Allemann. Rua Olimpíadas, 134 - Conj. 51 - São Paulo
(SP) - 04551-000 - Brasil - E-mail: [email protected]
1
147
Posicionamento das alças de lentes intraoculares implantadas intencionalmente no sulco ciliar
através da biomicroscopia ultrassônica
Durante o procedimento cirúrgico de implantação da LIO no
sulco ciliar, em muitos casos é difícil determinar com precisão o posi
cionamento correto das alças. A possibilidade de localização assimétrica entre as alças é bastante alta(6,7).
A biomicroscopia ultrassônica (UBM) permite o exame da câmara
posterior e a avaliação da posição das alças da LIO, avaliando a sua
proximidade com o sulco ciliar, íris e corpo ciliar(8,9).
O objetivo deste estudo é, através da UBM, avaliar a localização
das alças das LIO implantadas intencionalmente no sulco ciliar, em
olhos submetidos à cirurgia de catarata associada à complicação
intraoperatória de RCP, assim como correlacionar os achados com as
alterações clínicas observadas no exame oftalmológico.
MÉTODOS
Trata-se de um estudo observacional de uma série de casos de
pacientes submetidos à cirurgia de catarata pela técnica de facoe
mulsificação com a complicação de ruptura de cápsula posterior (RCP)
e nos quais a LIO foi implantada intencionalmente no sulco ciliar.
Os dados foram coletados entre o período de julho de 2011 a feve
reiro de 2012 e os pacientes que aceitaram participar do estudo,
aprovado pelo Comitê de Ética e Pesquisa da Universidade Federal
de São Paulo, sob o número CEP 0062/11; assinaram o termo de
consentimento livre e esclarecido e realizaram o exame de UBM e a
avaliação oftalmológica completa. O estudo aderiu aos princípios da
Declaração de Helsinki.
A técnica cirúrgica compreendeu o procedimento de facectomia
por facoemulsificação (equipamento Legacy® ou Infinity®, Alcon Inc.),
com incisão em córnea clara temporal superior ou nasal superior
(preferência de cada cirurgião), aspiração de córtex, e após a identificação da complicação de ruptura da cápsula posterior, também a
vitrectomia anterior automatizada, e posteriormente, o implante da
LIO no sulco ciliar, durante o mesmo procedimento.
Como critério de inclusão, os pacientes selecionados tinham diag
nóstico de catarata senil e período de pós-operatório acima de 60
dias. Como critérios de exclusão foram considerados casos de catarata de etiologia secundária, casos de deiscência zonular (descrita
pelo cirurgião no relatório cirúrgico), casos em que a cirurgia de ca
tarata foi associada a outro procedimento cirúrgico (trabeculectomia,
vitrectomia programada) e casos com cirurgia intraocular prévia no
olho estudado. Na data do exame de UBM os olhos não apresenta
vam utilização de medicação tópica que pudesse influenciar na po
sição da íris durante o exame.
Os exames de UBM foram realizados por um único profissional
experiente (AAGM), utilizando o aparelho UBM VUMAX II®, Sonomed,
que possui um transdutor de 50 MHz, com penetração de 13 mm e
excursão de 14 a 16 mm. Os pacientes adotaram a posição de decúbito dorsal horizontal e o exame foi realizado em ambiente iluminado,
para simular a miose fisiológica. O exame foi realizado após instilação
de colírio anestésico (Anestalcon®, Alcon), colocação de blefarostato
de acrílico entre as pálpebras, que funcionou também como recipiente para contenção de soro fisiológico a 0,9% para realização do
banho de imersão. O transdutor de 50 MHz é externo, realiza uma
excursão de vai-e-vem para promover a varredura e é introduzido no
meio líquido que permite a transmissão das ondas sonoras ao olho.
Depois de finalizado o exame, as imagens foram selecionadas a partir dos “videoclips” arquivados no equipamento e as medidas foram
realizadas utilizando-se o recurso “caliper” do software do aparelho.
Nas imagens obtidas com UBM foram analisados os seguintes
parâmetros:
- distância entre a face endotelial da córnea e a face anterior da
porção óptica da LIO (DEL) em mm, na área central, no corte
axial;
- abertura do ângulo da câmara anterior (ACA), que é formada
pela área tangente à rede trabecular e a tangente à superfície
anterior da íris, medida a partir do vértice do recesso da íris, em
148
graus, no corte radial ou longitudinal, nos meridianos de 12, 3,
6 e 9 horas;
- distância entre a borda da porção óptica da LIO e a face posterior da íris (DIL): para avaliação da inclinação da lente, tendo
sido considerada inclinada quando a diferença entre as duas
bordas da lente naquele corte e o plano da íris foi superior a
100 micra (0,10 mm), medida realizada, no corte axial, nos eixos
horizontal (meridianos de 3 e 9 horas) e vertical (meridianos de
12 e 6 horas)(6);
- localização da porção distal de cada uma das alças em relação a
referências anatômicas do segmento posterior, com as seguintes possibilidades: sulco ciliar, saco capsular, corpo ciliar (pars
plicata) e pars plana; em cortes radiais ou longitudinais.
No exame oftalmológico realizado em uma segunda consulta,
foram avaliados: melhor acuidade visual com correção; biomicroscopia do segmento anterior: presença de “flare” e de células na câmara
anterior, defeitos de transiluminação de íris, dispersão de pigmento
no ângulo (gonioscopia com lente de 4 espelhos), depósito de pigmentos na LIO, e descentração da LIO em midríase; aferição da PIO
com tonômetro de Goldmann, sendo considerada elevada quando
maior que 21 mmHg; e avaliação do segmento posterior: presença de
edema macular cistóide e de rotura retiniana periférica utilizando-se
oftalmoscopia indireta com lente de 20 D e biomicroscopia de fundo
com lente de 78 D.
O método estatístico utilizado foi a média aritmética simples.
RESULTADOS
Foram identificados 16 pacientes submetidos à facectomia por
facoemulsificação que apresentaram RCP e nos quais as alças da LIO
foram intencionalmente implantadas no sulco ciliar, mas 5 pacientes
não aceitaram participar do estudo devido à distância entre seu domicílio e o local dos exames. O estudo foi realizado com 11 olhos de
11 pacientes (nove mulheres e dois homens).
A tabela 1 mostra os dados demográficos dos participantes. A
média de idade foi de 75 ± 9 anos, um grupo considerado homogêneo. O tempo médio entre a cirurgia e o exame de UBM foi de 103,09
± 32,93 dias e os olhos não se apresentavam em uso de medicação
tópica. As lentes implantadas nesta amostra foram lentes pseudofácicas de câmara posterior: de três peças (modelos TYPE7B® e MA60AC®,
Alcon, Inc. e modelo Matrix Acrylic 401®, Medennium Inc.); e lentes
de peça única (modelo SLIM®, Mediphacos Inc.). O poder dióptrico
médio das lentes implantadas foi +21,72 ± 1,66 dioptrias (Tabela 1).
A tabela 2 mostra os achados no exame de UBM. A média da
distância central entre face endotelial da córnea e a LIO foi de 3,60 ±
0,37 mm. A média da distância entre a borda da lente e a face posterior da íris foi de 0,33 ± 0,20 mm. A média da abertura do ângulo
da câmara anterior foi de 40,71 ± 6,72 graus. Observou-se inclinação
e descentração da LIO em dois pacientes (18,1%). Em destaque na
tabela, observa-se que o paciente 3 apresenta uma diferença entre a
DIL no meridiano vertical (medidas de 0,2 mm no meridiano de 12h
e 1,00 mm no meridiano de 6 h) superior a 0,10 mm, caracterizando a
inclinação da LIO. O mesmo ocorre com o paciente 8, no meridianos
horizontal (medidas de 0,75 mm no meridiano de 3h e 0,15 mm no
meridiano de 9 h). Em 7 (63,6%) olhos, pôde-se observar contato da
LIO com a porção pupilar da íris.
Na tabela 3, que mostra a localização das alças das lentes, pode-se
observar que em 3 (27,2%) olhos ocorreu assimetria do posicionamento das alças: 2 (18,1%) olhos com uma alça no sulco ciliar e a outra
alça na pars plana e 1 (9%) olho com uma alça no sulco e a outra no
corpo ciliar (Figura 1). Nos 8 (72,7%) olhos restantes, ambas as alças
estavam simetricamente posicionadas no sulco ciliar.
A tabela 4 mostra os achados do exame oftalmológico. Na biomicroscopia em lâmpada de fenda não foi observada a presença
de “flare” e/ou células na câmara anterior em nenhum dos olhos. As
alterações irianas observadas em 5 (45,5%) olhos foram decorrentes
Rau R, et al.
Tabela 1. Dados demográficos pré-operatórios dos participantes submetidos a implante de lente intraocular (LIO) no sulco ciliar
durante cirurgia de catarata
Paciente
Sexo
Idade
(anos)
Olho
Seguimento
(dias)
Graduação
catarata
AV corrigida
pré-operatória
Modelo LIO
selecionado
PD LIO
selecionada
01
M
59
D
106
N1+/SCP2+
20/80
TYPE7B
+19.5
02
F
70
E
105
N2+
20/80
TYPE7B
+21.5
03
F
72
D
61
N3+
20/100
Mediphacos SLIM
+20.5
04
M
86
D
64
N3+
20/100
TYPE7B
+20.0
05
F
62
D
73
N2+/SCP1+
20/80
MA60AC
+25.0
06
F
79
E
143
N2+
20/70
Matrix Acrylic
+22.0
07
F
74
D
112
N2+/SCP3+
20/100
Mediphacos SLIM
+21.5
08
F
75
E
135
N1+
20/60
Mediphacos SLIM
+24.0
09
F
82
D
120
N1+/SCP1+
20/50
TYPE7B
+22.5
10
F
86
E
65
N2+/CA2+
20/60
TYPE7B
+20.5
11
F
81
D
150
N2+
20/70
Mediphacos SLIM
+22.0
M= masculino; F= feminino; D= direito; E= esquerdo; N= nuclear; SCP= subcapsular posterior; CA= cortical anterior; PD= poder dióptrico; AV= acuidade visual.
Tabela 2. Parâmetros analisados pela biomicroscopia ultrassônica em olhos submetidos a implante de lente intraocular (LIO) no
sulco ciliar durante cirurgia de catarata
DIL (mm)
ACA (graus)
DEL (mm)
12h
3h
6h
9h
12h
3h
6h
9h
Posição das alças
(meridiano horário)
01
4,08
0,37
0,48
0,46
0,54
44,70
49,90
47,70
45,70
1e7
02
3,37
0,19
0,00
0,21
0,00
48,10
0,00
49,50
33,10
11 e 5
03
3,48
0,20
0,40
1,00
0,41
45,80
43,90
44,90
41,60
6 e 12
04
4,00
0,56
0,60
0,54
0,66
32,30
43,20
34,60
40,90
6 e 12
05
3,33
0,12
0,00
0,11
0,00
43,20
47,60
46,60
43,30
3e9
06
3,37
0,16
0,16
0,16
0,16
42,50
42,80
40,30
38,60
2e8
07
3,58
0,36
0,26
0,41
0,30
44,70
47,10
46,80
46,20
6 e 12
08
3,04
0,35
0,75
0,40
0,15
29,30
0,00
30,10
38,50
4 e 10
09
3,75
0,11
0,12
0,13
0,12
36,90
44,50
41,90
48,00
6 e 12
10
4,24
0,64
0,56
0,71
0,58
40,30
45,20
40,40
46,50
1e7
11
3,33
0,26
0,29
0,27
0,26
40,00
47,70
45,10
45,10
3e9
Paciente
DEL= distância entre a face endotelial da córnea e LIO; DIL= distância entre a face posterior da íris e LIO; ACA= ângulo da câmara anterior.
Tabela 3. Localização relativa das alças de cada lente intraocular detectada pela UBM em olhos submetidos a implante de lente
intraocular no sulco ciliar durante cirurgia de catarata. Número total de olhos incluídos no estudo: 11, 22 alças de lente intraocular
Posicionamento da Alça 2
Posicionamento da Alça 1
Sulco ciliar
Sulco ciliar
Pars plicata
Pars plana
Saco capsular
Total
8 (72,72)
1 (9,09)
2 (18,18)
0
22
do trauma cirúrgico e caracterizaram-se por áreas localizadas de
atrofia do bordelete ou do estroma iriano. A descentração da LIO foi
observada em 2 (18,1%) olhos (Figura 2). A PIO média encontrada
na série foi de 15 ± 2 mmHg, sendo que um olho necessitou de
medicação antiglaucomatosa para controle da mesma. Em todos os
olhos (n=11) foi observada uma hiperpigmentação do trabeculado,
à gonioscopia. Na avaliação de fundoscopia, não foram observados
rotura periférica de retina e/ou edema de mácula.
DISCUSSÃO
O implante da LIO no sulco ciliar nos olhos que apresentam RCP,
onde há um suporte capsular periférico adequado, é um procedi-
mento bastante frequente, principalmente em centros de ensino de
cirurgia de catarata. Determinar com exatidão o posicionamento das
alças no sulco ciliar é muito difícil durante a cirurgia.
Assim como no presente estudo, que demonstrou assimetria das
alças em 3 (27,2%) olhos, outros autores também relataram com
frequência a assimetria da posição das alças nestas situações, como
Loya et al.(6), que em seu estudo com 36 olhos (36 pacientes) submetidos à facectomia extracapular complicada com RCP, observaram
15 (42,0%) olhos com assimetria das alças: uma implantada no sulco
ciliar e a outra no saco capsular, pars plicata ou pars plana. Vasavada et al.(4), em estudo com 10 olhos submetidos à facectomia por
facoemulsificação e implante de LIO acrílica de peça única no sulco
ciliar, também observaram assimetria das alças em 3 (30,0%) olhos.
149
Posicionamento das alças de lentes intraoculares implantadas intencionalmente no sulco ciliar
através da biomicroscopia ultrassônica
A
B
C
Figura 1. Biomicroscopia ultrassônica (ultrassonografia de 50 MHz) de olhos submetidos
a implante de lente intraocular pseudofácica no sulco ciliar. A alça é identificada como
uma estrutura cilíndrica de alta refletividade que causa um artefato de reverberação
(duplicação de ecos) disposto posteriormente. A) Paciente 8, demonstra a alça localizada
posteriormente aos processos ciliares, na pars plana (seta); B) Paciente 3, alça localizada
posteriormente na pars plana (seta); C) Paciente 2, alça localizada sobre a pars plicata,
ou seja, sobre os processos ciliares (seta).
Amino e Yamakawa(7) também relataram, após facectomia por facoe
mulsificação e implante de LIO de diferentes fabricantes, assimetria
em 3 (15,7%) dos 19 olhos estudados, sendo que nos três casos, a
segunda alça estava no corpo ciliar.
As medidas de DEL, DIL e ACA encontradas foram, respectivamente, de 3,60 ± 0,37 mm, 0,33 mm ± 0,20 mm e 40,71 ± 6,72 graus,
semelhantes às reportadas no estudo de Vasavada et al.(4): 3,47 ±
0,24 mm, 0,16 ± 0,07 mm e 40,2 ± 4,5 graus, respectivamente.
Utilizando o mesmo critério empregado no presente estudo, pa
ra a determinação de inclinação da LIO no exame de UBM, Loya et
al.(6) relataram 20 (56,0%) olhos que apresentaram inclinação da LIO,
enquanto Vasavada et al.(4) não observaram nenhum caso. Em nosso
estudo, foram descritos 2 (18,1%) casos, ambos também apresentaram assimetria das alças (uma alça no sulco e a outra na pars plana).
Loya et al.(6) relataram que não houve relação estatisticamente significativa entre a inclinação da lente e a assimetria das alças em seu
estudo.
Em nossa série de casos, a descentração da LIO foi encontrada em
dois olhos implantados com a LIO de peça única do modelo SLIM®
(Mediphacos Inc.), que não seria ideal para o posicionamento das
alças no sulco ciliar, pois apresenta comprimento alça-a-alça inadequado. Outros 7 olhos da amostra não demonstraram descentração
da LIO: 2 olhos com a LIO de peça única modelo SLIM (Mediphacos)
e 5 olhos com LIO de três peças modelo TYPE7B® (Alcon, Inc.), que
também não têm indicação para implante no sulco ciliar. Sugere-se
que outros fatores possam contribuir para a descentração de uma
LIO com alças posicionadas no sulco cililar e influenciar no resultado
pós-operatório. O trabalho retrospectivo com avaliação dos prontuários não permitiu determinar informações relevantes como: tamanho
da capsulorrexis, extensão da RCP (no pós-operatório imediato e no
acompanhamento), quantidade de perda vítrea, descrição do procedimento de vitrectomia anterior.
Considerando-se o exame oftalmológico, poucas alterações foram
encontradas na série. O seguimento pós-operatório prolongado é
fundamental para a observação de complicações que podem vir a
ocorrer após RCP e implante das alças da LIO no sulco ciliar. A média
de seguimento dos pacientes do presente estudo foi de 103,09 ±
32,93 dias, variando de 2 a 5 meses. A incidência de complicações
relatada na presente amostra pode ser relacionada ao tempo de seguimento mais curto em relação a outros estudos com seguimento
mais longo: 4 anos (variando entre 1 e 7 anos)(6) e de 7 a 85 meses(4).
Em todos os casos foi observada uma hiperpigmentação do trabeculado, provavelmente em decorrência ao trauma da íris durante
Tabela 4. Achados do exame oftalmológico da última visita pós-operatória em olhos submetidos a implante de lente intraocular no sulco ciliar
Biomicroscopia
Paciente
01
Flare/células
Alteração iriana
Depósito LIO
Descentração LIO
Tonometria
(mmHg)
Gonioscopia
(pigmentação)
Fundoscopia
RP/EM
AV corrigida
pós-operatória
Ausente
Ausente
Ausente
Ausente
17
2+
Ausente/Ausente
20/30
20/60
02
Ausente
Presente
Presente
Ausente
19
3+
Ausente/Ausente
03
Ausente
Presente
Ausente
Presente
16
3+
Ausente/Ausente
20/25
04
Ausente
Ausente
Ausente
Ausente
14
2+
Ausente/Ausente
20/20
05
Ausente
Ausente
Ausente
Ausente
15
2+
Ausente/Ausente
20/25
06
Ausente
Presente
Ausente
Ausente
12
2+
Ausente/Ausente
20/30
07
Ausente
Presente
Ausente
Ausente
17
2+
Ausente/Ausente
20/30
08
Ausente
Presente
Ausente
Presente
15
3+
Ausente/Ausente
20/40
09
Ausente
Ausente
Presente
Ausente
18
2+
Ausente/Ausente
20/30
10
Ausente
Ausente
Ausente
Ausente
16
2+
Ausente/Ausente
20/20
11
Ausente
Ausente
Ausente
Ausente
13
2+
Ausente/Ausente
LIO= lente intraocular; RP= rotura periférica de retina; EM= edema macular; AV= acuidade visual.
150
20/60
Rau R, et al.
A
B
Figura 2. Olho 8 da série de olhos submetidos a implante intencional da lente intraocular no sulco ciliar durante cirurgia de catarata. A) Fotografia em lâmpada de fenda
do olho esquerdo, em reflexo vermelho, sob midríase, demonstra a porção óptica da lente intraocular descentrada nasalmente, e também se observa a área da rotura
de cápsula posterior. B) Biomicroscopia ultrassônica (50 MHz) do mesmo olho demonstra, na varredura horizontal (meridianos 3 e 9 horas, representados à esquerda
e à direita da imagem, respectivamente), o deslocamento da porção óptica da lente intraocular em direção ao meridiano de 9 horas (nasal).
a cirurgia e/ou pelo contato da LIO com a porção pupilar da íris, que
foi observado no exame de UBM em 7 (63,6%) olhos. Porém, não se
observou defeitos de transiluminação de íris típicos do atrito entre a
LIO e a íris. Talvez se estes olhos forem avaliados por um período mais
longo, os defeitos irianos possam vir a ser identificados. As alterações
irianas, observadas em 5 (45,4%) olhos, mostraram-se características
de lesões causadas pela manipulação excessiva durante a cirurgia,
pois estavam localizadas nas regiões de entrada e saída dos instrumentos cirúrgicos através das incisões principal e acessória.
Somente um olho apresentou hipertensão ocular transitória após
o procedimento cirúrgico, sendo a mesma controlada com me
dicação antiglaucomatosa (maleato de timolol 0,5%) e, após seis
semanas, houve normalização da PIO e a medicação foi suspensa.
Nenhum caso de “flare” e/ou de células na câmara anterior foi observado. Vasavada et al.(4) também não observaram sinais de inflamação
nos olhos estudados, e apenas um caso de glaucoma foi relatado.
Também atentaram para a importância do monitoramento próximo
nestes olhos, uma vez que o contato entre LIO e a superfície posterior
da íris, principalmente nos implantes de LIO de peça única no sulco
ciliar, pode causar inflamação crônica e maior risco de glaucoma.
Durante o exame de biomicroscopia em lâmpada-de-fenda, co
mo o paciente está na posição sentada, muitas vezes o deslocamento
posterior da LIO pode não ser observado ou então pode ser mascarado pela posição do paciente; o mesmo não ocorre no exame de UBM,
uma vez que o paciente encontra-se deitado, sendo mais facilmente
observado o deslocamento posterior da LIO. Portanto, nos casos de
desestabilização do suporte capsular, o exame de UBM pode ser útil
na avaliação do parâmetro de deslocamento posterior da LIO.
Estes achados permitem identificar os olhos candidatos a um
acompanhamento seriado próximo para diagnóstico precoce de pos
síveis complicações relacionadas à técnica cirúrgica, como alteração
da íris e do trabeculado, modificação gradual do posicionamento da
LIO e desenvolvimento de hipertensão ocular.
Em conclusão, a biomicroscopia ultrassônica foi capaz de localizar as alças das lentes intraoculares implantadas intencionalmente
no sulco ciliar em olhos com ruptura da cápsula posterior durante
a cirurgia de catarata. Na amostra estudada, a técnica foi capaz de
relacionar os casos de descentração da lente intraocular com a implantação assimétrica das alças.
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2000;26(8):1102-3.
8. Pavlin CJ, Harasiewicz K, Foster FS. Ultrasound biomicroscopic analysis of haptic
position in late-onset, recurrent hyphema after posterior chamber lens implantation.
J Cataract Refract Surg. 1994;20(2):182-5.
9. Ozdal PC, Mansour M, Deschênes J. Ultrasound biomicroscopy of pseudophakic eyes
with chronic postoperative inflammation. J Cataract Refract Surg. 2003;29(6):1185-91.
151
Nova técnica de sutura ajustável para trabeculectomia
Vespasiano Rebouças-Santos1, Daniel Meira-Freitas1, Angelino Júlio Cariello1, Tiago dos Santos Prata1, Sergio Henrique Teixeira1
ABSTRACT
RESUMO
Purpose: To describe an adjustable suture (AS) experimental model that allows for
tightening, loosening and retightening of the suture tension in trabeculectomy.
Methods: Standard trabeculectomy was performed in fifteen pig eyeballs. All pig
eyes were tested twice: one test with conventional suture in both flap’s corners
(conventional suture group) and another test with a conventional suture at one
corner and an adjustable suture in the other corner (AS group). The order in which
each test was performed was defined by randomization. Intraocular pressure was
measured at three time points: T1) when the knots were tightened; T2) when the
AS was loosened or the conventional knot was removed; and T3) when the AS
was retightened in the AS group or five minutes after the knot removal in the
conventional suture group.
Results: The mean Intraocular pressure was similar between the two groups at
time point 1 (p=0.97). However, significant Intraocular pressure differences were
found between eyes in the conventional and adjustable suture groups at time
points 2 (12.6 ± 4.2 vs 16.3 ± 2.3 cmH2O, respectively, p=0.006) and 3 (12.2 ± 4.0 vs
26.4 ± 1.7cmH2O, respectively; p=0.001). While the conventional technique allowed
only Intraocular pressure reduction (following the knot removal; T2 and T3), the
AS technique allowed both Intraocular pressure reduction (T2) and elevation (T3)
through the management (loosening and retightening) of the suture.
Conclusion: This experimental model provides an effective noninvasive postoperative mechanism of suture tension adjustment.
Objetivo: Descrever uma nova técnica de sutura ajustável para o “flap” da trabecu
lectomia (TREC), que permite apertar e folgar a sutura no pós-operatório.
Métodos: Foram realizadas trabeculectoomia em 15 olhos de porco. Todos os olhos
de porco foram testados duas vezes; um teste com sutura convencional nas duas ex
tremidades do “flap” (grupo sutura convencional), outro teste com sutura convencional
em uma das extremidades e na outra extremidade a sutura ajustável proposta por
esse trabalho (grupo sutura ajustável). A ordem de qual teste seria realizado primeiro
em cada olho foi definida por sorteio. A pressão intraocular foi medida de forma di
reta em três momentos: T1) Todas as suturas apertadas; T2) Após lise de uma sutura
convencional ou de afrouxar a sutura ajustável; T3) Após apertar novamente a sutura
ajustável ou no caso do teste com as duas suturas convencionais após 5 minutos da
lise de uma das suturas.
Resultados: No primeiro momento de medida da pressão intraocular (T1) as pressões
médias foram similares entre os dois grupos (p=0.97). No entanto, diferenças significa
tivas em relação a pressão intraocular foram encontradas entre os grupos de sutura
convencional e ajustável nos tempos 2 (12,6 ± 4,2 vs 16,3 ± 2,3 cmH2O, respectivamente;
p=0,006) e 3 (12,2 ± 4,0 vs 26,4 ± 1.7cmH2O, respectivamente; p=0,001). Enquanto
a técnica convencional permitiu somente a redução da pressão intraocular após a
remoção da sutura (T2 e T3), a técnica de sutura ajustável permitiu tanto a redução
(T2) quanto a elevação da pressão intraocular (T3) através do manejo da sutura.
Conclusão: Esse modelo experimental demonstrou a eficácia de uma possível
técnica não-invasiva para ajuste da tensão da sutura do “flap” no pós-operatório da
trabeculectomia.
Keywords: Glaucoma/surgery; Trabeculectomy; Suture techniques; Intraocular
pressure; Animals; Swine
Descritores: Glaucoma/cirurgia; Trabeculectomia; Técnicas de sutura; Pressão in
traocular; Animais; Suínos
INTRODUCTION
Trabeculectomy has been well established as a safe and effective
surgical alternative for intraocular pressure (IOP) reduction(1,2). Overfiltration is a common postoperative complication, which may lead to
anterior chamber shallowness, choroidal detachment and hypotony
maculopathy(3). During the postoperative period, the physician can
intervene to maintain proper functioning of the surgical fistulae and
IOP reduction through the mechanical removal/loosening of the
adjustable suture (AS) or through laser suture lysis(1,4-6). The possibility of drainage reduction (IOP increase) through noninvasive suture
adjustment is not yet available to avoid ocular hypotony in cases of
trabeculectomy overfiltration.
The purpose of this study was to describe an ex vivo experimental
model of AS for the scleral flap of the trabeculectomy that allows for
the tightening, loosening and retightening of suture tension during
the postoperative period.
Submitted for publication: October 10, 2012
Accepted for publication: April 5, 2013
Study carried out at Glaucoma Service, Department of Ophthalmology, Universidade Federal de
São Paulo.
1
Physician, Department of Ophthalmology, Universidade Federal de São Paulo - UNIFESP - São
Paulo (SP) - Brazil.
152
METHODS
This study was conducted at the Surgical Research and Training
Center of the Department of Ophthalmology of the Federal University of São Paulo, and the protocol was previously approved by the
institutional Ethics Committee.
Porcine eyes
Freshly excised pig eyes were obtained from a local slaughterhouse, washed thoroughly and transported in 0.9% saline solution at a
temperature of 5°C. All eyes were examined under a surgical micros-
Disclosure of potential conflicts of interest: V.Rebouças-Santos, None; D.Meira-Freitas, None;
A.J.Cariello, None; T.S.Prata, None; S.H.Teixeira, None.
Correspondence address: Vespasiano Rebouças-Santos. Rua Botucatu, 822 - São Paulo (SP) 04023-062 - Brazil - E-mail: [email protected]
Institutional review board number (Comitê de Ética em Pesquisa da UNIFESP): 1322/10.
Rebouças-Santos V, et al.
cope, and those in unsatisfactory condition (e.g., corneal opacity or
perforation) were not included in the study.
Procedures
Each eyeball was fixed on a suitable support. All surgeries were
performed by the same surgeon according to the technique previously described by Lee et al.,(7). Initially, two clear cornea paracenteses were performed. Then, the surgeon made an incision through
the conjunctiva and created a partial-thickness scleral flap with a
crescent blade. Prior to perform the trabeculectomy, two 18-gauge
infusion cannulae were installed in the paracentesis, one with the
saline solution bottle at a 40 cm height and the other for the water
column (Figure 1). A conventional 10.0 nylon suture was performed
at the first corner of the scleral flap. The second suture was randomly
chosen to be a conventional suture (CS) or AS by a true random
number generator (random.org). All pig eyes were tested twice, one
test with CS in both flap’s corner (conventional suture group - CSG),
another test with conventional suture at one corner and other corner
the adjustable suture (adjustable suture group - ASG).
The water column technique was used to measure the IOP at
three different time points: 1) when the knots were tightened; 2)
when the AS was loosened in the ASG or the conventional knot was
removed in the CSG; and 3) when the AS was retightened or five
minutes after the second measurement in the conventional suture
group. The AS was loosened and retightened from its corneal end
without touching the sclera or scleral flap. At the end of the surgery,
the CS or AS technique was randomly chosen and performed on the
second corner of the scleral flap in a crossover fashion. Thus, both
suture techniques were tested in the same eyeballs.
Adjustable suture technique
This new AS was based in a slip-knot technique as shown in the
figure 2. The difference was to pass the two sutures ends into the
cornea two times. The corneal suture ends can be use for tighten or
loosening flap’s knot without touch the flap or conjunctival flap, simulating a postoperative management. The technique: the suture is
first passed through the corneal periphery, parallel to the limbus, and
then passed perpendicularly from the cornea to the limbus. Then, it
Figure 1. Representative picture of the water column system used for intraocular pres
sure measurement.
is passed through the intact sclera toward the scleral flap. The string
is pulled and the needle is positioned at the limbus. A single throw is
performed, grasping the needle end of the suture. The needle end of
the suture is pulled to tighten the slipknot. The suture is then passed
through the intact sclera, perpendicularly to the limbus, and then
through clear cornea, parallel to the limbus. The needle end of the
suture is cut flush with the cornea.
Statistical analysis
The intra and intergroup IOP variations and mean values were
compared using a mixed linear model. An open source statistical
software (R - version 2.15.1) was used for all analyses. Statistical significance was set at p<0.05.
RESULTS
Fifteen porcine eyes were included in the study. In the CSG, the
mean IOP at time point 1 was 26.8 ± 0.8 cmH2O, decreasing to 12.6
± 4.2 cmH2O at time point 2 (p<0.01) and remaining stable at 12.2 ±
4.0 cmH2O at the third time point (p<0.01). In ASG, the mean IOP at
time point 1 was 26.8 ± 0.9 cmH2O, decreasing to 16.3 ± 2.3 cm H2O at
time point 2 (p<0.01), and returning to 26.4 ± 1.7 cmH2O at time point
3 (p=0.31). Figure 3 shows the IOP variations at the three time points.
The mean baseline IOP was similar between the groups (p=0.97).
However, significant differences were found at time points 2 (12.6 ±
4.2 and 16.3 ± 2.3 cmH2O, respectively, p=0.006) and 3 (12.2 ± 4.0 and
26.4 ± 1.7cmH2O, respectively, p=0.001).
DISCUSSION
In this ex vivo experimental model, we described a novel AS for
the scleral flap used in trabeculectomy that allows for both increase
and reduction of the aqueous humor outflow through the surgical
fistulae during the postoperative period. Our results suggest that this
new suture technique might improve IOP control in patients with
glaucoma who undergo trabeculectomy.
Overfiltration in the early postoperative period of the trabeculectomy is a common complication that can lead to ocular hypotony(2). To
reduce the incidence of complications associated with overfiltration,
many surgeons advocate the use of a tight suture on the scleral flap
followed by laser suture lysis or suture loosening/removal in cases in
which releasable suture techniques were used(2). However, these me
thods carry an intrinsic risk for the development of hyperfiltration
after loosening or removal of the suture(5). Currently, the available
treatment for a hyperfiltrating trabeculectomy includes an occlusive
eyepad, a bandage contact lens, reduction of the use of steroid eye
drops, subconjunctival injection of autologous blood, contention suture, transconjunctival suture of the scleral flap and surgical revision with
resuture of the scleral flap after conjunctival opening(8-10).
The possibility of tightening, loosening and retightening of the
suture introduced in this study is a potential effective, reversible and
non-invasive approach to minimize trabeculectomy hyperfiltration.
The suture adjustment was easily performed through the manipulation of the corneal ends of the suture, without accessing the scleral
flap. We presume that this method could be applied in patients under
slit-lamp examination, avoiding a new surgical procedure.
Anatomical differences between human and porcine eyes, the
absence of blood circulation and infusion flow rates that were higher
than physiologic aqueous flow rates were the main limitations of
this experimental model. In this study, the same experimental model
was used to perform and compare the two suture techniques, which
probably mitigated the influence of the chosen method in our results.
CONCLUSION
This experimental study demonstrated this novel suture technique as an effective and non-invasive alternative for tightening,
153
Figure 2. Slipknot suture technique: 1) The suture is first passed through clear cornea, parallel to the limbus. It is then passed perpendicularly from the cornea to the limbus. 2) Passed through the scleral flap and through the intact sclera. 3) The needle is passed through the loop. 4) A single throw is performed surrounding the needle holder. 5-6) The needle
is pulled to tighten the slipknot. 7) The suture is then passed through the intact sclera, perpendicularly to the limbus, and then through clear cornea, parallel to the limbus. 8) The
needle end of the suture is cut close to the cornea.
A
B
Figure 3. Mean intraocular pressure variation at each time point. A) Conventional suture technique. B) Adjustable suture technique.
loosening and retightening the scleral flap during the postoperative
period in porcine eyes. Further in vivo experimental and clinical studies
could elucidate the potential advantages and safety of this new
suture technique.
REFERENCES
1. Caporossi A, Balestrazzi A, Malandrini A, Tosi GM, Caporossi T, Frezzotti P, et al. A
randomized prospective study comparing trabeculectomy with and without the use
of a new removable suture. Int Ophthalmol. 2009;29(5):359-65.
2. Simsek T, Citirik M, Batman A, Mutevelli S, Zilelioglu O. Efficacy and complications
of releasable suture trabeculectomy and standard trabeculectomy. Int Ophthalmol.
2005;26(1-2):9-14.
3. de Barros DS, Gheith ME, Siam GA, Katz LJ. Releasable suture technique. J Glaucoma.
2008;17(5):414-21.
4. Kayikcioglu OR, Emre S, Kaya Z. Trabeculectomy combined with deep sclerectomy
154
and scleral flap suture tension adjustment under an anterior chamber maintainer: a
new modification of trabeculectomy. Int Ophthalmol. 2010;30(3):271-7.
