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ISSN 2219-4665 VISION PAN-AMERICA Volumen X No.1 Marzo 2011 TRATAMIENTO PARA LINFOMAS INTRAOCULARES TREATMENT FOR INTRAOCULAR LYMPHOMAS Dr. Gian Paolo Giuliari NEW VITAL DYES TO STAIN INTRAOCULAR MEMBRANES AND TISSUES DURING VITRECTOMY Mauricio Maia MD PhD; Eduardo B. Rodrigues MD; Michel Eid Farah MD PhD; André Maia MD; Acácio Lima PhD; Octaviano Magalhães Jr MD; Eduardo Dib MD OZURDEX®, A NOVEL DEXAMETHASONE DELIVERY SYSTEM, FOR TREATMENT OF MACULAR EDEMA FOLLOWING RETINAL VEIN OCCLUSION Rubens Belfort Jr. MD PhD; Cristina Muccioli MD; Susan S Lee MS; Michael R. Robinson MD INCIDENCIA DE DESPRENDIMIENTO DE RETINA EN PACIENTES ALTOS MIOPES POSTOPERADOS DE IMPLANTE DE LIO FÁQUICO ARTISAN/ARTIFLEX Luis Fernando Rosales Rodriguez MD; Luis Oswaldo Izquierdo Villavicencio MD; Maria Alejandra Henríquez MD QUERATITIS POR ACANTHAMOEBA. A PROPÓSITO DE UN CASO ACANTHAMOEBA KERATITIS: A CASE REPORT Miriam García-Fernández; Begoña Baamonde Arbaiza MULTILAYERED FOLDED DEHYDRATED AMNIOTIC MEMBRANE GRAFT FOR SCLERAL DELLE MANAGEMENT FOLDED DEHYDRATED AMT FOR SCLERAL DELLE Jay C. Bradley MD TRULY UNILATERAL KERATOCONUS ASSOCIATED WITH ORBITAL FIBROSIS Alejandro Navas MD; Armando González-Gomar MD; Zoraida Espinosa MD; José Luis Tovilla-Canales MD; Tito Ramírez-Luquín MD; Enrique O. Graue-Hernández MD 4 : PAN-AMERICA Marzo 2011 Mark J. Mannis, MD University of California, Davis Sacramento, California Editor-in-Chief Teresa J. Bradshaw Arlington, Texas Managing Editor Cristián Luco, MD Santiago, Chile Associate Editor Terri L. Grassi Arlington, Texas Production Editor EDITORIAL BOARD Eduardo Alfonso, MD Miami, Florida USA Alfredo Sadun, MD Los Angeles, California USA Eduardo Arenas, MD Bogotá, Colombia Allan Slomovic, MD Toronto, Ontario, Canada J. Fernando Arévalo, MD Caracas, Venezuela Luciene Barbosa de Sousa, MD São Paulo, Brazil José A. Roca Fernández, MD Lima, Perú Lihteh Wu, MD San José, Costa Rica Denise de Freitas, MD São Paulo, Brazil Paulo Dantas, MD São Paulo, Brazil Marian Macsai, MD Chicago, Illinois USA Chun Cheng Lin Yang, MD MSc San José, Costa Rica David E. Pelayes, MD PhD Buenos Aires, Argentina OFFICERS Cristián Luco MD Santiago, Chile President, Pan-American Association of Ophthalmology Nelson R. Marques São Paulo, Brazil Chairman of the Board, Pan-American Ophthalmological Foundation PRODUCTION STAFF Director of Printed Matters CLM Eliana Barbosa Graphic Design CLM Catalina Lozano Ortega / Juan David Medina Databases and Distribution CLM Ximena Ortega Bernal telemarketing@clatinmedia.com Copyediting Piedad Camacho Vanessa Carmona Special thanks to Ana Carolina Vieira, Enrique Graue Hernandez, Mapy Padilla, and Cristian Luco for assistance in translation. Prepress Alejandro Bernal PAOF INDUSTRY SPONSORS Advanced Medical Optics Inc. Alcon Inc. • Allergan Inc. • Bausch & Lomb Inc. • Carl Zeiss Meditec Inc. • • CREATIVE LATIN MEDIA, LLC. 2901 Clint Moore, P.M.B 117 Boca Raton, FL 33496 Tel.: (561) 495 4728 • Fax: (561) 865 1934 E-mail: editorial@clatinmedia.com • info@clatinmedia.com Johnson & Johnson Vision Care Latin America • Merck & Co Inc. • Novartis International AG. • Santen Inc. • Prepress Creative Latin Media. Printed in Printer Colombiana - Colombia PAN-AMERICA MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT Editorial Mark J. Mannis, MD Editor en Jefe Vision Pan-America Del Editor: Con el 2011 comienza una nueva era para Vision Pan-America (VPA). Originalmente establecida como una comunicación científica de la PAAO hace una década, nuestra publicación ha crecido para convertirse en una revista pequeña pero de muy alta calidad de revisión por pares con una circulación y distribución mayor a muchas de las revistas de subespecialidad en lengua inglesa. Con artículos en inglés, español, portugués y en francés, VPA brinda a autores latinoamericanos, norteamericanos, del Caribe y Canadá una excelente oportunidad para que compartan su trabajo con una población de lectura muy amplia. Hemos sido beneficiados por un gran apoyo de la Fundación Oftalmológica Pan-Americana, la industria y la PAAO. Tenemos un cuerpo editorial pro-activo y dedicado, y quienes inclusive han contribuido regularmente con artículos, además hemos incluido a un grupo de revisores justos y considerados para asegurarnos de publicar trabajos con calidad. Por primera vez verán que tenemos un número ISSN, mismo que se puede ver en la portada de esta edición. Nuestra junta directiva trabaja sin cesar para asegurarnos que al final de este año, VPA esté totalmente indexada y por ende logre la exposición al mundo entero. Esperamos que todos ustedes consideren contribuir con su mejor producción científica; ya sea una revisión clínica, una serie o reporte de casos interesantes, descripción de nuevas tecnologías diagnósticas, farmacológicas o quirúrgicas, o bien reportes de ciencias básicas para su publicación en VPA. Por favor, tomen un momento para revisar las instrucciones para los autores incluidas al final de esta edición y escojan a VPA como el vehículo para transmitir su trabajo a toda América. Mark J. Mannis Editor en Jefe Vision Pan-America 2 PAN-AMERICA Marzo 2011 From the Editor Do Editor With 2011, we begin a new era for Vision PanAmerica (VPA). Established a decade ago as a scientific newsletter for the PAAO, our publication has grown into a small but very high quality peer-reviewed journal with a circulation larger than many of the English language subspecialty journals. With articles in English, Spanish, Portuguese and French, VPA provides a wonderful opportunity for Latin American, U.S., Caribbean, and Canadian authors to submit their work to a broad readership. We have benefited from strong support from the Pan-American Ophthalmological Foundation, the ophthalmic industry, as well as the PAAO office. We have had a dedicated and pro-active Editorial Board who, themselves, have regularly contributed articles to the journal, and we have enlisted fair-minded and thoughtful reviewers who ensure that we publish quality work. Com 2011, iniciamos uma nova era para a Vision Pan-America (VPA). Criada há uma década como um folheto científico informativo, tornou-se uma pequena revista, porém de altíssima qualidade, revisada pelos próprios pares e com maior circulação do que muitos journals publicados na língua inglesa dedicados a subespecialidades. Com artigos em Inglês, Espanhol, Português e Francês, VPA proporciona uma oportunidade maravilhosa a autores da América Latina, EUA, Caribe e Canadá de submeter seus trabalhos a um amplo público leitor. Temos nos beneficiado de grande apoio da Fundação Pan-Americana de Oftalmologia, da indústria oftálmica, assim como da PAAO. Temos um Conselho Editorial dedicado e pró-ativo que tem contribuído com artigos próprios regularmente e contamos com revisores cuidadosos e justos que garantem a publicação de trabalhos de qualidade. We now have an ISSN number—seen for the first time on the cover of this issue. And our Board is working hard to ensure that by the end of this year, VPA will be fully indexed, opening exposure of the journal to the entire world. Temos agora um número de ISSN – encontrado pela primeira vez na capa desta edição. E nosso Conselho está trabalhando para garantir que até o final deste ano, a VPA esteja totalmente indexada, ampliando a exposição da revista para todo o mundo. We hope that you will all consider contributing your best scientific work—whether it is a clinical review; case series; reports of interesting cases; descriptions of new diagnostic, pharmacologic or surgical technologies; or basic science reports—for publication in VPA. Please take a moment to look at the Instructions to Authors at the end of this issue and choose VPA as the vehicle for letting the Americas know about your work. Esperamos que todos vocês considerem publicar seus melhores trabalhos científicos na VPA – seja ele uma revisão clínica, série de casos, relato de casos interessantes, descrição de novas tecnologias para diagnóstico, farmacologia ou cirurgia, ou pesquisas de ciências básicas. Mark J. Mannis Editor-in-Chief Vision Pan-America Mark J. Mannis Editor Chefe Vision Pan-America Por favor, leiam as Instruções para Autores ao final desta edição e escolham a VPA como o veículo para mostrar às Américas o seu trabalho. PAN-AMERICA 3 MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT Editorial Cristián Luco, MD Presidente PAAO 2009-2011 Unidos en la Educación: Un mensaje del Presidente Europa unida. América desunida. Hay diferencias sociales, culturales, étnicas y económicas, pero tenemos en gran parte de nuestra región idiomas comunes, antecesores europeos comunes, creencias religiosas comunes y aún así somos desunidos. Tenemos grandes amigos, familias que vienen de igual tronco, uniones familiares, todas características que saltan las fronteras, pero seguimos desunidos. La PAAO es la unión de todos los oftalmólogos desde el Polo Norte hasta el Mar de Drake. Somos la mejor sociedad oftalmológica supranacional en América. Somos los oftalmólogos los que estamos más unidos sin diferencias de credos, intereses comerciales, colores, etc. En nuestros congresos somos todos iguales, todos con los mismos derechos, como las Naciones Unidas de la oftalmología. Los cursos y simposios son integrados por colegas de todos los países y juntos llegan a conclusiones válidas. Aunque el español, el inglés, el portugués y ahora el francés son el idioma de la PAAO, el simple sistema de tener diapositivas en inglés soluciona muchos problemas. En casos especiales se debe recurrir a traducción simultánea que es muy onerosa para los organizadores de algún evento. El idioma inglés, original de Inglaterra, derivó a Estados Unidos y a algunas islas del Caribe. Hoy día es el idioma universal de las comunicaciones científicas, así como alguna vez fue el latín y en el siglo XIX el francés. Hablamos y escribimos el inglés no por ser la lengua de dos o tres países, sino por ser la lengua franca universal. No distinguimos país alguno al usar ese idioma, sólo lo usamos como medio de comunicación global. Así, y sin sentirnos dependientes, usamos la sigla PAAO para referirnos a nuestra asociación y no confundirnos con la Asia Pacific Association of Ophthalmology (APAO). 4 PAN-AMERICA Pero más allá de las formas, debemos trabajar para unir aún más a los oftalmólogos de las Américas. Debemos hablar más en común, debemos hablar más de igual a igual; igual grado de conocimiento, igual grado de destreza. La destreza es un don, pero el conocimiento se puede adquirir. La educación de los residentes debe ser una preocupación fundamental de la PAAO. Los residentes son nuestro futuro. Esta frase parece muy “cliché”, pero es una obligación imperativa de los cuerpos docentes y la PAAO como entidad supranacional tiene un rol que jugar. La educación tiene información y formación. La formación depende de cada departamento docente en cada universidad en cada país y tiene características propias de cada lugar. La información no tiene fronteras ni geografía ni ideologías. La información es libre, está en el aire, no es secreta, está al alcance de todos. Solamente se debe encausar esta información en un currículo adecuado. El ICO ya está trabajando en un currículo de oftalmología y la PAAO debería hacer lo mismo en paralelo. Hay algunos currículos para residentes de oftalmología ya aprobados en nuestra región y sería necesario trabajar en ellos para uniformarlos. Conseguir que el “Currículo de la PAAO para residentes en oftalmología” sea una información consensuada entre los departamentos de oftalmología de los países de la PAAO sería un paso muy importante para igualar al menos la información entre nuestros residentes y sería el primer paso para que la enseñanza de la oftalmología sea igual en toda la región. Dr. Cristián Luco Presidente, PAAO Marzo 2011 United in Education: A Message from the President Europe united. America divided. Although there are social, cultural, ethnic, and economic differences across the Americas, in a large part of our region we share common languages, common European ancestors, and common religious beliefs. Even so, we are divided. We have great friends, families that come from the same roots, family connections, all of the characteristics that cross borders, but we continue to be divided. The PAAO represents the unification of all ophthalmologists from the North Pole to the Drake Passage. We are the finest supranational ophthalmologic society in America. We are the most united ophthalmologists despite our different creeds, commercial