5. Kobayashi H, Kobayashi K. A comparison of the intraocular pressure lowering effect
of adjustable suture versus laser suture lysis for trabeculectomy. J Glaucoma. 2011;
20(4):228-33.
6. Birchall W, Wells AP. The effect of scleral flap edge apposition on intraocular pressure
control in experimental trabeculectomy. Clin Experiment Ophthalmol. 2008;36(4):353-7.
7. Lee GA, Chiang MY, Shah P. Pig eye trabeculectomy-a wet-lab teaching model. Eye
(Lond). 2006;20(1):32-7.
8. Letartre L, Basheikh A, Anctil JL, Des Marchais B, Goyette A, Kasner OP, et al. Transconjunctival suturing of the scleral flap for overfiltration with hypotony maculopathy
after trabeculectomy. Can J Ophthalmol. 2009;44(5):567-70.
9. Maruyama K, Shirato S. Efficacy and safety of transconjunctival scleral flap resuturing
for hypotony after glaucoma filtering surgery. Graefes Arch Clin Exp Ophthalmol.
2008;246(12):1751-6.
10. Eha J, Hoffmann EM, Wahl J, Pfeiffer N. Flap suture--a simple technique for the revision
of hypotony maculopathy following trabeculectomy with mitomycin C. Graefes Arch
Clin Exp Ophthalmol. 2008;246(6):869-74.
Corneal thickness changes during corneal collagen cross-linking with UV-A irradiation
and hypo-osmolar riboflavin in thin corneas
Alterações na espessura da córnea durante “cross-linking” do colágeno com irradiação UV-A
e riboflavina hipo-osmolar em córneas finas
Belquiz Amaral Nassaralla1, Diogo Mafia Vieira1, Márcia Leite Machado1, Marisa Novaes Faleiro Chaves de Figueiredo1, João Jorge Nassaralla Jr.1,2
ABSTRACT
RESUMO
Purpose: To evaluate the thinnest corneal thickness changes during and after
corneal collagen cross-linking treatment with ultraviolet-A irradiation, using hy
po-osmolar riboflavin solution in thin corneas.
Methods: Eighteen eyes of 18 patients were included in this study. After epithelium
removal, iso-osmolar 0.1% riboflavin solution was instilled to the cornea every 3
minutes for 30 minutes. Hypo-osmolar 0.1% riboflavin solution was then applied
every 20 seconds for 5 minutes or until the thinnest corneal thickness reached
400 µm. Ultraviolet-A irradiation was performed for 30 minutes. During irradiation, iso-osmolar 0.1% riboflavin drops were applied every 5 minutes. Ultrasound
pachymetry was performed at approximately the thinnest point of the cornea
preoperatively, after epithelial removal, after iso-osmolar riboflavin instillation,
after hypo-osmolar riboflavin instillation, after ultraviolet-A irradiation, and at 1,
6 and 12 months after treatment.
Results: Mean preoperative thinnest corneal thickness was 380 ± 11 µm. After
epithelial removal it decreased to 341 ± 11 µm, and after 30 minutes of iso-osmolar
0.1% riboflavin drops, to 330 ± 7.6 µm. After hypo-osmolar 0.1% riboflavin drops,
mean thinnest corneal thickness increased to 418 ± 11 µm. After UVA irradiation,
it was 384 ± 10 µm. At 1, 6 and 12 months after treatment, it was 372 ± 10 µm,
381 ± 12.7, and 379 ± 15 µm, respectively. No intraoperative, early postoperative,
or late postoperative complications were noted.
Conclusions: Hypo-osmolar 0.1% riboflavin solution seems to be effective for
swelling thin corneas. The swelling effect is transient and short acting. Corneal
thickness should be monitored throughout the procedure. Larger sample sizes
and longer follow-up are required in order to make meaningful conclusions re
garding safety.
Objetivo: Avaliar as alterações da espessura mínima da córnea durante e após o crosslinking do colágeno corneano com radiação ultravioleta A e solução hipo-osmolar
de riboflavina em córneas finas.
Métodos: Dezoito olhos de 18 pacientes foram incluídos neste estudo. Após a remoção
do epitélio, solução iso-osmolar de riboflavina 0,1% foi instilada a cada 3 minutos por
30 minutos. Solução hipo-osmolar de riboflavina 0,1% foi então aplicada a cada 20
segundos por 5 minutos ou até que a espessura mínima da córnea atingisse 400 µm.
Irradiação UVA foi feita durante 30 minutos. Durante a irradiação, riboflavina isoosmolar 0,1% foi aplicada a cada 5 minutos. Paquimetria ultrassônica foi realizada
no ponto mais fino da córnea antes da cirurgia, após a remoção do epitélio, após a
instilação de riboflavina iso-osmolar, após a instilação de riboflavina hipo-osmolar,
após a irradiação com UVA e após 1, 6 e 12 meses do tratamento.
Resultados: Antes da cirurgia, a espessura mínima da córnea era de 380 ± 11 µm.
Após a remoção do epitélio, este valor foi reduzido para 341 ± 11 µm e após 30 minutos
de riboflavina iso-osmolar, caiu para 330 ± 7,6 µm. Após a riboflavina hipo-osmolar,
a espessura mínima da córnea aumentou para 418 ± 11 µm. Após a irradiação com
UVA, era de 384 ± 10 µm. Após 1, 6 e 12 meses do tratamento este valor era de 372 ±
10, 381 ± 12,7 e 379 ± 15 µm, respectivamente. Não foram observadas complicações
no intra ou no pós-operatório precoce ou tardio.
Conclusões: A solução de riboflavina hipo-osmolar 0,1% parece ser eficaz para
edemaciar córnea finas. Este efeito é transitório e de curta duração. A espessura da
córnea deveria ser monitorada durante todo o procedimento. Maior número de casos e
seguimento prolongado são necessários para tirarmos conclusões quanto à segurança.
Keywords: Keratoconus/therapy; Collagen/radiation effects; Riboflavin/therapeutic use; Ultraviolet therapy; Cross-linking reagents; Corneal pachymetry
Descritores: Ceratocone/terapia; Colágeno/efeitos de radiação; Riboflavina/uso
terapêutico; Terapia ultravioleta; Reagentes para ligações cruzadas; Paquimetria
da córnea
INTRODUCTION
Corneal collagen cross-linking (CXL) therapy is a technique that
uses a combination of riboflavin (vitamin B2) and ultraviolet-A light
(UVA) to induce cross-linking in stromal collagen and thereby increa
ses the mechanical rigidity of the cornea. The role of riboflavin in
this method is dual. It works as a photosensitizer for the induction of
cross-links and protects the underlying tissues from the deleterious
influence of UVA irradiation. CXL is currently used to treat progressive
corneal ectasia occurring in keratoconus(1-3) or following laser refracti-
ve surgery(4,5). It is thought to work by enhancing the biomechanical
properties of the tissue(1,2) and its resistance to enzymatic digestion(6).
The removal of the epithelium has been recommended as an
initial step of the CXL procedure since its lipophilic nature reduces
the diffusion of riboflavin into the corneal stroma(1-3). Moreover, the
epithelium may block UV rays(3). The photosensitizer riboflavin is
applied to the de-epithelialized surface of the cornea and allowed to
penetrate into the corneal stroma(7,8). The subsequent exposure of the
cornea to UVA light is thought to result in photodynamic cross-lin
Submitted for publication: June 14, 2012
Accepted for publication: March 21, 2013
Study carried out at Goiania Eye Institute.
1
2
Physician, Goiania Eye Institute, Goiânia (GO), Brazil.
Physician, Faculty of Health Sciences, University of Brasilia, Brasília (DF), Brazil.
Disclosure of potential conflicts of interest: B.A.Nassaralla, None; D.M.Vieira, None; M.L.Machado,
None; M.N.F.C.Figueiredo, None; J.J.Nassaralla Jr., None.
Correspondence address: Belquiz A. Nassaralla. Instituto de Olhos de Goiânia. Rua L, 53 - 12o
andar, Setor Oeste - Goiânia (GO) - 74120-050 - Brazil
E-mails: [email protected] / [email protected]
Protocol ID: #10/2012
Research Ethics Committee: Goiania Eye Institute, Goiania, Goias, Brazil
Protocol Registration ID: ClinicalTrials.gov ID- NTC01485211
155
king when the riboflavin, excited by UVA, creates free radicals leading
to cross-linking of collagen(7,8).
The currently used treatment parameters induce cross-links in
the anterior 250-350 µm of the corneal stroma(7). Thus, to protect
the endothelium and deeper ocular structures, CXL inclusion criteria require a minimal corneal thickness of 400 µm after epithelium
removal(7-9). However, a recent modification to the technique, in
which a hypo-osmolar riboflavin solution is applied to induce stromal swelling and increase stromal thickness prior to UVA irradiation,
has enabled the treatment to be performed on thinner keratoconus
corneas (<400 µm) that would not have previously been eligible for
riboflavin/UVA treatment(9,10).
This prospective study evaluated the intraoperative pachymetric
variations during the procedure and one year after CXL treatment
with UVA irradiation, using hypo-osmolar riboflavin solution to induce stromal swelling and increase the stromal thickness before CXL in
thin corneas with progressive keratoconus.
METHODS
Eighteen eyes of 18 patients, 11 men and 7 women, with pro
gressive keratoconus and thinnest corneal thickness (TCT) less than
400 µm (with the epithelium) were enrolled in this study. Mean patient age was 24 ± 4.2 years (range, 18-31 years).
Patients with one of the following criteria after the preoperative
examination were excluded: age younger than 16 or older than 35
years, corneal scars or opacities, pregnancy or lactation, active anterior
segment pathologic features, previous corneal or anterior segment
surgery, systemic connective tissue disease, ocular or systemic disease
that could affect the epithelial healing, and dry eye syndrome. Patients
using rigid contact lenses were asked to discontinue lens use for at
least 3 weeks before the preoperative evaluation.
An increase of 1.00 diopter (D) in maximum topographic K-value
(Kmax) and a reduction of corneal thickness with or without changes
in uncorrected visual acuity (UCVA) and best-spectacle corrected visual acuity (BSCVA) within the last year were considered as indications
of progression. Similarly, a decrease of 1.00 D in Kmax was considered
as indication of regression.
Preoperative and postoperative examinations included: UCVA,
BSCVA, slit-lamp biomicroscopy, Goldmann tonometry (Haag Streit,
Bern, Swiss), fundus examination (Sigma 150K, Heine, Germany),
specular microscopy (Konan, Hyogo, Japan), ultrasound pachymetry
(CompuScanTM P, Storz, St. Louis, MO, USA), and corneal topography
(Orbscan IIz, Technolas Perfect Vision GmbH).
The institutional ethics committee approved the study. All patients provided written informed consent in accordance with the
Declaration of Helsinki after receiving a detailed description of the
nature and risks of the treatment.
Treatment
Corneal CXL was conducted under sterile conditions in an opera
ting room.
All patients received a mild oral sedative (diazepam 5 mg) 30 minutes before surgery and two drops of topical 0.5% proximetacaine,
2 to 5 minutes before surgery. A wire eyelid speculum was placed for
exposure. Corneal epithelium was removed by mechanical scraping
over the central cornea (9.0-mm) with a blunt Paton spatula (Storz
Ophthalmic Instruments, St Louis, USA).
The lid speculum was removed. Iso-osmolar 0.1% riboflavin so
lution (402.7 mOsmol/L) with dextran T500 20% was instilled to the
cornea every 3 minutes for 30 minutes. A slit-lamp examination,
using a blue filter, ensured the presence of riboflavin in the anterior
chamber. Hypo-osmolar 0.1% riboflavin solution without dextran
(310 mOsmol/L) was then applied every 20 seconds for 5 more minutes or until the thinnest corneal thickness (TCT) reached 400 µm.
156
The lid speculum was replaced. Fixation during irradiation was
achieved by instructing the patient to focus on the light-emiting
diode on the UVA emitter. The surgeon’s thorough control ensured
the patient’s centration. Ultraviolet-A irradiation was performed for
30 minutes using a commercially available UVA system (UV-X, Peschke Meditrade) at a working distance of 5 cm with an irradiance
of 3 mW/cm2, corresponding to a surface dose of 5.4 J/cm2. During
irradiation, iso-osmolar 0.1% riboflavin drops were applied every 5
minutes to ensure saturation of the cornea with riboflavin. A topical
anesthetic agent (0,5% proximetacaine) was applied as needed.
Three consecutive ultrasound pachymetry (CompuScanTM P,
Storz, St. Louis, USA) measurements were obtained at approximately
the thinnest point of the cornea, based on the Orbscan corneal topography and pachymetry maps, and the thinnest measurement was
recorded. The probe tip of the pachymeter was held perpendicular
to the cornea. Measurements were performed preoperatively, after
epithelial removal, after iso-osmolar 0.1% riboflavin instillation, after
hypo-osmolar 0.1% riboflavin instillation, after UVA irradiation, and at
1, 6 and 12 months after CXL.
After treatment, patients were medicated with topical moxifloxacin 0.3% drops 4 times a day for 5 days, and ketorolac tromethamine 3
times a day for 3 days. Soft therapeutic lens was applied until complete
re-epithelialization of the cornea. Unpreserved artificial tears were recommended for mild irritation. Paracetamol-codeine pain medication
was also prescribed as needed for the first 2 to 3 days. Fluorometholone
eyedrops were then applied 3 times a day for 2 weeks.
Postoperative examinations were scheduled daily until complete
re-epithelialization and for 1, 6 and 12 months postoperatively.
Statistical analysis was performed using SPSS 17.0 (SPSS, Inc.) soft
ware package. The paired t-test was used to check the significance of
the difference between two dependent groups for every continuous
variable. The level of statistical significance was considered when
p-value was lower than 0.05.
RESULTS
After treatment, complete re-epithelialization was observed within
4 days in all patients.
Twelve months after CXL, 12 eyes (66.6%) had no change in their
BSCVA compared to preoperative data, and 6 eyes (33.3%) had an
increase of 1 line on the log MAR scale (P=0.013). No eye lost any line
of the BSCVA, however, 38.8% (7 eyes) of the fellow untreated eyes
lost 1 line, and 5.5% (1 eye) lost 2 lines on the logMAR scale in their
BSCVA (P=0.004).
The preoperative (-6.0 ± 2.6 D) and twelve months postoperative
(-5.6 ± 2.7 D) mean spherical equivalent (SE) had a slight improvement by an average of 0.33 D (P=0.004). In the fellow untreated eyes,
mean SE increased by an average of -0.5 D (P=0.000). Figure 1 shows
the mean SE before and 1 year after treatment in the treated and
untreated fellow eyes.
Mean preoperative TCT (with the epithelium) was 380 ± 11 µm
(range, 363 to 398 µm). After epithelial removal (abrasion), it decreased to 341 ± 11 µm (range, 328 to 365 µm), (P=0.000). After 30
minutes of iso-osmolar 0.1% riboflavin drops instillation these values
decreased to 330 ± 7.6 µm (range, 316 to 350 µm), with a mean TCT
decrease of 10.9 ± 6.2 µm (range, 4 to 27 µm). Statistical analysis revealed significant difference when comparing these data with both,
the preoperative and after abrasion values (P=0.000).
After hypo-osmolar 0.1% riboflavin drops, all eyes achieved the
minimum 400 µm threshold of corneal thickness. However, the
promptness of stromal swelling response and the amount of swelling
showed distinct interindividual variation (5 minutes to 14 minutes;
52 to 101 µm). Mean TCT increased to 418 ± 11 µm (range, 400 to
446 µm), with a mean increase of 77 ± 12.4 µm (range, 52 to 101 µm).
Statistical analysis revealed significant difference when comparing
these values with those found before-CXL (P=0.000), after abrasion
(P=0.000) and after iso-osmolar riboflavin drops (P=0.000).
Nassaralla BA, et al.
After UVA irradiation, mean TCT was 384 ± 10 µm (range, 368 to
412 µm). Statistical analysis revealed a significant difference when
comparing these results with those found after abrasion (P=0.000),
after iso-osmolar (P=0.000), and after hypo-osmolar riboflavin drops
(P=0.000). However, no significant difference was found between
mean TCT measurements before treatment and after UVA irradiation
(P=0.230).
At 1, 6 and 12 months after treatment, mean TCT was 372 ± 10 µm
(range, 358 to 388 µm), 381 ± 12.7 (range, 362 to 402 µm), and 379
± 13 µm (range, 360 to 402 µm), respectively. Statistically significant
difference was found between the data found before treatment and
after 1 month (P=0.000). However, no statistically significant difference was noted in the TCT at 6 (P=0.196) and 12 months after surgery
(P=0.847). Figure 2 shows the mean TCT (with standard deviation)
during and after corneal CXL over time.
Twelve months after surgery, analysis of the maximum topographic K-readings (Kmax) showed no progression of the keratectasia in
any treated eye. Slight regression was observed in 15 eyes (83.3%).
The mean Kmax decreased from 57.81± 6.32 D to 55.85± 6.02 D,
with an average reduction of 2.11 ± 1.04 D (P=0.000). In the fellow
untreated eyes, however, 14 of 18 eyes (77.7%) showed a continuous
progression of the Kmax by an average of 1.63 D (P=0.000). Figure 3
shows the mean Kmax before and 1 year after CXL, in the treated and
fellow untreated eyes.
No statistically significant difference was found between the
mean preoperative (11.56 ± 1.19 mmHg) and twelve months postoperative (11.33 ± 1.0 mmHg) intraocular pressure (P=0.331).
The preoperative and postoperative (12 months) endothelial
cell counts were 2228 ± 385 and 2287 ± 284 cells/mm2, respectively
(P=0.32).
No intraoperative, early post-operative, or late postoperative com
plications were observed in this series of patients. After 12 months, all
corneas remained transparent, without any scar in the stroma.
Figure 1. Average spherical equivalent before and one year after corneal collagen
cross-linking with ultraviolet-A irradiation and hypo-osmolar riboflavin solution. There
was a slight decrease in the mean spherical equivalent in the treated eyes (average:
0.33 D) and a slight increase in the fellow untreated eyes (average: 0.5 D).
DISCUSSION
Corneal CXL has gained popularity as a temporary block in the
progression of keratoconus. Preliminary results published in the
literature indicate that when a series of safety precautions are taken,
the technique has an excellent safety profile. These prerequisites are
(1) de-epithelialization of the cornea to facilitate the diffusion and
absorption of riboflavin, (2) use of riboflavin 0.1% for at least 30 minutes, (3) homogeneous UV irradiation and (4) a low minimum corneal
thickness of 400 μm after epithelium removal(7-9).
In many cases of progressive keratectasia, patients achieve a low
minimum corneal thickness less than the threshold amount (<400 μm)
that prohibits a safe CXL. Recent studies have shown that preoperative swelling of the cornea safely broadens the spectrum of CXL
indications to thin corneas that would not otherwise be eligible for
treatment(9,10). Corneal thickness was reported to increase by up to
30% after treatment(9). This phenomenon is not due to an increase in
the diameter of the collagen fibrils but rather to the hydrophilic capacities of the stromal proteoglycans, creating collagen-free “lakes”(11).
Some authors(12-14) have shown that saturation of the corneal
stroma using 0.1% iso-osmolar riboflavin solution and 30 minutes of
UVA irradiation with a wavelenght of 370 nm and a surface irradiance
of 3 mW/cm2 may limit keratocyte death to a depth of approximately
300 µm. In our study, iso-osmolar riboflavin solution was applied to
the de-epithelialized corneal surface, every 3 minutes for 30 minutes
to ensure penetration of riboflavin into the corneal stroma. By means
of slit lamp inspection using blue light, we could assure that riboflavin had appeared in the anterior chamber before UV-irradiation. The
yellow staining of the anterior chamber served as a safety feature,
indicating that riboflavin had penetrated the cornea and the cornea
was thoroughly saturated. Then, hypo-osmolar riboflavin solution
was applied to the cornea to induce stromal swelling, thus increasing
the stromal thickness prior to UVA irradiation. Mean TCT increased to
418 µm (range, 400 to 446 µm), reaching the threshold amount for
a safe procedure.
Recent studies(15,16) found significant TCT decrease of about 17
to 20% in central corneal thickness 30 minutes after iso-osmolar
riboflavin drops. In their studies, a lid speculum was kept in the eye
during the whole procedure. Another research(16) showed a two-
step TCT decrease of 19% during the 60-minute treatment: a slower
Figure 2. The mean thinnest corneal thickness changes during corneal collagen crosslinking with ultraviolet-A irradiation and hypo-osmolar riboflavin solution in thin
corneas.
Figure 3. Change in the mean maximum topographic K-readings (Kmax) before and
1 year after CXL. There was an average reduction of 2.11D in the treated eyes and an
average progression of 1.63 D in the fellow (untreated) eyes.
157
thinning during riboflavin instillation (without a lid speculum) and a
faster thinning when a lid speculum hold the lids open during UVA
exposure. In all these studies, corneal exposure may have contributed
to a higher corneal thickness decrease during the procedure and in
the early postoperative CXL course. In order to reduce drying and
dehydration of the cornea, we did not open the eye with a speculum
during the first part of the treatment (i.e., after epithelium removal
and before UVA irradiation). A small decrease of approximately 3%
in TCT after iso-osmolar riboflavin solution instillation was noted in
our patients. It was probably due to the hyperosmolar effect of the
dextran in a de-epithelialized cornea(15). These results corroborate the
statement of other authors(16) who recommend that, during the first
part of corneal CXL, the eyelid speculum is removed from the eye
and the patient asked to keep the eye closed as much as possible to
prevent evaporation of water from the corneal stroma.
After hypo-osmolar 0.1% riboflavin drops, mean TCT significantly
increased to 418 µm, with a mean increase of 77 ± 12.4 µm (range,
52 to 101 µm). However, at the end of UVA irradiation, mean TCT
had decreased to 384 µm, what is lower than the minimum 400 µm
required for safety. This artificial swelling effect is transient and it is
not steady throughout the surgery. Nevertheless, this finding was
not related to complications in this series of patients. However, as
previously suggested(10,17), the application of hypo-osmolar riboflavin
solution should be continued during the entire process of irradiation
to sustain the necessary concentration of the solution and to avoid
any desiccation of the cornea.
In our analysis of the change in corneal thickness over time, pa
chymetric measurements thinned until 1 month postoperatively and
appeared to increase after that. Six months after treatment, no
statistically significant difference was found between the postoperative and baseline values. The physiology of this initial thinning and
subsequent rethickening is unclear. Epithelial removal may increase
the rate of water evaporation from the stroma and, as the stroma has
no dehydration resistance, renders the cornea vulnerable to thinning(18,19). Epithelial remodeling, anatomic and structural changes in
corneal collagen fibrils(9,18), and keratocyte apoptosis(13), might be also
implicated. A temporary increase in endothelial pump activity that
may be caused by UVA exposure has been also suggested as a cause
of the initial corneal thinning after CXL(17).
Surgeons must be aware about the intraoperative and postoperative thinning of the cornea after CXL, especially in thinner corneas
(less than 400 μm). Therefore, corneal thickness should be monitored
throughout the procedure, and in case of readings lower than 400 µm
at any point during treatment, the cornea should be re-swelled by
administering the riboflavin hypotonic solution.
Statistical analysis revealed a slight, but statistically significant
improvement in SE, corneal steepness and visual performance as determined by the BSCVA. Our results are modest in light of the results
from previous studies in which corneas of a thickness of more than
400 μm treated with iso-osmolar riboflavin solution, resulted in significantly better improvements in such parameters. However, the aim
of the current study was not to cause improvement, but to broaden
the spectrum of CXL indications to corneas that would otherwise not
be eligible for CXL treatment, halting progression of keratoconus and
preserving usable visual acuity.
158
CONCLUSIONS
Hypo-osmolar 0.1% riboflavin solution seems to be effective for
swelling thin corneas that would otherwise not be eligible for CXL
treatment. However, the swelling effect is transient and short acting.
Corneal thickness should be monitored throughout the procedure.
Larger sample sizes and longer follow-up are required in order to
make meaningful conclusions regarding safety, stability and efficacy
of the procedure in these artificially swollen corneas.
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Vitrectomia e troca fluido-gasosa para o tratamento do descolamento seroso da
mácula por fosseta de disco óptico: avaliação de longo prazo
Vitrectomy and gas-fluid exchange for the treatment of serous macular detachment due to optic disc pit:
long-term evaluation
Carlos Augusto Moreira Neto1, Carlos Augusto Moreira Junior2
RESUMO
ABSTRACT
Objetivo: Avaliar 5 olhos com descolamento seroso da mácula devido à fosseta
de disco óptico que foram submetidos à vitrectomia via pars plana e seguidos
por pelo menos 7 anos.
Métodos: Os pacientes foram submetidos à vitrectomia via pars plana, remoção
da membrana hialoide posterior, injeção de soro autólogo e troca fluido-gasosa,
sem aplicação de fotocoagulação a laser, e foram testados quanto à acuidade visual,
tela de Amsler, retinografia e, recentemente, retinografia com autofluorescência
e OCT de alta resolução.
Resultados: Todos os 5 olhos operados tiveram significativa melhora da visão
após o procedimento cirúrgico, mantendo boa visão durante todo período de
acompanhamento. A acuidade visual pré-operatoria média foi de 20/400 enquanto
a acuidade visual final foi de 20/27 com um tempo médio de seguimento de 13,6
anos. Não foram observadas recorrências do descolamento seroso da mácula e
os exames de OCT mostraram a retina perfeitamente aplicada até a margem da
fosseta de disco óptico.
Conclusão: Descolamentos serosos da mácula causados por fosseta de disco óptico
são adequadamente tratados com vitrectomia via pars plana e troca fluido-gasosa,
sem a necessidade de fotocoagulação da retina, mantendo excelente acuidade
visual por vários anos após o procedimento, sem o aparecimento de recorrências.
Purpose: To evaluate 5 patients with serous macular detachment due to optic
disc pit that were submitted to pars plana vitrectomy and were followed for at
least 7 years.
Methods: Patients were submitted to pars plana vitrectomy, posterior hyaloid
removal, autologous serum injection and gas-fluid exchange, without laser photo
coagulation, and were evaluated pre and post-operatively with visual acuity and
Amsler grid testing, retinography, and recently, with autofluorescence imaging and
high resolution OCT.
Results: All 5 eyes improved visual acuity significantly following the surgical procedure
maintaining good vision throughout the follow-up period. Mean pre-operative visual
acuity was 20/400 and final visual acuity was 20/27 with a mean follow-up time of
13.6 years. No recurrences of serous detachments were observed. OCT examinations
demonstrated an attached retina up to the margin of the pit.
Conclusion: Serous macular detachments due to optic disc pits were adequately
treated with pars plana vitrectomy and gas fluid exchange, without the need for
laser photocoagulation, maintaining excellent visual results for a long period of time.
Descritores: Disco óptico; Descolamento retiniano/etiologia; Descolamento re
tiniano/cirurgia; Vitrectomia
Keywords: Optic disc; Retinal detachment/etiology; Retinal detachment/surgery;
Vitrectomy
INTRODUÇÃO
A fosseta de disco óptico congênita é uma depressão oval, geralmente, localizada no segmento ínfero-temporal do disco óptico e
que, frequentemente, está associada à presença de descolamento seroso da mácula(1,2). Sua incidência é em torno de uma para cada 11 mil
pessoas(1), acometendo ambos os olhos em apenas 15% dos casos(3).
Geralmente, a fosseta de disco óptico é assintomática, podendo
causar diminuição da visão por complicações maculares tais como
descolamento seroso, retinosquise ou alterações pigmentares(3).
Petersen(4) foi o primeiro a descrever a relação entre a presença
da fosseta de disco óptico e o descolamento seroso da retina que,
geralmente, está confinado à macula. Tais descolamentos ocorrem
entre 25 e 75% dos casos(5,6) e a grande maioria deles ocorrem nos
casos de fossetas localizadas na região temporal do disco óptico,
tornando-se sintomáticos por volta da terceira década de vida(3).
Embora a resolução espontânea do descolamento seroso da
mácula possa ocorrer, em geral, o prognóstico quanto à visão central
é ruim, especialmente nos casos de descolamentos serosos de longa
duração(5).
Diversos tratamentos foram propostos para a maculopatia por
fosseta de disco óptico. O presente estudo mostra resultados e acompanhamento de longo prazo de 5 olhos com o problema e que foram
submetidos a cirurgia intraocular.
Submetido para publicação: 17 de dezembro de 2012
Aceito para publicação: 20 de março 2013
Trabalho realizado no Hospital Olhos do Paraná, Curitiba.
1
2
Médico, Hospital de Olhos do Paraná - Curitiba (PR), Brasil.
Médico, Departamento de Oftalmologia, Universidade Federal do Paraná - UFPR, Curitiba (PR),
Brasil.
MÉTODOS
Cinco olhos de 5 pacientes, 3 homens e duas mulheres, com idade variando entre 16 e 39 anos e que apresentavam descolamento
seroso de mácula por fosseta de disco óptico foram submetidos a
vitrectomia via pars plana, remoção da membrana hialoide posterior,
Divulgação de potenciais conflitos de interesse: C.A.Moreira Neto, Nenhum; C.A.Moreira Junior,
Nenhum.
Autor correspondente: Carlos Augusto Moreira Neto. Rua Fernando Simas, 1010 - Curitiba (PR) 80430-190 - Brasil - E-mail: [email protected]
159
troca fluido-gasosa e injeção de soro autólogo, sem a aplicação de
fotocoagulação a laser na margem da fosseta.
Antes da cirurgia, os pacientes foram submetidos ao exame de
acuidade visual (AV) e de tela de Amsler, bem como, retinografia e/ou
angiografia fluoresceínica.
A cirurgia consistiu na remoção do vítreo e de toda a membrana
hialoide posterior, no mínimo além das arcadas que formam o polo
posterior da retina. Em caso de haver tecido glial no local da fosseta,
o mesmo foi removido cuidadosamente com pinças intraoculares.
Após retirar todo o líquido da cavidade vítrea através de troca fluidogasosa, foi injetado 0,2 ml de soro autólogo sobre a fosseta seguida
de injeção de gás C3F8 a 14%, preenchendo a cavidade vítrea.
O soro autólogo foi obtido a partir de 5 ml de sangue do paciente, centrifugado pouco antes do procedimento cirúrgico a 3.000
rotações por minuto por 10 minutos e armazenado a 4 graus Celsius
até o procedimento.
No período pós-operatório e no acompanhamento de longo
prazo foram feitas medidas da AV, exame com tela de Amsler e retinografia. Inicialmente, os pacientes foram acompanhados trimestralmente até o fim do primeiro ano após a cirurgia, quando passaram a
ter retorno anual ou se houvesse algum tipo de perda visual.
Mais tardiamente, na evolução dos casos, alguns deles foram
também submetidos à retinografia de autofluorescência (Canon
CX1, Tokyo, Japan) e OCT de alta resolução (Spectralis, Heildelberg
Engineering, Heidelberg, Germany).
RESULTADOS
A AV inicial média dos 5 pacientes foi de 20/400, variando entre
20/100 e 5/200. Todos os pacientes reclamaram de metamorfopsia e
mancha no centro da visão.
Sessenta dias após a cirurgia, os pacientes retornaram para
exames e neste momento a AV pós-operatória média foi de 20/27,
variando entre 20/25 e 20/30 (Figura 1). Os pacientes não mais se
queixavam de manchas no campo visual ou metamorfopsia, mostrando o exame com tela de Amsler dentro da normalidade.
Os pacientes foram acompanhados por um tempo médio de
13,6 anos, variando entre 7 e 20 anos após a cirurgia (Figuras 2 e 3).
A tabela 1 mostra a distribuição dos pacientes quanto à idade,
sexo, AV inicial, AV final e tempo de seguimento.
DISCUSSÃO
Para que tenhamos um tratamento apropriado à maculopatia
por fosseta de disco óptico é necessário que tenhamos um melhor
entendimento acerca da fisiopatologia do problema. Dois pontos
ainda permanecem obscuros: a origem do fluido e o mecanismo pelo
qual ocorre o descolamento sensorial da retina(7).
Existem quatro possíveis origens para o fluido sub-retiniano. Brown
et al.(8) acreditam que a origem do fluido está na cavidade vítrea. Em
1996, Krivoy(9) em estudo feito através de exames de OCT mostrou
uma comunicação direta entre a “schisis” retiniana e o espaço suba
racnoide. Nesse caso o fluido seria liquor produzido no espaço
subaracnoide. Recentemente, Kuhn et al.(10) relataram migração intracraniana de óleo de silicone em um caso de fosseta de disco óptico
que foi previamente tratado com vitrectomia. Menos provavelmente,
a origem do fluido seria vazamento de vasos sanguíneos na base
da fosseta, mesmo porque a angiofluoresceinografia não mostra
vazamento na área da fosseta(11). Por último, alguns acreditam que o
fluido tem origem no espaço orbitário que envolve a dura-máter(6).
Com respeito ao mecanismo pelo qual ocorre o descolamento
sensorial da mácula, Postel et al.(12) propuseram que há uma bolsa de
vítreo liquefeito sobre a fosseta e à medida que vetores tracionais se
desenvolvem ao longo dos anos, uma pequena rotura retiniana se
desenvolveria naquele espaço permitindo que o fluido levasse ao
descolamento sensorial da retina.
160
A
B
Figura 1. A) Retinografia “red-free” de paciente feminina, 23 anos de idade, com AV=
5/200 no OE, mostrando descolamento seroso com presença de fibrina na região do
polo posterior por fosseta na região temporal do disco óptico (seta). B) Retinografia
realizada 3 meses após cirurgia de vitrectomia pars plana, remoção de tecido glial do
interior da fosseta e troca fluido-gasosa, mostrando a fosseta de forma mais evidente
(seta). Houve resolução total do descolamento seroso do polo posterior, onde apenas
pode-se observar a alteração causada pelo edema sobre o epitélio pigmentado que
aparece mais claro. AV final foi de 20/30.
Tabela 1. Distribuição dos pacientes com descolamento seroso de
mácula por fosseta de disco óptico, que foram submetidos à cirurgia,
conforme sexo, idade, acuidade visual inicial e final e tempo de seguimento clínico
Pacientes
Sexo - idade (anos)
AV inicial
AV final
Seguimento
(anos)
M - 39
20/100
20/25
15
M - 17
05/200
20/25
20
07
F - 38
20/200
20/30
M - 16
20/100
20/25
17
F - 23
05/200
20/30
09
M= masculino; F= feminino; AV= acuidade visual.
Em nossos casos, os exames de OCT, realizados vários anos após
a reaplicação cirúrgica da mácula, demonstram claramente uma falta
de tecido do nervo óptico na região da fosseta e que se continua em
seu prolongamento posterior (Figuras 2 F e 3 F). Tal achado reforça a
ideia da comunicação direta com o espaço subaracnoide. Por outro
lado, percebemos que a remoção de vetores tracionais sobre a retina, através da cirurgia de vitrectomia acompanhada da remoção da
membrana hialoide e da retirada do tecido glial que se apresentava
sobre a fosseta, foi fator importante para a cura do descolamento
sensorial da mácula nos casos aqui apresentados.