interests, colors, etc. In our meetings, we are all equal, each with the same rights-- the “United Nations of ophthalmology.” Within our classes and symposia, colleagues from all countries are integrated and together draw valid conclusions. Although Spanish, English, Portuguese, and now French are the languages of the PAAO, the simple system of having slides in English solves many problems. In special cases, one must resort to simultaneous translation which can be quite onerous for the organizers of an event. The English language, originating in England, was brought to the United States and some Caribbean Islands. Today it is the universal language of scientific communication, just as Latin was once, and later French in the nineteenth century. We speak and write in English not because it is the language of two or three countries, but instead because it is the universal lingua franca of science. We do not distinguish any country using that language; we simply use it as a medium for global communication. And so, we use the acronym PAAO to refer to our association and to not confuse ourselves with the Asia Pacific Association of Ophthalmology (APAO) by using the Spanish acronym. But beyond form and language, we should work to further unite the ophthalmologists of the Americas. We should speak more as one, more as equal to equal with the same degree of both knowledge and skill. Skill is a gift, but knowledge must be acquired. For this reason, resident education should be a fundamental preoccupation of the PAAO. Our residents are our future. The phrase seems very much a “cliché”, but it is a necessary obligation of the teaching institutions as well as the PAAO, as a multinational entity. Education includes information and training. Training depends on every department’s faculty in every university in every country and, thus, bears the distinct characteristics of each place. Information, however, does not have borders or geography or ideology. Information is free; it is in the air; it is not secret; it is within everyone’s reach. This information can only be provided in an adequate curriculum that is relevant to all the Americas. The International Council of Ophthalmology (ICO) is already working on an ophthalmology curriculum, and the PAAO should do the same in parallel. There are curricula for ophthalmology residents already approved in our region, and it will be necessary to work to make these uniform. Fashioning the “PAAO Curriculum for Ophthalmology Residents” as a consensus among the departments of ophthalmology from the PAAO countries will be an important step to at least match the information between our residents, and it would be the first step in ensuring that the teaching of ophthalmology is uniform throughout the entire region. Cristián Luco MD PAAO President PAN-AMERICA 5 REVIEW Tratamiento para linfomas intraoculares Treatment for intraocular lymphomas Dr. Gian Paolo Giuliari1, 2 Correspondencias: 1 Av. Francisco de Miranda, Edificio CAVENDES Piso 6, Oficina 606, Los Palos Grandes Caracas-Venezuela, 1060 Email: gpgiuliari@gmail.com Teléfono: (58) (0212) 2852433 Fax: (58) (0212) 2850047 . Centro de Cirugía Oftalmológica (CECOF). Caracas-Venezuela. . Hospital Domingo Luciani. Departamento de Oftalmología. Caracas-Venezuela 2 El autor no reporta ningún conflicto de interés No funding support to disclose/no proprietary or financial interest to disclose Abstract Primary central nervous system lymphoma is a rare primary brain tumor, accounting for 1% to 3% of all central nervous system malignancies, which may affect the eye in up to a quarter of the cases. Failure to diagnose and treat the ocular component increases morbidity and mortality. Ninety-eight percent of the cases of intraocular lymphomas are non-Hodgkin’s B-cell. They may affect both the vitreous and the retina, while secondary invasion from a nodal lymphoma usually affects the uvea. Both forms frequently masquerade as intraocular inflammation. Systemic chemotherapy, alone or in combination with radiotherapy has been used for the treatment of these malignancies. However, when ocular involvement is present, due to the limited penetration through the blood-retina barrier of most of these drugs, adjuvant therapies should be employed. Ocular radiation have been administered in the past, however, due the high rate of recurrences, as well as the commonly seen side effects prompted additional modalities of treatment such intravitreal methotrexate and rituximab. Keywords: Ocular malignancy, Ocular lymphoma, Central nervous system lymphoma, reticulum cell sarcoma, Non-Hodgkin’s B cell lymphomas, Masquerade syndrome, Methotrexate and Rituximab. Resumen Los linfomas primarios del sistema nervioso central (SNC) son una causa poco común de tumores cerebrales, constituyendo sólo del 1 al 3% de todas las neoplasias del SNC, pudiendo afectar al ojo en un cuarto de los casos. La falla en el diagnóstico y el tratamiento del componente ocular incrementa la morbilidad y mortalidad de estos pacientes. En el 98% de los casos de linfoma intraocular se trata de un linfoma no Hodgkin de células B. Pueden afectar tanto el vítreo como la retina, mientras que una 6 PAN-AMERICA invasión secundaria a partir de un linfoma nodal puede afectar la úvea. Ambas formas pueden enmascararse como una inflamación intraocular. Quimioterapia sistémica, solo o en combinación con radioterapia ha sido el tratamiento de elección. Sin embargo, si existe un componente ocular, debido a la limitación en la penetración de estos medicamentos a través de la barrera hemato-retiniana, terapia co-adyuvante debe ser considerada. La radiación de los tejidos oculares ha sido empleada en el pasado, no obstante, debido a la alta tasa de recurrencias y a los frecuentes efectos secundarios se han estudiado otras opciones de tratamiento como la inyección intravítrea de metrotexate y rituximab. Palabras clave: Malignidad ocular, linfoma ocular, linfoma del sistema nervioso central, sarcoma de células reticulares, linfomas de células B no Hodgkin, síndromes de enmascaramiento, metrotexate, rituximab. Introducción Los linfomas primarios del sistema nervioso central (SNC) son una causa poco común de tumores cerebrales, constituyendo sólo del 1 al 3% de todas las neoplasias del SNC.1-3 El 98% de los linfomas primarios del SNC son linfomas no Hodgkin de células B, la mayoría de los cuales tienen su origen en un centro germinal.4 Usualmente se desarrollan en el cerebro, médula espinal, leptomeninges o en el ojo, de donde se pueden diseminar a través de todo el SNC.5-7 Epidemiología Los linfomas primarios del SNC afectan principalmente a pacientes en la sexta y séptima década de la vida, aunque también se han reportado casos en niños.8-9 Recientemente se ha visto una tendencia a presentarse más temprano, en especial en pacientes con deficiencias del sistema inmunológico, como es el caso de pacientes transplantados, o en pacientes con síndrome de inmunodeficiencia adquirida (SIDA).1,10,11 Manifestaciones clínicas Los linfomas primarios del SNC pueden presentarse aislados (confinados dentro de las estructuras del ojo), o presentar síntomas tanto oculares como del SNC.12 El compromiso ocular se puede presentar hasta en 1/4 de los pacientes.12 Por este motivo, en casos de linfomas intraoculares se debe llevar a cabo una búsqueda extensa de un posible compromiso del SNC, en un esfuerzo de reducir la morbilidad y mortalidad asociada en estos pacientes.13,14 Marzo 2011 En casos en los que hay compromiso ocular, las manifestaciones clínicas varían dependiendo del punto de infiltración de las células linfoides. Las estructuras mayormente afectadas son el vítreo, la retina, el espacio debajo del epitelio pigmentario y la cabeza del nervio óptico. Cuando la retina es afectada, generalmente pueden presentarse infiltrados amarillo-cremoso subretinales los cuales pueden producir desprendimientos localizados del epitelio pigmentario.4 (Figura 1) Cuando el linfoma intraocular es consecuencia de una invasión secundaria a partir de un centro nodal, generalmente la estructura mayormente afectada es la úvea. En estos pacientes, además de los síntomas oculares, generalmente se presentan con una afectación sistémica, con cuadros febriles, linfoadenopatías y pérdida de peso, lo cual facilita el diagnóstico.1-3 Los síntomas intraoculares más comúnmente asociados con linfomas intraoculares son la disminución de la agudeza visual y la presencia de flotadores, los cuales son secundarios al compromiso del vítreo.7,16,-17 Diagnóstico Para poder hacer el diagnóstico de linfoma intraocular o del SNC lo más importante es tenerlo presente dentro del grupo de diagnósticos diferenciales. El uso de estudios ancilares como la ultransonografía, en los que se puede observar engrosamiento coroido-escleral con abundante debris en el vítreo (Figura 2), al igual que puntos hiperfluorescentes en defectos de ventana, vasculitis y edema macular cistoideo en la angiografía con fluoresceína pueden facilitar el diagnóstico.18,19 (Figura 3) El diagnóstico definitivo requiere la identificación directa de las células malignas provenientes de fluidos y/o tejidos del ojo o del SNC. Estas células usualmente se presentan como células grandes y pleomórficas con hiperpigmentación del núcleo con nucleolos prominentes (Figura 4). La visualización de las células malignas se puede realizar principalmente mediante: (1) una punción lumbar con la extracción del fluido cerebroespinal; (2) una biopsia cerebral; y (3) una biopsia del vítreo mediante una vitrectomía.20,21 A su vez, diferentes métodos y técnicas se han desarrollado para facilitar el diagnóstico. Uno de ellos es la determinación de los niveles vítreos de interleuquina 10 (IL-10) e interleuquina 6 (IL-6).22 Se ha encontrado que en pacientes con inflamación ocular de origen linfoide existe un incremento en el ratio de IL-10:IL-6, mientras que en otras enfermedades inflamatorias hay un incremento de la IL-6. No obstante, se han encontrado niveles elevados de IL-10 en pacientes con uveítis no neoplásicas.23 Otro método recientemente utilizado es el uso de re-arreglo genético de la cadena pesada de inmunoglobulinas (IgH). Generalmente los linfomas de Figura 1. Montaje de fondo ocular en el cual se aprecian infiltrados amarillocremoso subretinales secundario a la infiltración de las células linfoides. (Cortesía del Massachusetts Eye Research and Surgery Institution) células B se presentan con un re-arreglo monoclonal de la IgH, pudiendo estar o no acompañados de un re-arreglo de la cadena liviana. Técnicas de análisis de Southern Blotting o por reacción de reacción en cadena de polimerasa (PCR) han mostrado beneficios en el diagnóstico.24 Tratamiento y pronóstico La quimioterapia sistémica con o sin radioterapia asociada ha sido el tratamiento de elección para los linfomas del SNC. La radiación cerebral con 50 gray (Gy), con un incremento de 10-Gy sobre la localización del tumor, ha mostrado índices de hasta un 90% de éxito en el tratamiento de linfomas no Hodgkin extranodales.25 Sin embargo, estudios recientes en el tratamiento de linfomas primarios del SNC han demostrado que la radiación como terapia única para el tratamiento de estos tumores, no sólo presenta un índice bajo de cura, sino una tasa alta de recurrencias, y una tasa alta de mortalidad en los primeros 5 años del diagnóstico; por lo que su uso en este tipo de neoplasias ha disminuido, principalmente en pacientes inmunocompetentes.26,27 El uso de protocolos con ciclosfosfamida, doxorubicin, vincristine y prednisona oral, no han demostrado un beneficio significativo con respecto al uso exclusivo de radioterapia.28-30 Esto se debe principalmente a la dificultad de la mayoría de estos agentes de penetrar adecuadamente la barrera hemato-cerebral. Por esta razón, combinaciones entre medicamentos sistémicos y locales son necesarias para obtener remisión de la enfermedad. La radiación orbital con 30-Gy ha sido un tratamiento efectivo en el manejo de pacientes con compromiso intraocular. No obstante, pueden presentarse con significativos efectos secundarios, como retinopatía secundaria a la radiación, cataratas, neuropatía óptica y síndrome de ojo seco, además que si la enfermedad ocular recurre, no se puede repetir la radiación.2,3,31 PAN-AMERICA 7 REVIEW Debido a estas limitantes en el tratamiento con radiación orbital, nuevos esfuerzos han sido empleados, con el uso de agentes quimioterapéuticos.32,33 Varios estudios han demostrado la eficacia y seguridad de inyecciones intravítreas de metrotexate en el tratamiento de neoplasias