Tais achados levam a crer que um mecanismo combinado de
tração vitreorretiniana junto à penetração de fluido originário no
espaço subaracnoide possa ser a fisiopatologia que melhor explica
o problema.
Ainda não existe um tratamento de consenso para o descolamento seroso da mácula por fosseta de disco óptico. Uma das razões
para isso é porque se trata de doença rara, sem grande número de
casos para permitir estudo prospectivo multicêntrico. De toda forma,
são vários os tratamentos propostos, desde a simples observação até
as cirurgias vitreorretinianas.
A terapêutica com repouso absoluto acompanhado de oclusão
ocular bilateral e uso de corticosteroides não se mostrou efetiva(13).
Outra opção de tratamento foi o uso da fotocoagulação na margem
da fosseta com o objetivo de reabsorção progressiva do fluido subretinano. Vários autores(11,13,14) relataram resultados parcialmente
positivos, entretanto, houve demora de 1 a 2 anos para a absorção
completa do fluido, bem como, alguns casos tiveram recidivas do
problema. Outros propuseram a técnica de injeção de gás intravítreo
combinado a fotocoagulação a laser(15).
Moreira Neto CA, Moreira Junior CA
A
D
B
C
E
F
Figura 2. A) Retinografia “red-free” de paciente masculino com 17 anos de idade, AV= 5/200 no OE, mostrando elevado descolamento seroso de mácula (seta) por fosseta na
região temporal inferior do disco óptico. B) Retinografia realizada 3 meses após a cirurgia, mostrando resolução total do descolamento seroso e melhora da visão para 20/25. C)
Retinografia realizada 20 anos após a cirurgia, mostrando situação estável do polo posterior, sem descolamento macular e mantendo 20/25 de visão. D) Retinografia autofluorescente realizada 20 anos após a cirurgia, mostrando a fosseta de disco óptico mais escura (seta). E) OCT realizado com 20 anos de seguimento, mostrando a passagem do “scan”
sobre a fosseta do disco óptico e sobre a região macular. Note que o mapa não mostra qualquer sinal de edema ou elevação na região macular. F) Corte de OCT de alta resolução
mostrando a ausência tecidual sobre a depressão da fosseta no disco óptico e a retina totalmente aderida na área macular.
A
D
B
E
C
F
Figura 3. A) Retinografia “red-free” em paciente masculino de 16 anos de idade, AV=20/100 no OD, mostrando descolamento seroso da mácula (seta) por fosseta da região central do
disco óptico. B) Retinografia realizada 3 meses após a cirurgia mostrando resolução completa do descolamento seroso com melhora da visão para 20/25. C) Retinografia realizada 17
anos após a cirurgia, mostrando situação estável do polo posterior, sem descolamento macular e mantendo 20/25 de visão. D) Retinografia autofluorescente realizada 17 anos após
a cirurgia, mostrando a fosseta de disco óptico mais escura (seta). E) OCT realizado com 17 anos de seguimento, mostrando a passagem do “scan” sobre a fosseta do disco óptico e
sobre a região macular. F) Corte de OCT de alta resolução mostrando a ausência tecidual sobre a depressão da fosseta no disco óptico e a retina totalmente aderida na área macular.
Recentemente, a maioria dos cirurgiões tem preferido a técnica
da retirada de todas as trações vítreas sobre a fosseta e retina, através
da vitrectomia via pars plana com remoção da membrana hialoide e
da membrana limitante interna em combinação com a fotocoagulação na margem da fosseta(16-18).
Em 2009, Georgalas et al.(19) relataram o tratamento de 3 casos
de fossetas de disco óptico com descolamento seroso da mácula
que foram tratados com sucesso apenas com o uso da vitrectomia
associada à remoção da membrana hialoide e membrana limitante
interna, sem a realização de fotocoagulação a laser.
161
Em nossos casos, a vitrectomia via pars plana associada a remoção
da membrana hialoide posterior e troca fluido gasosa parece ter sido
a maior responsável pela solução do problema. A injeção de soro
autólogo, feita à época baseava-se em relatos de alguns autores para
o tratamento do buraco de mácula(20,21). Rosenthal et al.(22) relataram
a completa resolução do descolamento seroso da mácula em uma
paciente de 44 anos com fosseta de disco óptico, tendo submetido a
mesma à vitrectomia pars plana, remoção da membrana hialoide posterior e injeção de concentrado de plaquetas autólogo sobre a fosseta.
Entretanto, a exemplo de outros autores(20,21), acreditamos que a injeção de soro autólogo ou concentrados plasmáticos com o objetivo de
assegurar a reaplicação da mácula pouco contribuem para a solução
do problema, sendo a vitrectomia com a remoção das trações vitreorretinianas e troca fluido-gasosa o melhor método terapêutico.
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Level of agreement among Latin American glaucoma subspecialists on the diagnosis
and treatment of glaucoma: results of an online survey
Nível de concordância entre subespecialistas de glaucoma latino-americanos sobre o diagnóstico
e tratamento do glaucoma: resultados de uma pesquisa digital
Daniel E. Grigera1, Paulo Augusto Arruda Mello2, Wilma Lelis Barbosa3, Javier Fernando Casiraghi4, Rodolfo Perez Grossmann5, Alejo Peyret6
ABSTRACT
RESUMO
Purpose: The aim of this research was to assess the level of agreement among
glaucoma experts in Latin America on key practices related to treatment and
diagnosis of glaucoma.
Methods: An online questionnaire was sent to a multinational panel of glaucoma
experts. The questionnaire contained 107 statements on the medical treatment
(Part 1) and diagnosis (Part 2) of glaucoma, and was developed in Spanish and
translated into English. Agreement was defined as ≥70% of respondents.
Results: Fifty participants from 14 countries completed the questionnaire. For the
medical treatment of glaucoma, nearly all respondents (98% or greater) confirmed
that medical treatment as first-line therapy is preferred to surgery, prostaglandin
analogs are the medication of first choice for primary open-angle glaucoma (POAG),
longitudinal monitoring of efficacy should include intraocular pressure, structural
and functional status, as well as if patients’ quality of life is impaired by the high cost
of medication. For the diagnosis of glaucoma section, all respondents confirmed
that, after initial examination, gonioscopy should be repeated over time, standard
automated perimetry is the most important functional examination for diagnosis
and monitoring of primary open-angle glaucoma, central corneal thickness is
important in assessment of glaucoma, and computerized imaging tests help in
clinical evaluation of optic disc.
Conclusions: This survey shows a high level of agreement on most aspects of
glaucoma diagnosis and treatment among Latin American glaucoma experts.
Areas of disagreement highlight the need for further evidence or education. These
findings will be useful for guiding future efforts to optimize glaucoma practice
by clinicians in Latin America.
Objetivo: Avaliar o nível de concordância entre os especialistas de glaucoma na
América Latina sobre as práticas mais importantes relacionadas ao tratamento e
diagnóstico de glaucoma. Métodos: Um questionário digital foi enviado a um painel multinacional de espe
cialistas em glaucoma. O questionário continha 107 declarações sobre o tratamento
médico (Parte 1) e diagnóstico (Parte 2) de glaucoma, e foi desenvolvido em espanhol
e traduzido para o Inglês. Concordância foi definida como ≥ 70% dos entrevistados. Resultados: Cinquenta participantes de 14 países responderam ao questionário.
Para o tratamento médico de glaucoma, quase todas as respostas (98% ou mais),
confirmaram que o tratamento médico como terapia de primeira linha é preferido
para a cirurgia, os análogos das prostaglandinas são os medicamentos de primeira
escolha para o glaucoma primário de ângulo aberto (GPAA), a monitoração longitu
dinal eficácia deve incluir a pressão intraocular o estado estrutural e funcional além
da qualidade de vida do paciente ser prejudicada pelo alto custo da medicação. Para
a seção sobre o diagnóstico de glaucoma, todos os entrevistados confirmaram que,
após análise inicial, a gonioscopia deve ser repetida ao longo do tempo, a perimetria
automatizada padrão é o exame funcional mais importante para o diagnóstico e
monitoramento do glaucoma primário de ângulo aberto, a espessura corneana central
é importante na avaliação do glaucoma e exames de imagem computadorizados
ajudam na avaliação clínica do disco óptico. Conclusões: Este estudo mostra um alto nível de concordância na maioria dos as
pectos do diagnóstico e tratamento de glaucoma entre os especialistas em glaucoma
latino-americanos. Áreas de desacordo destacam a necessidade de novas evidências
ou educação. Estes resultados serão úteis para orientar futuros esforços na otimização
de práticas em relação ao glaucoma por médicos da América Latina.
Keywords: Glaucoma/diagnosis; Glaucoma/therapy; Questionnaires; Humans
Descritores: Glaucoma/diagnóstico; Glaucoma/tratamento; Questionários; Humanos
INTRODUCTION
It has been estimated that almost 5.7 million people in Latin
America have glaucoma, principally the open-angle subtype, and
that this number will increase to approximately 8 million people by
2020(1). The burden of glaucoma is substantial in Latin America, where
it is one of the leading causes of blindness or visual impairment in
both adults and children(2-9) and has a significant negative impact
on quality of life(10). The burden of glaucoma may be higher in Latin
Study carried out at Headquarters of the Latin American Glaucoma Society - LAGS.
Funding: This survey was not sponsored.
Submitted for publication: February 15, 2013
Disclosure of potential conflicts of interest: D.E.Grigera has received payment from MSD for participa
ting in an expert meeting, and has payment for lectures and received travel/accommodation support
from Allergan and MSD. P.A.A.Mello has received payment for board membership, consultancy
and grants from Alcon and Allergan; payment for lectures, manuscript preparation educational
presentations and travel from Alcon, Allergan and Merck. W.L.Barbosa has received travel support
from Allergan in relation to development of a paper; received payment for board membership from
Allergan, payment for lectures from Alcon Laboratories and MSD. J.F.Casiraghi has received payment
for board membership from MSD, Allergan and Poen; consultancy fees from Allergan, MSD, Pfizer,
Peon, F Colon, Bausch and Lomb and HLB; payment for expert testimony from Allergan, Poen, F
Colon and HLB; grants from Allergan; payment for lectures from, Allergan and Pfizer; payment for
educational presentations from Allergan and Poen. R.P.Grossmann, None. A.Peyret has received
payment for lectures from MSD; payment for manuscript preparation from Allergan; payment for
educational presentations from Poen travel support from MSD.
Physician,
Physician,
Physician,
4
Physician,
Argentina.
5
Physician,
6
Physician,
1
2
3
Hospital Oftalmologico Santa Lucia, Buenos Aires, Argentina.
Universidade Federal de São Paulo - UNIFESP - São Paulo, Brazil.
Universidade de São Paulo - USP - São Paulo, Brazil.
Hospital de Clinicas, School of Medicine, University of Buenos Aires, Buenos Aires,
Instituto de Glaucoma y Catarata, Lima, Peru.
Hospital Universitario Austral, Buenos Aires, Argentina.
Correspondence address: Daniel E Grigera. Universidad del Salvador. Marconi 920, 1636 - Olivos Buenos Aires, Argentina - E-mail: [email protected]
163
Level of agreement among Latin American glaucoma subspecialists on the diagnosis and treatment of glaucoma:
America than in more developed regions because poverty acts as a
barrier to effective diagnosis and treatment(11,12), resulting in a high
proportion of patients presenting with advanced disease.
While diagnostic and treatment strategies for glaucoma have
evolved over the years, many gaps remain in our understanding of
optimal practice for diagnosis and management. Moreover, management practices differ between and even within countries, depending
on the health infrastructure. Recently, attempts have been made
by the World Glaucoma Association (WGA) to provide guidance on
international best practices in glaucoma diagnosis and treatment. To
this end, the WGA has developed a number of consensus statements,
providing guidance on a range of issues including structure and function in the diagnosis of glaucoma(13), closed-angle glaucoma (CAG),
intraocular pressure (IOP), and medical therapy(14).
Typically, consensus statements on glaucoma management prac
tices have been developed by a restricted panel working in two
phases: first surveying participants for their agreement on particular
questions relating to clinical practice, and then meeting to share the
results of the survey, before asking panelists to rate the questions
again(15,16). However, considerable insight into the level of agreement
among clinical experts can also be gained by administration of a single survey(17-19), which can then guide the development of guidelines
or highlight the need for further research or education on a national
or regional basis.
The Latin American Glaucoma Society (LAGS) developed a survey
among key clinical experts in the region to determine the level of
agreement on key practices related to the treatment and diagnosis
of glaucoma, including region-specific issues in Latin America. Here
we report the methodology and findings of this research initiative.
Methods
Questionnaire preparation
A multinational panel of ophthalmology experts developed a
two-part questionnaire: Part 1 was on the medical treatment of glaucoma and Part 2 was on the diagnosis of glaucoma. The questionnaire
consisted of a number of statements; respondents were asked to
rate their agreement with each statement using various scales. The
statements were developed by the panel based on an analysis of the
medical literature, a review of existing WGA consensus statements,
and their own clinical experience. Relevant medical literature was
identified by means of a PubMed search undertaken in September
2009. The following search terms were used: treatment strategies,
target IOP, general concepts about medical therapy, antiglaucoma
drugs, adverse events, neuroprotection, compliance, specific aspects
of treatment in Latin America and generic/copy medications, general
aspects of glaucoma diagnosis, clinical examination of the optic
nerve, examination of the nerve fiber layer, diagnosis in primary
closed-angle glaucoma (PCAG), gonioscopy, functional examination,
IOP, and structural examination by imaging. At the time of survey
development, WGA consensus statements were available for diagnosis(13) and IOP, but not for glaucoma treatment.
The survey development panel drafted 107 statements relating
to the medical therapy or diagnosis of glaucoma. The full results of
the survey are presented in this paper (see Appendix). The ques
tionnaire included open-ended and closed-ended questions (yes/
no, multiple choice, rating scale).
Survey
The survey was developed in Spanish, translated into English, and
uploaded to an online survey tool. An email invitation to complete
the survey was sent to 50 individuals from geographically diverse
parts of the region: 31 were members of the LAGS and 19 were others
who were identified by LAGS members as Latin American ophthalmologists with particular expertise in the field of glaucoma diagnosis
164
and treatment. The survey was completed between October 2009
and April 2010.
Analysis
Upon receipt of the questionnaire results, the level of agreement
or disagreement for each statement was calculated by assessing
the percentage of respondents giving each answer. Consensus was
defined a priori as agreement in >70% of the group. For Likert scale
questions, “strongly agree” and “agree”, “strongly disagree” and “disagree” were pooled together. Combining scores for the purposes of
categorization has been used in previous similar studies, in both glaucoma(15,16) and other indications(20). Internal consistency for each part
(medical treatment and diagnosis of glaucoma) and for each subcategory/topic, as well as overall consistency, was measured using a
standardized Cronbach’s coefficient alpha. A Cronbach’s coefficient
alpha of ≥0.65 was considered to indicate internal consistency.
Results
All 50 participants returned the survey and 48 participants completed all questions in the survey. Survey respondents were from Brazil (n=16), Argentina (n=9), Colombia (n=5), Mexico (n=4), Chile (n=3),
Peru (n=3), Venezuela (n=3), Costa Rica (n=1), Guatemala (n=1), Ecuador (n=1), Paraguay (n=1), Puerto Rico (n=1), Uruguay (n=1), and USA
(n=1). Most participants (n=30) worked in both private practice and
the public sector, but 17 worked solely in private practice and 1 solely in the public sector; 2 participants did not answer the question
on clinical practice type. Survey respondents had been in clinical
practice for between 2 and 50 years (mean ± standard deviation [SD]
22.68 ± 10.75 years).
Overall, the panel found agreement in 75 (70.1%) of 107 statements and no agreement in 32 (29.9%) (Tables 1 and 2). We will now
highlight the results of the survey; for full results, please refer to the
Appendix. In Part 1, medical treatment of glaucoma, respondents
unanimously agreed that knowing the hypotensive efficacy of different glaucoma medications was essential (question 15). Examples
of medical therapy questions on which no agreement was reached
were those related to achieving the greatest possible reduction in IOP
(question 10), what constitutes the maximal number of medications
(question 19), whether prostaglandin analogs reduce IOP in open-angle glaucoma (OAG) with peripheral anterior synechiae (question 25),
the maximum number of daily doses to maintain patient adherence
(question 37), and whether generic medications are bioequivalent
and interchangeable (question 46).
In Part 2 on glaucoma diagnosis, respondents unanimously agreed
on four issues: that after initial examination, gonioscopy should be
performed in all patients with glaucoma or suspected glaucoma and
repeated over time (questions 83 and 84), that standard automated
perimetry (SAP) is the most important functional examination for
the diagnosis and monitoring of primary open-angle glaucoma
(POAG) (question 88), that central corneal thickness is important in
the assessment of glaucoma or suspected glaucoma (question 92),
and that computerized imaging helps in clinical evaluation of the
optic disc (question 103). Examples of diagnostic questions where
no agreement was reached were those relating to initial assessment
of the optic nerve fiber layer (question 77), the most useful tonometric method to use in suspect glaucoma patients (question 98), use
of the Pascal tonometer (question 95) or ocular response analyzer
(ORA) (question 96) in preference to the Goldmann tonometer, tests
for early detection of glaucoma damage (question 105), and optimal
method of analyzing progression of nerve fiber layer (question 107).
Consistency scores for the full 107-question survey were
0.675619 for Part 1 on medical treatment of glaucoma, 0.640498 for
Part 2 on diagnosis of glaucoma, and 0.675030 overall, indicating a
general consistency in responses.
Grigera DE, et al.
Table 1. Medical treatment of glaucoma consensus statements (questions with 70% or greater agreement)
Question
No
No of
responses
Summary
n (%)
Treatment strategies
08
50
Medical treatment is preferred first-line (over surgery)
49 (098.0%)
Target intraocular pressure
09
50
Target IOP is a useful concept
48 (096.0%)
14
50
Target IOP concept is dynamic and must be individualized
48 (096.0%)
11
50
Target IOP must be determined for each patient
48 (096.0%)
12
50
IOP should be at stable target levels for over 24 hours
45 (090.0%)
13
50
Ideal medication decreases IOP, has minimal ocular side effects, and is affordable
47 (094.0%)
General concepts
15
50
Knowledge of hypotensive efficacy of medication is essential
50 (100.0%)
18
50
If hypotensive effect is <10%, medication is replaced with another
44 (088.0%)
21
50
Medication of first choice for POAG is prostaglandin analogs
49 (098.0%)
16
50
Longitudinal monitoring of efficacy should include IOP, structural and functional status
49 (098.0%)
17
50
Hypotensive efficacy, with reasonable safety, is more important for choosing medication
39 (078.0%)
20
50
Chronic use of benzalkonium chloride adversely affects prognosis for surgery
47 (094.0%)
24
50
There are no significant clinical differences in hypotensive efficacy between different prostaglandin analogs
38 (076.0%)
26
50
There are no significant clinical differences in hypotensive efficacy between different carbonic anhydrase inhibitors
43 (086.0%)
22
50
Prostaglandin analogs have a significantly higher hypotensive efficacy than β-blockers
50 (100.0%)
Adverse events
31
50
β-blockers have the best LOCAL safety profile
42 (084.0%)
32
50
Prostaglandin analogs have the best SYSTEMIC safety profile
45 (090.0%)
27
50
Hyperemia associated with the use of some glaucoma treatment medications is related to a mild inflammatory response
36 (072.0%)
33
50
No systemic medication has a proven neuroprotective action in humans
43 (086.0%)
34
50
No topical medication has a proven neuroprotective action in humans in addition to IOP lowering
46 (092.0%)
Neuroprotection
Compliance
39
50
Quality of life is impaired by the high cost of medication
48 (096.0%)
35
50
Lack of patient compliance is the main cause of glaucoma treatment failure
37 (074.0%)
36
50
Compliance with medical therapy is a major impediment affecting approximately 50% of patients
40 (080.0%)
41
50
Education for patients about their illness is critical for improving treatment compliance
48 (096.0%)
Specific aspects of treatment in Latin America
44
50
I agree with the use of prostaglandin/timolol combinations in Latin America
42 (084.0%)
42
50
Glaucoma therapy is unaffordable for most patients in Latin America
36 (072.0%)
45
50
It is not important for prostaglandin/timolol combinations to be approved by the FDA
35 (070.0%)
47
49
Copy medications are not bioequivalent and interchangeable
40 (081.6%)
50
49
We as a group should be doing something about access to quality medical therapy
47 (095.9%)
51
49
I would participate in a multicenter comparative study of original medications versus generic/“copy” medications designed
by the LAGS
46 (093.9%)
Generic/copy drugs
FDA= Food and Drug Administration; IOP= intraocular pressure; LAGS= Latin American Glaucoma Society; POAG= primary open-angle glaucoma.
Discussion
To our knowledge, this is the first region-wide survey of glaucoma diagnostic and treatment preferences among Latin American
ophthalmologists. Our study has found a substantial level of agreement among glaucoma specialists in Latin America for most diagnostic and treatment practices surveyed.
Our survey found consistent agreement among regional specialists surveyed about the importance of treating to target IOP and
maintaining a stable IOP over 24 hours, whereas the respondents did
not agree that the greatest possible decrease in IOP should be sought
in order to minimize the risk of progression of glaucoma damage. This
implies that, among two possible strategies for optimizing medical
165
Table 2. Diagnosis of glaucoma consensus statements (questions with 70% or greater agreement)
Question
No
No of
responses
Summary
n (%)
responding in
the affirmative
General concepts
055
48
Elevated IOP is not essential for diagnosis of POAG
41 (085.4%)
057
48
Blood flow to the optic nerve is important in POAG pathogenesis
35 (072.9%)
052
48
Structural and/or functional signs of damage are essential for diagnosis
44 (091.7%)
054
48
Glaucoma diagnosis requires characteristic change to optic disc or visual field defect
40 (083.3%)
056
48
Lack of defect in achromatic pathway is a requisite for pre-perimetric diagnosis
38 (079.2%)
067
48
Advisable to estimate optic disc size biomicroscopically by slit lamp and/or direct ophthalmoscopy
37 (077.1%)
068
48
Loss of shape of neuroretinal ring in normal-sized optic nerve heads is an early sign of glaucoma
42 (087.5%)
073
48
Clinical examination of the optic nerve should include disc size, keeping the ISNT rule, cup-disc ratio, asymmetry in the C-D
ratio, rim regularity, rim color and cupping, position of the blood vessels, presence of papillary and juxtapapillary hemorrhages,
peripapillary atrophy and conservation of the nerve fiber layer
43 (089.6%)
059
48
Clinical examination of optic nerve with dilated pupil in slit lamp using indirect magnification is the structural gold standard
for examining POAG
44 (091.7%)
060
48
Recording the condition of the optic nerve is essential in glaucoma and suspected glaucoma
46 (095.8%)
061
48
Recording of optic nerve condition should be by color spectrophotography, digital photography and/or structural imaging,
with itemized drawing if other technologies are unavailable
44 (091.7%)
062
48
Photographic documentation is the gold standard for structural evaluation in glaucoma
43 (089.6%)
063
48
Serial photography is the basic minimum structural method of recording progression in POAG
45 (093.8%)
064
48
Examination with indirect vision lenses (90, 78, and 60 diopters) is suitable for clinical evaluation of optic nerve
45 (093.8%)
072
48
Increase with time in area of cupping or cup-disc ratio is important in differentiating normal nerve and glaucoma
47 (097.9%)
074
48
It is advisable to examine the optic nerve’s condition in glaucoma patients at each visit
36 (075.0%)
058
48
An optic nerve examination is essential for the diagnosis and management of glaucoma
45 (093.7%)
065
48
Lenses with higher dioptric power (90D) provide satisfactory viewing in almost all pupil sizes, while the smaller ones, especially
that of 60D, require mydriasis, or at least that the pupil diameter not be reduced. The latter, however, provide a better view
of the details of the optic nerve
37 (077.1%)
069
48
Optic disc hemorrhages indicate the presence of glaucoma damage and suggest progression, and are most frequently found
in normal tension glaucoma
44 (091.6%)
070
48
Early or moderate optic nerve damage can be underestimated in small optical nerves, and a proper diagnosis may not be made
48 (100.0%)
071
48
In large optic nerves, the diagnosis of glaucoma is often overestimated
46 (095.9%)
Clinical examination of the optic nerve
Examination of the nerve fiber layer
075
48
Monitoring the condition of the nerve fiber layer in glaucoma is essential
35 (072.9%)
076
48
Diffuse defects of the nerve fiber layer in OAG are harder to detect than localized defects and are inferred by detailed observation of the vessels
47 (097.9%)
078
46
Localized defects of the nerve fiber layer are arch-shaped and extend to the edge of the optic disc
41 (085.4%)
084
48
After the initial examination, gonioscopy should be repeated over time
48 (0100.0%)
082
48
Gonioscopic evaluation is recommended as part of routine eye exam for all patients aged >40 years
34 (070.8%)
085
48
It is useful to adopt a particular gonioscopic-type classification of angle
37 (077.1%)
080
48
Van Herick’s technique for estimating anterior chamber depth is not a substitute for gonioscopy
45 (093.8%)
083
48
Gonioscopy should be performed in all patients with glaucoma or suspected glaucoma
48 (100.0%)
Diagnosis in PCAG/gonioscopy
Functional examination
088
48
SAP is the most important functional examination for diagnosis and monitoring of POAG
48 (100.0%)
090
48
Both frequency doubling perimetry and blue on yellow perimetry are useful in detecting functional defects before achromatic
perimetry is used
39 (081.3%)
102
48
The FDT should be utilized in a glaucoma suspect with normal SAP
37 (077.1%)
087
48
The computerized perimetry examination is essential for the diagnosis of POAG
35 (072.9%)
089
48
A multimodal functional assessment (not perimetry techniques) seems to be most effective in detecting early glaucoma defects
39 (081.3%)
091
48
The functional changes in glaucoma are progressive visual field deterioration and loss of sensitivity to colors
45 (093.8%)
166
Grigera DE, et al.
Table 2. Diagnosis of glaucoma consensus statements (questions with 70% or greater agreement) (continued)
Question
No
No of
responses
n (%)
responding in
the affirmative
Summary
Intraocular pressure
093
48
There are no suitable methods that are proven to be able to correct IOP correctly for corneal thickness
34 (070.8%)
097
48
Longitudinal studies are needed to assess importance of IOP fluctuation over 24 hours
43 (089.6%)
099
48
I request/perform IOP diurnal tension curve
40 (083.3%)
100
43
IOP diurnal tension curves should only be performed in cases of suspected glaucoma
36 (083.7%)
092
48
Central corneal thickness is important in assessment of glaucoma or suspected glaucoma
48 (100.0%)
094
48
Goldmann tonometer is the gold standard for measuring IOP
47 (097.9%)
101
48
The ibopamine test is not essential for the diagnosis of glaucoma
47 (097.9%)
103
48
Computerized imaging tests help in clinical evaluation of optic disc
48 (100.0%)
106
48
HRT is the structural method with greatest evidence of fitness for analyzing progression of optic nerve head
38 (079.2%)
104
48
Computerized imaging tests in glaucoma help in diagnosis and in longitudinal monitoring
42 (087.5%)
Structural examination by imaging
FDT= frequency doubling technology; IOP= intraocular pressure; ISNT= inferior ≥ superior ≥ nasal ≥ temporal; HRT= Heidelberg retinal tomography; OAG= open-angle glaucoma; PCAG=
primary closed-angle glaucoma; POAG= primary open-angle glaucoma; SAP= standard automated perimetry.
therapy (using target IOP or searching for the lowest possible IOP
with initial medication), the responders clearly preferred the first one.
Using target IOP to guide clinical management is a well-established
practice and one that is supported by the results of large-scale
studies such as the Collaborative Initial Glaucoma Treatment Study
(CIGTS)(21). This approach allows treatment to be targeted to the
individual’s baseline IOP, optic nerve appearance and visual function,
and to initiate more aggressive treatment at signs of deterioration.
It also allows physicians and patients to develop a partnership in
glaucoma management; if patients are aware of the target IOP they
are trying to reach, they may be more engaged and adherent with
treatment. While there is clear evidence that the lower the IOP, the
less the risk of glaucomatous progression, physicians may be reluctant to initiate aggressive therapy because this may limit their future
treatment options. Physicians may also fear that patients will develop
adverse effects, potentially impacting their adherence. For some patients, the aggressive therapeutic options (combination therapy or
surgery) may be unaffordable, particularly in developing countries.
These factors probably contributed to the lack of agreement about
achieving the greatest possible reduction in IOP in our survey.
Some statements in our survey have important educational im
plications. For example, the panelists consider it essential for a clinician
to know the rates of hypotensive efficacy of glaucoma medications.
They also agreed that a hypotensive effect of less than 10% is unacceptable and should prompt substitution with a more effective treatment.
It is also interesting to note that, in a region known historically
to favor low-cost medications such as β-blockers, the Latin American
glaucoma specialists in our sample considered prostaglandin analogs
to be the monotherapy of first choice. This probably reflects the
respondents’ assessment of drug efficacy and safety rather than affordability, since there was agreement that the cost of medical therapy
is not affordable for most patients in Latin America (question 42).
Prostaglandin analogs have demonstrated greater hypotensive efficacy compared with other classes of topical glaucoma therapies(22,23)
and a low rate of systemic adverse effects, a fact with which the Latin
American respondents to our survey also showed substantive agreement. The most common adverse event with prostaglandin analogs
is conjunctival hyperemia, whereas this is less frequent with topical
β-blockers(24). Latin American physicians agree that topical β-blockers
have the best ocular safety profile (question 31). Overall, respondents
believe that hypotensive efficacy with reasonable safety is more
important than safety alone (question 17). Therefore, taken together,
the survey findings indicate that Latin American physicians consider
that the greater efficacy of prostaglandin analogs and their improved
systemic safety profile outweigh concerns about ocular tolerability.
Agreement was not reached regarding the number of bottles that
constitute maximum medical therapy, or on the maximum number
of instillations compatible with good cooperation with the treatment. Presumably, this reflects the diversity of adherence behavior
between patients seen in routine clinical practice.
In our survey, most respondents (70.0%) did not think it was
important that certain medications (like a fixed combination of
prostaglandin analog plus β-blocker) have not been approved by
the US Food and Drug Administration (FDA). This may indicate an
acceptance of lower standards of rigor in the regulation of pharmaceutical products in Latin America compared with the US. While
many survey respondents agreed (59.2%) that generic medications
were bioequivalent and interchangeable, they also agreed (81.6%)
that “copy medications” were not. The World Bank has suggested
that Latin American regulatory agencies are under-resourced, and
has highlighted differences between countries in both registration
policies and terminology (including the use of the terms “generic”
and “bioequivalence”)(25,26). This may have led to different interpretations of the questions relating to generic medications in our survey
between respondents from different countries, and contributed to
the lack of agreement about the bioequivalence of generic and “copy”
medications (questions 46 and 47).
Regarding the diagnosis of glaucoma, Latin American physicians
agreed on the need to examine the condition of the optic nerve at
each visit, consistent with WGA recommendations(13). However, this
may be an area in which theory falls short of practice, since there are
data to suggest that, even in developed countries, optic nerve status
examination and documentation are suboptimal during routine
clinical practice(27,28). Our survey also found agreement on photographic documentation as the gold standard for structural evaluation in
glaucoma and the value of computerized imaging in the evaluation
of the optic disc. These approaches are also consistent with WGA
consensus recommendations(13), and can produce more accurate and
quantitative assessment of structural changes than can be achieved
with annotated drawings or written chart entries(29). Nevertheless,
Latin American survey participants agreed that an itemized drawing
can be a useful resource when technology is unavailable.
167
Latin American physicians agreed on the importance of gonioscopy in first examination for all patients over 40 years to detect the
presence of CAG, and its repetition over time when examining a CAG
patient or a CAG suspect. Direct epidemiologic data on prevalence of
CAG in Latin America are limited. They range from a general estimation of 5.7% of glaucoma cases(1) to 21.4% in one sample from South
Brazil(30). Unpublished surveys indicate that CAG rates may be high in
some native ethnic populations within Latin America.
Not surprisingly, no agreement was obtained on the new methods of tonometry such as the Pascal dynamic contour tonometer
or the ORA. This may reflect a concern among Latin American physicians that more published evidence and clinical experience with
these devices are required. However, there was agreement about the
importance of measuring central corneal thickness in order to gain a
more accurate assessment of IOP.
A limitation of the present research is that the 107 items in the
survey could not cover all the issues involving diagnosis and treatment of glaucoma. Although we created the questionnaire based
on a detailed review of the literature, there may have been other
relevant topics that were not included. Further investigation, possibly
including the distribution of a second questionnaire to experts in
this field, may be needed for further validation. Such a survey could
also identify any changes over time in the opinions of Latin American ophthalmologists toward optimal practice in the diagnosis and
management of glaucoma.
Conclusion
This survey, the largest one to date on diagnosis and therapy of
glaucoma among Latin American experts, has demonstrated a high
level of agreement on optimal practices in the diagnosis and medical
management of glaucoma. There was consensus for more than twothirds of the questions, indicating a high level of agreement across
the region on evidence-based recommendations. However, many
barriers toward optimal detection and treatment of glaucoma exist in
Latin America. The information gained from this survey can be used
to inform future educational efforts in the region, with the aim of
further improving glaucoma diagnosis and management.
Acknowledgments
The following individuals have participated as part of the “LAGS
Plus Survey Panel” in the development of this survey: Alvaro Abelenda
(Uruguay), Jorge Acosta (Argentina), John Jairo Aristizábal (Colombia), Paulo A. Arruda Mello (Brazil), George Arzeno (Puerto Rico, USA),
Marcos Boissiere (Venezuela), Héctor Borel (Chile), Javier Casiraghi
(Argentina), Rosendo Castellanos (Venezuela), Carlos Luis Chacón
(Ecuador), Ralph Cohen (Brazil), Javier Córdoba Umana (Costa Rica),
Sebastiao Cronemberger (Brazil), Felicio da Silva (Brazil), Geraldo
Vicente de Almeida (Brazil), María Fernanda Delgado (Colombia),
Mauricio Della Paolera (Brazil), José Di Martino (Paraguay), Juan Dios
(Peru), Héctor Fontana (Argentina), Mara Fontes (Brazil), Alfonso
García López (Mexico), Fernando Gómez Goyeneche (Colombia), Alejandro Gonella (Argentina), Marcos Geria (Argentina), Daniel Grigera
(Argentina), Curt Hartleben (Mexico), Jesús Jiménez Román (Mexico),
Fabián Lerner (Argentina), Eugenio Maul (Chile), Felipe Medeiros
(USA), Juan José Mura (Chile), Carlos Akira Omi (Brazil), Marcelo Palis
Ventura (Brazil), Augusto Paranhos (Brazil), Juan Camilo Parra (Colombia), Rodolfo Pérez Grossmann (Peru), Joao Antonio Prata Jr (Brazil),
Alejo Peyret (Argentina), Juan Carlos Rueda (Colombia), Lisandro
Sakata (Brazil), Walter Schieber (Guatemala), Remo Susanna Jr (Brazil),
Iván Maynart Tavares (Brazil), Enrique Vargas (Peru), Roberto Murad
Vessani (Brazil), Juan Vieira (Venezuela), Riuitiro Yamane (Brazil), and
Jaime I. Yankelevich (Argentina).
Dr Grigera organized and ran the survey. Statistics were calculated for internal consistency alpha by Lori A. Christman at STATKING
168
Clinical Services; this work was funded by ACUMED. Editorial/medical
writing support was provided by G Devgan at ACUMED (New York,
NY, USA) and was funded by Pfizer Inc.
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16o Congresso de Oftalmologia USP e
15o Congresso de Auxiliar de Oftalmologia
29 e 30 de novembro de 2013
Centro de Convenções Rebouças
São Paulo (SP)
Informações:
Secretaria Executiva
Organização de Eventos JDE
Tels.: (11) 5082-3030 / 5084-9174
Site: www.jdeeventos.com.br / www.oftalmologiausp.com.br
169
Sensitivity and specificity of machine learning classifiers for glaucoma diagnosis
using Spectral Domain OCT and standard automated perimetry
Sensibilidade e especificidade dos classificadores de aprendizagem de máquina para o diagnóstico
de glaucoma usando Spectral Domain OCT e perimetria automatizada acromática
Fabrício R. Silva1, Vanessa G. Vidotti1, Fernanda Cremasco1, Marcelo Dias2, Edson S. Gomi2, Vital P. Costa1
ABSTRACT
RESUMO
Purpose: To evaluate the sensitivity and specificity of machine learning classifiers
(MLCs) for glaucoma diagnosis using Spectral Domain OCT (SD-OCT) and standard
automated perimetry (SAP).
Methods: Observational cross-sectional study. Sixty two glaucoma patients and
48 healthy individuals were included. All patients underwent a complete ophthalmologic examination, achromatic standard automated perimetry (SAP) and retinal
nerve fiber layer (RNFL) imaging with SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec
Inc., Dublin, California). Receiver operating characteristic (ROC) curves were
obtained for all SD-OCT parameters and global indices of SAP. Subsequently, the
following MLCs were tested using parameters from the SD-OCT and SAP: Bagging
(BAG), Naive-Bayes (NB), Multilayer Perceptron (MLP), Radial Basis Function (RBF),
Random Forest (RAN), Ensemble Selection (ENS), Classification Tree (CTREE), Ada
Boost M1(ADA),Support Vector Machine Linear (SVML) and Support Vector Machine Gaussian (SVMG). Areas under the receiver operating characteristic curves
(aROC) obtained for isolated SAP and OCT parameters were compared with MLCs
using OCT+SAP data.
Results: Combining OCT and SAP data, MLCs’ aROCs varied from 0.777(CTREE) to
0.946 (RAN).The best OCT+SAP aROC obtained with RAN (0.946) was significantly
larger the best single OCT parameter (p<0.05), but was not significantly different
from the aROC obtained with the best single SAP parameter (p=0.19).
Conclusion: Machine learning classifiers trained on OCT and SAP data can successfully discriminate between healthy and glaucomatous eyes. The combination
of OCT and SAP measurements improved the diagnostic accuracy compared with
OCT data alone.
Objetivo: Avaliar a sensibilidade e especificidade dos classificadores de aprendizagem
de máquina no diagnóstico de glaucoma usando Spectral Domain OCT (SD-OCT) e
perimetria automatizada acromática (PAA).
Métodos: Estudo transversal observacional. Sessenta e dois pacientes com glaucoma
e 48 indivíduos normais foram incluídos. Todos os pacientes foram submetidos a
exame oftalmológico completo, e perimetria automatizada acromática (24-2 SITA;
Humphrey Field Analyzer II, Carl Zeiss Meditec, Inc., Dublin, CA) e exame de imagem
da camada de fibras nervosas utilizando SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec
Inc., Dublin, California). Curvas ROC (Receiver operator characteristic) foram obtidas
para todos os parâmetros do SD-OCT e índices globais do campo visual (MD, PSD,
GHT). Subsequentemente, os seguintes classificadores de aprendizagem de máquina
(CAMs) foram testados usando parâmetros do OCT e CV: Bagging (BAG), Naive-Bayes
(NB), Multilayer Perceptron (MLP), Radial Basis Function (RBF), Random Forest (RAN),
Ensemble Selection (ENS), Classification Tree (CTREE), Ada Boost M1(ADA), Support
Vector Machine Linear (SVML) e Support Vector Machine Gaussian (SVMG). Áreas
abaixo da curva ROC (aROC) obtidas com os parâmetros isolados do campo visual
(CV) e OCT foram comparados com os CAMs usando dados associados do OCT e CV.
Resultados: Combinando os dados do OCT e do CV, aROCs dos CAMs variaram entre
0,777(CTREE) e 0,946 (RAN). A maior aROC dos CAMs OCT+CV obtida com RAN (0,946)
foi significativamente maior que o melhor parâmetro do OCT (p<0,05), mas não houve
diferença estatística significativa com o melhor parâmetro do CV (p=0,19).
Conclusão: Os classificadores de aprendizagem de máquina treinados com dados
do OCT e CV podem discriminar entre olhos normais e glaucomatosos com sucesso.
A combinação das medidas do OCT e CV melhoraram a acurácia diagnóstica com
parados aos parâmetros do OCT.
Keywords: Glaucoma/diagnosis; Diagnostic techniques, ophthalmological/classification; Tomography, optical coherence/instrumentation; Sensitivity and specificity
Descritores: Glaucoma/diagnóstico; Técnicas de diagnóstico oftalmológico/classi
ficação; Tomografia de coerência óptica; Sensibilidade e especificidade
INTRODUCTION
Glaucoma is a neuropathy characterized by visual field loss with
gradual thinning of the retinal nerve fiber layer (RNFL) and cupping
of the optic nerve head (ONH)(1). The diagnosis of glaucoma is currently based on the appearance of the ONH and standard automated
perimetry (SAP) testing results. Recent randomized clinical trials
including the Ocular Hypertension Treatment Study and the European
Glaucoma Prevention Study reported that the first detectable damage
in patients with glaucoma can be either structural or functional(2,3).
This suggests that using structural and functional testing in combination may improve glaucoma detection.
Optical coherence tomography (OCT), first described in 1991 by
Huang et al.(4), is a noncontact, high-resolution technique using a
scanning interferometer to produce cross-sectional images of the
retina and peripapillary RNFL in vivo(4,5). Previous reports have shown
that time domain (TD) OCT (Stratus, Carl Zeiss Meditec, Inc., Dublin,
CA) has high sensitivity and specificity for diagnosing glaucoma, and
has good correlation with VF findings detected with SAP(5-8).
Funding: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo
(FAPESP): 07/51281-9 (Dr. Vital P. Costa)
Study carried out at Department of Ophthalmology, Universidade Estadual de Campinas, Campinas
(SP), Brazil.
Disclosure of potential conflicts of interest: F.R.Silva, None; V.G.Vidotti, None; F.Cremasco, None;
M.Dias, None; E.S.Gomi, None; V.P.Costa, None.
Physician, Glaucoma Service, Department of Ophthalmology, Universidade Estadual de Campinas,
Campinas (SP), Brazil.
Engineer, Department of Engineering, Universidade de São Paulo, São Paulo (SP), Brazil.
Correspondence address: Fabrício Reis da Silva. Rua Madre Maltez, 92 - Pouso Alegre - (MG) 37550-000 - Brazil - E-mail: [email protected]; [email protected]
1
2
170
Número do projeto: 406/2005, Comitê de Ética em Pesquisa da Faculdade de Ciências Médicas
da UNICAMP.
Silva FR, et al.
Recently, several companies have developed newer versions of
OCT employing spectral domain (SD) technology. SD-OCTs have
higher axial resolution and scan speed than conventional TD-OCTs.
The Cirrus HD-OCT (Carl Zeiss Meditec, Inc.) has an axial resolution of
5 microns and a scan speed of 27,000 A-scans per second, whereas
the Stratus OCT has an axial resolution of 8 to 10 microns and a scan
speed of 400 A-scans per second. The higher sampling rates of the
newer OCTs allow more data to be collected at shorter scan times.
Studies comparing these two technologies have demonstrated that
the sensitivity and specificity of various RNFL parameters using the
Cirrus OCT are excellent and equivalent to the Stratus OCT(9-13).
Since 1990 (Goldbaum MH, et al. IOVS 1990;31; ARVO Abstract 503),
machine learning classifier (MLC) techniques have been applied to
optical imaging and visual function measurements to improve glaucoma detection, with results suggesting that these techniques are as
good as or better than currently available methods at classifying eyes
as glaucomatous or healthy(14-24). Classifiers usually employ a form of
supervised learning, where the program learns from positive and
negative training examples, representing cases where, for example,
there are signs of glaucoma on data obtained by examination of the
visual field (positive examples) or not (negative examples). The training is repeated several times with the provision of various training
data, with the positive or negative classification previously performed
by an ophthalmologist, until the concept (identification of signs of
glaucoma in one test) can be properly learned by the system.
To the best of our knowledge, there is no study in the literature
evaluating the use of MLCs with combined SD-OCT and SAP for the
diagnosis of glaucoma. The purpose of this study was to investigate
the sensitivity and specificity of MLCs for the diagnosis of glaucoma
combining structural and functional parameters, using data obtained
with SD-OCT and SAP.
METHODS
Subjects
This observational cross-sectional study included 110 eyes of
110 participants (62 patients with glaucoma and 48 healthy control
subjects) older than 40 years and enrolled in the Glaucoma Service
of the University of Campinas, Campinas, Brazil, between August
2008 and November 2010. All subjects underwent a comprehensive
ophthalmic evaluation, including review of medical history, best
corrected visual acuity, slit lamp biomicroscopy, intraocular pressure
measurement with Goldmann applanation tonometry, gonioscopy,
dilated slit lamp fundus examination with a 78-D lens, SAP using the
24-2 Swedish Interactive Threshold Algorithm (SITA; Humphrey Field
Analyzer II, Carl Zeiss Meditec, Inc., Dublin, CA) and RNFL imaging
with Cirrus HD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec Inc., Dublin,
California). To be included in the study, participants had to have a
best-corrected visual acuity better than or equal to 20/40, spherical
refraction within ± 5.0 D, cylinder correction within ± 3.0 D, open
angles on gonioscopy, and a reliable SAP with false-positive errors
<33%, false-negative errors <33% and fixation losses <20%. Eyes with
coexisting diabetes, retinal disease, uveitis, nonglaucomatous optic
neuropathy, pseudophakia or aphakia, significant cataract according
to the criteria of Lens Opacification Classification System III (defined
as the maximum nuclear opacity (NC3, NO3), cortical (C3) and subcapsular (P3)), were excluded. One eye was randomly selected if both
eyes were found to be eligible.
For healthy individuals, inclusion criteria were: IOP ≤21 mmHg,
with no history of elevated IOP, 2 consecutive and reliable normal
visual fields and normal appearance of the optic nerve. Glaucomatous eyes were defined as those with 2 or more IOP measurements
>21 mmHg, a glaucomatous VF defect confirmed by 2 reliable and
consecutive VF examinations and with glaucomatous appearance of
the optic disc. Eyes with glaucomatous VF defects were defined as
those fulfilling at least two of the following criteria: (1) cluster of 3
points with a probability of <5% on a pattern deviation map in a single hemifield including ≥1 point with a probability of <1%; (2) glaucoma hemifield test (GHT) outside 99% of the age-specific normal
limits; and (3) pattern standard deviation (PSD) outside 95% of the
normal limit. Glaucomatous appearance of the optic disc was defined
as the presence of at least 2 of the following findings: cup-disc ratio
greater than 0.6, focal defects of the neuroretinal rim, acquired pit of
the optic nerve and peripapillary hemorrhage.
The severity of glaucomatous damage was determined accor
ding to the following criteria: a) early damage: mean deviation (MD)
≥-6 dB; b) moderate damage: MD between -6 dB and -15 dB; c) advanced damage: MD ≤-15 dB. Only patients with early or moderate
damage were included in the study.
Informed consent was obtained from all participants before en
rollment. All procedures conformed to the Declaration of Helsinki
and the study was approved by the University of Campinas Medical
Institutional Review Board.
Optical coherence tomography
Participants underwent ocular imaging with the commercially
available Cirrus HD-OCT (software version 3.0, Carl Zeiss Meditec,
Inc.), which uses spectral domain technology. The optic disc cube
mode consists of 200 A-scans that are derived from 200 B-scans
and covers a 6-mm2 area centered on the optic disc. After creating
a RNFL thickness map from the 3-dimensional cube data set, the
software automatically determines the center of the disc and extracts a circumpapillary circle (1.73-mm radius) for RNFL thickness
measurement. All images were acquired with undilated pupils by a
single, well-trained ophthalmologist (VGV), who was masked to the
diagnosis. The OCT technology provides RNFL thickness maps with
17 parameters: average thickness, 4 quadrants (superior, inferior, na
sal, and temporal) and 12 clock hour measurements. All OCT data
were aligned according to the orientation of the right eye. Hence,
clock hour 9 of the circumpapillary scan represented the temporal
side of the optic disc for both eyes. Only well-centered scans, with no
evidence of eye movement or segmentation within the area of RNFL
analysis, and with a signal strength ≥6 were included.
Standard automated perimetry
All visual fields included were obtained with the 24-2 Swedish
interactive threshold algorithm (SITA) of the Humphrey field Analyzer
II, Carl Zeiss Meditec, Inc., Dublin, CA). Glaucoma subjects required
at least two reliable visual field examinations, with the most recent
examination within 3 months of the enrollment date. SAP parameters
included in the analysis were MD, PSD, and GHT. For the GHT results,
we assigned within normal limits (WNL) a value of 1; borderline, 2;
and outside normal limits (ONL), 3.
Machine learning classifiers
Based on patient data obtained from the Cirrus OCT and SAP,
machine learning classifiers were developed using the following
algorithms: Bagging (BAG), Naive-Bayes (NB), Multilayer Perceptron
(MLP), Radial Basis Function (RBF), Random Forest (RAN), Ensemble
Selection (ENS), Classification Tree (CTREE), Ada Boost M1 (ADA),
Support Vector Machine Linear (SVML) and Support Vector Machine
Gaussian (SVMG). Initially, MLC training sessions were supervised
with all 17 parameters of the SD-OCT and 3 parameters of the SAP,
a total of 20. Subsequently, a backward feature selection was used
to find the minimal number of features that resulted in the highest
aROC for each classifier. The analysis started with the evaluation of
the classifiers performance over the full-dimensional feature set containing the 17 SD-OCT and 3 SAP features. Sequentially, the feature
that presented the lowest aROC, computed over the SD-OCT data
alone, was removed and the classifier’s accuracy was computed. This
171
Sensitivity and specificity of machine learning classifiers for glaucoma diagnosis using Spectral Domain OCT
2.5 mmHg, respectively) (p=0.062), although glaucoma patients were
using a mean number of 2.2 ± 1.2 medications to lower IOP. Mean
MD values were -4.1 ± 2.4 dB for glaucoma patients and -1.5 ± 1.6 dB
for healthy individuals (p<0.001). Among the glaucoma patients,
51 (82.3%) were classified as having early damage and 11 (17.7%)
as having moderate damage. Among the 62 eyes with glaucoma, 5
(8.06%) showed poor agreement between structural and functional
measurements. In all cases, the visual field defect was more pronounced in the hemisphere opposite to the expected (based on the area
of greater optic nerve damage).
SAP parameters with the greatest aROCs were: PSD (0.915 - CI
0.846-0.956), GHT (0.866 - CI 0.787-0.923) and MD (0.828 - CI 0.7450.894) (Table 2).
SD-OCT parameters with the greatest aROCs were: inferior qua
drant (0.813 - CI 0.727-0.881), average thickness (0.807 - CI 0.721-0.876),
7 oćlock position (0.765 - CI 0.674-0.840) and 6 oćlock position
(0.754 - CI 0.663-0.831) (Table 2). For a fixed specificity of 80%, the best
sensitivities were observed with 7 o’clock position (64.5%) average
thickness (62.1%), inferior quadrant (61.3%), and superior quadrant
(57.6%) (Table 2).
Combining all OCT and SAP data using MLCs, the aROCs varied
from 0.777 (CTREE) to 0.933 (RAN) (Table 3). Using optimized classifiers (features in peak feature set) aROCs varied from 0.879 (CTREE, 2
features) to 0.946 (RAN, 4 features) (Table 3). The best OCT+SAP aROC
obtained with RAN trained with 4 features (0.946) was significantly
larger than the best single OCT parameter (0.813) (p<0.05), but was
not significantly different from the aROC obtained with the best single SAP parameter (0.915) (p=0.37) (Figure 1).
process of dimension reduction, based on aROCs of the SD-OCT and
SAP parameters sorted in descending order, was performed 19 times.
It started with the exclusion of the parameter with the lowest aROC
and stopped only when the parameter with the best aROC was used.
The criterion for evaluating the algorithms involved the analysis of
ROC curves generated from the results of several classification tasks
for each classifier.
The classifiers were developed using a machine learning environment software called Weka(25) version 3.7.0 (Waikato Environment
for Knowledge Analysis, The University of Waikato, New Zealand). The
examination data and images were collected at the Department of
Ophthalmology, University of Campinas and temporarily stored in a
local workstation. The data was transferred to the server located at
the Engineering Laboratory of Knowledge (KNOMA) from the Program of Computer and Digital Systems of the University of Sao Paulo.
To maximize the use of our collected data, the 10-fold cross-va
lidation resampling method was employed. Accordingly, all data we
re randomly divided into 10 subsets, each containing approximately
the same proportion of healthy and glaucomatous OCT thickness
measurements. Nine subsets were used as training data, while the
remaining subset was used as testing data. This process was performed 10 times, until each of the 10 folders had been used as a test set.
The test results were averaged to estimate the classifier’s accuracy.
Statistical analysis
All analyses were performed using MedCalc software version
11.0.1 (MedCalc Software, Mariakerke, Belgium). Continuous variables
were compared using the Student’s T test, whereas categorical variables were analyzed using the Chi-Square or the Fisher Exact test.
Receiver operating characteristic (ROC) curves were obtained for
all SD-OCT parameters (average, 4 quadrants, and 12 clock-hours
RNFL thickness measurements) and SAP parameters (MD, PSD e
GHT). aROCs obtained for each SD-OCT and SAP parameter and
each machine learning classifier, before and after optimization, were
compared using the z test. P values <0.05 were considered to be
statistically significant.
DISCUSSION
Our study investigated the sensitivity and specificity of MLCs
with the new version SD- OCT. To our knowledge, this study was the
first to use MLCs with data obtained from SD-OCT and SAP. Many
studies have been published assessing the sensitivity and specificity
of TD-OCT, and some compared the diagnostic ability of TD-OCT
and SD-OCT, demonstrating that they show similar and adequate
performances(9-13). In a previous study, we reported the results of the
SD-OCT in the diagnosis of glaucoma(25).
The diagnosis of glaucoma requires functional and structural
analysis and the combination of structural and functional tests may
improve glaucoma detection. Lauande-Pimentel et al.(26) showed
enhancement of diagnostic accuracy when structural (scanning laser
polarimetry) and functional (SAP) data were used in combination.
Shah et al.(27) demonstrated that the combination of structural parameters (scanning laser polarimetry (GDX), OCT or confocal scanning
laser ophthalmoscopy (CSLO)) with frequency doubling perimetry
RESULTS
One hundred and ten eyes of 110 individuals were included in
this study. Among the 110 individuals, 62 patients had glaucoma and
48 were healthy control subjects.
Table 1 demonstrates the clinical characteristics of the study population. The mean age was 57.0 ± 9.2 years for healthy individuals
and 59.9 ± 9.0 years for glaucoma patients (p=0.103). There was no
significant difference between the control and glaucoma groups
regarding intraocular pressure (IOP) (14.8 ± 2.8 mmHg and 13.8 ±
Table 1. Demographic characteristics of the study population
Age (years; mean ± SD)
Range
Healthy (N=48)
Glaucoma (N=62)
p value
57.0 ± 9.2
59.9 ± 9.0
<0.103
45-82
43-78
-
Gender (Male[%]:Female[%])
23[47.9]: 25[52.1]
31[50]: 31[50]
<0.830
Race (Caucasian[%]:African american[%])
37[77.1]: 11[22.9]
46[74.2]: 16[25.8]
<0.461
VA logMAR (mean ± SD)
00.04 ± 0.09
00.1 ± 0.1
<0.003
SE (D; mean ± SD)
01.53 ± 2.15
01.2 ± 1.9
<0.467
IOP (mmHg; mean ± SD)
14.80 ± 2.80
13.8 ± 2.5
<0.062
Medications (mean ± SD)
0
02.2 ± 1.2
<0.001
MD (dB; mean ± SD)
-1.50 ± 1.60
-4.1 ± 2.4
<0.001
PSD (dB; mean ± SD)
01.80 ± 0.80
04.3 ± 2.4
<0.001
VA= visual acuity; SE= spherical equivalent; D= diopters; dB= decibels; MD= mean deviation; PSD= pattern standard deviation.
172
Silva FR, et al.
Table 2. Areas under the ROC curve (aROC) and sensitivities (%)
at fixed specificities of 80% and 90% for each SAP and SD-OCT
parameters
aROC
(95% CI)
Specificity
80%
Specificity
90%
0.828 (0.745-0.894)
62.9
56.4
SAP
MD
PSD
0.915 (0.846-0.959)
88.7
75.1
GHT
0.866 (0.787-0.923)
91.9
70.9
0.807 (0.721-0.876)
62.1
54.0
Temporal
0.675 (0.579-0.761)
50.0
33.1
Superior
0.737 (0.645-0.816)
56.4
46.7
Nasal
0.685 (0.590-0.771)
49.2
26.6
Inferior
0.813 (0.727-0.881)
61.3
53.2
1
0.703 (0.608-0.786)
45.2
29.8
2
0.723 (0.630-0.804)
51.6
34.7
3
0.574 (0.476-0.668)
29.8
22.6
4
0.605 (0.507-0.696)
29.0
11.3
5
0.671 (0.575-0.757)
43.5
27.4
6
0.754 (0.663-0.831)
47.6
33.9
7
0.765 (0.674-0.840)
64.5
38.7
8
0.631 (0.534-0.721)
42.7
27.4
9
0.625 (0.527-0.715)
44.3
36.3
10
0.699 (0.604-0.783)
50.8
42.0
11
0.740 (0.648-0.819)
40.3
33.9
12
0.672 (0.576-0.759)
38.7
21.0
OCT
Average thickness
Quadrant
Clock hour
CI = confidence interval.
Table 3. aROC and sensitivities (%) at fixed specificities of 80% and
90% obtained with OCT and SAP data using MLCs
MLC
aROC
(all 20 features)
BAG
0.893
NB
0.912
MLP
RBF
aROC
(# features)
Specificity
80%
Specificity
90%
0.913(8)
91.93
74.19
0.928 (5)
93.54
83.87
0.845
0.934 (5)
90.32
77.41
0.857
0.934 (4)
93.54
79.03
RAN
0.933
0.946 (4)
95.16
82.25
ENS
0.910
0.910 (20)
90.32
79.03
CTREE
0.777
0.879 (2)
82.25
56.45
ADA
0.932
0.933 (15)
93.54
83.87
SVMG
0.913
0.930 (8)
93.54
83.87
SVML
0.929
0.938 (12)
93.54
83.87
MLC= machine learning classifier; aROC= area under the ROC curve; BAG= Bagging; NB=
Naive-Bayes; MLP= Multilayer Perception; RBF= Radial Basis Function; RAN= Random
Forest; ENS= Ensemble Selection; CTREE= Classification Tree (J48); ADA - Ada Boost M1;
SVMG= Support Vector Machine Gaussian; SVML= Support Vector Machine Linear.
aROC RAN=0.946; aROC PSD=0.915; aROC Inferior=0.813
Figure 1. aROCs obtained with OCT+SAP (RAN), SAP (PSD), OCT (inferior).
(FDT) or short wavelength automated perimetry (SWAP) led to a significant increase in sensitivity, which was higher than those obtained
with structural parameters alone.
MLC techniques have also been employed with various technologies designed to perform structural and functional evaluation of
glaucoma, including TD-OCT(15,17,19,23), HRT(18,22,24), GDx(16,20), and visual
field(13,18,20,21). Several studies have used MLC techniques to combine
functional and imaging data in attempt to improve diagnostic accuracy(19,22). Bowd et al.(19) trained MLCs (RVM and subspace Mixture of
Gaussians) on Stratus OCT and SAP data and showed that combining
OCT and SAP measurements using MLCs increased diagnostic performance marginally compared with MLC analysis of data obtained
with each technology alone.
Mardin et al.(22) showed better performance for combined CSLO
and SAP data compared with CSLO alone. However, combining CSLO
and SAP data did not improve the accuracy compared with SAP data
alone. We have also observed that combining OCT and SAP data
using MLCs provided aROCs significantly larger than the best single
OCT parameter (p<0.05), but not significantly different from the aROC
obtained with the best single SAP parameter (p=0.37). This is likely
due to a selection bias, as healthy controls were required to have normal visual field results and glaucoma patients were required to have
abnormal visual fields. On the other hand, the purpose of MLCs is to
replace human judgment exploiting all the information available,
which justifies the inclusion of SAP in this case.
One way to reduce this interference would be to test the MLCs
with structural and functional tests that are not used to define glau
coma. Racette et al.(28) used both SAP and stereophotographs as
selection criteria, but used other devices (HRT and SWAP) to train
and test MLCs. They have shown that the RVM classifier trained on optimized combinations of structural and functional parameters differentiated between glaucomatous and nonglaucomatous eyes better
than the RVM trained on functional or structural parameters alone.
The case control study design has almost certainly overestimated
the diagnostic performance of the MLCs by creating two distinct
populations of healthy and disease subjects(29). However, our series
should be seen as a preliminary study comparing different classifiers
and sets of variables (SAP and OCT). Another limitation of our study
is that we trained and tested the MLCs within the same population.
Although we employed cross validation techniques to minimize
this source of bias, it would be interesting to test our model on an
independent data set. The above mentioned limitations could be
overcome by including a consecutive case series of glaucoma suspects followed in a longitudinal study, allowing time to define what
is disease.
173
Sensitivity and specificity of machine learning classifiers for glaucoma diagnosis using Spectral Domain OCT
In conclusion, MLCs trained on OCT and SAP data can successfully
discriminate between healthy and glaucomatous eyes. The combination of OCT and SAP measurements improved the diagnostic accuracy compared with OCT data alone. Further studies are necessary
to investigate the accuracy of these MLCs in different populations.
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Clinical characteristics and outcomes of patients admitted with presumed microbial
keratitis to a tertiary medical center in Israel
Características clínicas e desfechos dos pacientes internados com diagnóstico de ceratite microbiana em
um centro terciário em Israel
Fabio Lavinsky1, Noah Avni-Zauberman1, Irina S Barequet1
ABSTRACT
RESUMO
Purposes: Microbial keratitis is commonly diagnosed worldwide, and continues
to cause significant ocular morbidity, requiring prompt and appropriate treatment.
The objective of this study is to describe the clinical characteristics and outcomes
of patients with presumed microbial keratitis admitted to The Goldschleger Eye
Institute, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
Methods: A cross-sectional study was conducted, in which the medical records
of patients with presumed microbial keratitis admitted during a period of 3 years
were reviewed.
Results: Keratitis was diagnosed in 276 patients (51% males and 48.9% females).
The mean age was 39.29 ± 22.30 years. The hospital length of stay ranged from
1 to 65 days (mean 5.69 ± 5.508). Fortified antibiotics were still used at discharge
in 72% of the cases. Overall visual acuity improved significantly from the time of
admission to the 1st-week follow up visit showing a p<0.001 on the Wilcoxon
signed ranks test. Contact lens wearing was present in 36.1% of the patients,
although there was no significant relation with severity of the presentation and
visual outcome (p>0.05). The degree of hypopyon and cells in the anterior chamber
was significantly related to the hospital length of stay (r Spearman=0.31; p<0.001
and r Spearman=0.21; p<.001, respectively) as well as to a worse visual outcome
(r Spearman=0.32; p<0.01 and r Spearman=0.18; p=0.01, respectively). Of all
patients, 2.3% required an urgent therapeutic penetrating keratoplasty, and 1%
underwent evisceration. There was no enucleation.
Conclusion: Treating keratitis aggressively and assuring patient compliance is
imperative for a good final visual outcome. Inpatient treatment may have a po
sitive impact on this outcome.
Objetivos: Ceratite microbiana é comumente diagnosticada em todo mundo e ainda
continua a causar uma significante morbidade ocular. É necessário tratá-la de forma
imediata e apropriada. O objetivo deste estudo é descrever as características clínicas e
os desfechos dos pacientes com ceratite microbiana presumida que foram internados
no Goldschlager Eye Institute, Sheba Medical Center, Tel Aviv University, Israel.
Métodos: Um estudo transversal foi realizado onde arquivos hospitalares dos pacien
tes internados com ceratite microbiana presumida durante um periodo de três anos
foram analisados e revisados.
Resultados: Ceratite foi diagnosticada em 276 pacientes (51% masculinos e 48,9%
femininos). A média de idade foi 39,29 ± 22,30 anos. A duração da internação foi de 1
a 65 dias (média 5,69 ± 5,508). Antibióticos fortificados permaneceram usados na alta
em 72% dos casos. A acuidade visual do seguimento da primeira semana após a alta
em relação a internação melhorou na media de forma estatisticamente significativa
(p<0,001 usando Wilcoxon signed ranks test). O uso de lentes de contato estava presente
em 36,1% dos pacientes, porém não houve relação estatisticamente significativa entre
a gravidade da apresentação clínica e a acuidade visual nestes pacientes (p>0,05). O
grau de hipópio e células na câmara anterior foram estatisticamente significativos em
relação ao tempo de internação (r Spearman=0,0.31; p<0,001 and r Spearman=0,21;
p<0,001, respectivamente) e para a acuidade visual (r Spearman=0,32; p<0,01 e
r Spearman=0,18; p=0,01, respectivamente). De todos os pacientes, apenas 2,3%
necessitaram ceratoplastia penetrante urgente e 1% necessitaram evisceração. Não
houve enucleações.
Conclusões: Tratar a ceratite de forma agressiva e garantir a aderência do paciente
ao tratamento é imperativo para o bom resultado visual final. O tratamento internado
pode ter um impacto positivo neste desfecho.
Keywords: Cornea; Keratitis/diagnosis; Eye infection, bacterial; Eye infection, fungal;
Prognosis; Cross-sectional studies; Tertiary healthcare; Israel
Descritores: Córnea; Ceratite/diagnóstico; Infecções oculares bacterianas; Infecções
oculares fúngicas; Prognóstico; Estudos transversais; Atenção terciária à saúde; Israel
INTRODUCTION
Microbial keratitis is commonly diagnosed worldwide, and continues to cause significant ocular morbidity, requiring prompt and appropriate treatment(1,2). A large retrospective cohort recently reported
an incidence of ulcerative keratitis of 27.6/100,000 person- years (95%
confidence interval, 24.6-30.9)(3).
Predisposing factors for microbial keratitis described in the literature, include: previous ocular surgery, contact lens use, trauma and
metal foreign body, surgical sutures, ocular surface disease, topical
corticosteroid use, herpetic keratitis, lid misalignment, and systemic
diseases such as diabetes and smoking(4-16). Predictive factors for out
come such as initial visual acuity at admission have not been widely
described in previous studies.
Previous reports describe a variability of etiological agents in
different centers around the world(2,4,5,7,8,13,14,16). Empirical, broadspectrum treatment of keratitis is a strategy selected by many ophthalmologists(17-21). However the increased resistence of the causative
microorganism to currently available anti-infective drugs requires
ongoing assessment of the trends of clinical and microbiological
evaluation of the patients(22).
Submitted for publication: May 21, 2012
Accepted for publication: May 29, 2013
Study carried out at Goldschleger Eye Institute, Sheba Medical Center, Tel Aviv University Sackler,
Faculty of Medicine, Tel Hashomer, Israel.
1
Physician, Goldschleger Eye Institute, Sheba Medical Center, Tel Aviv University Sackler, Faculty of
Medicine, Tel Hashomer, Israel.
Disclosure of potential conflicts of interest: F.Lavinsky, None; N.Avni-Zauberman, None; I.S.Barequet,
None.
Correspondence address: Fabio Lavinsky. Rua Quintino Bocaiúva, 673 - 3o andar - Porto Alegre
(RS) - 90440-051 - Brazil - E-mail: [email protected]
175
Clinical characteristics and outcomes of patients admitted with presumed microbial keratitis to a tertiary medical center in Israel
An earlier survey from a decade ago of the causative agents of
ophthalmic infections in an Israeli ophthalmology service showed
that coagulase-positive staphylococcus was the most common iso
late from corneal ulcers (33.3%)(23). The combination of warm and
humid climate along with the popularity of the contact lens wear
may predispose to unique features of microbial keratitis in this region. Therefore, in the current study, we analyzed the demographic
and clinical characteristics, the risk factors and the clinical outcomes
of patients with keratitis admitted to our department that serves as
primary, secondary and tertiary center.
METHODS
In this cross-sectional study, records of all patients admitted to
our department with a diagnosis of keratitis over a period of 24 months
were analyzed. The department serves as a primary, secondary and
tertiary referral center. The admitting policy includes hospitalization
when the infiltrate is more severe than very mild. Patients are discharged when the infiltrate is responding to treatment, the epithelial
defect is closed, and there is no anterior chamber reaction.
Cases were excluded from the analysis if no follow-up visit was
registered on the records. The review of the charts was authorized by
the hospital directory. The legislation rules of the ethical committee at
our institution did not require at that time approval for retrospective
data analysis. Data was abstracted for age, gender, hospital length of
stay, and season of admission. Predisposing factors such as contact
lens use, previous ocular surgery, trauma and foreign body were also
recorded. Visual acuity was measured with Snellen charts with the
best correction obtained with spectacles or pinhole. The size of the
infiltrate was ranked from 1 to 3, where 1 corresponds to an infiltrate
of up to 1 mm of diameter, 2 refers to 1 to 2 mm and 3 means over
2 mm. Anterior chamber reaction was measured according to standard parameters of the ophthalmological practice. Cells and flare were
measured in a 1-4 scale and hypopyon was measured in millimeters.
In addition, the microbiological profile was accessed: the results of
cultures of patients that underwent scrapings were analyzed and their
relationship with visual outcome was assessed and compared with
the population that has not undergone scrapings. The initial antibiotic
treatment was also reviewed. The fact that patients are discharged
with the same criteria validates the analysis performed using visual
acuity at the 7-day post-discharge follow-up visit as an outcome.
The following risk factors for keratitis were analyzed: previous
systemic diseases, previous ocular diseases, previous ocular surgeries,
wearing of contact lenses, trauma and foreign body.
The statistical analysis was performed using the SPSSTM software.