linfoides intraoculares.33,34 Estos reportes, han demostrado una dramática desaparición de las células malignas del vítreo de estos pacientes luego de repetidas administraciones; en muchos casos correlacionados con una disminución de los niveles altos iniciales de IL-10. Smith y colaboradores33 describieron un protocolo para estos pacientes en los que se administra una fase de inducción con inyecciones de metrotexate intravítreo bisemanal por un periodo de un mes con dosis de 400 μg en 0.1 ml. Subsecuentemente hay una fase de mantenimiento en la que se administran inyecciones mensuales por un año. Dentro de las complicaciones más frecuentemente encontradas en pacientes tratados con metrotexate intravítreo se encuentran el desarrollo de cataratas en más del 70% de los casos y el desarrollo de una epiteliopatía corneal en el 58%, la cual se resuelve luego de alargar los intervalos de tratamiento.33 Hemorragia vítrea, maculopatía y endoftalmitis estéril son complicaciones menos frecuentes.33-35 Otro medicamento recientemente utilizado de manera local para el tratamiento de los linfomas con compromiso intraocular es el rituximab, un anticuerpo monoclonal quimérico ratón/humano dirigido contra las células B CD20 positivas, lo cual lo hace muy eficiente como tratamiento para estos linfomas, debido a que la gran mayoría de los linfomas primarios del SNC son linfomas no Hodgkin de células B que expresan tanto CD19 como CD20.4,36-41 El rituximab tiene una penetración limitada a través de las barreras hemato-cerebral y hemato-retinianas, con lo que se previene el acceso de anticuerpos al SNC y al ojo.42 Reportes de casos sugieren que el uso de rituximab intratecal e intraocular en el tratamiento de linfomas del SNC con compromiso ocular es seguro y efectivo.43-45 A pesar que la mayoría de estos pacientes presentan una buena respuesta al tratamiento inicial, las recurrencias son frecuentes. La sobrevida de pacientes con linfoma intraocular fue calculada en 26 meses por Freeman y colaboradores,16 mientras que para aquellos pacientes con compromiso del SNC es solo de 13.5 meses.12 Char y colaboradores demostraron que la terapia agresiva con la combinación de quimioterapia intratecal asociada con radioterapia de la órbita y el cerebro pueden mejorar la sobrevida de estos pacientes.13 El tratamiento del componente ocular, aunque es de vital importancia para el manejo de estos pacientes, no mejora la sobrevida final.46 8 PAN-AMERICA Figura 2. Ultransonografía de un paciente con linfoma intraocular de células B no Hodgkin que muestra engrosamiento coroido-escleral con abundante debris en el vítreo (Cortesía del Massachusetts Eye Research and Surgery Institution) Figura 3. Angiografía de la retina con fluoresceína en fase tardía, en un paciente con linfoma intraocular mostrando múltiples puntos hiperfluorescentes en defectos de ventana. (Cortesía del Massachusetts Eye Research and Surgery Institution) Figura 4. Espécimen vítreo citocentrifugado que muestra las células pleomórficas con tinción para el marcador CD20 de células B. (Cortesía del Massachusetts Eye Research and Surgery Institution) Marzo 2011 Conclusiones Los linfomas primarios del SNC son un tipo de neoplasia insidiosa, agresiva y poco común que puede presentarse en muchos casos como procesos inflamatorios intraoculares. En la mayoría de los casos son linfomas no Hodgkin de células B, pudiendo comprometer al ojo hasta en 1/4 de los pacientes.12 El retraso en el diagnóstico y tratamiento precoz del componente intraocular incrementa la morbilidad y mortalidad de estos pacientes. Las estructuras oculares más frecuentemente afectadas son el vítreo, la retina, el espacio debajo del epitelio pigmentario y la cabeza del nervio óptico. Los síntomas oculares y las manifestaciones clínicas dependerán de cuales son las estructuras afectadas.1-3 El uso de agentes quimioterapéuticos como terapia única, o en combinación con radiación, han sido empleados comúnmente en el tratamiento de los linfomas del SNC. Sin embargo, si hay evidencia de compromiso intraocular, debido a la mala penetración de la mayoría de estos agentes a través de las barreras hemato-retinianas, se debe aplicar terapia local coadyuvante. En el pasado la radiación ocular se convirtió en el tratamiento de elección, no obstante debido a los frecuentes efectos secundarios y a la imposibilidad de repetir el tratamiento en caso de recurrencias, se ha incrementado la utilización de agentes inmunosupresores intravítreos, como es el caso del metrotexate y el rituximab.32,33,35,47,48 Debido a que los linfomas intraoculares son enfermedades poco comunes y la mayoría de las publicaciones en la literatura se basan sólo en reportes de casos, se requerirá de la realización de estudios multi-céntricos para reclutar un número de pacientes suficiente para poder diseñar estudios prospectivos, enmascarados y placebo-control para entonces poder evidenciar cual de estas nuevas opciones terapéuticas es más segura y eficaz para estos pacientes. REFERENCIAS 1. Mohile NA, Abrey LE. Primary central nervous system lymphoma. Neurol Clin 2007,25(4),1193-1207. system lymphoma incidence and survival rates. Neuro Oncol 2009 Mar 9 [Epub ahead of print]. hemorrhage and delayed deterioration after sterotactic brain biopsy. J Neurosurg 1998;89:31-35. 2. Chan C-C, Wallace DJ. Intraocular lymphoma: update on diagnosis and management. Cancer Control 2004,11(5),285-95. 11. DeAngelis LM, Gutin PH, Leibel SA, et al. Intracranial tumors. Diagnosis and treatment 1st edition. London: Martin Dunitz;2002. 3. Kim SK, Chan C-C, Wallace DJ. Management of primary intraocular lymphoma. Curr Oncol Rep 2005,7(1),74-79. 12. Hochberg FH, Miller DC: Primary central nervous system lymphoma. J Neurosurg 1988,68(6),835-53. 22. Chan CC, Whitcup SM, Solomon D, Nussenblatt RB.Interleukin-10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol 1995,120(5),671-3. 30. Shibamoto Y, Tsutsui K, Dodo Y, Yamabe H, Shima N, Abe M. Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy. Cancer 1990,65(9),1907-12. 23 Akpek EK, Maca SM, Christen WG, Foster CS. Elevated vitreous interleukin-10 level is not diagnositic of intraocular central nervous system lymphoma. Ophthalmology 1999,106(12),2291-5. 31. Schlegel U, Schmidt-Wolf IGH, Deckert M. Primary CNS lymphoma. Clinical presentation, pathological classification, molecular pathogenesis and treatment. J Neurol Sci 2000,181(1-2),1-12. 24. Cossman J, Zehnbauer B, Garrett CT, et al. Gene rearrangements in the diagnosis of lymphoma/leukemia. Guidelines for use based on a multiinstitutional study. Am J Clin Pathol 1991,95(3),347-54. 32. Fishburne BC, Wilson DJ, Rosenbaum JT, Neuwelt EA. Intravitreal methotrexate as an adjunctive treatment of ocular lymphoma. Arch Ophthalmol 1997,115(9),1152-1156. 42. Pels H, Schulz H, Schelegel U, Engert A. Treatment of CNS lymphoma with the anti-CD20 antibody rituximab. Onkologie 2003,26(4),351-354. 33. Smith JR, Rosenbaum JT, Wilson DJ, et al. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology 2002,109(9),1709-1716. 43. Itty S, Olson JH, O’Connell DJ, Pulido JS. Treatment of primary intraocular lymphoma (PIOL) has involved systemic, intravitreal or intrathecal chemotherapy and/or radiotherapy. Retina 2009,29(3),415-6. 34 Sou R. Ohguro N, Maeda T. Saishin Y. Tano Y. Treatment of primary intraocular lymphoma with intravitreal methotrexate. Jpn J Ophthalmol 2008,52(3),167-174. 44. Itty S, Pulido JS. Rituximab for intraocular lymphoma. Retina 2009,29(2),129-32. 4. Ferreri AJM, A brey LE, Blay J-Y, et al. Summary statement on primary central nervous system lymphomas from the Eigth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002. J Clin Oncol 2003,21(12),2407-14. 13. Char DH, Ljung BM, Miller T, Phillips T. Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management. Ophthalmology 1988,95(5),625-30. 14. Merchant A, Foster CS. Primary intraocular lymphoma. Int Ophthalmol Clin 1997,37(4),101-15. 5. DeAngelis LM, Yahalom J, Thaler H, et al. Combined modality therapy for primary CNS lymphoma. J Clin Oncol 1992;10:635-43. 15. Corriveau C, Easterbrook M, Payne D: Lymphoma simulating uveitis (masquerade syndrome). Can J Ophthalmol 1986,21(4),144-9. 6. Appen RE. Posterior uveitis and primary cerebral reticulum cell sarcoma. Arch Ophthalmol 1975;93:123-124. 16. Freeman LN, Schachat AP, Knox DL, et al. Clinical features, laboratory invstigations, and survival in ocular reticulum cell sarcoma. Ophthalmology 1987;94:1631-39. 7. Rockwood EJ, Zakov ZN, Bay JW. Combined malignant lymphoma of the eye and CNS (reticulum-cell sarcoma). J Neurosurg 1984;61:369-374. 8. Gass JDM: Neoplastic diseases of the retina and optic disc in Gass JDM (ed): Stereoscopic atlas of macular diseases, diagnosis and treatment,. St. Louis, Mosby, 1997, Vol. 2 Chapter 11, pp 867-902. [21] O’Neill BP. Epidemiology of Primary CNS Lymphoma. In: Batchelor TT, ed. Lymphoma of the Nervous System Boston, MA: Butterworth-Heinemann, 2004. 9. Jahneke K, Hummel M, Korfel A, et al. Detection of subclinical systemic disease in primary CNS Lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes. J Clin Oncol 2006,24(29),4754-7. 10. Pulido JS, Vierkant RA, Olson JE, Abrey L, Schiff D, Oâ Neill BP. Racial differences in primary central nervous 17. Barr CC, Green WR, Payne JW, et al. Intraocular reticulum-cell sarcoma: clinicopathologic study of four cases and review of the literature. Surv Ophthalmol 1975;19:224-39. 18. Ursea R, Heinemann MH, Silverman RH, Deangelis LM, Daly SW, Coleman DJ. Ophthalmic, ultrasonographic findings in primary central nervous system lymphoma with ocular involvement. Retina 1997,17(2),118-23. 19. Cassoux N, Merle-Beral H, Leblond V, et al. Ocular and central nervous system lymphoma: clinical features and diagnosis. Ocul Immunol Inflamm 2000,8(4),243-50. 20. Bernstein M, Parrent AG. Complications of CT-guided sterotactic biopsy of intra-axial brain lesions. J Neurosurg 1994;81:165-168. 21. Kulfarni AV, Guha A, Lozano A, Bernstein M. Incidence of silent 25. Chen MG, Prosnitz LR, GonzalezServa A, Fischer DB. Results of radiotherapy in control of stage I and II non-Hodgkins lymphoma. Cancer 1979,43(4),1245-54. 26. de Smet MD, Nussenblatt RB, Davis JL, et al. Large cell lymphoma masquerading as a viral retinitis. Int Ophthalmol 1990;14:413-417 27. Nelson DF. Radiotherapy in the treatment of primary central nervous system lymphoma (PCNSL). J Neurooncol 1999,43(3),241-7. 28. Lachance DH, Brizel DM, Gockerman JP, et al. Cyclophosphamide, doxorubicin, vinvristine, and prednisone for primary central nervous system lymphoma: short-duration response and multifocal intracerebral recurrence preceding radiotherapy. Neurology 1994,44(9),1721-7. 29. Schultz C, Scott C, Sherman W, et al. Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06. J Clin Oncol 1996,14(2),556-64. 35. de Smet MD, Vancs VS, Kohler D, Solomon D, Chan CC. Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma. Br J Ophhtalmol 1999,83(4),448-51. 36. Bataille B, Delwail V, Menet T, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 2000,92(2),261-266. 37. Schabet M. Epidemiology of primary CNS lymphoma. J Neurooncol 1999,43(3),199-201. 38. Kadoch C, Treseler P, Rubenstein JL. Molecular pathogenesis of primary central nervous system lymphoma. Neurosurg Focus. 2006;21(5):E1. 39. Vajkoczy P, Schilling L, Ullrich A, Schmiedek P, Menger M. Characterization of angiogenesis and microcirculation of high-grade glioma: an intravital multifluorescence microscopic approach in the athymic nude mouse. J Cereb Blood Flow Metab 1998,18(5),510-520. 40. Mineo JF, Scheffer A, Karkoutly C, et al. Using human CD20-transfected murine lymphomatous B cells to evaluate the efficacy of intravitreal and intracerebral rituximab injections in mice. Invest Ophthalmol Vis Sci 2008,49(11),4738-4745. 41. Kitzmann AS, Pulido JS, Moheney BG, et al. Intraocular use of rituximab. Eye 2007,21(12),1524-1527. 45. Kim H, Csaky KG, Chan C-C, et al. The pharmacokinetics of rituximab following an intravitreal injection. Exp Eye Res 2006;82:760-766. 46. Grimm, S.A.; McCannel, C.A.; Omuro, A.M.P.; et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology, 2008, 71 (17), 1355-60. 47. Skarin AT, Zuckerman KS, Pitman SW, et al. High-dose methotrexate with folinic acid in the treatment of advanced non-Hodgkin lymphoma including CNS involvement. Blood 1977,50(6),1039-47. 48. Balis FM, Poplack DG. Central nervous system pharmacology of antileukemic drugs. Am J Pediatr Hematol Oncol 1989,11(1),74-86 PAN-AMERICA 9 REVIEW New Vital Dyes to Stain Intraocular Membranes and Tissues during Vitrectomy Authors: Mauricio Maia MD PhD; Eduardo B. Rodrigues MD; Michel Eid Farah MD PhD; André Maia MD; Acácio Lima PhD; Octaviano Magalhães Jr MD; Eduardo Dib MD Vision Institute, Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil Correspondence: Mauricio Maia MD PhD 901 Otto Ribeiro Assis, SP Brazil 19800-320 Email: retina@femanet.com.br ACKNOWLEDGMENTS /DISCLOSURE: Funding / Support: - Fundação de Amparo a Pesquisa do Estado de Sao Paulo – FAPESP - Pan-American Association of Ophthalmology (PAAO)/Pan-American Ophthalmological Foundation (PAOF) Abstract Introduction Purpose: To present the current state-of-the-art information regarding the properties, indications, surgical techniques, and toxic effects of current and past applications of vital dyes in chromovitrectomy. Dyes may be designated “vital” when they are used to stain living tissues or cells. In ophthalmology, vital dyes have become very effective and useful surgical tools for ocular tissues identification. One especial surgical technique has been recently named chromovitrectomy, which concerns the use of vital dyes or crystals to improve the visualization of intraocular tissues during vitrectomy, thereby improving specific procedures such as internal limiting membrane (ILM) peeling.1-10 Design: Critical analysis and surgical perspective of the literature, recent studies and personal contributions. Methods: Review, interpretation, and comments regarding the most relevant experimental as well as clinical studies including the authors’ clinical and laboratory research. Results: The evolution of vitreoretinal surgical techniques has been worldwide reported. Chromovitrectomy plays an important hole in these innovations and is very useful to improve the surgical results. There is a consensus that application of vital dyes facilitates the delicate removal of intraocular membranes during vitreoretinal surgery. Controversy still remains around various issues, mainly potential toxicity and safety. The dyes currently used for different steps in chromovitrectomy are: triamcinolone acetonide for vitreous identification; indocyanine green, infracyanine green, and brilliant blue for internal limiting membrane identification and trypan blue for epiretinal membrane identification. The indocyanine green may be toxic for the retinal pigment epithelium if subretinal migration occurs during the surgical procedure. Efforts to avoid subretinal migration of dyes are very important during macular hole surgery. The physiological osmolarity around 270-320mOsm as well as ideal concentrations of the vital dyes during vitreoretinal surgery are important subjects. Conclusions: The state-of-the-art staining-assisted procedures should be performed using concentrations and volumes as low as possible. Triamcinolone acetonide is the ideal dye for vitreous; indocyanine green, infracyanine green and brilliant blue are the ideal dyes for internal limiting membrane; trypan blue is the ideal dye for epiretinal membrane identification. 10 PAN-AMERICA Chromovitrectomy – principles Chromovitrectomy has been introduced with the goal of avoiding ocular complications related to ILM peeling, poor removal of the vitreous and incomplete removal of the ERM. Since 2000, chromovitrectomy has become a popular approach among vitreoretinal specialists.9 Dyes have a variety of different chemical structures, which include a moiety responsible for the color, the so-called chromophore.1-10 Although highly important in organic chemistry, Figure 1 - Intraoperative view from the posterior hyaloid detachment assisted by triamcinolone, showing that posterior hyaloid is detached from the optic nerve in a diabetic retinopathy eye. Marzo 2010 Figure 2 - Autofluorescence and OCT images before macular hole surgery (upper left and lower left) and autofluorescence as well as OCT images after macular hole surgery and ILM peeling guided by 0.05% ICG staining (upper right and lower right). Note the absence of hyperautofluorescence image after surgery (upper right) and also the sealed hole by OCT (lower right). BCVA improved from 20/400 (upper left and lower left) to 20/30 (upper right and lower right). the identification of chromophores in vital dyes relevant to chromovitrectomy has not been well studied yet. Such field of research is important because the chromophore could be separated from other parts of the molecule resulting in a safer vital dye for the retina.1-10 vitreous cavity at the end of chromovitrectomy and minimal amounts of the drug may be left at the vitreous cavity following this technique.36 There is controversy regarding the possible decrease of macular hole closure rates following intraoperative triamcinolone use.36 Triamcinolone acetonide ICG and infracyanine green may be considered the gold standard dyes for staining and visualizing the ILM by the majority of vitreoretinal surgeons worldwide for surgical therapy of MH, DME and even ERM. ICG may possess a great affinity for the matrix components of the ILM such as collagen type 4 or laminin.2,18 ICG-guided chromovitrectomy initially gained worldwide popularity, and a large number of studies showed easier and less traumatic ICG-guided peeling with good clinical results in MH surgery. However, subsequent studies revealed the risk of ICG toxicity to the retina. For instance, clinical data showed that ICG could remain intravitreally or deposit persistently on the optic disc after MH surgery, or ICG could also diffuse to the subretinal space through the MH causing retinal pigment epithelium (RPE) damage (Figure 2).19, 20 The state-of-the-art staining agent for identification of the vitreous is the white steroid triamcinolone acetonide.2 Its crystals bind avidly to the vitreous gel and thereby enable the visualization of a clear contrast between the empty vitreous cavities (without vitreous) in comparison to areas where the vitreous fibers are still present. The surgical technique reported so far for triamcinolone acetonide application consists in a simple injection of 0.1-0.3 ml of the agent at a concentration of 40 mg/ml (4%) into the vitreous cavity directed toward the area to be visualized. In addition, this steroid injection during vitrectomy, for management of retinal detachment may prevent fibrin reaction and PVR postoperatively.15 The steroid improves identification of the tissues by deposition of crystals, and this effect helps the achievement of a complete detachment and removal of the posterior hyaloid, improving the results of primary vitrectomy for retinal detachment management and also for diabetic retinopathy in young patients (Figure 1).16,17 The main side effects following 12 months of intraocular injection of 4mg of triamcinolone acetonide are: cataract around 30-40% of eyes and increase of intraocular pressure in 20-30% of eyes.16 Cataract is more prevalent following 12 months follow up and increase of intraocular pressure after 2-3 months follow-up.16 However, it is supposed that these findings may be not true following its use at the intraoperative period because the steroid is removed from the Indocyanine green and infracyanine green It has been postulated that the use of ICG at low concentrations in ILM peeling could be a safer alternative, since lower rates of RPE abnormalities have been observed with ICG at a concentration of 0.5mg/ml (0.05%) or less and osmolarity of around 290 mOsm.21 Infracyanine green is a dye that contains no iodine in its formulation either as free ion or as part of the dye moiety2. For this reason, infracyanine green is believed to have less potential for RPE toxicity, since iodine and its derivates may be toxic to the RPE.14 In summary, the presumed safer infracyanine green profile may represent an alternative for ICG use during ILM peeling in chromovitrectomy due to the lack of sodium iodine in its formulation and physiological osmolarity.2,14 Indocyanine green toxicity The publications on retinal damage induced by ICG involve various hypotheses, and they may be divided in the following manner: Osmolarity of ICG solutions: Intravitreal ICG injections may change the osmolarity in the vitreous cavity, thereby damaging either the neurosensory retina or the RPE cells directly.14,22,23,24 PAN-AMERICA 11 REVIEW ICG molecule: Several investigations in various animal models have shown that ICG may be hazardous to the RPE or neuroretinal cells. Experiments showed that moderate to high doses (2.5 to 25 mg/ml or 0.25 to 2.5%) of intravitreal ICG are toxic to retinochoroidal cells, and impairment of retinal function was described even at low doses of ICG (0.025 mg/ml or 0.25%). (Figure 3).24,25,26 Ions: ICG molecule has around 5% iodine in its final solution and no sodium or calcium.2,14,34 Nevertheless, it is suggested that removal of sodium from the saline solution used for diluting the dye may decrease the risk of RPE damage.27 ICG-potentiated light toxicity: It has been speculated that ICG injection into the vitreous cavity may absorb light and that this interaction may lead to photodynamic effect thereby inducing retinal damage. It was demonstrated that subretinal ICG injection plus light exposure in rabbits may result in functional retinal damage and RPE changes.2,20,26,34 Figure 3 – Fundus phototographs after subretinal indocyanine green and trypan blue injection in rabbits. Source: Penha FM, Maia M, Eid Farah M et al. Effects of subretinal injections of indocyanine green, trypan blue, and glucose in rabbit eyes. Ophthalmology 2007;114:899-908. Fundus photograph 1 hour after subretinal injection of 0.5% ICG using a 41-gauge cannula (upper left) (arrow and arrowhead). Fluorescein angiogram (upper right) 1 week after subretinal ICG injection (arrow) and subretinal BSS injection (arrowhead), showing atrophic changes in positions related to previous subretinal injection of ICG (arrow) Fundus photograph 1 hour after subretinal ICG and TB injection (middle left); Fluorescein angiogram shows a more substantial damage of RPE in positions related to previous subretinal ICG(arrow) (middle right) compared to subretinal TB (arrowhead). (middle right) Fundus photograph 1 week after subretinal ICG (arrow) and TB (arrowhead) injection (down left); Fluorescein angiogram shows a more substantial damage of RPE in positions related to previous subretinal ICG (arrow) (lower right), compared to subretinal TB (arrowhead) (lower right). Decomposition products of ICG solution: Once diluted in any solvent and exposed to light, ICG may undergo various chemical reactions by self-sensitized oxidation since it is chemically unstable; such phenomena may be also called decomposition.29 It was demonstrated that independently of the light exposure, singlet oxygen (photodynamic type 2 reaction) is generated by ICG leading to dioxetanes by cycloaddition of singlet oxygen.29 Furthermore, dioxetanes thermally decompose into several carbonyl compounds; the decomposition of ICG was blocked by sodium azide, a quencher of singlet oxygen. This supports the rationale for future use of quenchers in chromovitrectomy. 