The statistical methods used were the chi-square test, univariate
analysis of variance (ANOVA), the Wilcoxon signed ranks test and
Spearman’s rho.
RESULTS
The review of the charts of patients admitted with the diagnosis
of keratitis identified 276 patients (51% males and 48.9% females). The
mean age was 39.29 ± 22.30 years, with a wide range between one
month old and 92 years old (Figure 1).
The hospital length of stay ranged from 1 to 65 days (mean 5.69 ±
5.508). The discharge criteria were healed epithelial defect, decreased
inflammation or infection signs and absence of anterior chamber
reaction. Fortified antibiotics were continued after discharge in 72%
of the cases.
The mean visual acuity at admission was 0.60 logMAR (n=272).
The mean visual acuity at the first follow-up visit at the outpatient
clinic was 0.42 logMAR (n=223). Comparison of visual acuity of the
patients that had assessments both at admission and follow-up visit
showed a statically significant improvement. (p=0.0001 Wilcoxon
signed ranks test).
176
The use of contact lenses was noted in 110 patients (36.1%), their
average age was 25.9 years-old (range 0-75 years-old) and 61.46%
were females. The inpatient admission period was longer in non-con
tact lens wearers with a median of 5 days versus 4 days in contact
lens wearers (p<0.003 Mann-Whitney test). The presence of anterior
chamber reaction (fibrin, cells and hypopyon) was not significantly
associated with contact lens wearing. The 7 day post-discharge visual
acuity was better in wearers than in non-wearers (p<0.001) (Table 1).
Assessment of age as a prognostic factor showed that patients
over 34 years old had a significantly longer hospital stay as well as
a worse visual acuity at the 7-day post-discharge follow-up visit
(p=0.001 Mann-Whitney test).
There were also 28 (9.2%) cases of keratitis associated with foreign
bodies and 31 (11.2%) cases related to previous intraocular surgeries.
This latter group had a worse clinical course than the former. The
patients were older (mean age 68.9) and their hospital length of stay
was longer (mean 8.7 days). The improvement of the mean visual
acuity was significantly lower than in the overall population: 1.62
logMAR at admission to 1.47 logMAR at the first follow-up against
0.43 logMAR and 0.25 logMAR in the overall population (p<0.01 on
the Mann-Whitney and Wilcoxon tests).
Figure 1. Age distribution of the population.
Table 1. Visual acuity outcome in wearers and non-wearers of contact lenses
BCVA at 1st
follow-up visit
BCVA at
admission
Mean
0.76970
0.6070
Median
0.30000
0.1800
Std. deviation
0.83405
0.7481
Mean
0.36630
0.1780
Median
0.18000
0.1000
Std. deviation
0.55462
0.3182
Non-Wearers (n=154)
Wearers (n=107)
P<0.001
Lavinsky F, et al.
The size of the infiltrate at admission was 149 (48.9%) in grade
1 (up to 1 mm), 46 (15.1%) in grade 2 (from 1 to 2 mm), and 50
(16.4%) in category 3 (over 2 mm). In 19.6% of the cases records did
not clearly defined the grade of the infiltrate. Patients with large
infiltrates (grade 3) had a worse visual acuity both at presentation
and at the 7-day follow-up visit compared with the other categories
(p<0.0001Spearman´s rho).
Anterior chamber reaction was frequently noted at admission:
41.6% of the cases had cells (>+1), 19.8%. had fibrin and 11.1% had
hypopyon. The amount of cells and the measurement of hypopyon
were related to a worse prognosis. There was a statiscally significantly
relationship between length of hospitalization and visual acuity with
positive inflammatory signs at admission. (p=0.001) (Figure 2).
Cultures were obtained from 194 cases. In 111 (36.6%) cases an
tibiotic treatment was used prior to admission. After admission,
patients were initially treated empirically and changes were made
accordingly. The most frequent antibiotic regimen included combination of fortified antibiotics such as cefazolin (50 mg/mL) with
gentamicin (13.6 mg/mL) (23%) or vancomycin (33 mg/mL) with
ceftazidime (40 mg/mL) (29.2%).
From the cultures taken (194 cases), only 36% (n=71) were positive. The microbiological profile of our population is shown in table
2. Patients with positive cultures had a significantly worse baseline
visual acuity as compared with cases with negative cultures and with
the group which cultures were not taken (p<0.0001)
The improvement of visual acuity at the 7-day post discharge
follow-up visit was statistically significantly smaller in the positiveculture group as compared with the negative-culture group and with
the no-culture group (p<0.0001) (Figure 3). The hospital length of stay
of the positive-culture patients was longer: mean 7.37 days (p=0.001).
The rate of urgent surgical intervention was low: tarsorrhaphy in
3.7% (n=10), therapeutic penetrating keratoplasty (PK) in 2.3% (n=7),
vitrectomy due to endophthalmitis in 1% (n=3) and evisceration in
1% (n=3).
The impact of previous ocular surgeries such as PK, extracapsular
cataract extraction (ECCE) or combined PK + ECCE (n=31) was eva
luated. The mean age of this group was higher as compared the
non-previous surgery group (68.96 years ± 20.0 versus 39.29 years
± 22.3 years, respectively).Their mean visual acuity at admission and
at the 7-post discharge follow-up visit were statistically significantly
worse in the previous surgery group (1.62 logMAR and 1.47 logMAR
respectively) than in the non-previous surgery group (0.43 logMAR
Figure 2. Correlation between anterior chamber reaction and hospitalization days.
and 0.25 logMAR respectively respectively). (p<0.01 Mann-Whitney
and Wilcoxon signed ranks tests). The rate of positive cultures were
higher in the previous surgery group (61%) as compared with patiens
that have not undergone surgery. The rate of urgent surgical intervention was significantly higher in the previous surgery group (30%)
as compared with the non-previous surgery group (8.7%) (p<0.01).
The most common urgent surgical intervention in the previous
surgery group was the need for urgent PK (14%) against 0.4% in the
non-previous surgery group (p<0.01).
DISCUSSION
Microbial keratitis is an ophthalmological emergency that requires immediate treatment. Our study evalueted characteristics and
Table 2. Culture results
Frequency
Percent
No growth
123
40.3
Not taken not specified
111
36.4
Staphylococcus aureus
018
05.9
Pseudomonas sp
015
04.9
Serratia sp
008
02.6
Streptococcus pneumoniae
006
02.0
Bacillus sp
005
01.6
Moraxella
004
01.3
Fusarium sp
003
01.0
Stenotrophomonas maltophila
002
00.7
Streptococcus viridans
002
00.7
Candida
002
00.7
Dematiaceous mold
001
00.3
Gram-negative rods
001
00.3
Acremonium sp
001
00.3
Neisseria diphtheroids
001
00.3
Klebsiella pneumoniae
001
00.3
Corynebacterium sp
001
00.3
Total
305
100%
Figure 3. Correlation between culture status and best-corrected visual acuity (logMAR)
at admission and at the 7-day post discharge follow-up visit. Note that smaller numbers
represent better visual acuity.
177
Clinical characteristics and outcomes of patients admitted with presumed microbial keratitis to a tertiary medical center in Israel
outcomes of 276 consecutive patients admitted with a diagnosis of
presumed keratitis. The early diagnosis and the intensive inpatient
treatment may have resulted into the overall clinical and visual improvement seen in our population.
Daniell et al.(18) described different strategies for approaching pa
tients diagnosed with presumed microbial keratitis. Patients with small
peripheral lesions could be treated empirically with topical fluorquinolones, whereas the ones with central larger lesions should undergo
scrapings for culture and topical quinolone associated with a cephalosporin should be started. In our department, taking cultures and the
initial treatment were based on the clinical judgment of the attending
ophthalmologist who examined the patient at the emergency ward.
Some authors(22) studied a model to determine the impact of
minimal inhibitory concentration (MIC) on the clinical outcome. It included patients who received monotherapy with a fluoroquinolone
who had no subsequent change in their treatment and whose ulcers
healed without surgical intervention. He found significant linear associations between clinical outcome and MIC for Pseudomonas spp.
(P=0.047), Staphylococcus aureus (P=0.04), and Enterobacteriaceae
(P=0.045), but not for Streptococcus spp. (P=0.85) and coagulase-
negative staphylococci (CNS) (P=0.88).
In the population we studied, 36.6% were already using some
kind of topical treatment that failed. The treatment approach was the
use of fortified topical antibiotics given every hour at the beginning,
which included either cefazolin and gentamicin or vancomycin and
ceftazidime. Treatment modifications were made according to culture results and clinical outcome on a case by case basis. Hospitalization
assured treatment compliance until stabilization and may be related
to the good visual outcome and low complication rate seen in our
population.
The risk factors in our population are compatible with the ones
described in the literature. Contact lens wearing was the major predisposing condition in our population (36%), comparable with the
prevalence found in an Australian study (33.7%)(10) and in a Taiwanese
study (44.3%)(2).
In our study, contact lens wearers had a significantly better final
visual outcome. This fact may be due to their younger age and to
early ophthalmological examination performed in this population.
Age and clinical presentation influenced the hospital length of
stay. Patients older than 34 years stayed longer (mean of 6.88 days
against 4.56 days of younger patients) and their final visual acuity was
also significantly worse than those patients under 34 years old. Parmar
et al., showed that the elderly tend to have more severe presentations
of keratitis with a worse outcome, suggesting that this may be due to
the lower immunocompetence of this age group(12). The high prevalence of patients aged 18 to 21 years in our study group may be due
to the referrals from the military medical corps to our tertiary center.
The recruits and soldiers can seek medical attention promptly, thus
their clinical presentation is usually mild.
The best-corrected visual acuity (BCVA) measured at admission
improved significantly compared with the one measured at the first
follow-up visit, 1 week after discharge with a closed ulcer and no anterior chamber reaction. Other studies showed overall visual loss(2,4,7).
By analyzing the clinical characteristics at presentation we found
that ulcers larger than 2 mm and with hypopyon greater than 1 mm
were significantly related to worse visual acuity at admission and at
the first follow-up visit. The hospital length of stay was longer in the
presence of those findings. This underlines that seeking an ophthalmologist as soon as symptoms appear has a tremendous impact
on the final visual outcome and on the public health expenses on
hospitalization and antibiotic treatment. However, other authors(9)
demonstrated in their study of an Australian population that the cost
to treat was significantly associated only with clinical severity and
type of pathogen, not with delay in presentation.
In our series, cultures were obtained in194 of the patients admitted (70.3%). The reasons for not obtaining cultures by scrapings inclu178
ded: uncooperative patients, ulcers that are peripheral and small and
without anterior chamber reaction, keratitis may be treated empirically. The UK ofloxacin study suggested that the microbiological investigation of ulcers smaller than 2 mm is probably not worthwhile(24).
Another study from a Nepalese population by Feilmeir et al.,
demonstrated that microorganisms were grown from 40% of the
corneal scrapings. Pure bacterial cultures were obtained from 39%
of the positive scrapings and pure fungal cultures were obtained
from 61%(25).
The most prevalent microorganism in our cultures was coagulase-positive Staphylococcus (25.3% of positive cultures), followed by
Pseudomonas (21.1%). These results were compatible with the study
of the Israeli microbiological profile of ocular infections also showed
that coagulase-positive Staphylococcus was also the most prevalent
agent in corneal isolates(23).
Patients with positive cultures (35%) had a longer hospital stay
(mean of 7.37 days) and a worse visual prognosis.
Previous ocular surgery has been described as a predisposing factor for microbial keratitis(2,26). In our population, patients with previous
ECCE, PK or combined surgery were older and had a significantly
worse visual acuity either at admission or at the 7-day follow up visit.
The rate of positive cultures was significantly higher in this group
(61%), and Gram-positive bacteria were the most common etiologic
agents isolated from the scrapings. Moreover, the need of secondary
intervention such as urgent PK or evisceration was significantly
higher in this subgroup. However, Green et al.(27) demonstrated in a
longitudinal study that there is a trend towards decreased incidence
of keratitis in patients with previous surgeries.
CONCLUSION
There are some limitations to our study. The data is based on
retrospective charts analyzing only patients with keratitis that were
addmited to the ward. The decision to admit the patient was based
on clinical appearance, on previous treatment failure in the community and on the evaluation of patient’s possible limitations to comply
with the treatment, therefore some mild cases may not have included. The ones discharged at the emergency room were not included.
There are some patients that missed the follow-up and were also
excluded from the analysis. Adittional prospective controlled studies
in this geographic area are needed to confirm our results.
Nevertheless, this present study has a large number of patients
studied is able to demonstrate clinical trends such as microbial
keratitis must be treated aggressively and promptly to achieve a
good visual outcome. Furthermore, age, anterior chamber cells and
hypopyon, positive cultures and previous surgery were risk factors
related to lengthier hospitalization and a worse BCVA at the 7-day
follow-up visit.
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37o SIMASP
13 a 15 de fevereiro de 2014
Maksoud Plaza Hotel
São Paulo (SP)
Informações:
Realização: Depto. de Oftalmologia da UNIFESP
179
Intravitreal bevacizumab combined with infliximab in the treatment of choroidal
neovascularization secondary to age-related macular degeneration: case report series
Administração intravítrea de bevacizumabe combinado com infliximabe no tratamento da neovascularização
coroidiana secundária à degeneração macular relacionada à idade: relato de uma série de casos
Luiz Guilherme Azevedo de Freitas1,2, David Leonardo Cruvinel Isaac2, William Thomas Tannure2, Luís Alexandre Rassi Gabriel2, Ricardo Gomes dos Reis2,
Alan Ricardo Rassi2, Clovis Arcoverde de Freitas3, Marcos Pereira de Ávila2,3
ABSTRACT
RESUMO
Purpose: To evaluate the feasibility of the combined use of bevacizumab (Avastin®)
and combined with infliximab (Remicade®) in the treatment of naive choroidal
neovascularization due to age-related macular degeneration eyes.
Methods: Intravitreal injections of bevacizumab combined with infliximab in
6 neovascular age-related macular degeneration eyes. All patients underwent
complete ophthalmologic examination on the initial visit and at days 1, 30, 60,
90, 120, 150 and 180 following the first injection. Optical coherence tomography
and fluorescein angiography were performed during at initial visit and monthly
during the 6 months follow-up period. Electroretinography was performed before
and 30 days after initial injection, in order to evaluate retinal toxicity induced by
such treatment.
Results: Thirty days after the first injection, 5 eyes (83%) shown decrease in macular thickness. No change was seen in electroretinogram in any eyes compared
to initially performed electroretinogram. All phakic eyes developed cataract. One
patient developed vitritis and was submitted to medical treatment successfully.
At the end of the 6 months follow-up period, 4 patients showed significant improvement in the exudative process of choroidal neovascularization. One eye had
mild persistent submacular fluid without active choroidal neovascularization, and
another eye had persistent amount of intraretinal fluid due to active choroidal
neovascularization.
Conclusion: The combined use of bevacizumab with infliximab in eyes with neo
vascular age-related macular degeneration was effective in reducing leakage
and improving the macular thickness. However, it is not possible to assert that
the results were related to synergic effects of the combination therapy. A controlled study with more cases is necessary to precisely define the complicat ion
rates; however the dosage and/or association of drugs studied in this research
should not be recommended in clinical practice due to cataract as well as in
flamm atory reaction.
Objetivo: Avaliar a viabilidade do uso combinado do bevacizumabe (Avastin®) e do
infliximabe (Remicade®) no tratamento da degeneração macular relacionada à idade
neovascular em pacientes sem tratamentos prévio.
Métodos: Foram realizadas injeções intravítreas de bevacizumabe combinado com
infliximabe em 6 pacientes portadores de degeneração macular relacionada à idade
neovascular. Todos foram submetidos ao exame oftalmológico completo, no primeiro
dia de consulta, no dia seguinte a cada injeção e mensalmente até completar seis
meses após a primeira injeção. Foram realizados tomografia de coerência óptica
e angiografia fluoresceínica na primeira consulta e mensalmente, até completar 6
meses após o primeiro procedimento. Eletrorretinografia também foi realizada antes
da injeção e 30 dias após, no intuito de avaliar toxidade retiniana.
Resultados: Ao final de 30 dias da primeira injeção, 5 (83%) pacientes apresentaram
diminuição na espessura macular. Não foi visualizada alteração à eletrorretinografia
em relação ao exame inicial em 100% os pacientes. Cinco pacientes (100% dos fá
cicos) desenvolveram catarata. Um paciente desenvolveu vitreíte e foi tratado com
sucesso. Ao final dos 6 meses, 4 pacientes apresentaram melhora significativa da
neovascularização de coroide, porém ainda com foco de neovascularização em
atividade, um paciente apresentava discreta persistência de fluido submacular sem
neovascularização ativa e 1 paciente persistia importante quantidade de fluido in
trarretiniano com neovascularização em atividade.
Discussão: Avaliou-se o uso combinado do bevacizumabe com infliximabe em
pacientes portadores de degeneração macular relacionada à idade neovascular e
a associação mostrou-se eficaz na redução do vazamento da neovascularização de
coroide e da espessura macular ao tomografia de coerência óptica. Não é possível,
no entanto, afirmar se os resultados apresentam efeitos sinérgicos pela associação
entre as duas drogas. Um estudo com maior número de casos é necessário para definir
exatamente as taxas de catarata e vitreíte da associação entre as drogas, no entanto,
ao menos na dosagem estudada no presente trabalho, a associação não deveria ser
recomendada na prática clínica.
Keywords: Retina; Macular degeneration/complications; Choroidal neovascularization/etiology; Intravitreal injections; Optical coherence tomography; Angiogenesis inhibitors/therapeutic use
Descritores: Retina; Degeneração macular/complications; Neovascularização reti
niana/etiologia; Injeções intravítreas; Tomografia de coerência óptica, Inibidores da
angiogênese/uso terapêutico
Study conducted at the Centro de Referência em Oftalmologia, Hospital das Clínicas UFG (CEROF/
HC/FM/UFG).
1
2
Physician, Hospital de Olhos Santa Luzia, Recife (PE), Brazil.
Physician, Department of Ophthalmology, Universidade Federal de Goiás, Goiânia (GO), Brazil.
Physician, Centro Brasileiro da Visão - CBV, Brasília (DF), Brazil.
3
180
Disclosure of potential conflicts of interest: L.G.A.de Freitas, None; D.L.C.Isaac, None; W.T.Tanure,
None; L.A.R.Gabriel, None; R.G.dos Reis, None; A.R.Rassi, None; C.A.de Freitas, None; M.P.de
Ávila, None.
Correspondence address: Luiz Guilherme Azevedo de Freitas. Hospital de Olhos Santa Luzia.
Estrada do Encanamento, 909 - Recife (PE), Brazil - 52070-000 - E-mail: [email protected]
Freitas LGA, et al.
INTRODUCTION
Age-related macular degeneration (ARMD) is the leading cause
of central vision loss in individuals over 60 years of age. In the United
States, it is related to 54.4% of visual impairment cases and 22.9% of
legal blindness in Caucasian population(1,2). The neovascular form of
ARMD has more aggressive and devastating effect, accounting for
80% of the cases of legal blindness by the disease(3).
The treatment for neovascular ARMD with drugs inhibiting vas
cular endothelial growth factor (VEGF) such as ranibizumab and be
vacizumab are currently the most widely used(4,5). The efficacy and
safety of the use of ranibizumab was proven in studies such as MARINA and ANCHOR, which determined the benefit of using monthly
injections of the drug. In both studies patients showed significant
visual gain after 3 applications of medication(4,5).
Other studies such as PIER and PRONTO assessed alternative sche
dules for the use of ranibizumab involving fewer injections. Both
studies showed the benefit of using ranibizumab but with results for
visual acuity slightly worse than the MARINA and ANCHOR studies(6,7).
Whether ranibizumab or bevacizumab, a factor of this therapeutic modality is the necessity for multiple injections to maintain the
visual benefit achieved in the first applications.
A recent study compared the efficacy and safety of bevacizumab with ranibizumab for the treatment of neovascular age-related
macular degeneration. It was noted that both showed equivalent
results with regard to visual acuity when administered monthly or as
needed, for a year(8).
The limitation of this therapeutic modality is the need for multiple injections to maintain the visual benefit achieved in the first
applications.
One way to try to extend the anatomic and visual benefits would
be to try to block another agent of the angiogenic pathway. An important molecule in the formation of neovascularization is the tumor
necrosis factor (TNF). It is released in the early stages of the disease
and participates in the cyclic inflammatory process in the formation
of choroidal neovascularization (CNV)(9).
The blockage of TNF expression can be achieved through the use
of monoclonal chimeric antibodies such as infliximab. This drug is
used in the treatment of rheumatoid arthritis, spondyloarthropathies
and Crohn’s disease. Intravenous infusion of the drug in the treatment
of arthritis patients who also carried the neovascular form of ARMD,
led to improvement in visual acuity and regression of the CNV. Neither
ocular nor extraocular effects were observed in these patients(10).
Giganti et al., in a pilot study evaluating the safety of intravitreal
infliximab in rabbits, showed no electrophysiological or histological
damage in dosage up to 1.7 mg(11). Theodossiadis et al., also demonstrated the safety of intravitreal infliximab in New Zealand white rabbits, which received intravitreal injections of up to 2 mg of infliximab,
and Rassi et al., demonstrated safety in the use of 2 mg of 2 to 3 serial applications in rabbits of the same breed(12,13).
The intravitreal use of infliximab in humans was first reported in
2009, when three selected eyes with active CNV previously and unsuccessfully treated with bevacizumab received intravitreous injections of 0.05 ml of infliximab in each eye and resulted in improvement
in best-corrected visual acuity (BCVA) as well as the resolution of
central macular thickness(14).
The purpose of this study is to evaluate the feasibility of the
combined use of bevacizumab (Avastin®, Roche, Brazil) and infliximab (Remicade®, Schering-Plough, United States) in the treatment of
neovascular ARMD.
METHODS
The study was approved by the Ethics Committee of Federal University of Goias. It was conducted a prospective, interventional treatment study in the period from March to October 2011, where patients
with neovascular ARMD were selected.
Inclusion criteria: Eyes with CNV secondary to ARMD diagnosed by means of fluorescein angiography (FA) (Topcon TRC 50DX®, Topcon, Japan) and by optical coherence tomography (Stratus - OCT®, Carl
Zeiss Meditec Inc, USA); central macular thickness ≥ 300 µm by
Thickness Map Report on OCT®; only one eye in each patient could
be enrolled in the study; eyes should not be previously treated
with antiangiogenic drugs; and the patient should provide a signed
consent form.
Exclusion criteria: Eyes with cataracts or corneal opacities that
precluded adequate visualization of the retina; cataract surgery performed less than three months before the possible intravitreal in
jection; eyes with retinal diseases other than ARMD; vitreoretinal
surgery or previous treatment for neovascular AMD at any time; and
refusal by the patient to participate in the study.
All intravitreal injections were performed by the same surgeon,
with 30-gauge needle positioned at 3.5 mm from the limbus. Two separate injections were made with measurements at 2 different sites. After the injections, anterior chamber paracentesis was performed.
Infliximab (Remicade®, Schering-Plough, United States) is available in a bottle containing 100 mg. Its aliquotation was performed in
a sterile environment (Laminar Flow AHC-2D1, ESCO, USA) using
Eppendorf vials containing 2 mg of infliximab. After aliquotation, the
vials were kept under refrigeration at 2-8°C.
Patients enrolled in the study underwent a complete ophthalmologic examination, on the first day of medical appointment, the
day after each injection and monthly until completion of six months
from the first injection.
The FA and optical coherence tomography (OCT) examinations were performed at the first visit and then monthly until completion
of the six months after the first procedure. Full field electroretinography (ERG) examinations were performed in all patients before the
injection and 30 days after each injection in order to evaluate the
possibility of retinal toxicity. To classify the lens status, the LOCS III(15)
classification system was used.
RESULTS
Six eyes (6 patients) treated with combined bevacizumab and
infliximab were evaluated. Regarding gender, 5 patients (83%) were
female and all of them aged over 70 years.
On biomicroscopic examination, one patient was pseudophakic and five patients had NO3 NC3 cataract.
Two consecutive injections were performed in 5 patients and
3 injections in 1 patient in the follow-up period of 6 months.
Thirty days after the first injection, 5 (83%) patients showed de
crease in macular thickness. In one patient a significant presence
of macular fluid was present, but the FA has shown less leakage in
late phases when compared to the pre-injection (Figures 1 and 2).
Thirty days after each injection, no patient had abnormal electroretinogram findings compared to initial examination. Two months after the first injection, two eyes developed NO4
NC4 cataract and 3 eyes developed NO5 NC5 cataract, these last, it
was necessary to perform phacoemulsification with implantation
of intraocular lens for better retinal visualization and performance of
FA and OCT exams (Table 1).
Anterior chamber cells were observed in 3 patients (50%) in
the first days after each injection. One patient showed vitritis and
vasculitis 1 month after the second application. Treatment was conducted, showing improvement of the retinal vascular process after
30 days (Figure 3). Treatment was performed with prednisolone eye
drops 6/6h for 15 days. After 6 months, 4 eyes showed significant
improvement of CNV fluid and retinal edema. However focusing on
active CNV, one eye had mild persistent submacular fluid without active CNV, and another eye had persistent amount of intraretinal fluid
due to active CNV.
The intraocular pressure remained within normal limits during
the study (Table 1).
181
Intravitreal bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary
Figure 1. In this patient can notice significant reduction of macular thickness by the OCT and in the fluorescein angiography show less leakage in late phases when compared to
the pre-injection phase.
Figure 2. Significant persistence of fluid in the macula 30 days after first injection. But can notice less leakage in late phases when compared to the pre-injection.
DISCUSSION
There are many advances in the treatment for neovascular ARMD
involving monoclonal antibodies. The results of treatments using anti-VEGF drugs have been proven through various studies, although,
therapies with drugs that inhibit TNF are still being investigated(16).
182
The tumor necrosis factor is a very active pro-inflammatory cytokine and can stimulate specific and nonspecific immune systems. It
activates B and T lymphocytes, and macrophages, increases the levels
of pro-inflammatory cytokines such as interleukin 1, 6 and 8 (IL-1, IL-6
and IL-8), increases the attraction of neutrophils to the inflammatory
Freitas LGA, et al.
Table 1. Clinical eye exams before and after injections
BCVA
Before
treatment
BCVA
30 days after
first injection
BCVA
90 days after
first injection
IOP
Before
treatment
IOP
90 days after
first injection
Anterior chamber
inflammatory reaction
by biomicroscopy
First day after each injection
Cataract
Before
treatment
Cataract
2 months after
first injection
Eye 1
0,2
0,4
0,5
16
14
+
NO4
NC4
Eye 2
HM
CF 3’
CF 3’
14
13
-
NO4
NC4
Eye 3
0,1
0,1
0,15
14
18
+
NO5
NC5
Eye 4
CF 4’
CF 4’
CF 4’
14
12
-
NO5
NC5
Eye 5
CF 7’
CF 7’
CF 1’
12
13
-
NO5
NC5
Eye 6
CF 4’
CF 4’
CF 4’
13
12
+
Pseudophakic
Pseudophakic
BCVA= best-corrected visual acuity; IOP= intraocular pressure; HM= hand motion; CF 1’= count finger at one foot; CF 3’= count finger at three feet; CF 4’= count finger at four feet; CF
7’= count finger at seven feet.
Figure 3: A patient who showed vitritis and vasculitis 30 days after the second injection
(figure above). After 30 days of treatment showing improvement of the retinal vascular
process (figure below).
site when it stimulates the synthesis of adhesion molecules and the
activation of neutrophils(16,17). Oh et al., in 1999, investigated the distribution of inflammatory mediators such as IL-1, TNF and angiogenic
cytokines and as well as vascular endothelial growth factor (VEGF),
in the choroidal neovascularization process. Results showed that IL-1
and TNF alpha, secreted by macrophages can promote at least in part,
angiogenesis in CNV by stimulating the production of VEGF by retinal
pigment epithelium (RPE) cells(18).
Studies have shown that TNF alpha plays an active role in the
pathogenesis of inflammatory eye diseases and neurodegenerative eye diseases, macular edema, retinal neovascularization and proliferative vitreoretinopathy (PVR). Intravitreal injection of TNF alpha
in mice causes inflammation and abnormal permeability in inner
blood-retinal barrier, manifesting an inflammatory process, as well as
increased levels of this cytokine in the eye(19-22).
The blockage of TNF can be obtained by use of chimeric monoclonal antibodies such as infliximab. This drug has been used to treat rheumatoid arthritis, spondyloarthropathies and Crohn’s disease. Intravenous infusion of this drug in the treatment of arthritis patients who
also carried the neovascular form of ARMD, led to improvement in
visual acuity and regression of choroidal membrane. No adverse ocular
or extraocular effect was presented in these patients(10,13).
The safety of intravitreal infliximab has been demonstrated by studies in experimental animal models indicating that it can be safely
administered at a dose of 2 mg. In these studies electrophysiological tests were performed which showed normal results in all rabbit
eyes that were injected with 1 or 2 mg infliximab(14). In this current
study, we selected the dose of 2 mg of infliximab to be injected into
the vitreous cavity of these eyes.
Electrophysiology was performed before injection and at 30
and 60 days. All results were normal. For these findings it is supposed
that this association may be non-toxic to the human retina controlled. Studies with more patients should be performed to improve the
reliability of results.
Arias et al., reported the use of intra-vitreous infliximab (2 mg/
0.05 ml) in patients with neovascular ARMD does not respond to serial injections of bevacizumab and ranibizumab. In this series of cases, reaction was observed in the anterior chamber and vitritis in
50%(23). In this study, three patients had anterior chamber reaction
(1+) with flare and cells in the first postoperative day.
Some authors in 2011 evaluated the use of infliximab in rabbits
(2 mg). In the study, the presence of few lymphocytes in the retina
of two rabbits was seen and had an important inflammatory membrane on the surface of the vitreous and retinal posterior cortex. Despite inflammatory findings, the electroretinogram study in the
rabbits was normal, as in this current study(13).
Thus, despite the findings of inflammation in the eyes treated
with infliximab, it did not alter the electroretinography (ERG) suggesting no specific toxicity to the retina and its operation.
In one patient uveitis and retinal vasculitis was detected, during
a visit of 30 days. The patient was treated with steroids. After 15 days
of treatment, the patient had regression of angiographic signs of
vasculitis.
Inflammatory reactions were also observed by Wu and colleagues
in 8 patients with diabetic macular edema (20% of total patients) who
underwent intravitreal injection of infliximab (2 mg)(24) similar to 4
cases reported by Giganti and colleagues who injected infliximab
(0.5 mg) in 2 patients with macular edema and 2 patients with neovascular ARMD where 100% of the patients showed uveitis(25).
Both infliximab and bevacizumab are monoclonal humanized antibodies. Bevacizumab is comprised of 5% murine to 95% human framework while infliximab is 25% murine and 75% human framework.
One might suppose that the greater presence of murine components in infliximab would be an important factor for the greatest potential to generate vitritis in treated eyes, in the current series. Other
anti-TNF drugs such as adalimumab are 100% humanized and is
believed that it might have have fewer inflammatory components
than infliximab.
Other adverse effect was observed. All phakic eyes (5 patients)
had progression of cataracts in the two months following the injection
and in 3 additional eyes (50% of patients) the phacoemulsification was
necessary in order to provide the possibility of fundus evaluation.
In none of the animal studies and case series in humans the
progression of cataract was demonstrated(13,23). As in studies with
183
Intravitreal bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary
anti-VEGF (MARINA, ANCHOR and CATT) there is no cataract progression. It could be presumed that the association between infliximab and bevacizumab could accelerate cataract progression.
CONCLUSION
The combination was effective in reducing the leakage of CNV and macular thickness in OCT. However, it is not possible to assert
that the results are due to synergic effects of both drugs combination. Despite the small number of patients and not evidence
of functional changes by the ERG, the findings of vitritis and the
progression of cataracts in eyes submitted to this treatment were
evident.
A controlled study with more number of eyes is necessary to precisely define the rates of cataract and vitritis development as well as
therapeutical effect of the bevacizumab/infliximab association; however, due to the clinical findings observed, the dosage analysed in
this study and, should not be recommended in clinical practice. By an
unknown; however this hypotheses should be evaluated by futures
studies designed for this purpose.
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Persistência da vasculatura fetal: características oftalmológicas, manuseio da catarata e resultados cirúrgicos
Marcia Beatriz Tartarella1, Rodrigo Ueno Takahagi1, Ana Paula Braga2, João Borges Fortes Filho3
ABSTRACT
RESUMO
Purposes: To describe ocular features, management of cataract and functional
outcomes in patients with persistent fetal vasculature.
Methods: Retrospective, descriptive case series of patients with persistent fetal
vasculature. Data were recorded from the Congenital Cataract Section of Federal
University of São Paulo, Brazil from 2001 to 2012. All patients were evaluated for
sex, age at diagnosis, systemic findings, laterality, age at surgery, and initial and
final follow-up visual acuities. Follow-up and complications after cataract surgery
were recorded. Ultrasound was performed in all cases and ocular eco-Doppler
was performed in most.
Results: The study comprised 53 eyes from 46 patients. Age at diagnosis ranged
from 5 days of life to 10 years-old (mean 22.7 months). Twenty-seven patients
were male (58.7%). Persistent fetal vasculature was bilateral in 7 patients (15.2%).
Forty-two eyes (79.2%) had combined (anterior and posterior forms) PFV presentation, 5 eyes (9.4%) had only anterior persistent fetal vasculature presentation
and 6 eyes (11.3%) had posterior persistent fetal vasculature presentation. Thirtyeight eyes (71.7%) were submitted to cataract surgery. Lensectomy combined
with anterior vitrectomy was performed in 18 eyes (47.4%). Phacoaspiration with
intraocular lens implantation was performed in 15 eyes (39.5%), and without lens
implantation in 5 eyes (13.2%). Mean follow-up after surgery was 44 months. Postoperative complications were posterior synechiae (3 cases), retinal detachment
(2 cases), phthisis (3 cases), posterior capsular opacification (8 cases), inflammatory
pupillary membrane (5 cases), glaucoma (4 cases), intraocular lens implantation
displacement (1 case) and vitreous hemorrhage (2 cases). Complications were
identified in 19 (50%) of the 38 operated eyes. Visual acuity improved after cataract
surgery in 83% of the eyes.
Conclusions: Patients with persistent fetal vasculature have variable clinical presentation. There is an association of persistent fetal vasculature with congenital
cataract. Severe complications are related to cataract surgery in patients with
persistent fetal vasculature, but 83% of the operated eyes improved visual acuity.
Objetivos: Descrever as características oftalmológicas, o tratamento da catarata
e os resultados funcionais em pacientes com o diagnóstico de persistência da vas
culatura fetal.
Métodos: Estudo retrospectivo e descritivo de série de casos de pacientes com persis
tência da vasculatura fetal. Dados foram obtidos dos arquivos do Setor de Catarata
Congênita da Universidade Federal de São Paulo, Brasil, durante o período entre 2001
a 2012. Todos os pacientes foram avaliados quanto ao sexo, idade ao diagnóstico,
achados sistêmicos, lateralidade, idade à cirurgia e acuidade visual inicial e final ao
seguimento. Complicações após a cirurgia da catarata foram analisadas. Ultrassom
foi realizado em todos os casos e eco-Doppler foi realizado na maioria dos pacientes.