29 Recently, it was reported that ICG may cause hipotony in 11% of eyes submitted to epiretinal membrane peeling and no fluid-air exchange; however, the intraocular pressure was normal in eyes that fluid-air exchange was used; the authors hypothesized that ICG in contact with the ciliar body may result in hipotony and suggest caution because postoperative ocular hypotony may occur in some cases of ICG-assisted macular surgery. Brilliant blue, trypan blue and patent blue In humans, brilliant blue caused adequate ILM staining in an iso-osmolar solution of 0.25 mg/ml (0.025%) with good clinical results and no signs of toxicity in multifocal ERG2. In brief, brilliant blue has become a good option for ICG and infracyanine green in chromovitrectomy due to its remarkable affinity for the ILM, although limited toxicity data in its application still warrant further investigations for confirmation of these observations; however, we have recently demonstrated that subretinal migration Figure 4 - Surgical techniques of internal limiting membrane (ILM) peeling ILM peeling guided by ICG staining in macular hole surgery (upper left) ILM peeling guided by brilliant blue staining in a macular hole surgery (upper right) Technique of “double staining” using brilliant blue and triamcinolone acetonide injected over the retinal surface using a soft tip cannula while the BSS infusion remained closed (lower left) ILM peeling guided by double staining technique after epiretinal membrane removal. Staining was performed with 0.2 ml of 40 mg/ml triamcinolone along with 0.2 ml of 0.25% brilliant blue (lower right) 12 PAN-AMERICA Marzo 2010 of the dye may cause RPE atrophic changes and therefore, we strongly suggest avoidance of brilliant blue exposure to the RPE during chromovitrectomy.35 TB may not enable ILM visualization as well as ICG, but this blue dye remains an alternative dye for this purpose.2 In order to enhance the TB staining property, this blue dye may be injected into the posterior pole after fluid air exchange or it may be mixed with glucose at 5 to 10% to thereby create a “heavy TB”, which is denser than BSS.2,33 However, higher glucose concentrations should be avoided because glucose 50% has a highly toxic osmolarity of 2020 mOsm/L and should be avoided.2 In summary, current state-of-the-art TB usage recommends blue-dye application mainly for ERM-staining.2,33 (Figure 5). For this reason, it has an affinity for epiretinal glial tissues such as the ERM, and therefore, we consider TB the best dye for staining the ERM. It is suggested to mix 0.3 ml of TB with 0.1 ml of glucose 10%, resulting in a 1 mg/ml (0.1%) solution and osmolarity of 300mOsm.2,32,33 Additionally, many authors have been reported the safety of trypan blue dye in prospective chromovitrectomy studies either for ERM or ILM peeling.38,39 Figure 5 - Surgical techniques of epiretinal membrane (ERM) peeling ERM peeling using no dyes (upper left) ERM peeling using 0.2ml of 40 mg/ml triancinolone acetonide (upper right) ERM peeling using trypan blue (TB) (lower left) ERM peeling using TA and TB, called the “doublestaining” technique. Staining was performed with 0.2 ml of 40 mg/ml triamcinolone along with 0.2 ml of 0.05% trypan blue (lower right). Double staining technique The double-staining technique (Figures 4 and 5) is an elegant procedure that may facilitate the identification of the posterior hyaloid and epiretinal membrane as well as the posterior hyaloid and ILM. In this technique, the initial step consists in the injection of a dye with high affinity to the vitreous to enable vitreous removal, followed by a second injection of a dye such as infracyanine green, ICG, TB or brilliant blue to stain and peel pre-retinal membranes.2 As an alternative technique, two dyes may be injected initially before both peeling procedures. REFERENCIAS 1. Jacobs DS, Cox TA, Wagoner MD, Ariyasu RG, Karp CL; American Academy of Ophthalmology; Ophthalmic Technology Assessment Committee Anterior Segment Panel. Capsule staining as an adjunct to cataract surgery: a report from the American Academy of Ophthalmology. Ophthalmology 2006;113:707-13. 2. Rodrigues EB, Maia M, Meyer CH, Penha FM, Dib E, Farah ME. Vital dyes for chromovitrectomy. Curr Opin Ophthalmol 2007;18:179-87. 3. Eckardt C, Eckardt U, Groos S, Luciano L, Reale E. Removal of the internal limiting membrane in macular holes. Clinical and morphological findings. Ophthalmologe 1997;94:545-51. 4. Rodrigues EB, Meyer CH, Farah ME, Kroll P. Intravitreal staining of the internal limiting membrane using indocyanine green in the treatment of macular holes. Ophthalmologica 2005;219:251-62. 5. Mester V, Kuhn F. Internal limiting membrane removal in the management of full-thickness macular holes. Am J Ophthalmol 2000;129:769-77. 6. Kwok AK, Li WW, Pang CP, et al. Indocyanine green staining and removal of internal limiting membrane in macular hole surgery: histology and outcome. Am J Ophthalmol 2001;132:178-83. 7. Engelbrecht NE, Freeman J, Sternberg P Jr, et al. Retinal pigment epithelial changes after macular hole surgery with indocyanine green-assisted internal limiting membrane peeling. Am J Ophthalmol 2002;133:89-94. 8. Haritoglou C, Gandorfer A, Gass CA, Schaumberger M, Ulbig MW, Kampik A. Indocyanine green-assisted peeling of the internal limiting membrane in macular hole surgery affects visual outcome: a clinicopathologic correlation. Am J Ophthalmol 2002;134:836-41. 9. Burk SE, Da Mata AP, Snyder ME, Rosa RH Jr, Foster RE. Indocyanine green-assisted peeling of the retinal internal limiting membrane. Ophthalmology 2000;107:2010-4. 10. Feron EJ, Veckeneer M, ParysVan Ginderdeuren R, Van Lommel A, Melles GR, Stalmans P. Trypan blue staining of epiretinal membranes in proliferative vitreoretinopathy. Arch Ophthalmol 2002;120:141-4. 11. Peyman GA, Cheema R, Conway MD, Fang T. Triamcinolone acetonide as an aid to visualization of the vitreous and the posterior hyaloid during pars plana vitrectomy. Retina 2000;20:554-5. 12. Hiebl W, Günther B, Meinert H. Substances for staining biological tissues: use of dyes in ophthalmology. Klin Monatsbl Augenheilkd. 2005;222:309-11. 13. Haritoglou C, Yu A, Freyer W, et al. An evaluation of novel vital dyes for intraocular surgery. Invest Ophthalmol Vis Sc 2005;46:3315-22. 14. Penha FM, Maia M, Farah ME, et al. Morphologic and clinical effects of subretinal injection of indocyanine green and infracyanine green in rabbits. J Ocul Pharmacol Ther 2008;24:52-61. 15. Cheema RA, Peyman GA, Fang T, Jones A, Lukaris AD, Lim K. Triamcinolone acetonide as an adjuvant in the surgical treatment of retinal detachment with proliferative vitreoretinopathy. Ophthalmic Surg Lasers Imaging. 2007;38:365-70. 16. Maia M, Farah ME, Belfort RN, et al. Effects of intravitreal triamcinolone acetonide injection with and without preservative.Br J Ophthalmol 2007;91:1122-4. 17. Abrams GW, Topping T, Machemer R. An improved method for practice vitrectomy. Arch Ophthalmol 1978;96:521-5. 18. Wollensak G, Spoerl E, Wirbelauer C, Pham DT. Influence of indocyanine green staining on the biomechanical strength of porcine internal limiting membrane. Ophthalmologica 2004;218:278-82. 19. Tadayoni R, Paques M, Girmens JF, Massin P, Gaudric A. Persistence of fundus fluorescence after use of indocyanine green for macular surgery. Ophthalmology. 2003;110:604-8. 20. Maia M, Haller JA, Pieramici DJ, et al. RPE abnormalities after ILM peeling guided by ICG staining. Retina 2004; 24:157-160. 21. Rodrigues EB, Meyer CH. Metaanalysis of chromovitrectomy with indocyanine green in macular hole surgery. Ophthalmologica 2008;222:123-9. 22. Stalmans P, Van Aken EH, Veckeneer M, Feron EJ, Stalmans I. Toxic effect of indocyanine green on retinal pigment epithelium related to osmotic effects of the solvent. Am J Ophthalmol 2002;134:282-5. 23. Marmor MF. Retinal detachment from hyperosmotic intravitreal injection. Invest Ophthalmol Vis Sci 1979;18:1237-44. 24. Penha FM, Maia M, Eid Farah M, et al. Effects of subretinal injections of indocyanine green, trypan blue, and glucose in rabbit eyes. Ophthalmology 2007;114:899-908. 25. Enaida H, Sakamoto T, Hisatomi T, Goto Y, Ishibashi T. Morphological and functional damage of the retina caused by intravitreous indocyanine green in rat eyes. Graefes Arch Clin Exp Ophthalmol. 2002;240:209-13. 26. Maia M, Kellner L, de Juan E Jr, et al. Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits. Retina 2004;24:80-91. 27. Ho JD, Chen HC, Chen SN, Tsai RJ. Reduction of indocyanine greenassociated photosensitizing toxicity in retinal pigment epithelium by sodium elimination. Arch Ophthalmol 2004;122:871-8. 28. Kadonosono K, Takeuchi S, Yabuki K, et al. Absorption of short wavelengths of endoillumination in indocyanine green solution: implications for internal limiting membrane removal. Graefes Arch Clin Exp Ophthalmol 2003;241:284-6. 29. Engel E, Schraml R, Maisch T, et al. Light-induced decomposition of indocyanine green.Invest Ophthalmol Vis Sci 2008;49:1777-83. 30. Koto T, Inoue M, Shinoda K, Ishida S, Tsubota K. Residual crystals of triamcinolone acetonide in macular hole may prevent complete closure. Acta Ophthalmol Scand 2007;85:913-4. 31. Maia M, Penha FM, Farah ME, et al. Subretinal injection of preservativefree triamcinolone acetonide and supernatant vehicle in rabbits: an electron microscopy study. Graefes Arch Clin Exp Ophthalmol 2008;246:379-88. 32. Uno F, Malerbi F, Maia M, Farah ME, Maia A, Magalhães O Jr. Subretinal trypan blue migration during epiretinal membrane peeling. Retina. 2006 Feb;26(2):237-9. 33. Maia M, Penha F, Rodrigues EB, et al. Effects of subretinal injection of patent blue and trypan blue in rabbits. Curr Eye Res. 2007 Apr;32(4):309-17. 34. Costa E, Rodrigues EB, Farah ME, et al. Vital dyes and light sources for chromovitrectomy: comparative assessment of osmolarity, pH, and spectrophotometry. Invest Ophthalmol Vis Sci. 2009 Jan;50(1):385-91. Epub 2008 Aug 8. 35. Maia M; Farah ME; Rodrigues EB; Malerbi F. Subretinal brilliant blue G migration during internal limiting membrane peeling. British Journal of Ophthalmology, v.93, p.330-331, 2009 36. Farah ME, Maia M, Rodrigues. Dyes in ocular surgery: principles for use in chromovitrectomy. Am J Ophthalmol. 2009;148(3):332-40 37. Iwase T, Jo YJ, Tanaka N. Ocular hypotony after the use of indocyanine green for epiretinal membrane surgery.Cutan Ocul Toxicol. 2010 Jun;29(2):130-6. 38. Mackenzie SE, Gandorfer A, Rohleder M, Schumann R, et al.Ultrastructure and retinal imaging of internal limiting membrane: a clinicopathologic correlation of trypan blue stain in macular hole surgery. Retina. 2010 Apr;30(4):655-61. 39. Mackenzie SE, Gandorfer A, Rohleder M, Schumann R, et al.Ultrastructure and retinal imaging of epiretinal membrane: a clinicopathologic correlation of trypan blue staining in epiretinal membrane surgery.Retina. 2010 Apr;30(4):648-54 PAN-AMERICA 13 CLINICAL SCIENCES Ozurdex®, a Novel Dexamethasone Delivery System, for Treatment of Macular Edema Following Retinal Vein Occlusion Rubens Belfort Jr. MD PhD1; Cristina Muccioli MD1; Susan S Lee MS2; Michael R. Robinson MD2 1 Deptartment of Ophthalmology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil Department of Ophthalmic Clinical Research, Allergan, Inc.; Irvine, CA, USA 2 Financial disclosures: Drs. Rubens Belfort and Cristina Muccioli are consultants to and have received research funding from Allergan, Inc. Mrs. Susan S. Lee and Dr. Michael R. Robinson are employees of Allergan, Inc. Resumen El tratamiento efectivo del edema macular representa un desafío principalmente debido a la limitada accesibilidad de fármaco vítreo para establecer y mantener niveles terapéuticos a largo plazo. El implante intravítreo de dexametasona (implante DEX; Ozurdex®) es actualmente el único sistema de aplicación de fármaco ocular biodegradable aprobado por la Administración de Alimentos y Medicamentos de EE.UU. que proporciona liberación del fármaco a una tasa estable por hasta 6 meses en el vítreo. Estudios clínicos recientes indican que el implante DEX emerge como una opción terapéutica efectiva y segura para el tratamiento de edema macular secundario a diversas enfermedades subyacentes. Abstract Effective treatment of macular edema is challenging primarily because of the limited vitreous drug accessibility to establish and maintain long-term therapeutic levels. Dexamethasone intravitreal implant (DEX implant; Ozurdex®) is currently the only biodegradable ocular drug delivery system approved by the US Food and Drug Administration that provides sustained drug release at a stable rate for up to 6 months in the vitreous. Recent clinical studies indicate that DEX implant is emerging as an effective and safe therapeutic option for treatment of macular edema secondary to a variety of underlying diseases. Introduction Retinal vein occlusion is the second most common retinal vascular disease after diabetic retinopathy. In branch retinal vein occlusion (BRVO), the occlusion is typically at an arteriovenous intersection while in central retinal vein occlusion (CRVO), the occlusion is at or 14 PAN-AMERICA Address for Correspondence: Rubens Belfort Jr. MD PhD Department of Ophthalmology Federal University of Sao Paulo Rua Botucatu 822 Sao Paulo, SP 04023-062, Brazil Phone: (55-11) 5085-2010 Fax: (55-11) 5573-4002 Email: clinbelf@uol.com.br proximal to the lamina cribrosa of the optic nerve, where the central retinal vein exits the eye.1,2 As with diabetic retinopathy and uveitis involving the posterior segment, BRVO and CRVO are associated with macular edema, which is the primary cause of vision loss.3-5 Macular edema is characterized by swelling of the macula due to breakdown of the blood–retinal barrier through a pathological process involving inflammatory cells, intercellular adhesion molecules, cytokines, and growth factors such as vascular endothelial growth factor (VEGF).6-11 Current strategies for the management of macular edema secondary to BRVO and CRVO are laser photocoagulation, vitrectomy, and pharmacotherapy with anti-VEGF agents and