Resultados: O estudo incluiu 53 olhos de 46 pacientes. Idade ao diagnóstico variou
de 5 dias de vida até 10 anos (média 22,7 meses). Vinte e sete pacientes eram mascu
linos (58,7%). A persistência da vasculatura fetal foi bilateral em 7 pacientes (15,2%).
Quarenta e dois olhos (79,2%) apresentaram formas combinadas (anterior e posterior)
da persistência da vasculatura fetal, 5 olhos (9,4%) tinham somente a forma anterior
da persistência da vasculatura fetal e 6 olhos (11,3%) tinham a forma posterior de
apresentação da persistência da vasculatura fetal. Trinta e oito olhos (71,7%) foram
operados de catarata. Lensectomia com vitrectomia anterior foi realizada em 18 olhos
(47,4%). Facoaspiração com implante de lente intraocular foi realizada em 15 olhos
(39,5%) e sem implantação de lente em 5 olhos (13,2%). O seguimento médio após
cirurgia foi de 44 meses. Complicações pós-operatórias foram: sinéquias posteriores (3
casos), descolamento da retina (2 casos), atrofia do globo ocular (3 casos), opacificação
da cápsula posterior (8 casos), membrana pupilar inflamatória (5 casos), glaucoma
(4 casos), deslocamento da lente implantada (1 caso) e hemorragia vítrea (2 casos).
Complicações foram identificadas em 19 (50%) dos 38 olhos operados. Acuidade visual
melhorou após a cirurgia da catarata em 83% dos olhos.
Conclusões: Pacientes com persistência da vasculatura fetal tem apresentações clínicas
variáveis. Existe uma associação da persistência da vasculatura fetal com catarata
congênita. Complicações graves são associadas com a cirurgia da catarata nesses
pacientes, mas 83% dos olhos operados melhoraram a acuidade visual nesse estudo.
Keywords: Persistent hyperplastic primary vitreous/pathology; Cataract/congenital; Ophthalmologic surgical procedures
Descritores: Persistência do vítreo primário hiperplásico/patologia; Catarata/con
gênito; Procedimentos cirúrgicos oftalmológicos
INTRODUCTION
Persistent fetal vasculature (PFV) is a congenital developmental
anomaly of the eye resulting from failure of the embryological
primary vitreous and hyaloid vasculature to regress. PVF typically
presents unilaterally without association with systemic findings, but
sometimes PFV may be associated with rare systemic syndromes as
Walker-Warburg anencephaly, oculo-dento-osseous dwarfism, oculopalato-cerebral dwarfism, Patau syndrome, or others(1,2). Bilateral cases
account for less than 10% of the cases(3). Persistent fetal vasculature
can be classified as anterior, posterior and combined forms, according
to the affected intraocular structures. This heterogeneity of clinical
presentation makes PFV a challenge to surgical management(4).
Persistent fetal vasculature is related to congenital cataract(5,6).
However, surgeries for cataract in patients with PFV are more difficult
to perform and are related to higher rates of postoperative complications as: retinal detachment, hyphema, intraocular hemorrhage,
glaucoma, secondary opacification of the visual axis and extensive
inflammatory response with pupillary block(7-10).
Submitted for publication: November 14, 2012
Study performed at Universidade Federal de São Paulo.
Physician, Department of Ophthalmology, School of Medicine, Universidade Federal de São Paulo,
São Paulo (SP), Brazil.
Orthoptist, Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo (SP), Brazil.
3
Physician, Department of Ophthalmology, School of Medicine, Universidade Federal do Rio Grande
do Sul, Porto Alegre (RS), Brazil.
1
2
Disclosure of potential conflicts of interest: M.B.Tartarella, None; R.U.Takahagi, None; A.P.Braga,
None; J.B.Fortes Filho, None.
Correspondence address: João Borges Fortes Filho. Hospital de Clínicas de Porto Alegre. Rua
Ramiro Barcelos, 2350 - Porto Alegre (RS) - 90035-903 - Brazil
185
This study aims to describe ocular features, management of
cataract and visual acuity (VA) outcomes of patients with PFV after
cataract surgery.
METHODS
Study design
A retrospective, noncomparative and descriptive case series of
patients with PFV were recorded from the files of Congenital Cataract
Section of Federal University of São Paulo, Brazil during the period
from 2001 to 2012.
Patients and ophthalmological examination
All patients were evaluated for sex, age at diagnosis, associated
systemic abnormalities, laterality, biomicroscopic examination,
ocular axial length (contact A-scan measurements), initial and final
follow-up VA, and intraocular pressure. Age at surgery, follow-up period and complications after cataract surgery were recorded. Indirect
ophthalmoscopy and A- and B-scan ultrasonography were performed in all patients in order to evaluate components of anterior and
posterior forms of PVF. Ocular eco-Doppler was performed in most
patients to assess vascular blood flow. Persistent fetal vasculature was
classified according to the structural ocular involvement as anterior,
posterior or combined form(11).
Surgical techniques used for cataract extraction
Lensectomy by 25 gauge bimanual vitrectomy technique was
performed through the pars plicata or limbal approaches. The
nucleus and cortex were aspirated in the bag. Anterior vitrectomy
for removal of the PFV was performed in all cases operated by this
technique. Endodiathermy was used if bleeding or in patients when
the eco-Doppler examination disclosed vascular blood flow inside
the fibrovascular stalk.
Phacoaspiration with or without intraocular lens implantation
(IOL) was performed through limbal incision, lens aspiration and IOL
in the bag implantation. Posterior capsulorhexis, anterior vitrectomy
and fibrovascular stalk management were performed via pars plana
with 25 gauge vitrectomy system. Endodiathermy of permeable fi
brovascular stalk was performed when necessary.
All surgeries were performed under general anesthesia by the
same author (MBT).
Criteria for surgery indication and main outcomes evaluated
Surgery was indicated in cases with VA of 20/150 or less in eyes
with no macular involvement. Exclusion criteria included microph
thalmia and eyes with no light perception.
Postoperative VA and rate of postoperative complications were
obtained. Visual acuity was assessed with age-appropriated tests such
as the Teller Acuity Cards, Lea-Gratings Visual Chart, Snellen Chart, or
Sweep VEP (Sweep Visual Evoked Potentials). Postoperative corrected
distance VA results were compared, when possible, with preoperative
values and classified as: no-change; improvement or deterioration.
Ethics
The authors certify that the study protocol was approved by the
Ethics Committee and that the protocol for the research project is
conforming to the provisions of the Declaration of Helsinki in 1995
(as revised in Edinburgh 2000). Authors declare no financial support
or relationships that may pose a conflict of interest.
RESULTS
The study group comprised 53 eyes from 46 patients. Age at diagnosis ranged from 5 days of life to 10 years-old (mean 22.7 months).
186
Twenty-seven patients were male (58.7%). Persistent fetal vasculature was bilateral in 7 patients (15.2%) and unilateral in 39 patients
(84.8%). Among the bilateral cases one patient was diagnosed as
Patau syndrome and one patient had juvenile rheumatoid arthritis.
In the entire group the initial VA varied from non-light perception
to 20/50.
Forty-two eyes (79.2%) had combined (anterior and posterior
forms) PFV presentation, 5 eyes (9.4%) had only posterior PFV
presentation and 6 eyes (11.3%) had predominantly anterior PFV
presentation.
Thirty-eight eyes (71.7%) were submitted to cataract surgery.
Age at surgery ranged from one month-age to 4 years (mean 14
months). Initial VA in the operated group of patients varied from light
perception (31 eyes) to 20/150. There was no indication for surgery
in patients with no-light perception and severe microphthalmia.
Lensectomy combined with anterior vitrectomy was performed in 18
eyes (47.4%). Phacoaspiration with IOL implantation was performed
in 15 eyes (39.5%), and without IOL implantation in 5 eyes (13.2%).
Fifteen eyes were not submitted to cataract surgery including one
patient presenting unilateral PFV with VA of 20/50 in the affected eye.
Mean follow-up after surgery was 44 months. Postoperative complications were posterior synechiae (3 cases), retinal detachment
(2 cases), phthisis bulbi (3 cases), posterior capsular opacification
(8 cases), inflammatory pupillary membrane (5 cases), glaucoma (4
cases), IOL displacement (1 case) and vitreous hemorrhage (2 cases).
Those complications were identified in 19 (50%) of the 38 operated
eyes.
Final corrected distance VA was obtained in 36 eyes and VA im
proved after surgery in 83% of eyes. Three eyes (8.3%) developed
phthisis bulbi after surgery and showed no-light perception. A total
of 12 eyes (33%) had final VA under 20/200. Seventeen eyes (47%)
showed VA between 20/200 and 20/40. Three eyes (8.3 %) achieved
20/40 or better.
None of the 15 non-operated eyes improved VA and, in this
group, a total of 6 eyes decreased VA during the follow up period of
the study.
DISCUSSION
This study reported predominance of unilateral cases and both
anterior and posterior PFV presentation. These findings are in agree
ment with some previous published studies(10,11). Some authors
discuss that most cases of unilateral congenital cataracts are due
to different presentations of PFV(5,7), and that minimal fetal vascular
remnants were found in 100% of a case series of 31 patients operated
for unilateral congenital cataract(5).
Cataract surgery in patients with PFV presents different degrees
of difficulty, and initial surgical plan may change depending on the pre
and intraoperative conditions. Ocular eco-Doppler findings showing
extensive blood flow from the optic nerve to the posterior face of the
lens is a predictive factor of possible intraoperative hemorrhage. The
surgeon must be aware of the situation and be prepared with endocoagulation instruments and techniques to deal with the situation.
Intraocular hemorrhage is a common cause of bad prognosis and
poor outcomes in this PFV cases.
Membranous cataract or fibrovascular plaques at pupillary site or
in the retrolental space may need further surgical manipulation with
the use of micro-scissors to create a clear visual axis.
Some eyes with PFV and cataract are associated with variable
degrees of microphthalmia. In these cases, the visual improvement
after cataract surgery may be limited. Early surgical intervention with
microsurgical 25 gauge lensectomy or phacoaspiration techniques
combined with anti-amblyopic therapy resulted in favorable visual
outcome in many operated eyes(10).
Nineteen eyes (50%) presented postoperative complications in
our study. Severe complications as retinal detachment and phthisis
Tartarella MB, et al.
bulbi occurred in 5 eyes (13%) leading to loss of vision in those eyes.
All these five eyes presented microphthalmia, combined form of
PFV, a large stalk with internal blood flow and posterior retinal folds.
Literature report with modern closed chamber cataract surgery in
PFV showed a complication rate of 27%(8).
Figure 1. Patient with cataract affecting the visual axis and persistent fetal vasculature.
Figure 2. Ultrasound image of patient with persistent fetal vasculature in combined
(anterior and posterior forms) presentation. Width of the stalk determines poor prognosis
for visual acuity recovery after cataract surgery.
The prognosis after cataract surgery seems to be linked to the
presentation forms of the PFV and associated preoperative ocular
features. Anatomical results depend on the fibrovascular stalk width,
presence of blood flow inside the stalk, type of presentation (anterior,
posterior or combined form of PFV) and associated microphthalmia.
Those variables are associated with the higher incidence of postoperative complications. Visual and functional results depend on age
of lens opacity occurrence (congenital or latter acquired cataract
formation), age at surgery and presence of major or minor macular
involvement.
In our study 82% of the included eyes had initial VA of light perception and final corrected distance VA improved after surgery in
83% of the eyes despite the high rate of complications while none of
the 15 non-operated eyes improved VA. Specific circumstances and
clinical variables, as the occurrence of glaucoma after surgery and
poor adhesion to occlusive therapy with severe amblyopia, may have
also affected the final VA in those children.
New studies concerning cumulative factors that could predict
prognosis for each case are necessary to help ophthalmologists to
decide whether to perform surgery. Among the main pre-operatory
clinical variables are: lens and vitreous opacities affecting the visual
axis (Figure 1), width and occurrence of blood flow inside de stalk
detected by eco-Doppler (Figures 2 and 3), retrolental vascularized
plaque also detected by eco-Doppler (Figure 4), form of PFV presen
tation with major or minimal macular involvement (Figure 5), presence of microphthalmia and patient’s age at surgery.
The surgeon and patient’s parents must be aware of severe
postoperative complications after cataract surgery in eyes with PFV
thus causing in some cases poor VA or unfavorable outcomes. Early
diagnosis, early surgery and prompt anti-amblyopic therapy after
cataract surgery are important factors to be considered as functional
prognostic factors.
CONCLUSIONS
Our study related that patients with persistent fetal vasculature
had variable clinical presentations and there is a clear association
of persistent fetal vasculature with congenital cataract. Although
severe complications are related to cataract surgery in patients with
persistent fetal vasculature our study disclosed that more than 80% of
the operated eyes improved visual acuity despite high occurrence of
intra and postoperative complications. Eco-Doppler can help in order
to predict intraoperative hemorrhage and poor visual prognosis in
severe forms of persistent fetal vasculature.
In spite of the limitations of this study regarding its retrospective
and noncomparative design we observed visual acuity improvement
in 83% of the eyes after cataract surgery and anti-amblyopic therapy
in a mean postoperative follow-up of 44 months.
Figure 3. Eco-Doppler showing vascularized stalk from persistent fetal vasculature. Width and vascularization inside the stalk determines poor
prognosis for visual acuity recovery after cataract surgery.
187
Figure 4. Eco-Doppler showing retrolental vascularized plaque from persistent fetal vasculature.
Figure 5. Persistent fetal vasculature in predominantly posterior presentation. Left: Major macular involvement suggests poor visual prognosis after
cataract removal. Right: Minor macular involvement indicates better visual acuity after cataract removal.
REFERENCES
1. Alexandrakis G, Scott IU, Flynn HW Jr, Murray TG, Feuer WJ. Visual acuity outcomes
with and without surgery in patients with persistent fetal vasculature. Ophthalmology. 2000;107(6):1068-72.
2. Dhir L, Quinn AG. Persistent fetal vasculature and spontaneous hyphema in a patient
with Klippel-Trénaunay-Weber syndrome. J AAPOS 2010;14(2):190-2.
3. Kumar A, Jethani J, Shetty S, Vijayalakshmi P. Bilateral persistent fetal vasculature: a
study of 11 cases. J AAPOS. 2010;14(4):345-8.
4. Sisk RA, Berrocal AM, Feuer WJ, Murray TG. Visual and anatomic outcomes with
or without surgery in persistent fetal vasculature. Ophthalmology. 2010;117(11):
2178-83.e1-2.
5. Müllner-Eidenböck A, Amon M, Moser E, Klebermass N. Persistent fetal vasculature
and minimal fetal vascular remnants: a frequent cause of unilateral congenital cataracts. Ophthalmology. 2004;111(5):906-13.
6. Müllner-Eidenböck A, Amon M, Hauff W, Klebermass N, Abela C, Moser E. Surgery in
unilateral congenital cataract caused by persistent fetal vasculature or minimal fetal
188
vascular remnants: age-related findings and management challenges. J Cataract
Refract Surg. 2004;30(3):611-9.
7. Paysse EA, McCreery KM, Coats DK. Surgical management of the lens and retrolenti
cular fibrotic membranes associated with persistent fetal vasculature. J Cataract
Refract Surg. 2002;28(5):816-20. Comment in J Cataract Refract Surg. 2003;29(7):
1250.
8. Vasavada AR, Vasavada SA, Bobrova N, Praveen MR, Shah SK, Vasavada VA, et al. Out
comes of pediatric cataract surgery in anterior persistent fetal vasculature. J Cataract
Refract Surg. 2012;38(5):849-57.
9. Vasavada VA, Dixit NV, Ravat FA, Praveen MR, Shah SK, Vasavada V, et al. Intraoperative
performance and postoperative outcomes of cataract surgery in infant eyes with
microphthalmos. J Cataract Refract Surg. 2009;35(3):519-28.
10.Anteby I, Cohen E, Karshai I, BenEzra D. Unilateral persistent hyperplastic primary
vitreous: course and outcome. J AAPOS. 2002;6(2):92-9.
11. Dass AB, Trese MT. Surgical results of persistent hyperplastic primary vitreous. Oph
thalmology. 1999;106(2):280-4.
Relato de Caso |
Case Report
Enhanced depth imaging optical coherence tomography and fundus autofluorescence
findings in bilateral choroidal osteoma: a case report
Tomografia de coerência óptica com profundidade de imagem aprimorada e resultados autofluorescência
de fundo em osteoma de coroide bilateral: relato de caso
Muhammet Kazim Erol1, Deniz Turgut Coban1, Basak Bostanci Ceran1, Mehmet Bulut1
ABSTRACT
RESUMO
The authors present enhanced depth imaging optical coherence tomography (EDI
OCT) and fundus autofluorescence (FAF) characteristics of a patient with bilateral
choroidal osteoma and try to make a correlation between two imaging techniques.
Two eyes of a patient with choroidal osteoma underwent complete ophthalmic
examination. Enhanced depth imaging optical coherence tomography revealed a
cage-like pattern, which corresponded to the calcified region of the tumor. Fundus
autofluorescence imaging of the same area showed slight hyperautofluorescen
ce. Three different reflectivity patterns in the decalcified area were defined. In
the areas of subretinal fluid, outer segment elongations similar to central serous
chorioretinopathy were observed. Hyperautofluorescent spots were evident in
fundus autofluorescence in the same area. Calcified and decalcified portions of
choroidal osteoma as well as the atrophy of choriocapillaris demonstrated different
patterns with enhanced depth imaging and fundus autofluorescence imaging.
Both techniques were found to be beneficial in the diagnosis and follow-up of
choroidal osteoma.
Os autores apresentam tomografia de coerência óptica com profundidade de ima
gem aprimorada (EDI OCT) e autofluorescência de fundo (FAF) características de um
paciente com osteoma de coroide bilateral e tentam correlacionar as duas técnicas
de imagem. Dois olhos de um paciente com osteoma de coroide foram submetidos a
exame oftalmológico completo. Tomografia de coerência óptica com profundidade de
imagem aprimorada revelou padrão em gaiola, correspondente à região de calcificação
do tumor. Imagens de autofluorescência de fundo da mesma área mostraram ligeira
autofluorescência positiva. Três padrões de refletividade diferentes foram definidos na
área descalcificada. Nas áreas com fluido sub-retiniano, foram observados prolonga
mentos dos segmentos externos semelhantes aos da coroidorretinopatia serosa central.
Manchas autofluorescentes positivas foram evidentes em autofluorescência de fundo
na mesma área. Porções calcificadas e descalcificadas do osteoma de coroide, bem
como a atrofia da camada coriocapilar, demonstraram diferentes padrões de tomo
grafia de coerência óptica com profundidade de imagem aprimorada e de imagens
de autofluorescência de fundo. Ambas as técnicas se mostraram úteis no diagnóstico
e acompanhamento de osteoma de coroide.
Keywords: Choroid neoplasms/diagnosis; Osteoma; Tomographpy, optical co
herence; Fluorescein angiography; Image enhancement; Humans; Female; Adult;
Case report
Descritores: Neoplasias da coroide/diagnóstico; Osteoma; Tomografia de coerência
óptica; Angiofluoresceinografia; Aumento da imagem; Humanos; Feminino; Adulto;
Relato de caso
INTRODUCTION
Choroidal osteoma is a rare benign tumor of the choroid. It was
first described by Gass in 4 young females who had slightly elevated
yellowish juxta-papillary lesions with well defined borders(1). It is
unilateral in 80% of the patients and mostly seen in the second and
third decades. Fifty percent of patients with choroidal osteoma were
reported to have decreased visual acuity to 20/200 or worse. Tumor
growth, decalcification and choroidal neovascularization may lead
to visual loss(2).
Choroidal osteomas show high reflectivity in B-scan ultrasono
graphy because of the presence of calcium and demonstrate acous
tic shadowing. Moreover, a hyper dense plaque is visible in the choroi
dal plane with computerized tomography (CT).
Optical coherence tomography (OCT) is widely used in the diag
nosis and follow-up of many retinal disorders. Technological developments in OCT have put into the use of spectral domain OCT (SD
OCT). The image acquisition speed of SD OCT is 43 to 100 times faster
than time-domain OCT and provides a clearer image of the retinal
structures with a 5 nm resolution(3). Enhanced Depth Imaging OCT
(EDI OCT) is relatively a new enhancement enabling the visualization
of the choroid and is now available in commercial SD OCT’s.
Fundus autofluorescence (FAF) imaging is also used for the diagnosis of many retinal disorders. The main source of autofluorescence
is the lipofuscin pigment which is the waste product of protein,
fatty acids and retinoids that accumulates in lysosomes after the pha
gocytosis of the damaged outer photoreceptor layer and shows func
tion of retinal pigment epithelium (RPE)(4).
We aim to represent the SD OCT and FAF findings of a patient
with bilateral choroidal osteoma in this study.
Submitted for publication: April 8, 2013
Accepted for publication: May 29, 2013
Study carried out at Antalya Training and Research Hospital, Department of Ophthalmology.
1
Antalya Training and Research Hospital, Department of Ophthalmology, Antalya, Turkey.
CASE REPORT
A 28-year-old woman presented with visual loss in the right eye
(RE), which was ongoing for 10 days. Her visual acuities were 20/400
in RE and 20/25 in the left. Intraocular pressures were 12 mmHg and
14 mmHg respectively. Anterior segment findings were unremarkable. Fundus examination revealed an orange central fovea (calcified
area) surrounded temporally and nasally by a yellow-white region
Disclosure of potential conflicts of interest: M.K.Erol, None; D.T.Corban, None; B.B.Ceran, None;
M.Bulut, None.
Correspondence address: Muhammet Kazim Erol. Antalya Training and Research Hospital, Oph
thalmology Department. Antalya, Turkey - E-mail: [email protected]
189
Enhanced depth imaging optical coherence tomography and fundus autofluorescence findings
in bilateral choroidal osteoma: a case report
(decalcified area). Her LE fundoscopic exam showed the atrophic
choriocapillaris nasal to the disc, a decalcified area between the disc
and the fovea, and a calcified area temporally (Figure 1A).
Cirrus HD OCT (Carl Zeiss, Dublin, CA) was used in EDI OCT mode
to demonstrate the decalcified and calcified portions of the retina.
Fundus photos and FAF imaging was performed with Visucam NM-FA
fundus camera (Carl Zeiss Meditec, Germany) in 45 degree mode with
510-580 nm light wavelength and 670-735 nm emission wavelength.
Fundus auto fluorescence and OCT findings were overlapped with a
photoshop program in order to see where exactly the findings in OCT
correspond in FAF imaging.
We observed a cage-like reflective pattern with the EDI OCT,
which corresponds to the calcified region of the choroidal osteoma
(Figure 2A). In some regions, a hyper-reflective band was visible bet
ween the calcified tumor tissue and unaffected choroid (Figure 3).
The retinal tissue covering the calcified areas seemed intact (Figure
2, 3). FAF imaging of the calcified areas showed slight hyperauto
fluorescence indicating the integrity of RPE (Figure 1B).
We described three different reflectivity patterns in the decalcified area. First one was a thick hump-like hyper-reflective band,
which had posterior acoustic shadowing and had a non-intact RPE
overlying it (Choroidal neovascular membrane - CNVM) (Figure 2B).
The outer retinal structures (RPE, IS-OS line and external limiting
membrane) of the second pattern were disintegrated, the tumor
plane was irregular and the vascular structures of the tumor were
visible. In addition, the second pattern showed less acoustic sha
dowing compared to the first one. The third pattern was an irregular
hyper-reflective pattern partially beneath or over the RPE and Bruch
membrane. In FAF imaging, decalcified areas were mostly hypoautofluorescent although showed hyperautofluorescence in some parts
(Figure 1C).
Choroidal thickness was increased in the RE, which had choroidal
neovascularization. In addition, intra and subretinal serous fluid was
observed. Outer segment elongations similar to the ones in central
serous chorioretinopathy (CSCR) were evident. Hyperautofluorescence spots were evident in FAF imaging which correspond to the areas
of serous fluid (Figure 1B).
DISCUSSION
In a previous histopathologic study, choroidal osteoma was demonstrated to be a tumor between the choriocapillaris and choroid,
where the spongious dense bone trabeculae surround bone marrow
with loose connective tissue and vessels(5). In this case, using the EDI
OCT, we described a lattice-like reflective pattern that corresponds
to the spongy bone in the choroid. Eduardo et al. have described a
similar pattern in their study previously(6). The hyper-reflective line between the tumor and choroid in this study may be explained by the
interface in-between or the choroidal melanocytes pushed towards
the sclera by the tumor as described by Williams et al(5).
There have been earlier studies defining the calcified areas of
choroidal osteoma as isoautofluorescent(6). In our case we have observed slightly increased autofluorescence in calcified areas of both
eyes. We believe that the excitation wavelength (510-580 nm) that
we used in our study may excite the calcium and collagen tissue and
cause autofluorescence.
Time domain OCT and tomodensitometry (TD) (TD OCT) may
reveal retinal disorders in cross sectional analysis but is able to show
only a trace amount of choroidal details. TD OCTs of 22 choroidal
osteoma patients showed the relation between photoreceptor
atrophy with tumor decalcification(7). SD OCT has many advantages
A
B
A
C
B
Figure 1. Fundus of RE and LE tumor vessels known as spiders are indicated with arrows.
(A) Autofluorescence imaging of RE and LE: Hypoautofluorescence in the decalcified
areas, slightly increased hyperautofluorescence in calcified regions in some parts. (B)
CT of the orbit (C).
190
Figure 2. The lattice-like pattern characterized by the hyper-reflective spots surrounding
the hypo-reflective spaces is shown in the vertical cross section of fovea of RE (asterisk)
(A), CNVM between the calcified and decalcified tumor (shadowing and obscuring the
view of the structures beneath (B).
Erol MK, et al.
Figure 3. Horizontal section beneath fovea, hyper-reflective line between the tumor
tissue and choroid (up arrow). Retinal structures are well preserved in the calcified area.
White arrow on the left represents a vessel passing over the tumor surface.
tachment area is related to outer segment elongations as described
by Matsumoto et al. in cases with CSCR(8). In this case we were first to
demonstrate the retinal vessels described by Gass et al. on the tumor
surface beneath the retina with the EDI OCT(1).
As a conclusion, we believe that the case we are presenting is
unique because of its bilaterality, and for featuring all the lesions that
may be demonstrated in an osteoma such as the calcified, decalcified
areas and atrophy of choriocapillaris. EDI OCT and FAF imaging were
found to be beneficial in the diagnosis and follow up of choroidal
osteomas. In addition, EDI OCT seems to be useful in showing the
structure of osteomas in vivo. EDI OCT and FAF studies of a larger
number of choroidal osteomas would provide further information
about the etiopathogenesis of this disorder.
REFERENCES
over TD OCT in means of high scanning rate and resolution. We have
observed a similar correlation between photoreceptor atrophy with
tumor decalcification. Atrophy of the RPE, serous retinal detachment
and defects in outer segment of photoreceptor layer were observed
in the decalcified area. The yellow-white region in the tumor was defined as decalcification. The yellow-white color is probably due to the
degeneration of the orange RPE with tumor decalcification(1). Based
on that, we may state that tumor decalcification is directly related to
RPE atrophy. In addition, defects in Bruch membrane and RPE may
contribute to CNVM formation and subsequently, serous retinal detachment. We defined CNVM as the hyper-reflective band between
calcified and decalcified tumor, shadowing the structures beneath it.
Optical coherence tomography shows total disintegration of RPE
in the area of serous detachment and elongation of outer segments.
The decalcified areas were hypofluorescent due to the disintegration
RPE configuration and function. We believe that the hyperfluorescence of focal points may be related to the remaining decalcified
osteoma tissue, scleral collagen or metaplasia of the RPE. In addition,
we also believe the granular hyperfluorescent area in the serous de-
1. Gass JD, Guerry RK, Jack RL, Harris G. Choroidal osteoma. Arch Ophthalmol. 1978;
96(3):428-35.
2. Shields CL, Sun H, Demirci H, Shields JA. Factors predictive of tumor growth, tumor
decalcification, choroidal neovascularization, and visual outcome in 74 eyes with
choroidal osteoma. Arch Ophthalmol. 2005;123(12):1658-66.
3. Wojtkowski M, Srinivasan V, Fujimoto JG, Ko T, Schuman JS, Kowalczyk A, et al. Threedimensional retinal imaging with high-speed ultrahigh-resolution optical coherence
tomography. Ophthalmology. 2005;112(10):1734-46.
4. Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG Weiter JJ. In vivo fluorescence
of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics.
Invest Ophthalmol Vis Sci [Internet]. 1995[cited 2011 Apr 2];36(3):718-29. Available
from: http://www.iovs.org/content/36/3/718.long
5. Williams AT, Font RL, Van Dyk HJ, Riekhof FT. Osseous choristoma of the choroid simulating a choroidal melanoma. Association with a positive 32P test. Arch Ophthalmol.
1978;96(10):1874 -7.
6. Navajas EV, Costa RA, Calucci D, Hammoudi DS, Simpson ER, Altomare F. Multimodal
fundus imaging in choroidal osteoma. Am J Ophthalmol. 2012;153(5):890-5.e3.
7. Shields CL, Perez B, Materin MA, Mehta S, Shields JA. Optical coherence tomography
of choroidal osteoma in 22 cases: evidence for photoreceptor atrophy over the
decalcified portion of the tumor. Ophthalmology. 2007;114(12):e53-8.
8. Matsumoto H, Kishi S, Sato T, Mukai R. Fundus autofluorescence of elongated photoreceptor outer segments in central serous chorioretinopathy. Am J Ophthalmol.
2011;151(4): 617-23.
191
Relato de Caso |
Case Report
Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome
in a young man: case report
Oclusão unilateral da artéria central da retina como único sinal de apresentação da síndrome de Susac
em jovem do sexo masculino: relato de caso
Samira Luiza dos Apóstolos-Pereira1, Lúcia B. Passos Kara-José2, Paulo Euripedes Marchiori1, Mário Luiz Ribeiro Monteiro2
ABSTRACT
RESUMO
We report the case of a 24-year-old man presenting with sudden visual loss in the
left eye from a central retinal artery occlusion. An extensive clinical investigation
revealed no etiology. Three weeks later, however, the patient developed hearing
loss followed by encephalopathy and multiple branch retinal artery occlusions in
the right eye. Fluorescein angiography confirmed retinal vascular occlusions with
no sign of vasculitis. The neurological examination revealed a diffuse encephalopathy while the MRI scan disclosed several small areas of infarcts in the brain.
Bilateral sensorineural hearing loss was confirmed on audiometry. The patient
was diagnosed with Susac syndrome and treated with methylprednisolone and
cyclophosphamide, resulting in slight improvement and stabilization. This case
shows that Susac syndrome may be diagnosed late due to the absence at onset
of one or more of the symptoms of the classic triad (encephalopathy, multiple
branch retinal artery occlusions and hearing loss). This case also serves to emphasize
that Susac syndrome should be considered in the differential diagnosis of central
retinal artery occlusion, even in apparently healthy young men.
Descrevemos um paciente de 24 anos, sexo masculino, que se apresentou com perda
súbita da visão do olho esquerdo causado por oclusão da artéria central da retina. Ele
foi submetido à investigação clínica detalhada sem encontrar uma causa. Três semanas
depois, no entanto, desenvolveu surdez, encefalopatia e múltiplas oclusões de ramo
arterial da retina no olho direito. Angiofluoresceinografia confirmou as oclusões de
ramo arterial no OD e oclusão da artéria central da retina no OE, sem qualquer sinal de
vascutile. O exame neurológico revelou encefalopatia difusa, enquanto que o estudo
efetuado por ressonância nuclear magnética mostrou várias áreas de enfarte do cérebro
e a audiometria demonstrou perda auditiva neurosensorial bilateral. A síndrome de
Susac foi diagnosticada e tratamento com metilprednisolona e ciclofosfamida insti
tuido com melhora discreta, seguida de estabilização clínica. Este caso é importante
para chamar a atenção de que nem todos os três critérios diagnósticos (encefalopatia,
oclusão de ramo arterial retiniano e surdez) para a síndrome de Susac precisam estar
presentes de início, o que pode causar confusão diagnóstica. O diagnóstico deve
portanto ser incluído no diferencial de oclusão da artéria central da retina mesmo
quando ocorre em homem sem outros sintomas associados.
Keywords: Retinal artery occlusion; Susac syndrome/diagnosis; Susac syndrome/
drug therapy; Methylprednisolone/therapeutic use; Cyclophosphamide/therapeutic use; Hearing loss; Encephalopathy; Case report
Descritores: Oclusão da artéria retiniana; Síndrome de Susac/diagnóstico; Síndrome
de Susac/quimioterapia; Metilprednisolona/uso terapêutico; Ciclofosfamida/uso te
rapêutico; Perda auditiva; Encefalopatia; Relato de caso
INTRODUCTION
Susac syndrome (SS) is an arterial occlusive disease associated
with a triad of symptoms: encephalopathy, hearing loss and multiple
branch retinal artery occlusions (MBRAO)(1-3). Other findings include
diffuse neurological signs as headache, psychiatric disturbances, cog
nitive changes, memory loss, and confusion that may rapidly progress
to dementia. Magnetic resonance imaging (MRI) shows a distinctive
pattern of hyperintense white matter lesions (on T2 and FLAIR sequences) with preferential involvement of the central callosal fibers
and the development of central callosal holes as the active lesions
resolve(4). SS is presumably autoimmune in origin and treatment is
still uncertain, but steroids, cyclophosphamide, azathioprine, plasmapheresis and intravenous immunoglobulin have been used with
some success to halt disease progression(4,5).
Though rare, SS may be readily suspected in the presence of the
classic triad of symptoms. However, one or more of these symptoms
may be absent at onset, leading to diagnostic confusion. The purpose
of this paper was to describe a case of SS presenting with the sole
finding of unilateral central retinal artery occlusion (CRAO) and, consequently, to propose the inclusion of SS in the differential diagnosis
of CRAO, particularly in young patients without other risk factors for
arterial occlusive disease.
Submitted for publication: June 18, 2013
Accepted for publication: June 22, 2013
CASE REPORT
A 24-year-old Afro-Brazilian man developed sudden visual loss
in the left eye (OS). The ophthalmologic examination revealed visual acuity of 20/20 in the right eye (OD) and finger counting in
OS. A marked relative afferent papillary defect was observed in OS.
Ophthalmoscopy was normal in OD but revealed a CRAO in OS (Fi
gure 1). The initial neurological and clinical findings were unremarkable. An investigation involving carotid duplex scan, trans-esophageal
echocardiography, cranial computerized tomography scan, complete blood count and serum glucose level revealed no abnormalities.
The patient was prescribed 100 mg acetyl salicylic acid/day.
Study carried out at Hospital das Clínicas, Universidade de São Paulo - USP - São Paulo (SP), Brazil.
Disclosure of potential conflicts of interest: S.L.Apóstolos-Pereira, None; L.B.P.Kara-José, None;
P.E.Marchiori, None; M.L.R.Monteiro, None.
Physician, Department of Neurology, Universidade de São Paulo - USP - São Paulo (SP), Brazil.
Physician, Division of Ophthalmology, Universidade de São Paulo - USP - São Paulo (SP), Brazil.
Correspondence address: Mário Luiz R. Monteiro. Av. Angélica, 1757 - Conj. 61 - São Paulo - SP 01227-200 - Brazil - E-mail: [email protected]
1
2
192
Apóstolos-Pereira SL, et al.
Three weeks later the patient developed tinnitus and sudden
right hearing and visual loss followed by headache, apathy, confusion
and somnolence. A repeat neurological examination showed the
patient to be torporous, with brisk reflexes, bilateral extensor plantar
responses and pseudobulbar speech. Visual acuity was 20/100 in OD
and finger counting in OS. The fundus examination revealed MBRAO
involving the superonasal and the infero-temporal branches of the
central retinal artery in OD (Figure 2) and a CRAO in OS. The MRI scan
disclosed several small areas of hyperintense signal on T2-weighted
images in the gray and white matter, including the involvement of
the central fibers of the corpus callosum (Figure 3). A lumbar puncture
revealed clear and colorless cerebro-spinal fluid with 9 cells (92%
lymphocytes) and a protein level of 126 mg/dl. Retinal fluorescein
angiography confirmed MBRAO in OD and a CRAO in OS.
The blood sedimentation rate and the levels of C reactive protein,
antinuclear antibodies, serum complement, IgG and IgM anticardiolipin antibodies and lupic anticoagulant were within normal ranges.
SS was diagnosed and immunosuppressive therapy with intravenous
methylprednisolone (1 g/day for 5 days) and cyclophosphamide was
prescribed. The patient’s mental status improved slightly over the
following two months, followed by stabilization. Oral prednisone was
prescribed at 60 mg/day for two months, then tapered to 40 mg/day
for one month, then to 20 mg/day. When tinnitus returned, the
dose was raised to and maintained at 40 mg/day. Six months later,
the patient remained stable despite the persistence of visual field
deficits, hearing deficit and tinnitus. Prednisone was tapered and
discontinued. After 3 years of follow-up, the patient remains stable,
with no recurrences.
DISCUSSION
When confronted with a patient with CRAO, most authors recommend routine screening for possible sources of emboli, especially
the cardiac valves and the carotid artery(6,7). Once embolism is ruled
out, conditions such as vasculitis and coagulation disorders should
be considered, particularly in young adults. Our case is interesting
in that our SS patient presented initially with only one symptom:
unilateral isolated CRAO. Despite careful investigation, no cause was
found. However, three weeks later MRAO developed in the contralateral eye associated with headache, hearing loss and encephalopathy. The manifestation of these additional symptoms allowed to
diagnose the patient with SS.
Susac syndrome was first described in 1979 by Susac and co
workers as a microangiopathy of the brain and retina(1). In two
subsequent papers, SS was defined as a microangiopathic syndro
me of arterial occlusive disease leading to the classic triad of encephalopathy, hearing loss and MBRAO(2,3) The pathogenesis of SS
remains unknown, but presumably an autoimmune process leads to
Figure 1. Fundus photograph of the left eye at presentantion showing central retinal
artery occlusion.
Figure 2. Fundus photograph of the right eye showing branch retinal artery occlusions
in the regions superonasal and inferotemporal to the optic disc.
Figure 3. Magnetic resonance imaging showing hyperintense lesions (arrows) in the
white matter (above) and in the central fibers of the corpus callosum (below).
193
Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome in a young man: case report
damage and inflammation-related occlusion of the microvessels in
the brain, retina, and inner ear(5). Because the first 20 cases reported
were women aged 21-41 years, the syndrome was initially believed
to affect only young females. Later, however, the condition was
shown to occur in males as well, but with a female preponderance
of approximately 3 to 1(5,8). The diagnosis is based primarily on the
clinical presentation, the documentation of MBRAO by fluorescence
angiography, and characteristic findings on cerebral MRI. A variety
of differential diagnoses have to be considered, including multiple
sclerosis, acute disseminated encephalomyelitis, vasculitis of the
central nervous system, infectious encephalitis, Menière’s disease
and Cogan syndrome(5).
Only one previous case of SS presenting with CRAO has been
reported. Adatia and Sheidow(9) reported the case of a 36-year-old
woman with slurred speech, decreased hearing, paresthesia, weakness
and acute visual loss in OS due to CRAO. Despite the associated
neurological symptoms, the diagnosis of SS was not made until one
month later when MBRAO developed in the contralateral eye(9). Permanent morbidity appears to be more severe when the diagnosis of
SS is delayed. Thus, a high level of suspicion is recommended. The
case reported here adds to the spectrum of the disease and shows
that CRAO can be the sole presenting sign of SS, even in young and
apparently healthy men.
REFERENCES
1. Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology.1979;29(3):313-6.
2.Monteiro ML, Swanson RA, Coppeto JR, Cuneo RA, DeArmond SJ, Prusiner SB. A
microangiopathic syndrome of encephalopathy, hearing loss, and retinal arteriolar
occlusions. Neurology.1985;35(8):1113-21.
3. Coppeto JR, Currie JN, Monteiro ML, Lessell S. A syndrome of arterial-occlusive retinopathy and encephalopathy. Am J Ophthalmol. 1984;98(2):189-202.
4. Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac’s syndrome: 1975-2005 microan
giopathy/autoimmune endotheliopathy. J Neurol Sci. 2007;257(1-2):270-2.
5. Kleffner I, Duning T, Lohmann H, et al. A brief review of Susac syndrome. J Neurol Sci.
2012;322(1-2):35-40.
6. Graham EM. The investigation of patients with retinal vascular occlusion. Eye (Lond).
1990;4 (Pt 3):464-8.
7. Sharma S, Naqvi A, Sharma SM, Cruess AF, Brown GC. Transthoracic echocardiographic
findings in patients with acute retinal arterial obstruction. A retrospective review.
Retinal Emboli of Cardiac Origin Group. Arch Ophthalmol. 1996;114(10):1189-92.
8.Gross M, Banin E, Eliashar R, Ben-Hur T. Susac syndrome. Otol Neurotol 2004;25(4):
470-3.
9. Adatia FA, Sheidow TG. Central retinal artery occlusion as the initial ophthalmic pre
sentation of Susac’s syndrome. Can J Ophthalmol. 2004;39(3):288-91.
Simpósio Internacional de Córnea
do Hospital de Olhos de Sorocaba
24 a 26 de outubro de 2013
Sorocaba (SP)
Organização:
Hospital de Olhos de Sorocaba
Informações:
Tel.: (15) 3212-7077
194
Relato de Caso |
Case Report
Ceratocone e estabilidade corneana após ceratectomia radial no outro olho: relato de caso
Jacqueline Martins Sousa1, Flavio Eduardo Hirai1, Elcio Hideo Sato1
ABSTRACT
RESUMO
Keratoconus has usually been described as bilateral but asymmetric disease. Corneal ectasia is one of the long-term complications of modern refractive surgery,
especially those submitted to laser in situ keratomileusis (LASIK). We describe a
patient with keratoconus in the right eye that was submitted to radial keratectomy
(RK) in the left eye 19 years ago with no progression of the ectatic cornea and no
complications related to the refractive surgery. Because unilateral keratoconus is
rare, we believe that RK was performed on an already ectatic cornea (not clinically
detected) or with fruste keratoconus. However, neither corneal ectasia progressed,
nor ectasia was induced by RK in the fellow eye.
O ceratocone é descrito como uma doença bilateral porém assimétrica e vários dados
na literatura comprovam que a ectasia corneana é uma das complicações de longo
prazo da cirurgia refrativa moderna, especialmente do laser in situ keratomileusis
(LASIK). Nós descrevemos um caso de uma paciente com ceratocone no olho direito
e que foi submetida à ceratotomia radial no olho esquerdo há 19 anos, desde então
sem sinais de progressão da ectasia corneana nem de complicações relativas à cirurgia
refrativa. Como o ceratocone unilateral é raro, acreditamos que a cirurgia refrativa
tenha sido realizada num olho com ectasia corneana não detectada clinicamente ou
com ceratocone frustro. Entretanto, a ectasia do olho direito não progrediu e também
não houve sinais de ectasia no olho submetido à cirurgia refrativa nesse período de
19 anos de acompanhamento.
Keywords: Cornea/pathology; Corneal diseases; Corneal topography; Keratomileusis, laser in situ; Humans; Male; Case report
Descritores: Córnea/patologia; Doenças da córnea; Topografia da córnea; Cerato
mileuse assistida por excimer laser in situ; Humanos; Feminino; Relato de caso
INTRODUCTION
Keratoconus (KC) is a non-inflammatory corneal disease characterized by progressive corneal protrusion, apical thinning, irregular
astigmatism and central scarring at the cornea. It has usually been
described as bilateral but asymmetric disease(1,2). Clinical evidence of
unilateral keratoconus may be as high as 41% of the population. However, only 1.8 - 4% actually present diagnostic criteria for unilateral
keratoconus when using the computerized corneal topography(3,4).
Corneal ectasia is one of the long-term complications of modern
refractive surgery, especially those submitted to laser in situ keratomileusis (LASIK). The main potential risk factors are preexisting corneal disease such as KC or mechanical instability as a consequence
of weakened residual corneal stromal bed after LASIK(5). Although
previously described in the literature(6,7), corneal ectasias have been
less commonly seen in patients submitted to other types of refractive
surgery such as photorefractive keratectomy (PRK) or radial keratotomy (RK).
We describe a patient with keratoconus in the right eye submitted to RK in the left eye who has been followed with no progression of
the ectatic cornea and no complications following refractive surgery
for 19 years.
the right eye due to “lack of ideal conditions” (sic). At that time, the
patient was fitted with rigid contact lens in the right eye. Biomicroscopic examination revealed right eye with signs of keratoconus and
left eye with 8 healed radial keratotomy scars. Visual acuity was 20/20
with correction (contact lens) in the right eye and 20/25 without
correction in the left eye.
The patient has been followed-up since then and the same signs
of keratoconus were seen in the right eye with visual acuity of 20/25
with rigid contact lens. After 19 years of RK, her left cornea was stable
and visual acuity was 20/25p with rigid contact lens. Corneal topographical maps of the right eye showed a typical pattern seen in patients
with keratoconus with an asymmetric inferior corneal steepening in
the vertical meridian. Figure 1 A shows the last topographical map of
the right eye (2012) with comparison to a map taken in 2006 (Figu
re 1 B). No significant differences were seen between the two maps.
Topographical maps of the left eye showed a flatter cornea after RK
(Figure 2 A). Similarly to the right eye, no significant differences were
seen between two maps (Figure 2 B) taken 6 years apart.
CASE REPORT
A 42-year-old healthy woman was referred to our service for
regular ophthalmic examination in 2000. Ocular history included left
eye RK in 1994. According to the patient, RK was not performed in
DISCUSSION
Corneal ectasia after refractive surgery is a rare event but can
be very frustrating for both surgeon and patient. Randleman et al.,(8)
reported an approximate incidence of 1 in 2,500 cases of keratectasia
after LASIK.
In LASIK, it is believed that the creation of the corneal flap could
be the major “triggering” factor of keratectasias. In the case of RK, he-
Submitted for publication: May 23, 2013
Accepted for publication: June 14, 2013
Study carried out at Department of Ophthalmology, Universidade Federal de São Paulo.
Correspondence address: Jacqueline M. Sousa. Rua Botucatu, 821 - São Paulo (SP) - 04023-062
- Brasil - E-mail: [email protected]
1
Physician, Department of Ophthalmology, Paulista School of Medicine, Federal University of São
Paulo - UNIFESP, São Paulo (SP), Brazil.
Disclosure of potential conflicts of interest: J.M.Sousa, None; F.E.Hirai, None; E.H.Sato, None.
195
A
B
Figure 1. A) Corneal topography of the right eye in 2012. B) Corneal topography of the right eye in 2006.
A
B
Figure 2. A) Corneal topography of the left eye in 2012. B) Corneal topography of the left eye in 2006.
xagonal keratotomy produces a hyperopic effect due to steepening
of central cornea which theoretically may result in greater chance of
developing iatrogenic keratoconus(6). Nevertheless, Utine et al.(9), described radial keratotomy as a reasonable option for the rehabilitation
of a selected group of keratoconus patients in the early or moderate
stages, with improvement in the best spectacle corrected visual
acuities, decrease of the preoperative myopic spherical refraction and
flattening of the corneal curvature.
Unilateral keratoconus has a low incidence of around 4%(3,4). Some
studies showed that fellow eyes may show a certain low-expressivity
morphologic feature of keratoconus, and that approximately 50% of
clinically normal fellow eyes will progress to KC within 16 years and
the greatest risk is during the first 6 years of the onset(10). Because
unilateral keratoconus is rare(3,4), we believe that RK was performed
in our patient on an already ectatic cornea (not clinically detected) or
with fruste keratoconus. However, neither corneal ectasia progressed,
nor ectasia was induced by RK in the fellow eye.
Corneal ectasias involve complex processes and careful ophthalmic examination should be performed in refractive surgery patients,
with special attention to candidates for LASIK.
196
REFERENCES
1. Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal
thinning disorders. Surv Ophthalmol. 1984;28(4):293-322.
2. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297-319.
3.Holland DR, Maeda N, Hannush SB, Riveroll LH, Green MT, et al. Unilateral keratoconus. Incidence and quantitative topographic analysis. Ophthalmology. 1997;104(9):
1409-13.
4. Khor WB, Wei RH, Lim L, Chan CM, Tan DT. Keratoconus in Asians: demographics, clinical characteristics and visual function in a hospital-based population. Clin Experiment
Ophthalmol. 2011;39(4):299-307.
5. Binder PS. Ectasia after laser in situ keratomileusis. J Cataract Refract Surg. 2003;29(12):
2419-29. Comment in: J Cataract Refract Surg. 2004;30(12):2460-1; author reply 2461-2.
6.Kim H, Choi JS, Joo CK. Corneal ectasia after PRK: clinicopathologic case report.
Cornea. 2006;25(7):845-8.
7. Shaikh S, Shaikh NM, Manche E. Iatrogenic keratoconus as a complication of radial
keratotomy. J Cataract Refract Surg. 2002;28(3):553-5.
8. Randleman JB, Russell B, Ward MA, Thompson KP, Stulting RD. Risk factors and prognosis for corneal ectasia after LASIK. Ophthalmology. 2003;110(2):267-75.
9. Utine CA, Bayraktar S, Kaya V, Kucuksumer Y, Eren H, Perente I, et al. Radial keratotomy
for the optical rehabilitation of mild to moderate keratoconus: more than 5 years’
experience. Eur J Ophthalmol. 2006;16(3):376-84.
10.Li X, Rabinowitz YS, Rasheed K, Yang H. Longitudinal study of the normal eyes in
unilateral keratoconus patients. Ophthalmology. 2004;111(3):440-6.
Relato de Caso |
Case Report
Recuo assimétrico dos músculos retos horizontais para correção
de incomitância alfabética: relato de caso
Asymmetric recession of the horizontal rectus muscles for correction alphabetical incomitance: case report
Alyne Borges Corrêa1, Tomás Fernando Scalamandré Mendonça1
RESUMO
ABSTRACT
Os autores relatam o caso de um homem de 21 anos com estrabismo divergente
incomitante, anisotropia em “V”, hiperfunção de músculo oblíquo inferior direito e
hipofunção de obliquo superior direito, no qual foi realizado, sob anestesia tópica,
um recuo assimétrico das fibras dos músculos retos horizontais para correção da
incomitância alfabética. O resultado cirúrgico imediato foi considerado muito
bom (ortotrópico e sem incomitância alfabética), já que pela técnica cirúrgica
convencional não se obteve sucesso.
The authors report a case of 21-year-old man with divergent noncomitant stra
bismus, “V” pattern anisotropy, right inferior oblique muscle overaction and right
superior oblique muscle hypofunction, which was performed under topical anes
thesia an asymmetrical recession of the horizontal rectus muscles fibers to correct
alphabetical incomitance. The immediate surgical outcome was considered very
good (orthotropic, no “V” or “A” pattern), since the success was not obtained through
conventional surgical technique.
Descritores: Estrabismo; Exotropia; Estrabismo/cirurgia; Músculos oculomotores/
cirurgia; Procedimentos cirúrgicos oftalmológicos/métodos; Relatos de casos
Keywords: Strabismus; exotropia; Strabismus/surgery; Oculomotor muscles/surgery;
Ophthalmologic surgical procedures/methods; Case reports
INTRODUÇÃO
As anisotropias alfabéticas são formas de estrabismo em que o
tamanho do ângulo de desvio horizontal varia entre supraversões e
infraversões, ou seja, apresentam incomitâncias horizontais quando
os olhos se movem para cima e para baixo, ao redor de um eixo
frontal que passa pelo centro de rotação do olho, o eixo X de Fick.
Apresentam-se, principalmente nas formas de anisotropias em “A”
e “V”. Existem outros padrões menos frequentes de anisotropias
verticais: X, Y e λ, que são consideradas variações dos padrões em
“A” e em “V”(1,2).
Na anisotropia em “A” encontramos uma esotropia (ET) maior em
supraversão do que em infraversão ou exotropia (XT) maior em infraversão do que em supraversão. Ao contrário, na anisotropia em “V”
ocorre ET maior em infraversão do que em supraversão ou XT maior
em supraversão do que em infraversão(1). Em resumo, na incomitância
em “A” os olhos estão mais afastados entre si em infraversão do que
em supraversão e na incomitância em “V” estão mais próximos entre
si em infraversão do que em supraversão.
A causa das anisotropias alfabéticas já foi atribuída às disfunções
dos músculos retos horizontais(3). Também foi descrito que o pro
blema primário estaria nos retos verticais e secundariamente nos
oblíquos(4). Atualmente, atribui-se como causa da maioria das inco
mitâncias alfabéticas a disfunção dos músculos oblíquos, mas há
casos em que não são observados acometimento destes músculos.
Quando existe disfunção de músculos oblíquos, as cirurgias
são realizadas nestes músculos. Na anisotropia em “A” é comum
a hiperfunção dos oblíquos superiores (OSs) e mais raramente
hipofunção dos oblíquos inferiores (OIs). Na anisotropia em “V” é
comum a hiperfunção dos OIs ou hipofunção dos OSs. A cirurgia visa
enfraquecer os músculos oblíquos hiperfuncionantes, ou reforçar os
hipofuncionantes.
Quando ocorre anisotropia sem disfunção dos músculos oblíquos, a técnica cirúrgica utilizada com mais freqüência é o deslocamento vertical dos retos horizontais(5,6), pois isto modifica o seu
vetor de força conforme o olho se movimenta. Por exemplo: quando
o eixo medial é deslocado inferiormente, sua força fica menor em
infraversão do que em supraversão, por isso corrige incomitância
em “V”. Outras técnicas que podem ser utilizadas são: deslocamento
dos retos verticais medialmente ou lateralmente; e o deslocamento
vertical unilateral dos retos horizontais. Para corrigir o padrão em
“A” é realizado o deslocamento superior dos músculos RMs e/ou
deslocamento inferior dos RLs. Quanto ao padrão em “V”, a correção
é realizada com o deslocamento inferior dos RMs ou superior dos
RLs(1). No deslocamento horizontal dos retos verticais, altera-se a ação
adutora destes músculos, que é aumentada se o deslocamento for
medial e reduzida se for temporal. Desta maneira, os retos superiores (RSs) podem ser deslocados temporalmente quando existe “A” e
medialmente quando “V”, enquanto os retos inferiores (RIs) são deslocados temporalmente em “V” e medialmente nas incomitâncias em
“A”(1). O deslocamento vertical de ambos retos horizontais do mesmo
olho foi proposto por Goldstein(7), no entanto, tal procedimento pode
causar torção ocular.
Bietti em 1970(8) propôs uma maneira de corrigir as incomitâncias
alfabéticas através do recuo assimétrico das fibras dos músculos retos
Submetido para publicação: 24 de novembro de 2011
Aceito para publicação: 22 de junho de 2013
Trabalho realizado no Departamento de Oftalmologia da Universidade Federal de São Paulo UNIFESP - São Paulo (SP) Brasil.
Endereço para correspondência: Tomás Fernando Scalamandré Mendonça. Rua Botucatu, 821 São Paulo (SP) - 04023-062 - Brasil - E-mail: [email protected]
1
Médico, Departamento de Oftalmologia, Escola Paulista de Medicina, Universidade Federal de São
Paulo - UNIFESP - São Paulo (SP), Brasil.
Divulgação de potenciais conflitos de interesse: A.B.Corrêa, Nenhum; T.F.S.Mendonça, Nenhum.
Comitê de Ética: Aprovado no CEP UNIFESP, número: 1476/10
197
Recuo assimétrico dos músculos retos horizontais para correção de incomitância alfabética: relato de caso
horizontais. Em seu estudo, para os casos de ET com “V”, recuou mais
a parte inferior dos RMs, nos casos de ET com “A” recuou mais a parte
superior dos RMs. Para os pacientes com XT e “V” foi recuado mais a
parte superior dos RLs e nos casos de XT com “A” o recuo dos RLs foi
maior na parte inferior. A diferença entre a parte superior e a inferior
dos músculos recuados foi de 2 mm em cada caso.
O método utilizado foi um recuo assimétrico das fibras dos músculos retos horizontais, seguindo o mesmo raciocínio de Bietti, porém
de uma maneira modificada, onde a assimetria não fica limitada pela
largura do músculo. Inicialmente é feito um “split” (divisão ao meio
das fibras musculares superiores e inferiores) e a seguir, em cada
hemimúsculo é feita uma sutura tipo “hang back”. Assim, é possível
recuar cada metade do músculo de maneira bem assimétrica e na
quantidade necessária para correção da incomitância.
RELATO DE CASO
Paciente do sexo masculino, 21 anos, com história de desvio
ocular desde a infância que piorou na adolescência.
Ao exame apresentava refração estática no olho direito (OD) de
-0,25 DE -0,75 DC 120° (acuidade visual 1,00) e no olho esquerdo
(OE) -0,50 DE -0,50 DC 30° (acuidade visual 1,00). Ao exame de motilidade ocular, XT de 40∆ com hipertropia à direita (HTD) de 5∆ em
posição primária do olhar (PPO) e anisotropia em “V” de 25∆ (XT de
50∆ em supraversão e XT de 25∆ em infraversão). Nas versões: -1 de
reto lateral direito (RLD), +4 de oblíquo inferior direito (OID) e -2 de
oblíquo superior direito (OSD). Em destroversão XT de 35∆ e HTD 2∆
e em levoversão XT de 40∆ e HTD 30∆ (Figura 1). Ao teste de Maddox,
extorsão de 5° no OD. Biomicroscopia, pressão intraocular e fundo
de olho sem alterações.
Foi indicada cirurgia corretora de estrabismo sob anestesia tópica
(apenas colírio anestésico e leve sedação) para ajustes per-operatórios. Todas as avaliações per-operatórias do desvio foram realizadas
com o paciente sentado fixando objetos tanto para longe quanto
para perto, nas diferentes posições do olhar.
Realizamos em um primeiro momento um recuo do RLD de 8
milímetros (mm) a partir de sua inserção e miectomia do OID. Porém,
apesar de eliminada a hiperfunção do OID, persistia tanto o XT quanto a anisotropia em “V”. Então um recuo do RLE de 8 mm foi efetuado,
com elevação de uma inserção, ou seja, a extremidade inferior do RLE
foi reposicionada 8 mm mais distante da sua inserção original e na
altura de onde antes era a sua extremidade superior. Apesar de terem
diminuído, tanto o XT quanto a anisotropia em “V” permaneceram. A
seguir, o músculo RMD foi ressecado 4 mm e a nova inserção foi deslocada ¾ (aproximadamente 7 mm) inferiormente. Neste momento,
o XT estava corrigido em PPO, porém, ainda persistia a incomitância
em V.
Figura 1. Versões.
198
Na tentativa de correção da incomitância em “V” remanescente,
optamos por modificar a forma de recuo que havia sido realizada no
RLE, da seguinte maneira: o músculo foi dividido longitudinalmente
ao meio, até 15 mm posterior à sua inserção prévia, sendo a parte
superior do RLE recuado 12 mm e a parte inferior mantida a 8 mm,
a partir da inserção. Foi observada uma melhora importante do V,
persistindo, porém desvio residual.
Em seguida, optamos por realizar o mesmo procedimento no
RLD. O músculo foi dividido ao meio, até 15 mm posterior à sua inserção prévia, a parte inferior foi mantida recuada a 8 mm e a parte
superior recuada 12 mm de sua inserção (Figura 2).
Observamos no per-operatório que o paciente ficou ortotrópico
em PPO, sem hipertropia e a anisotropia em V foi resolvida.
No sétimo dia de pós-operatório o paciente permanecia ortotrópico, sem extorsão ao Maddox e sem incomitância alfabética.
DISCUSSÃO
O recuo em “leque” das fibras dos retos horizontais para correção
da incomitância alfabética proposto por Bietti(8) tem suas limitações
pela própria anatomia do músculo, ou seja, a assimetria do procedimento é limitada pela largura do músculo, o que não ocorre com o
método que aqui propomos, sendo possível recuar cada metade do
músculo na quantidade necessária para correção da incomitância.
A vantagem em relação à transposição vertical dos músculos
horizontais é que não há indução do desvio vertical e se mantém a
linha de ação do músculo(7,8).
Neste caso, onde já havíamos feito uma miectomia do OI hiper
funcionante, deslocamento das inserções dos músculos RLE e RMD,
e ainda assim a incomitância alfabética persistia, optamos por este
procedimento de recuo assimétrico dos retos laterais com uma
assimetria maior do que a proposta por Bietti, e conseguimos um
resultado cirúrgico satisfatório. Ou seja, apesar da técnica descrita
ter sido realizada em um músculo com inserção elevada anteriormente, ela somente foi feita após a avaliação per-operatória de que
a elevação da inserção não teria sido suficiente para a correção total
da incomitância em V.
A realização desse procedimento sob anestesia tópica foi de im
portância fundamental neste caso, pois pudemos observar no peroperatório que, mesmo após a realização dos procedimentos convencionais, a incomitância em “V” persistia e melhorou nitidamente
após o recuo assimétrico dos músculos retos. O grau de vigília do
paciente, bem como avaliação no momento da cirurgia, nos permitiu
uma avaliação eficaz no per operatório, pois foi realizado com mínima
sedação, apenas colírio anestésico como anestesia e solicitando que
o paciente ficasse sentado e fixando objetos tanto para perto quanto
para longe, nas diferentes posições do olhar.
Corrêa AB, Mendonça TFS
Um novo estudo, do tipo caso/controle, já está em andamento,
utilizando apenas a técnica modificada de recuo assimétrico dos
músculos retos horizontais, sem associação de miectomia do OI e
sem deslocamento vertical das inserções, para podermos padronizar
melhor sua eficácia.
O método que aqui descrevemos é uma alternativa de correção
das incomitâncias alfabéticas para os casos sem disfunção de músculos oblíquos, ou mesmo nos casos em que a cirurgia realizada nestes
músculos não for suficiente para corrigir a incomitância alfabética.
Este novo procedimento provavelmente causa menor efeito torsional, pois não há deslocamento de inserções.
REFERÊNCIAS
Figura 2. Recuo assimétrico do músculo reto lateral direito (RLD).
Conforme observado no momento da cirurgia, somente a miectomia e a transposição não foram suficientes para a correção do “V”
neste caso especificamente, e acreditamos que a realização dessas
alterações em três tempos provavelmente teriam os mesmos resultados, porém, gerariam maiores despesas e transtornos ao paciente.
1. Prieto-Díaz J, Souza-Dias C. Estrabismo. 2a ed. São Paulo: Roca;1986. p.247-85.
2.Wright KW. Strabismus and pediatric ophthalmology. New York: Springer-Verlag;
2003. p.297-309.
3.Urist M. Recession and upward displacement of the medial rectus muscles in A pattern esotropia. Am J Ophthalmol. 1968;65(5):769-73.
4.Brown HW. Symposium strabism, vertical deviations. Trans Am Acad Ophthalmol
Otolaryngol. 1953;57(2):157-62.
5. Knapp P. Vertically incomitant horizontal strabismus. The so-called “A”’ and “V” syndromes. Trans Am Ophthalmol Soc 1959;57:666-99.
6. Von Noorden GK, Burian HM. Binocular vision and ocular motility. St. Louis, The C.V.
Mosby Co 1974; p.337-40.
7.Goldstein JH. Monocular vertical displacement of the horizontal rectus muscles in
the A and V patterns. Am J Ophthalmol. 1967;64(2):265-7.
8.Bietti GB. [On a technical procedure (recession and fan-shaped oblique reinsertion
of the horizontal rectus muscles) for correction of V or A exotropias of slight degree
in concomitant strabismus]. Boll Ocul. 1970;49(11):581-8. Italian.
Encontro Anual da
Academia Americana de Oftalmologia
16 a 19 de novembro de 2013
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Informações:
Site: www.aao.org
199
Artigo de Revisão |
Review Article
Tumor vasoproliferativo da retina
Eduardo Ferrari Marback1,2, Ricardo Leitão Guerra2, Otacilio de Oliveira Maia Junior2, Roberto Lorens Marback1,2
ABSTRACT
RESUMO
Retinal vasoproliferative tumor is a rare disease that has capillary hemangioma
as the most frequent diferential diagnosis. The tumor is considered to be of reac
tive nature. It can be idiophatic or secondary to other ocular diseases such as:
uveitis, retinitis pigmentosa, sickle cell disease, previous surgery and retinopathy
of prematurity. Lesions with no exsudation or visual decrease can be observed.
Lesions that need treatment can be managed by on or more modalities such as
cryotherapy, a variety of lasers, surgical excision, radiation, and antiangiogenic
intravitreal injections.
O tumor vasoproliferativo da retina é uma lesão rara, cujo principal diagnóstico
diferencial é o hemangioma capilar da retina. O tumor tem natureza reacional. Pode
ser idiopático ou secundário a outras doenças como: uveítes, retinose pigmentar,
retinopatia da anemia falciforme, cirurgia prévia e retinopatia da prematuridade.
Lesões sem exsudação ou baixa visual podem ser observadas. Quando há indicação
de tratamento este pode ser feito pela crioterapia, vários tipos de lasers, excisão
cirúrgica, radioterapia e injeções intravítrea de antiangiogênicos, isoladamente
ou em associação.
Keywords: Retina/pathology; Retinal neoplasms/diagnosis; Retinal neoplasms/
pathology; Retinal neoplasms/therapy
Descritores: Retina/patologia; Neoplasias da retina/diagnóstico; Neoplasias da
retina/patologia; Neoplasias da retina/terapia
INTRODUCTION
The histopathological description of what we now know as reti
nal vasoproliferative tumor (RVPT) was first done by Henkind and
Morgan back to 1966, based in findings that they quoted as “Coat’s
like” appearance in eyes enucleated due to other diseases(1). From that
starting point, eventual case reports and small case series describing
the clinical aspects of primary and secondary peripheral vascular retinal tumors posing a diagnostic dilemma with uveal melanoma and
retinal capillary hemangioma started to came out(2-6). In 1995, Shields
et al. reported 103 cases of peripheral acquired retinal vascular tumor
and proposed the term RVPT(7).
Our goal is to review the clinical picture, differential diagnosis,
etiology, histopathological aspect and management of RVPT, based
on major publications about the topic and on our personal experience with this rare disease at the Federal University of Bahia and
Hospital São Rafael, two major regional referral centers for eye tumors
in Bahia - Brazil.
medical attention complaining of decrease in visual acuity, although
some cases are discovered on routine evaluation(7-13). Floaters, photopsias and metamorphopsia are other common complaints.
RVPT usually presents as a solitary mass in the retinal periphery.
The inferior retina is affected in 60 to 90% of cases and the temporal
retina in 42 to 75% of cases (Figure 1)(7,13). Bilateral lesions or even mul
tiple lesions in the same eye can be seen, specially in secondary RVPTs
(Figure 2 A). Shields et al. report multiple tumors in 6% of primary and
41% of secondary RVPTs(7). We have managed and followed 10 eyes of
8 patients with RVPTs, all tumors were temporal, 8 in the inferior and 2
in the superior retina. Three cases were considered to be secondary:
2 patients with retinitis pigmentosa and bilateral RVPTs; and 1 patient
with type 2 neurofibromatosis and a blind painful eye due to neovascular glaucoma after two episodes of blunt trauma.
RVPTs usually exhibit a red to orange color and can present with
hard exsudates originating in the tumor, subretinal fluid, subretinal
or even vitreous hemorrhage, vitreous cells, cystoid macular edema,
epiretinal membrane, subretinal membrane and hypertrophy of retinal pigmented epithelium (RPE) (Figure 3)(7-10,13).
RVPTs may exhibit feeder vessels, although with less dilation and
tortuosity than that seen on retinal capillary hemangioma, its major
differential diagnosis(7,8,13). Among other lesions that can be confounded with RVPTs are: choroidal amelanotic melanoma - that can be dif
ferentiated based on its choroidal location and typical echographic
findings of low and decreasing internal reflectivity with choroidal
shadowing; peripheral hemorrhagic and exsudative choroidopathy
- that usually occurs in older patients; and inflammatory lesions like
Clinical picture and differential diagnosis
RVPT can be primary (idiopathic) or secondary (associated) to other
ocular diseases like retinitis pigmentosa, sickle cell retinopathy, Coat’s
disease, retinopathy of prematurity, toxoplasmosis, toxocariasis, tuberculosis, other uveitis, ocular trauma, retinalchoroidal coloboma
and retinal detachment(1-3,7-13). Primary tumors correspond from 53 to
80% of the cases in the major reported series(7,9,13).
RVPT affects patients of both genders and all ages, but there is a
predominance of women after the 5th decade(7,8,13). Most patients seek
Submitted for publication: August 23, 2012
Study carried out at Universidade Federal da Bahia e Hospital São Rafael, Salvador (BA), Brazil.
Disclosure of potential conflicts of interest: E.F.Marback, None; R.L.Guerra, None; O.O.Maia Jr.,
None; R.L.Marback, None.
Physician, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador (BA), Brazil.
Physician, Hospital São Rafael, Fundação Monte Tabor, Salvador (BA), Brazil.
Correspondence address: Eduardo Marback. Rua Eduardo José dos Santos, 147 - Sala 808 - Sal
vador (BA) - 41940-455 - Brazil - E-mail: [email protected]
1
2
200
Marback EF, et al.
A
A
B
C
B
Figure 1. A) Typical tumor location in the inferior temporal periphery with massive
exsudation, note in the insert that this was a 4.04 mm thick RVPT. B) Same case after
cryotherapy followed by bevacizumab injection.
uveal tuberculoma and granuloma due to sarcoidosis - lesions that
frequently are located in the periphery and frequently exhibit vitreous cells, just like a RVPT, but lack the typical vascular component
and usually have a pale aspect(12,14).