corticosteroids.1,2 Laser therapy is the standard of care for treatment of macular edema secondary to BRVO and CRVO. Although laser therapy decreases macular edema, the improvements in visual acuity are either marginal and occurring slow (in BRVO patients) or absent (in CRVO patients).12,13 Retrospective studies report that pars plana vitrectomy with internal limiting membrane peeling may improve visual acuity, warranting large scale, controlled clinical studies to establish the efficacy and safety.14,15 Recently introduced anti-VEGF agents significantly improve visual acuity in patients with macular edema secondary to BRVO and CRVO.16,17 To sustain the efficacy, however, anti-VEGF agents are to be administered every month, raising concerns about safety risks, patient compliance, logistical feasibility, and cost.18,19 Corticosteroids counteract many pathological processes that play a role in the development of macular edema, including prevention of leukocyte migration, inhibition of prostaglandin and pro-inflammatory cytokine synthesis, and reduction of fibrin deposition.20 Corticosteroids also inhibit the expression of VEGF as well as enhance the barrier function of tight junctions between vascular endothelial cells.21,22 Marzo 2010 Challenges in Treatment of Macular Edema with Corticosteroids The efficacy of corticosteroids to treat macular edema is primarily dependent on their potency and long-term bioavailability to the back of the eye. Betamethasone and dexamethasone are the most potent corticosteroids, with an anti-inflammatory activity that is at least 5-fold greater than that of triamcinolone (Table 1).23,24 Unfortunately, oral, topical, peribulbar, and subconjunctival corticosteroid administrations may deliver sub therapeutic vitreous drug levels that can be associated with relatively high systemic corticosteroid concentrations and significant adverse events (Table 2).25-29 Direct intravitreal corticosteroid injection, however, bypasses the blood–retinal barrier, leading to high local drug concentrations with few or no systemic adverse events. Yet, intravitreal administration is prone to rapid clearance of potent hydrophilic corticosteroids such as dexamethasone.29 Instead, the crystalline form of a less potent but relatively more hydrophobic corticosteroid, triamcinolone acetonide (Kenalog®-40, Bristol-Myers Squibb; Princeton, NJ, USA), has been used off-label for treatment of macular edema.30-32 Triamcinolone acetonide preparations have a heterogeneous particle size—varying substantially from batch to batch—that is randomly solubilized in the vitreous over several months.33 Although direct intravitreal injection of triamcinolone acetonide has gained some clinical success, it was associated with a high rate of elevated intraocular pressure (IOP) and cataract formation.34-36 Hence, new strategies providing more controlled and sustained drug release are needed to increase efficacy and improve safety. Drug Delivery Systems for the Posterior Segment In recent years, several intraocular drug delivery systems using implantable devices or injectable particles have been tested to achieve a more controlled drug release at a stable rate over a long period of time with a potentially lower rate of adverse events. Retisert® (Bausch & Lomb, Rochester, NY, USA), Iluvien® (Alimera Sciences, Alpharetta, GA, USA), and I-vation™ (SurModics, Inc., Eden Prairie, MN, USA) contain fluocinolone acetonide (Retisert® and Iluvien®) or triamcinolone acetonide (I-vation™) in a nonbiodegradable reservoir.37-39 Retisert® is approved for the treatment of chronic noninfectious uveitis affecting the posterior segment, while Iluvien® and I-vation™ are under development for treatment of diabetic macular edema.40,41 Both Retisert® and I-vation™ are inserted surgically, whereas Iluvien® is injected into the vitreous using an applicator in an office setting.42 All 3 implants, however, may need to be surgically removed once the drug release is complete because nonbiodegradable devices are not metabolized in vivo. In addition, there is an increa- figure 1 (a) Macula Implant Applicator (b) Figure 1. DEX Implant with Approximate Ocular Location After Implantation (a) and Dexamethasone Posterior Segment Drug Delivery System applicator (b). Table 1. Relative Potency of Corticosteroids23,24 Corticosteroid Relative Potency to Cortisol Cortisol 1 Cortisone 0.8 Prednisolone 4 Methylprednisolone 5 Triamcinolone 5 Fluocinolone 10-20 Betamethasone 25-40 Dexamethasone 30 Table 2. Peak Vitreous and Serum Dexamethasone Concentrations (Cmax) After Varying Routes of Administrations25-29 Route Dose (mg) Vitreous (Cmax, ng/mL) Serum (Cmax, ng/mL) Oral 7.5 5.2 61.6 Topical 0.5 1.1 0.7 Peribulbar 3.8 13 60 Subconjunctival 1.9 72.5 32.4 Intravitreal 0.4 100000 – PAN-AMERICA 15 CLINICAL SCIENCES sed risk for such adverse events as retinal detachment, vitreous hemorrhage, and endophthalmitis while retrieving and reimplanting nonbiodegradable devices.43 Figure 2. Before Implantation 3 weeks After Implantation Figure 2. Biodegradation of DEX Implant’s Copolymer Matrix.46 Used with permission from S. Karger AG, Basel. Figure 3. (A) Intravitreal Gd-D TPA Injection (0.2 mg) (B) DEX Implant (0.7 mg) Sustained-release dexamethasone intravitreal implant (DEX implant; Ozurdex®; Allergan, Inc.; Irvine, CA, USA) is the only biodegradable ocular drug delivery system approved by the US Food and Drug Administration (Figure 1a). DEX implant is indicated for the treatment of macular edema following RVO and for the treatment of non-infectious uveitis affecting the posterior segment of the eye.44 DEX implant is inserted into the vitreous cavity by an applicator in an office setting (Figure 1b).45 It contains dexamethasone within a biodegradable copolymer of lactic acid and glycolic acid (Novadur®; Allergan, Inc.) (Figure 2).44,46 DEX implant releases drug in a biphasic fashion, with higher doses for up to 6 weeks followed by lower doses for up to 6 months.47 In sharp contrast to rapid clearance of directly injected gadopentetate-diethylenetriamine pentaacetic acid (Gd-DTPA; Magnevist®, Bayer HealthCare Pharmaceuticals; Montville, NJ, USA)48—a magnetic resonance imaging (MRI) contrast agent with a similar molecular weight (570.0 Daltons) as dexamethasone (392.5 Daltons) that is used as a surrogate to study ocular pharmacokinetic of low molecular weight drugs such as corticosteroids49-51—DEX implant has been observed 6 months after implantation (Figure 3).47 Inside the eye, the copolymer is metabolized into carbon dioxide and water. Sequential implants can be placed in an office setting without the need for surgical removal. Clinical Applications of DEX Implant Figure 3. Temporal Kinetics of Gd-DTPA and Dexamethasone in Vitreous. (A) Gd-DTPA, a small molecular weight MRI contrast agent with a similar molecular weight to dexamethasone (i.e. < 1000 Daltons) was injected into the vitreous of 1 eye of an anesthetized rabbit. High resolution MRI was performed to image the drug depot in the vitreous (black arrow) over time. The contrast agent was completely cleared from the vitreous 2.5 hours after direct injection (0.2 mg).48 (B) In contrast, a DEX implant containing dexamethasone (0.7 mg) remained in monkey eyes for up to 6 months.48 Gd-DTPA = gadopentetate-diethylenetriamine pentaacetic acid; MRI = magnetic resonance imaging. 16 PAN-AMERICA A prospective, randomized, dose ranging, phase 2 trial evaluated the safety and efficacy of DEX implant in patients with macular edema secondary to CRVO, BRVO, diabetic retinopathy, uveitis, or Irvine-Gass syndrome persisting for ≥ 90 days after laser or medical therapy.52 Participants (N = 315) were randomly assigned to observation or treatment with DEX implant at 2 doses, 0.35 mg or 0.7 mg. At days 90 and 180, a significantly higher proportion of patients treated with DEX implant 0.7 mg had a ≥ 10-letter or a ≥ 15-letter improvement in BCVA than those in the observation group. While the improvement in BCVA was statistically similar in the observation group and the DEX implant 0.35 mg group, treatment with DEX implant at both doses (0.35 mg and 0.7 mg) significantly decreased central retinal thickness and fluorescein angiographic leakage at day 90 compared to the observation group.52 Subset analyses demonstrated that the treatment effect with DEX implant 0.7 mg was similar across the underlying causes of persistent macular edema (Table 3).52-54 The phase 2 study reported relatively few adverse events, including mild cases of IOP elevation. Overall, 3% of the observation patients, 12% of the DEX implant 0.35 mg patients, and 17% of the DEX implant 0.7 mg patients had an incidence of a ≥ 10 mm Marzo 2010 30 Table 3. Efficacy of DEX Implant 0.70 mg in Improving BCVA Stratified by the Underlying Cause of Macular Edema of Patients Who Participated in the Phase 2 Trial52-54 Patients with ≥ 10-Letter Improvement in BCVA at Day 90 (%) Underlying Disease Retinal vein occlusion (n = 34a) Inflammatory diseaseb (n =14c) Diabetic retinopathy (n = 57) Observation DEX Implant 15.0 31.0 P ND Percentage of Patients With > 15-Letter Improvement From Baseline BCVA at Day 180 a p =.017 compared to sham 26a 25 19 20 17.0 15 10 5 0 14.3 53.8 .029 12.3 33.3 .007 a n = 35 for DEX implant 0.70 mg. Inflammatory disease = uveitis or Irvine-Gass syndrome. n = 13 for DEX implant 0.70 mg. ND = not determined. b c Hg increase in IOP from baseline. Most of these patients (> 65%) had only a single occurrence of an IOP increase of this magnitude or greater.52 Two identical, multicenter, masked, clinical studies randomly assigned 1267 patients with vision loss due to clinically detectable macular edema associated with CRVO or BRVO to either a sham procedure or treatment with DEX implant at the dose of 0.35 mg or 0.7 mg.55 Compared to eyes receiving sham treatment, a significantly greater proportion of eyes receiving either dose of DEX implant achieved a 15-letter improvement from baseline BCVA from day 30 to day 90 (11% vs 29% and 29% at peak on day 60; P < .001). A similar significant difference was also found between the sham group and the DEX implant 0.7 mg group at day 180 after excluding patients who had the last study visit after 180 days (Figure 4). The time to achieve 15 letters of improvement from baseline BCVA was also significantly shorter in patients treated with either dose of DEX implant compared to those receiving sham procedure (P < .001). When analyzed by the underlying cause of macular edema, eyes with CRVO did not respond to the therapy for as long as did the eyes with BRVO, and they were not improved without therapy, suggesting that CRVO is a more visually disabling disorder than BRVO.55 Treatment with either dose of DEX implant significantly decreased the mean central retinal thickness compared to sham treatment at day 90 (P < .001), but not at day 180.55 Overall, DEX implants had favorable safety profiles and were associated with generally transient, moderate, and readily manageable adverse events. The proportion of patients experiencing an IOP elevation of 10 mm Hg or greater from baseline peaked at day 60 and was less than 1% in the sham group and approximately 15% in both DEX implant groups.55 Based on Sham DEX Implant 0.35 mg DEX Implant 0.70 mg (n = 208) (n = 216) (n = 229) Figure 4. Patients Achieving at Least 15 Letters of Improvement From Baseline BCVA at Day 180 in Phase 3 Trial of Patients With Retinal Vein Occlusion.55 Patients who had the last study visit later than 180 days were excluded from this analysis. these pivotal trials, DEX implant 0.7 mg was approved in the United States and Europe for treatment of macular edema due to RVO. Subsequently, DEX implant 0.7 mg was approved in the United State for the treatment of non-infectious uveitis affecting the posterior segment of the eye and in Brazil for treatment of macular edema due to RVO and uveitis. Ongoing clinical studies are evaluating the safety and efficacy of DEX implant for treating macular edema in uveitic and vitrectomized diabetic patients as monotherapy and in diabetic patients and those with choroidal neovascularization secondary to exudative age-related macular degeneration (AMD) as combination therapy with laser photocoagulation or ranibizumab, respectively. Preliminary findings indicate that DEX implant improves visual acuity in uveitic, vitrectomized diabetic, and diabetic patients and reduces the need for repeated ranibizumab injections in patients with AMD-induced choroidal neovascularization.56-59 Conclusions DEX implant significantly decreases central retinal thickness and improves BCVA in patients with macular edema caused by BRVO or CRVO. The current clinical experience indicates the potential of the DEX implant to emerge as a new treatment modality for improving vision of patients suffering from macular edema secondary to a variety of underlying diseases. Acknowledgment Editorial assistance in the preparation of this manuscript was provided by Hadi Moini PhD, of Pacific Communications, a wholly owned subsidiary of Allergan, Inc. PAN-AMERICA 17 CLINICAL SCIENCES REFERENCIAS 1. Wong TY, Scott IU. Clinical practice. Retinal-vein occlusion. N Engl J Med, 2010; 363 (22): 2135-2144. 