Complementary tests include echography, fluorescein angiogra
phy (FA) and optical coherence tomography (OCT). Echography
shows a solid tumor with medium to high internal reflectivity and
lacking choroidal shadowing (Figure 2 B and C). Echography is also
useful to measure (most of RVPTs are less than 3 mm high) and follow
RVPTs’ response to treatment(7,10,13). FA is usually of limited value due
to the preferred peripheral location of RVPTs. When feasible RVPTs’
AF reveals early filling in the arterial phase with increasing hyper
fluorescence and late leakage(7,10,15). OCT also has a limited role for the
same reason as AF, but is frequently used to document and follow
the secondary retinal findings like edema and membrane formation
(Figure 3)(15).
Despite its benign nature, RVPT can cause severe visual loss due
to the secondary compromise of the vitreous and retina (epiretinal
and subretinal membranes, vitreous hemorrhage, subretinal fluid
and exsudation) or, less frequently, neovascular glaucoma the can
result in a blind painful eye and may prompt removal of the globe(8).
Etiology and histopathology
The etiology of RVPT is yet to be completely understood. Although
most RVPTs are supposedly of idiopathic nature, the study of lesions
Figure 2. A) Secondary retinal vasoproliferative tumor in association to retinitis pigmentosa (arrow). Asterisks highlight previous cryotherapy scar. B) B scan echography reveals
a dome shape lesion with medium high internal reflectivity. C) Note the A scan aspect
of medium high reflectivity.
obtained by endoresection or from eyes enucleated due to neovascular glaucoma suggests a reactive, rather than neoplastic nature.
The microscopic study reveals a mix of vascular and glial proliferation.
The glial component usually exhibits fusiform and rather uniform
cells. Vascular component show dilated vessels with mural hyalinization and occasional thrombosis (Figure 4). Proliferative index is
low. RPE cells can permeate the tumor mass, exhibiting a variety of
phenotypes like macrophages, fibroblasts, cuboidal and pseudoadenomatous with tubuloacinar aspect(8,16-18). The preferential location of
RPE cells around blood vessels or in areas of previous hemorrhage in
RVPTs, highlights the reactive nature of those cells(18).
The reactive nature of VPRTs is questioned to be a variant of proliferative retinopathy(18). Hiscott and Mudhar, studied 6 enucleated
eyes harboring RVPT. They found epiretinal and subretinal membranes containing RPE cells in association with RVPTs in all eyes(18). While
Shankar et al. highlighted the vascular content of a surgical excised
epiretinal membrane associated to RVPT, calling attention to the
resemblance to epiretinal membranes from diabetic patients and
questioning the role of RVPTs as a source of vasoactive citokyns(19).
Treatment and prognosis
The ideal treatment scheme for RVPTs is yet to be determined. A
number of different treatment approaches have been described with
variable success rates, usually on case reports or small case series(7,9,10).
201
lators. All of them can be used alone or in combination, as we will
discuss in the following sections.
Cryotherapy
It seems to be the most frequently employed treatment modality
for RVPTs(7,9). As RVPTS are usually located in the periphery, cryotherapy can be applied in a transconjunctival way, under observation
through binocular indirect ophthalmoscopy. The treatment goal is
to freeze all tumor, allowing slow thawing and repeating the whole
process 2 or 3 times. More than one cryotherapy section can be
necessary to achieve complete tumor involution specially, in thick
tumors. Figure 1 shows a large RVPT measuring 4.04 mm thick that
was successfully treated by cryotherapy followed by one anti VEGF
injection for macular edema after the tumor has regressed. A similar
approach was successfully employed by Rodrigues et al. who treated
a 2.25 mm RVPT with cryotherapy, associated to triamcinolone intravitreous injection(12).
Cryotherapy can cause some adverse effects like the persistence
of macular edema and the occurrence of retinal detachment arising
in a retinal tear adjacent to the scared area.
A
Laser photocoagulation
Although its use has been reported in RVPTs, it has a limited role.
Probably laser photocoagulation should be reserved for small tumors
and, most often, as a complement to other treatment modalities,
since it is incapable to destruct thick tumors(7).
Photodynamic therapy (PDT)
B
Figure 3. A) Tumor in the temporal superior periphery with massive exsudation. B)
Optic coherence tomography of the same case showing cystoid macular edema and
epiretinal membrane.
PDT has been reported as an effective treatment in retinal and
choroidal vascular tumors(20-22). There are a few reports of its successful
use in RVPT even for larger tumors, like the ones reported by Blasi
et al., with a thickness varying from 2.03 to 4.45 mm(23-25). Its major
limitation is the technical difficulties to reach the typical peripheral
location of RVPTs.
Brachytherapy
Its major indication in RVPTs is for large lesions (more than 2.5 mm
thick) and lesions associated to retinal detachment. In these clinical
situations, cryotherapy is prone to wide tissue destruction, intense
inflammatory reaction, vitreous hemorrhage and an increase in
subretinal fluid. There are reports of well successful brachytherapy
for RVPTs using either Ruthenium106 or Iode125, reaching total tumor
remission in 88 and 97% of the cases respectively(7,13,26). However,
when there is associated neovascular glaucoma, brachytherapy failed
to achieve disease control(26). It is also important to remember the
risk of developing some adverse effects of eye irradiation: dry eyes,
cataracts, actinic optic neuropathy, actinic retinopathy and neovascular glaucoma.
Surgical resection
Figure 4. Microscopic aspect of a retinal vasoproliferative tumor in a blind painful eye
enucleated with neovascular glaucoma. The vascular component is composed of dilated vessels (white asterisk) some with partial thrombosis of the lumen (black asterisk).
White arrowhead points to an area of gliosis. Black arrowhead points to an area of retinal
pigment epithelial proliferation at tumor’s base.
In the largest published series on RVPTs, Shields et al. used the presence of subretinal fluid, macular edema, epiretinal membrane close
to the macula or exsudates close to the macula as criteria to treat
or observe RVPTs’ patients(7). Based on these criteria 51% of the eyes
needed treatment in their series(7).
Various treatment modalities are available including cryotherapy,
laser photocoagulation, photodynamic therapy (PDT), brachytherapy, surgical resection, intravitreous injections and immunomodu202
It is seldom indicated. There are reports of surgical resection for
RVPTs that failed to respond to cryotherapy in association to intravi
treous injections of antiangiogenics or as a primary treatment in an
eye harboring multiple RVPTs and vitreous hemorrhage(27,28). The
surgery can be performed through pars plana vitrectomy or by a
transcleral route(15,27,28). Cataract is a common complication after vitrectomy in phakic eyes, specially when silicone oil or gas is used to
seal the retinotomies necessary to perform tumor’s endoresection.
Intravitreous injections
There are a few reports of antiangiogenic intravitreous injections
for RVPTs, like bevacizumab, ranicizumab and triamcinolone(9,12,29).
Although the exact effect of these substances on RVPTs is lacking, it
seems reasonable to consider their use in association to or after other
Marback EF, et al.
destructive modalities (like cryotherapy) when there is visual acuity
decrease due to macular edema.
Immunomodulators
Japiassú et al. reported an isolated case of bilateral RVPTs that
showed regression after systemic treatment with infliximab (antibody anti tumor necrosis factor) for associated mixed collagen disease(30). In spite of being an isolated report, it is worth of note when we
consider the known association of RVPTs with inflammatory ocular
processes.
Final comments
RVPTs is a rare disease that harbors the potential to result in variable visual acuity decrease or even in complications that cause eye
loss. Its exact etiology is not known, although reactive mechanisms
are, at least in part, clearly implicated. The ideal treatment is yet to be
established, since most of what we known is based on isolated case
reports or small case series and a major trial comparing the multiple
treatment options available is lacking.
From our personal perspective, faced to a new RVPT case the first
point to be addressed is the decision to treat or observe. It seems
reasonable that patients with good visual acuity, small and stable
tumor, no subretinal fluid (or very limited and non progressive) and
lacking exsudation can be securely observed on a 3 to 4 months
basis. These patients should be oriented to frequently perform self
visual acuity test with immediate return if any visual acuity drop or
initiation of other symptoms like photopsias or floaters are noted. For
symptomatic patients, and even for patients with good vision but
exhibiting signs of impending visual acuity risk (like growing tumors
with progressive subretinal fluid or exsudates) we advocate immediate treatment. After the decision to treat is taken, one should decide
which treatment modality to use. Some authors recommend that
tumors thicker than 2.5mm should be treated with brachytherapy as
an initial approach(7,8,13,26). Nevertheless, brachytherapy is an expensive treatment that is not easy available in most centers. On the other
way, successful treatment of thicker RVPT with multiple sessions of
cryotherapy, PDT, photocoagulation or the association of cryotherapy
with intravitreous injectons of antiangiogenic for the secondary retinal changes were reported(7,8,25,29,31). Such approaches are probably
much more commonly employed in the treatment of RVPTs than brachytherapy worldwide(9,31). From our personal perspective, treatment
decision should be based on specific tumors characteristics, but also
on local availability. For instance, brachytherapy can be considered an
indication in thicker tumors, but it should not be considered as the
only possible treatment option specially when considered its costs
and the fact that it is not available in most referral centers and that
other modalities have been successfully employed, even for thicker
tumors(31). Probably a tumor located on a PDT amenable position, in
a center where PDT is available, will be suitable for PDT treatment,
whereas successive gentle cryotherapy sections can be successfully
employed in thicker tumors specially if combined to intravitreous injections of triamcinolone or anti VEGF agents (Figure 1)(9,12,31). It is also
important to note that immediately after treatment and for at least a
few weeks after, it is common to find an increase in tumor dimensions
that is probably caused by intratumoral inflammation or hemorrhage.
So the decision to give more treatment or to change the treatment
modality should not be done in a precipitated fashion.
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30. Japiassú RM, Brasil OF, Cunha AL, de Souza EC. Regression of vasoproliferative tumor
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31. Damato B. Vasoproliferative retinal tumour. Br J Ophthalmol. 2006;90(4):399-400. Com
ment on Br J Ophthalmol. 2006;90(4):447-50.
203
Instruções para Autores |
O ARQUIVOS BRASILEIROS DE OFTALMOLOGIA (ABO, ISSN 00042749 - versão impressa e ISSN 1678-2925 - versão eletrônica), publi
cação bimestral oficial do Conselho Brasileiro de Oftalmologia, objetiva divulgar estudos científicos em Oftalmologia, Ciências Visuais e
Saúde Pública, fomentando a pesquisa, o aperfeiçoamento e a atua
lização dos profissionais relacionados à área.
Metodologia
São aceitos manuscritos originais, em português, inglês ou
espanhol que, de acordo com a metodologia empregada, deverão
ser caracterizados em uma das seguintes modalidades:
Estudos Clínicos
Estudos descritivos ou analíticos que envolvam análises em
seres humanos ou avaliem a literatura pertinente a seres humanos.
Estudos Epidemiológicos
Estudos analíticos que envolvam resultados populacionais.
Estudos de Experimentação Laboratorial
Estudos descritivos ou analíticos que envolvam modelos ani
mais ou outras técnicas biológicas, físicas ou químicas.
Estudos Teóricos
Estudos descritivos que se refiram à descrição e análise teórica
de novas hipóteses propostas com base no conhecimento existente
na literatura.
Tipos de Manuscritos
A forma do manuscrito enviado deve enquadrar-se em uma das
categorias a seguir. Os limites para cada tipo de manuscrito estão
entre parênteses ao final das descrições das categorias. A contagem
de palavras do manuscrito refere-se do início da introdução ao final
da discussão, portanto, não participam da contagem a página de
rosto, abstract, resumo, referências, agradecimentos, tabelas e figuras incluindo legendas.
Editoriais
Os editoriais são feitos a convite e devem ser referentes a
assuntos de interesse atual, preferencialmente relacionados a arti
gos publicados no mesmo fascículo do ABO (limites máximos: 1.000
palavras, título, 2 figuras ou tabelas no total e 10 referências).
Artigos Originais
Artigos originais apresentam experimentos completos com
resultados nunca publicados (limites máximos: 3.000 palavras, título, resumo estruturado, 7 figuras ou tabelas no total e 30 referên
cias). A avaliação dos manuscritos enviados seguirá as prioridades
abaixo:
1.Informação nova e relevante comprovada em estudo com
metodologia adequada.
2.Repetição de informação existente na literatura ainda não
comprovada regionalmente baseada em estudo com meto
dologia adequada.
3.Repetição de informação existente na literatura e já comprovada
regionalmente, desde que baseada em estudo com metodologia
adequada.
* Não serão aceitos manuscritos com conclusões especulativas, não
comprovadas pelos resultados ou baseadas em estudo com me
todologia inadequada.
Instructions to Authors
Relatos de Casos ou Série de Casos
Relatos de casos ou série de casos serão considerados para
publicação se descreverem achados com raridade e originalidade
ainda não comprovadas internacionalmente, ou quando o relato
apresentar respostas clínicas ou cirúrgicas que auxiliem na elu
cidação fisiopatológica de alguma doença (limites máximos: 1.000
palavras, título, resumo não estruturado, 4 figuras ou tabelas no
total e 10 referências).
Cartas ao Editor
As cartas ao editor serão consideradas para publicação se incluí
rem comentários pertinentes a manuscritos publicados anterior
mente no ABO ou, excepcionalmente, resultados de estudos originais com conteúdo insuficiente para serem enviados como Artigo
Original. Elas devem introduzir nova informação ou nova interpre
tação de informação já existente. Quando seu conteúdo fizer referência a algum artigo publicado no ABO, este deve estar citado no
primeiro parágrafo e constar das referências. Nestes casos, as cartas
estarão associadas ao artigo em questão, e o direito de réplica dos
autores será garantido na mesma edição. Não serão publicadas cartas
de congratulações (limites máximos: 700 palavras, título, 2 figuras
ou tabelas no total e 5 referências).
Manuscritos de Revisão
Manuscritos de revisão seguem a linha editorial da revista e são
aceitos apenas por convite do editor. Sugestões de assuntos para
artigos de revisão podem ser feitas diretamente ao editor, mas os
manuscritos não podem ser enviados sem um convite prévio (limi
tes máximos: 4.000 palavras, título, resumo não estruturado, 8 figuras
ou tabelas no total e 100 referências).
Processo Editorial
Para que o manuscrito ingresse no processo editorial, é fundamental que todas as regras tenham sido cumpridas. A secretaria
editorial comunicará inadequações no envio do manuscrito. Após
a notificação, o autor correspondente terá o prazo de 30 dias para
adequação do seu manuscrito. Se o prazo não for cumprido, o ma
nuscrito será excluído.
Os manuscritos enviados ao ABO são avaliados inicialmente
pelos editores quanto à adequação do seu conteúdo à linha edito
rial do periódico. Após essa avaliação, todos os manuscritos são
encaminhados para análise e avaliação por pares, sendo o anonima
to dos avaliadores garantido em todo o processo de julgamento. O
anonimato dos autores não é implementado.
Após a avaliação editorial inicial, os comentários dos avaliado
res podem ser encaminhados aos autores como orientação para as
mod ificações que devam ser realizadas no texto. Após a imple
mentação das modificações sugeridas pelos avaliadores, o manuscrito revisado deverá ser encaminhado, acompanhado de carta
(enviada como documento suplementar) indicando pont ualm en
te todas as modificações realizadas no manuscrito ou os motivos
pelos quais as modificações sugeridas não foram efetuadas. Manuscritos que não vierem acompanhados da carta indicando as
modificações ficarão retidos aguardando o recebimento da mes
ma. O prazo para envio da nova versão do manuscrito é de 90 dias
após a comunicação da necessidade de modificações, sendo
excluído após esse prazo. A publicação dependerá da aprovação
final dos editores.
Os trabalhos devem destinar-se exclusivamente ao Arquivos
Brasileiros de Oftalmologia, não sendo permitido envio simultâneo a outro periódico, nem sua reprodução total ou parcial, ou
tradução para publicação em outro idioma, sem autorização dos
editores.
205
Autoria
Os critérios para autoria de manuscritos em periódicos médi
cos está bem estabelecido. O crédito de autoria deve ser baseado
em indivíduos que tenham contribuído de maneira concreta nas
seguintes três fases do manuscrito:
I. Concepção e delineamento do estudo, coleta dos dados ou
análise e interpretação dos dados.
II. Redação do manuscrito ou revisão crítica do manuscrito com
relação ao seu conteúdo intelectual.
III. Aprovação final da versão do manuscrito a ser publicada.
O ABO requer que os autores garantam que todos os autores
preenchem os critérios acima e que nenhuma pessoa que preencha
esses critérios seja preterida da autoria. Apenas a posição de chefia
de qualquer indivíduo não atribui a este o papel de autor, o ABO não
aceita a participação de autores honorários.
É necessário que o autor correspondente preencha e envie o
formulário de Declaração de Contribuição dos Autores como docu
mento suplementar.
Preparação do Artigo
Os artigos devem ser enviados exclusivamente de forma eletrô
nica, pela Internet, na interface apropriada do ABO. As normas que se
seguem foram baseadas no formato proposto pelo International
Committee of Medical Journal Editors (ICMJE) e publicadas no artigo:
Uniform Requirements for Manuscripts Submitted to Biomedical Journals.
O respeito às instruções é condição obrigatória para que o tra
balho seja considerado para análise.
O texto deve ser enviado em formato digital, sendo aceitos
apenas os formatos .doc. ou .rtf. O corpo do texto deve ser digitado
em espaço duplo, fonte tamanho 12, com páginas numeradas em
algarismos arábicos, iniciando-se cada seção em uma nova página.
As seções devem se apresentar na sequência: Página de Rosto,
Abstract e Keywords, Resumo e Descritores, Introdução, Métodos,
Resultados, Discussão Agradecimentos (eventuais), Referências, Tabelas (opcionais) e Figuras (opcionais) com legenda.
1. Página de Rosto. Deve conter: a) título em inglês (máximo
de 135 caracteres, incluindo espaços); b) título em português ou
espanhol (máximo de 135 caracteres, incluindo espaços); c) título
resumido para cabeçalho (máximo 60 caracteres, incluindo os
esp aços); d) nome científico de cada autor; e) titulação de cada
autor (área de atuação profissional*, cidade, estado, país e, quando houver, departamento, escola, Universidade); f ) nome, endereço, telefone e e-mail do autor correspondente; g) fontes de auxilio
à pesquisa (se houver); h) número do projeto e instituição responsável pelo parecer do Comitê de Ética em Pesquisa; i) declaração dos
conflitos de interesses de todos os autores; j) número do registro
dos ensaios clínicos em uma base de acesso público.
*Médico, estatístico, enfermeiro, ortoptista, fisioterapeuta, estudante etc.
Aprovação do Comitê de Ética em Pesquisa. Todos os estudos
que envolvam coleta de dados primários ou relatos clínico-ci
rúrgicos, sejam retrospectivos, transversais ou prospectivos, devem
indicar, na página de rosto, o número do projeto e nome da Ins
tituição que forneceu o parecer do Comitê de Ética em Pesquisa.
As pesquisas em seres humanos devem seguir a Declaração de
Helsinque, enquanto as pesquisas envolvendo animais devem
seguir os princípios propostos pela Association for Research in Vision
and Ophthalmology (ARVO).
É necessário que o autor correspondente envie, como documento
suplementar, a aprovação do Comitê de Ética em Pesquisa ou seu
parecer dispensando da avaliação do projeto pelo Comitê. Não cabe
ao autor a decisão sobre a necessidade de avaliação pelo Comitê de
Ética em Pesquisa.
206
Declaração de Conflito de Interesses. A página de rosto deve
conter a declaração de conflitos de interesse de todos os autores
(mesmo que esta seja inexistente). Para maiores informações sobre
os potenciais conflitos de interesse acesse: Chamon W, Melo LA Jr,
Paranhos A Jr. Declaração de conflito de interesse em apresenta
ções e publicações científicas. Arq Bras Oftalmol. 2010;73(2):107-9.
É necessário que todos os autores enviem os Formulários para Decla
ração de Conflitos de Interesse como documentos suplementares.
Ensaios Clínicos. Todos os Ensaios Clínicos devem indicar, na página
de rosto, número de registro em uma base internacional de regis
tro que permita o acesso livre a consulta (exemplos: U.S. National
Inst it utes of Health, Australian and New Zealand Clinical Trials
Registry, International Standard Randomised Controlled Trial Number
- ISRCTN, University Hospital Medical Information Network Clinical Trials
Registry - UMIN CTR, Nederlands Trial Register).
2. Abstract e Keywords. Resumo estruturado (Purpose, Methods,
Results, Conclusions) com, no máximo, 300 palavras. Resumo não
estruturado com, no máximo, 150 palavras. Citar cinco descritores
em inglês, listados pela National Library of Medicine (MeSH - Medical Subject Headings).
3. Resumo e Descritores. Resumo estruturado (Objetivos, Métodos, Resultados, Conclusões) com, no máximo 300 palavras. Resumo não estruturado com, no máximo, 150 palavras. Citar cinco des
critores, em português listados pela BIREME (DeCS - Descritores
em Ciências da Saúde).
4. Introdução, Métodos, Resultados e Discussão. As citações no
texto devem ser numeradas sequencialmente, em números arábicos sobrescritos e entre parênteses. É desaconselhada a citação
nominal dos autores.
5. Agradecimentos. Colaborações de pessoas que mereçam
reconhecimento, mas que não justificam suas inclusões como
autores, devem ser citadas nessa seção. Estatísticos e editores médicos podem preencher os critérios de autoria e, neste caso, dev em
ser reconhecidos como tal. Quando não preencherem os critérios de autoria, eles deverão, obrigatoriamente, ser citados nesta seção. Não são aceitos escritores não identificados no manuscrito, portanto, escritores profissionais devem ser reconhecidos
nesta seção.
6. Referências. A citação (referência) dos autores no texto deve
ser numérica e sequencial, na mesma ordem que foram citadas
e identificadas por algarismos arábicos sobrescritos. A apresenta
ção deve estar baseada no formato proposto pelo International
Committee of Medical Journal Editors (ICMJE), conforme os exemplos que se seguem.
Os títulos de periódicos devem ser abreviados de acordo com o
estilo apresentado pela List of Journal Indexed in Index Medicus, da
National Library of Medicine.
Para todas as referências, cite todos os autores, até seis. Nos traba
lhos com sete ou mais autores, cite apenas os seis primeiros,
seguidos da expressão et al.
Exemplos de referências:
Artigos de Periódicos
Costa VP, Vasconcellos JP, Comegno PEC, José NK. O uso da mitomicina C em cirurgia combinada. Arq Bras Oftalmol. 1999; 62(5):577-80.
Livros
Bicas HEA. Oftalmologia: fundamentos. São Paulo: Contexto; 1991.
Capítulos de livros
Gómez de Liaño F, Gómez de Liaño P, Gómez de Liaño R. Exploración
del niño estrábico. In: Horta-Barbosa P, editor. Estrabismo. Rio de
Janeiro: Cultura Médica; 1997. p. 47-72.
Anais
Höfling-Lima AL, Belfort R Jr. Infecção herpética do recém-nascido.
In: IV Congresso Brasileiro de Prevenção da Cegueira; 1980 Jul 28-30,
Belo Horizonte, Brasil. Anais. Belo Horizonte; 1980. v.2. p. 205-12.
Teses
Schor P. Idealização, desenho, construção e teste de um ceratômetro cirúrgico quantitativo [tese]. São Paulo: Universidade Federal
de São Paulo; 1997.
Documentos Eletrônicos
Monteiro MLR, Scapolan HB. Constrição campimétrica causada por
vigabatrin. Arq Bras Oftalmol. [periódico na Internet]. 2000 [citado
2005 Jan 31]; 63(5): [cerca de 4 p.]. Disponível em:http://www.scielo.
br/scielo.php?script=sci_arttext&pid=S0004-274920000005000
12&lng=pt&nrm=iso
7. Tabelas. A numeração das tabelas deve ser sequencial, em alga
rismos arábicos, na ordem em que foram citadas no texto. Todas
as tabelas devem ter título e cabeçalho para todas as colunas
e serem apresentadas em formatação simples, sem linhas verticais
ou preenchimentos de fundo. No rodapé da tabela deve constar
legenda para todas as abreviaturas (mesmo que definidas previa
mente no texto) e testes estatísticos utilizados, além da fonte
bibliográfica quando extraída de outro trabalho. Todas as tabelas
devem estar contidas no documento principal do manuscrito após
as referências bibliográficas, além de serem enviadas como documento suplementar.
8. Figuras (gráficos, fotografias, ilustrações, quadros). A nu
meração das figuras deve ser sequencial, em algarismos arábi
cos, na ordem em que foram citadas no texto. O ABO publicará as
figuras em preto e branco sem custos para os autores. Os manus
critos com figuras coloridas apenas serão publicados após o
pagamento da respectiva taxa de publicação de R$ 500,00 por
manuscrito.
Os gráficos devem ser, preferencialmente, em tons de cinza, com
fundo branco e sem recursos que simulem 3 dimensões ou profundidade. Gráficos do tipo torta são dispensáveis e devem ser substi
tuídos por tabelas ou as informações serem descritas no texto.
Fotografias e ilustrações devem ter resolução mínima de 300 DPI
para o tamanho final da publicação (cerca de 2.500 x 3.300 pixels,
para página inteira). A qualidade das imagens é considerada na
avaliação do manuscrito.
Todas as figuras devem estar contidas no documento principal do
manuscrito após as tabelas (se houver) ou após as referências bibliográficas, além de serem enviadas como documento suplementar.
No documento principal, cada figura deve vir acompanhada de sua
respectiva legenda em espaço duplo e numerada em algarismo
arábico.
Os arquivos suplementares enviados podem ter as seguintes extensões: JPG, BMP, TIF, GIF, EPS, PSD, WMF, EMF ou PDF, e devem
ser nomeados conforme a identificação das figuras, por exemplo:
“grafico_1.jpg” ou “figura_1A.bmp”.
9. Abreviaturas e Siglas. Quando presentes, devem ser precedidas
do nome correspondente completo ao qual se referem, quando
citadas pela primeira vez, e nas legendas das tabelas e figuras
(mesmo que tenham citadas abreviadas anteriormente no texto).
Não devem ser usadas no título e no resumo.
10. Unidades: Valores de grandezas físicas devem ser referidos de
acordo com os padrões do Sistema Internacional de Unidades.
11. Linguagem. A clareza do texto deve ser adequada a uma
publicação científica. Opte por sentenças curtas na forma direta e
ativa. Quando o uso de uma palavra estrangeira for absolutamente
necessário, ela deve aparecer com formatação itálica. Agentes
terapêuticos devem ser indicados pelos seus nomes genéricos
seguidos, entre parênteses, pelo nome comercial, fabricante, ci
dade, estado e país de origem. Todos os instrumentos ou apare
lhos de fabricação utilizados devem ser citados com o seu nome
comercial, fabricante, cidade, estado e país de origem. É necessária
a colocação do símbolo (sobrescrito) de marca registrada ® ou ™
em todos os nomes de instrumentos ou apresentações comerciais
de drogas. Em situações de dúvidas em relação a estilo, terminologia, medidas e assuntos correlatos, o AMA Manual of Style 10th
edition deverá ser consultado.
12. Documentos Originais. Os autores correspondentes devem ter
sob sua guarda os documentos originais como a carta de aprovação
do comitê de ética institucional para estudos com humanos ou
animais; o termo de consentimento informado assinado por todos
os pacientes envolvidos, a declaração de concordância com o con
teúdo completo do trabalho assinada por todos os autores e declaração de conflito de interesse de todos os autores, além dos registros
dos dados colhidos para os resultados do trabalho.
13. Correções e Retratações. Erros podem ser percebidos após a
publicação de um manuscrito que requeiram a publicação de
uma correção. No entanto, alguns erros, apontados por qualquer
leitor, podem invalidar os resultados ou a autoria do manuscrito.
Se alguma dúvida concreta a respeito da honestidade ou fidedignidade de um manuscrito enviado para publicação for levantada,
é obrigação do editor excluir a possibilidade de fraude. Nestas
situações o editor comunicará as instituições envolvidas e as agências financiadoras a respeito da suspeita e aguardará a decisão
final desses órgãos. Se houver a confirmação de uma publicação
fraudulenta no ABO, o editor seguirá os protocolos sugeridos pela
International Committee of Medical Journal Editors (ICMJE) e pelo
Committee on Publication Ethics (COPE).
Lista de Pendências
Antes de iniciar o envio do seu manuscrito o autor deve confir
mar que todos os itens abaixo estão disponíveis:
□Manuscrito formatado de acordo com as instruções aos autores.
□Limites de palavras, tabelas, figuras e referências adequados
□Todas as figuras e tabelas inseridas no documento principal
□Todas as figuras e tabelas na sua forma digital para serem
□Formulário
para o tipo de manuscrito.
do manuscrito.
enviadas separadamente como documentos suplementares.
de Declaração da Participação dos Autores
preenchido e salvo digitalmente, para ser enviado como
documento suplementar.
□Formulários de Declarações de Conflitos de Interesses de
todos os autores preenchidos e salvos digitalmente, para
serem enviados como documentos suplementares.
□Número do registro na base de dados que contem o protocolo do ensaio clínico constando na folha de rosto.
□Versão digital do parecer do Comitê de Ética em Pesquisa
com a aprovação do projeto, para ser enviado como documento suplementar.
207
Lista de Sítios da Internet
Interface de envio de artigos do ABO
http://www.scielo.br/ABO
Formulário de Declaração de Contribuição dos Autores
http://www.cbo.com.br/site/files/Formulario Contribuicao dos Autores.pdf
International Committee of Medical Journal Editors (ICMJE)
http://www.icmje.org/
Uniform requirements for manuscripts submitted
to biomedical journals
http://www.icmje.org/urm_full.pdf
Declaração de Helsinque
http://www.wma.net/en/30publications/10policies/b3/index.html
Princípios da Association for Research in
Vision and Ophthalmology (ARVO)
http://www.ar vo.org/eweb/dynamicpage.aspx?site=ar vo2&
webcode=AnimalsResearch
Chamon W, Melo LA Jr, Paranhos A Jr. Declaração de conflito de
interesse em apresentações e publicações científicas.
http://www.scielo.br/pdf/abo/v73n2/v73n2a01.pdf
Princípios de Autoria segundo ICMJE
http://www.icmje.org/ethical_1author.html
Australian and New Zealand Clinical Trials Registry
http://www.anzctr.org.au
International Standard Randomised Controlled
Trial Number - ISRCTN
http://isrctn.org/
University Hospital Medical Information Network
Clinical Trials Registry - UMIN CTR
http://www.umin.ac.jp/ctr/index/htm
Nederlands Trial Register
http://www.trialregister.nl/trialreg/index.asp
MeSH - Medical Subject Headings
http://www.ncbi.nlm.nih.gov/sites/entrez?db=mesh&term=
DeCS - Descritores em Ciências da Saúde
http://decs.bvs.br/
Formatação proposta pela International Committee
of Medical Journal Editors (ICMJE)
http://www.nlm.nih.gov/bsd/uniform_requirements.html
List of Journal Indexed in Index Medicus
http://www.ncbi.nlm.nih.gov/journals
AMA Manual of Style 10th edition
http://www.amamanualofstyle.com/
Formulários para Declaração de Conflitos de Interesse
http://www.icmje.org/coi_disclosure.pdf
Protocolos da International Committee of
Medical Journal Editors (ICMJE)
http://www.icmje.org/publishing_2corrections.html
U.S. National Institutes of Health
http://www.clinicaltrials.gov
Protocolos da Committee on Publication Ethics (COPE)
http://publicationethics.org/flowcharts
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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
MINIMIZAR OS RISCOS DE REAÎÍO ALÏRGICA SEM PERFUME NÍO Ï GORDUROSO LIMPA DE FORMA ADEQUADA AS PÈLPEBRAS ! SUA FØRMULA s &ACILITA A ADERÐNCIA DO PRODUTO s 0RODUZ UMA AGRADÈVEL SENSAÎÍO DE FRESCOR DESCONGESTIONANDO AS PÈLPEBRAS E RESPEITANDO
O P( DA PELE s .ÍO DEIXA RESÓDUOS Precauções de utilização: s 0RODUTO DESTINADO A APLICAÎÍO SOBRE AS PÈLPEBRAS E CÓLIOS NÍO APLICAR NO OLHO s .ÍO UTILIZAR EM CRIANÎAS .°/ 53!2 %- 0%,% ,%3)/.!$! /5 )22)4!$! Modo de usar: Em média duas
vezes por dia, de manhã e à noite, ou quantas vezes seja necessária a limpeza das pálpebras. 1) Aplicar uma pequena quantidade de BLEPHAGEL® sobre uma gaze limpa e macia. 2) &RENTE AO ESPELHO APLICAR COM DELICADEZA A
gaze sobre as pálpebras e a base dos cílios com o olho fechado. 3) Passar suavemente, várias vezes a gaze com o BLEPHAGEL® sobre as pálpebras e a base dos cílios, friccionar com pequenos movimentos circulares a
fim de retirar todos os resíduos. 4) Eliminar o BLEPHAGEL® restante com a ajuda de uma gaze limpa. 5) Repetir cada etapa para o outro olho utilizando sempre gazes limpas. Reg. M.S. nº 2.5203.0006. Importado por:
5.)°/ 15¶-)#! &!2-!#³54)#! .!#)/.!, 3! 2UA #EL ,UIZ 4ENØRIO DE "RITO n %MBU'UAÎU n 30 n #%0 n 3!# n #.0* n &ARM 2ESP $ANIELA "ATISTA 0AIVA n
#2&-' N Fabricado por: ,!"/2!4/)2%3 4(²! n RUE ,OUIS "LÏRIOT n #,%2-/.4&%22!.$ #EDEX n &2!.#% &2!.±!
Material dirigido exclusivamente a profissionais habilitados a prescrever e/ou dispensar medicamentos.
Produzido em: Abril/2013
Referência Bibliográfica: 1) Bula do produto: Blephagel®. Registro MS nº2.5203.0006.001-4.
Varilux S series®, Varilux S 4D®, Varilux S fit®, Varilux S design® e Varilux S design short® são marcas registradas da Essilor International.
NOVA GAMA DE LENTES VARILUX.
EQUILÍBRIO EM MOVIMENTO
COM AMPLO CAMPO DE VISÃO.
Até hoje nenhuma lente multifocal havia sido capaz de eliminar o efeito de flutuação sem prejudicar a amplitude dos campos de
visão. Varilux S series rompe esta barreira com uma nova concepção em lentes multifocais. As novas tecnologias Nanoptix e
SynchronEyes, presentes em toda a linha Varilux S series, proporcionam equilíbrio em movimento com amplos campos de visão.
A versão Varilux S 4D explora um parâmetro inédito de personalização medido pelo Visioffice: o olho dominante, que aprimora o
tempo de resposta visual, proporcionando ao usuário foco imediato. É a visão absoluta que os usuários de lentes multifocais
sempre buscaram.
VISÃO ABSOLUTA.
SAC 0800 727 2007 | www.varilux.com.br

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