2. Jonas J, Paques M, Mones J, Glacet-Bernard A. Retinal vein occlusions. Dev Ophthalmol, 2010; 47: 111-135. 3. Durrani OM, Tehrani NN, Marr JE, Moradi P, Stavrou P, Murray PI. Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol, 2004; 88 (9): 1159-1162. 4. Ferris FL, III, Patz A. Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol, 1984; 28 Suppl: 452-461. 5. Orth DH, Patz A. Retinal branch vein occlusion. Surv Ophthalmol, 1978; 22 (6): 357-376. 6. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW. Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes, 1998; 47 (12): 1953-1959. 7. Campochiaro PA, Hafiz G, Shah SM, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther, 2008; 16 (4): 791-799. 8. Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol, 2002; 133 (1): 70-77. 9. Rossetti L, Autelitano A. Cystoid macular edema following cataract surgery. Curr Opin Ophthalmol, 2000; 11 (1): 65-72. 10. Patel JI, Tombran-Tink J, Hykin PG, Gregor ZJ, Cree IA. Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: Implications for structural differences in macular profiles. Exp Eye Res, 2006; 82 (5): 798-806. 11. Vinores SA, Youssri AI, Luna JD, et al. Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease. Histol Histopathol, 1997; 12 (1): 99-109. 12. Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am J Ophthalmol, 1984; 98 (3): 271-282. 13. Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology, 1995; 102 (10): 1425-1433. 14. Mandelcorn MS, Nrusimhadevara RK. Internal limiting membrane peeling for decompression of macular edema in retinal vein occlusion: a report of 14 cases. Retina, 2004; 24 (3): 348-355. 15. Raszewska-Steglinska M, Gozdek P, Cisiecki S, Michalewska Z, Michalewski J, Nawrocki J. Pars plana vitrectomy with ILM peeling for macular edema secondary to retinal vein occlusion. Eur J Ophthalmol, 2009; 19 (6): 1055-1062. 16. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology, 2010; 117 (6): 1124-1133. 18 PAN-AMERICA 17. Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology, 2010; 117 (6): 1102-1112. 18. Mones J. A review of ranibizumab clinical trial data in exudative age-related macular degeneration and how to translate it into daily practice. Ophthalmologica, 2010; 225 (2): 112-119. 19. Pieramici DJ, Rabena M, Castellarin AA, et al. Ranibizumab for the treatment of macular edema associated with perfused central retinal vein occlusions. Ophthalmology, 2008; 115 (10): e47-e54. 20. Leopold IH. Nonsteroidal and steroidal anti-inflammatory agents. In: Sears ML, Tarkkanen A, eds. Surgical Pharmacology of the Eye. Raven Press, New York, 1985:83-133. 21. Nauck M, Karakiulakis G, Perruchoud AP, Papakonstantinou E, Roth M. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol, 1998; 341 (2-3): 309-315. 22. Antonetti DA, Wolpert EB, DeMaio L, Harhaj NS, Scaduto RC, Jr. Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem, 2002; 80 (4): 667-677. 23. Goldfien A. Adrenocorticosteroids and adrenocortical antagonists. In: Katzung BG, ed. Basic and clinical pharmacology. 6th ed. Prentice Hall International, London, 1995: 592-607. 24. Pace WE. Topical corticosteroids. Can Med Assoc J, 1973; 108 (1): 11-13. 25. Weijtens O, van der Sluijs FA, Schoemaker RC, et al. Peribulbar corticosteroid injection: vitreal and serum concentrations after dexamethasone disodium phosphate injection. Am J Ophthalmol, 1997; 123 (3): 358-363. 26. Weijtens O, Schoemaker RC, Cohen AF, et al. Dexamethasone concentration in vitreous and serum after oral administration. Am J Ophthalmol, 1998; 125 (5): 673-679. 27. Weijtens O, Feron EJ, Schoemaker RC, et al. High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection. Am J Ophthalmol, 1999; 128 (2): 192-197. 28. Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC. Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology, 2002; 109 (10): 1887-1891. 29. Kwak HW, D’Amico DJ. Evaluation of the retinal toxicity and pharmacokinetics of dexamethasone after intravitreal injection. Arch Ophthalmol, 1992; 110 (2): 259-266. 30. Ip MS, Kumar KS. Intravitreous triamcinolone acetonide as treatment for macular edema from central retinal vein occlusion. Arch Ophthalmol, 2002; 120 (9): 1217-1219. 31. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology, 2002; 109 (5): 920-927. 32. Antcliff RJ, Spalton DJ, Stanford MR, Graham EM, ffytche TJ, Marshall J. Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study. Ophthalmology, 2001; 108 (4): 765-772. 33. Kamppeter BA, Cej A, Jonas JB. Intraocular concentration of triamcinolone acetonide after intravitreal injection in the rabbit eye. Ophthalmology, 2008; 115 (8): 1372-1375. 49. Kim H, Lizak MJ, Tansey G, et al. Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging. Ann Biomed Eng, 2005; 33 (2): 150-164. 34. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology, 2008; 115 (9): 1447-9, 1449. 50. Vexler VS, Clement O, Schmitt-Willich H, Brasch RC. Effect of varying the molecular weight of the MR contrast agent Gd-DTPApolylysine on blood pharmacokinetics and enhancement patterns. J Magn Reson Imaging, 1994; 4 (3): 381-388. 35. Ip MS, Scott IU, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Arch Ophthalmol, 2009; 127 (9): 1101-1114. 36. Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol, 2009; 127 (9): 1115-1128. 37. Mohammad DA, Sweet BV, Elner SG. Retisert: is the new advance in treatment of uveitis a good one? Ann Pharmacother, 2007; 41 (3): 449-454. 38. Kane FE, Burdan J, Cutino A, Green KE. Iluvien: a new sustained delivery technology for posterior eye disease. Expert Opin Drug Deliv, 2008; 5 (9): 1039-1046. 39. Barnett PJ. Mathematical modeling of triamcinolone acetonide drug release from the Ivation intravitreal implant (a controlled release platform). Conf Proc IEEE Eng Med Biol Soc, 2009; 2009: 3087-3090. 40. Jaffe GJ, Martin D, Callanan D, Pearson PA, Levy B, Comstock T. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology, 2006; 113 (6): 1020-1027. 41. Kuno N, Fujii S. Biodegradable intraocular therapies for retinal disorders: progress to date. Drugs Aging, 2010; 27 (2): 117-134. 42. Kiernan DF, Mieler WF. The use of intraocular corticosteroids. Expert Opin Pharmacother, 2009; 10 (15): 2511-2525. 43. Martin DF, Ferris FL, Parks DJ, et al. Ganciclovir implant exchange. Timing, surgical procedure, and complications. Arch Ophthalmol, 1997; 115 (11): 1389-1394. 44. Ozurdex® [package insert]. Irvine, CA: Allergan, Inc.; 2009. 45. Haller JA, Dugel P, Weinberg DV, Chou C, Whitcup SM. Evaluation of the safety and performance of an applicator for a novel intravitreal dexamethasone drug delivery system for the treatment of macular edema. Retina, 2009; 29 (1): 46-51. 46. Kuppermann BD, Loewenstein A. Drug delivery to the posterior segment of the eye. Dev Ophthalmol, 2010; 47: 59-72. 47. Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of the sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci, 2010. 48. Data on file, Allergan, Inc. 51. Les SS, Edelhauser HF, Sharma P, Harutyunyan I, D’Argenio DZ, Moats RA. Understanding Drug Gradients in the Human Vitreous Using MRI. Invest Ophthalmol Vis Sci, 2009; 50: E-Abstract 5950. 52. Kuppermann BD, Blumenkranz MS, Haller JA, et al. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol, 2007; 125 (3): 309-317. 53. Haller JA, Kuppermann BD, Blumenkranz MS, et al. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol, 2010; 128 (3): 289-296. 54. Williams GA, Haller JA, Kuppermann BD, et al. Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol, 2009; 147 (6): 1048-1054. 55. Haller JA, Bandello F, Belfort R, Jr., et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology, 2010; 117 (6): 1134-1146. 56. Lightman S, Belfort R, Lowder C, Cui H, Li XY, Whitcup S. Double-masked, sham-controlled, randomized study of dexamethasone intravitreal implant for the treatment of uveitis. Presented at: 10th European Society of Retina Specialists (EUTORETINA) Congress; September 2-5, 2010; Paris, France. 57. Tabandeh H, Gupta S, Patel S, Lou J, Li XY, Whitcup S. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients: A prospective, 6-month, open-label study. Presented at: 10th European Society of Retina Specialists (EUTORETINA) Congress; September 2-5, 2010; Paris, France. 58. Lim Gupta S, Boyer D, Callanan D, Liu R, Li XY, Whitcup S. Safety and efficacy of intravitreal dexamethasone implant plus laser photocoagulation versus laser alone for treatment of diffuse diabetic macular edema. Presented at: 10th European Society of Retina Specialists (EUTORETINA) Congress; September 2-5, 2010; Paris, France. 59. Kuppermann B, Singer M, Tufail A, Lou J, Li XY, and Whitcup S. Ozurdex (dexamethasone intravitreal implant) as adjunctive therapy to lucentis in patients with choroidal neovascularization secondary to age-related macular degeneration. Presented at: 10th European Society of Retina Specialists (EUTORETINA) Congress; September 2-5, 2010; Paris, France. Marzo 2010 Incidencia de desprendimiento de retina en pacientes altos miopes postoperados de implante de LIO fáquico Artisan/Artiflex Luis Fernando Rosales Rodriguez MD; Luis Oswaldo Izquierdo Villavicencio MD; Maria Alejandra Henríquez MD Ninguno de los autores tiene interés comercial en el presente trabajo Correspondencias: Instituto de Ojos Oftalmosalud Avenida Javier Prado Este 1142, San Isidro, Lima, Perú Abstract Resumen Purpose: To described the incidence of retinal detachment (RD) in patients with preoperative high myopic value after five year of phakic intraocular lens (pIOL) was implant Artisan/Artiflex. Propósito: Describir la incidencia del desprendimiento de retina (DR) en pacientes altos miopes evaluados a un año de seguimiento posterior al implante del lente intraocular fáquico (pIOL) Artisan/Artiflex. Setting: Instituto de Ojos Oftalmosalud, Lima, Peru. Methods: This retrospective study included a review of 203 medical records (271 eyes) of patients with myopic refraction that underwent pIOL implantation by the same experimented surgeon between January 2004 to 2009, with a minimum postoperative follow-up of 1 year. The inclusion criteria were patients over 18 years old, a spherical equivalent (SE) over -6.00 Diopter (D) or with an axial length greater than 26mm, stable refraction for at least 2 years with best visual acuity (BVA) better than 20/100, without abnormalities in the anterior segment, and minimum endothelial cell count of 2,000 cells/mm3. Results: The average age of patients was 28.5 years (21-39 years). The women/men ratio was 1.7: 1 (36% men, 64% women). The average preoperative SE was -12.39 D (-8.00 to -23.00). In 69.74% (203 patients) we implant pIOL in both eyes. 189 eyes (69.74%) and 82 eyes (30.26%) had Artisan and Artiflex implanted respectively. The incidence of RD after pIOL implantation was 1.1% (3/271 eyes) of them was after artisan lens implant. Conclusion: The pIOL implant is a safe and effective option of correction high myopia. The incidence of RD was not different from the natural history of RD in myopic patients or high myopic patients with anterior segment surgery. Likewise, the prompt surgical management of this complication led to a satisfactory visual resolution in these patients. Lugar: Instituto de Ojos Oftalmosalud, Lima, Perú. Métodos: Estudio retrospectivo en el que se incluyeron 203 historias clínicas (271 ojos) de pacientes con alta miopía a los que se les implanto pIOL entre enero de 2004 a 2009, por un solo cirujano experto, con un año de seguimiento post operatorio. Los criterios de inclusión fueron pacientes mayores de 18 años, con equivalente esférico (EE) superior a -6.00 dioptrías (D) o longitud axial mayor de 26 mm, con una refracción estable de 2 años previos, agudeza visual mejor corregida (AVCC) mejor de 20/100, sin anormalidades en el segmento anterior y con un contaje de células endoteliales mínimo de 2,000 cel/mm3. Resultados: La media de edad de los pacientes fue de 28.5 años (21 – 39 años). La relación mujer/hombre fue de 1.7:1 (36% hombres, 64% mujeres). La media de Equivalente esférico preoperatorio fue de -12.39 D (-8.00 a -23.00). En el 74.90% (203 pacientes) fue implantado pIOL en ambos ojos. A 189 ojos (69.74%) y 82 ojos (30.26%) les fue implantado el pIOL Artisan y Artiflex respectivamente. La incidencia de DR posterior a la implantación de pIOL fue 1.1% (3/271 ojos). Todos ellos presentados en pacientes a los que se les implantó el pIOL Artisan. (3 ojos). Conclusión: El implante de pIOL es una opción segura y efectiva para la corrección de alta miopía. La incidencia de DR no fue diferente frente a la historia natural del DR en pacientes miopes o en cirugías del segmento anterior. No obstante, el manejo precoz de dicha complicación lleva a una recuperación satisfactoria de su AV en estos pacientes. Introducción La alta miopía se define como un aumento de la longitud axial del globo ocular por encima de 2 mm con respecto a la longitud axial del ojo emétrope ( 23 mm)1 o de un poder dióptrico superior de -6 dioptrías (d). La incidencia de desprendimiento de retina (DR) en pacientes miopes oscila entre 0.7 al 6%. Se estima que en pacientes miopes con más de -5.00d la incidencia es del 4.2% durante los primeros 60 años de su vida2, en comparación con pacientes emétropes cuya incidencia es de tan solo 0.06%2. En los pacientes miopes que son sometidos a cirugías de catarata, la inciPAN-AMERICA 19 CLINICAL SCIENCES Tabla 1. Características de cada paciente que presentó DR posterior al implante de pIOL. Paciente 1 2 3 Edad (años) 26 20 36 Sexo Femenino Femenino Femenino AVSC preoperatoria CD CD CD AVCC preoperatoria 20/30 20/40 20/40 EE preoperatorio -7.00 -12.0 -9.00 pIOL implantado Artisan Artisan Artisan Día postoperatorio de diagnóstico de DR 37 días 4 mes 5 mes Características del DR DR superior (meridianos 11 a 3 horas) DR superior (meridianos 11 a 2 horas) DR total Involucro Macular No No Sí Tratamiento quirúrgico del DR Retinopexia neumática, con vitrectomía. Con aplicación de láser al opérculo para sellar el desgarro retinal. Retinopexia neumática con C3F8 (Octafluoropropano) con vitrectomía, Endoláser al opérculo para sellar el defecto. Complicaciones Post cirugía de retina Ninguna Ninguna AVCC postoperatoria 20/40 20/40 20/60 Seguimiento post cirugía de retina 1 año (AVCC 20/40) 1 año (AVCC 20/40) 7 meses (20/60) Característica Retinopexia neumática con C3F8 (Octafluoropropano) con vitrectomía, Endoláser para sellar múltiples puntos de desgarro en área temporal superior. A los 36 días presentó DR, se realizó vitrectomía con cerclaje escleral e implante de banda de silicona 360°, y retinopexia neumática con C3F8 AVSC postoperatoria dencia es entre del 1 al 2%3 y en aquellos sometidos a implante de lentes intraoculares fáquicos (pIOL por sus siglas en inglés) esta incidencia no varía.4 Los pIOL evaluados en el presente estudio son: Artisan y Artiflex. El pIOL Artisan (Figura 1) es un lente rígido de polimetilmetacrilato (PMMA) que se ingresa a cámara anterior (CA) por una incisión corneoescleral de 6.5mm mientras el pIOL Artiflex (Figura 2) es un lente plegable que se ingresa a CA por una incisión corneoescleral de 3.00 mm cuyo material es de PMMA para la háptica y polysiloxane en la óptica3. La zona óptica del lente Artisan está disponible en diámetros de 5 y 6 mm: sus rangos de poder varían de -2.00 d a -23.5 d (cuya óptica es de 5 mm) y de -2.00 d a -15.5 d (cuya óptica es de 6 mm). Su grosor 20 PAN-AMERICA en el eje óptico es 0.2 mm. En el caso del Artiflex sus rangos de poder varían de -2.00D a -15.00D1 con óptica de 6 mm. Por otra parte, existen pIOL con poderes positivos, que han sido diseñados para pacientes áfacos, que en el presente estudio no se incluyeron6. El objetivo del presente estudio es evaluar la incidencia de DR en pacientes altos miopes, postoperados de implante de pIOL Artisan o Artiflex a un año de evaluación. Materiales y métodos Estudio retrospectivo de 203 pacientes miopes (271 ojos) a los cuales se les había sometido a cirugía de implante de pIOL, por el mismo cirujano con experiencia, entre enero de 2004 y enero de 2009, y con seguimiento postoperatorio mínimo a un año de cirugía. Marzo 2010 Conclusión La incidencia del DR no fue diferente a la historia natural del DR en pacientes miopes, ni operados de cirugía de catarata7. Así mismo, el manejo quirúrgico del DR llevó a una resolución satisfactoria de la visión en dichos pacientes. Discusión Figura 1: Lente Artiflex. Figura 2: Inyector del lente Artiflex. Los criterios de inclusión fueron pacientes mayores de 18 años con un equivalente esférico (EE) > -6.00 d, o con una longitud axial > 26 mm, refracción estable por lo menos 2 años, agudeza visual mejor corregida (AVCC) menor de 20/100, sin anormalidades en el segmento anterior, recuento de células endoteliales > 2000 cel/ mm3. Se excluyó a pacientes con cirugía de retina previa. La evaluación pre y postimplantación de pIOL (se realizó a los 1, 15vo día y 1,3, y 12 meses), incluyó AVSC, AVCC, refracción con y sin ciclopléjicos, examen oftalmológico a la biomicroscopia y examen de fondo de ojo, con midriasis farmacológica, usando oftalmoscopio indirecto con lupa de +20 D y + 90 D. Los equipos utilizados para el cálculo de la longitud axial y del poder dióptrico del lente fue el IOL Master (versión 3.01 de la marca Zeiss), utilizando una fórmula computarizada provista por el fabricante de los pIOL, el contaje de células endoteliales se realizó con el microscopio especular Topcon SP-2000P, y topografía corneal con el topógrafo córneal Keratron Scort optikon 2000. La cirugía fue realizada con incisión corneo-escleral superior (6.5 mm para el implante de pIOL Artisan y 3 mm para el Artiflex) e implante de pIOL con fijación iridiana. En el caso del Artiflex el implante del LIO se realizó a través de su inyector. El cierre de herida quirúrgica con Nylon 10-0 de la marca Johnson & Johnson en los casos de Artisan y con hidratación corneal en los casos de Artiflex. Resultados La edad media de los pacientes fue de 28.5 años (rango 21 - 39 años). La relación mujer/hombre fue 1.7:1 (36% a 64%) respectivamente, el EE preoperatorio promedio fue -18.3 (rango -8.00 a -23.00 d). La media de seguimiento fue de 14 meses (rango 12 – 22 meses). En el 74.90% de los pacientes se les implantó pIOL en ambos ojos (203 pacientes), de los cuales fueron 189 Artisan (69.74%) y 82 Artiflex (30.26). La incidencia del DR posterior al implante de pIOL fue del 1.1%. (3 /271). La edad media de estos pacientes fue de 27.3 años (rango 20 a 36). El rango del EE preoperatorio fue entre -7 y – 12D. Se reportó DR en 3 ojos (1.1%), los cuales (100%) fueron sometidos a vitrectomía vía pars plana (VVPP), reportándose una recurrencia del DR en 1 paciente (33.33%), el cual fue sometido a una segunda intervención, recuperándose satisfactoriamente. Los pacientes que presentaron DR fueron intervenidos por un cirujano de retina y vítreo. Se utilizó anestesia peribulbar y se intervino con equipo de vitrector Dorc, con puertos de 20 gauge (g). Tabla 1 muestra las caracteristicas de cada paciente que presentó DR. Según nuestros resultados el implante de un pIOL tiene riesgo similar al descrito en la literatura en pacientes altos miopes sometidos a cirugía de catarata8. Además, si bien es cierto que el riesgo de presentar un DR aumenta al momento de un evento quirúrgico en un paciente alto miope3, también lo es que esta complicación se presenta en el postoperatorio mediato3. En todos los casos del presente estudio, el DR se presentó dentro de los primeros 6 meses postoperatorios, por lo que consideramos de suma importancia el seguimiento postoperatorio de estos pacientes a largo plazo, con evaluación de fondo de ojo dilatado por especialista de retina. Por lo tanto, y basados en el presente estudio, concluimos que la incidencia de DR en implante de pIOL es baja y que el implante de estos lentes es eficaz pero no exento de complicaciones. REFERENCIAS 1. Kaufman, Paul, Alm Albert. Fisiología del Ojo, Decima edición, Mosby 2. Törnquist R. Stenkula, Törnquist P. Retinal detachment, a study of population – based patient material in Sweden 1971 – 1981. i. Epidemiology., Acta Opthalmol (Copenh) 1987 Apr. 65 (2) 213-22 3. Martínez–Castillo V, Boixadera A, Verdugo A, Elíes D, Coret A, García–Arumí. Rhegmatogenous retinal detachment in phakic eyes after posterior chamber phakic intraocular lens implantation for severe myopia. J. Ophthalmology, 2005 apr 112 (4) 580-5. 4. Navarro R, Gris O, Broc L, Corcóstegui B. Bilateral gigant retinal tear following posterior chamber phakic intraocular lens implantation. J Refract Surg. 2005 May – Jun; 21 (3): 298-300. 5. Ruiz-Moreno JM, Montero JA, De La Vega C, Alió JL, Zapater P. Retinal detachment in myopic eyes after phakic intraocular lens implantation. J Refract Surg. 2006 Mar; 22 (3): 247-52 6. Budo C, Hessloehl JC, Izak M & Cols. Multicenter study of the artisan phakic intraocular lens. J Cataract Refract Surg. 2000 Aug; 26 (8): 1163-71. 7. Maloney RK, Nguyen LH, John ME. Artisan phakic intraocular lens for myopia: short-tem results of a prospective, multicenter study. Ophthalmology, 2002 Sep; 109 (9): 1631-41. 8. Camille JR, Budo MD, The Artisan Lens, Highlights of Ophthalmology, 2004. PAN-AMERICA 21 CASE REPORT Queratitis por Acanthamoeba. A Propósito de un Caso Acanthamoeba Keratitis: A Case Report Miriam García-Fernández1; Begoña Baamonde Arbaiza2 Correspondencias: 1 Licenciado en Medicina 2 Doctor en Medicina Los autores certifican que este trabajo no ha sido publicado ni está en vías de consideración para publicación en otra revista. Asimismo transfieren los derechos de propiedad (copyright) del presente trabajo a Vision Pan-Americana. Dra. Miriam García Fdez c/Dionisio Ridruejo, No. 5, 11º D Oviedo, CP 33007 Spain E-mail: migarci@hotmail.es Institución responsable Hospital Universitario Central de Asturias (H.U.C.A) Acanthamoeba Keratitis. A Case Report Case report: A 33 year-old male, with hyperemic painful eye and no improvement after antibiotic and corticoid topic therapy. By biomicroscopy: annular infiltrate with inferior de-epithelialization, and limbal inflammation. Due to the suspicion of Acanthamoeba keratitis, we started treatment with clorhexidine 0.02%, polimyxin B+neomicin+ gramicidin (Oftalmowell®) and propamidine isethionate (Brolene®). A microbiological diagnosis confirmed the presence of Acanthamoebae, and diagnosis of Acanthamoeba keratitits was established. We observed a satisfactory evolution, with formation of a central corneal leukoma, followed by penetrating keratoplasty, with good results. Discussion: Clinical and microbiological early diagnoses are fundamental, since inappropirate treatment will lead to the development of cysts, and treatment resistance. Figura 1. a) Infiltrado anular inicial. B) Defecto epitelial centrocorneal inicial con limbitis importante. Keywords: Acanthamoeba keratitis, early diagnosis, microbiological diagnosis. Queratitis por Acanthamoeba. A Propósito de un Caso Caso clínico: Varón de 33 años con ojo hiperémico, doloroso, sin mejoría tras tratamiento con antibióticos y corticoides tópicos. A la exploración biomicroscópica: infiltrado anular desepitelizado por la parte inferior, con limbitis. Ante la sospecha de queratitis por Acanthamoebae, se inició tratamiento con clorhexidina 0.02%, polimixina B+neomicina+gramicidina (Oftalmowell®) e isetionato de propamidina (Brolene®). El estudio microbiológico confirmó el crecimiento de Acanthamoebae, por lo que se estableció el diagnóstico de queratitis por Acanthamoeba. La evolución fue satisfactoria, con formación de leucoma corneal central, que llevó a queratoplastia penetrante, con buenos resultados. 22 PAN-AMERICA Discusión: Un diagnóstico precoz, clínico y microbiológico es fundamental, pues un tratamiento inicial poco acorde dará lugar al enquistamiento y resistencia al tratamiento. Palabras clave: Queratitis por Acanthamoeba, diagnóstico precoz, diagnóstico microbiológico. Queratitis por Acanthamoeba. A Propósito de un Caso Introducción Las Acanthamoebae son protozoos ubicuos libres que se encuentran en aguas corrientes y en el suelo. Pueden existir como trofozoítos móviles o quistes latentes. Marzo 2010 La mayoría de estas queratitis (70%) se asocian al uso de lentes de contacto. Es frecuente que el tratamiento se retrase debido a diagnósticos erróneos tales como queratitis por herpes simple o por hongos. Caso clínico Varón de 33 años, que acude al Servicio de Urgencias por ojo derecho hiperémico, doloroso, con irradiación a región periorbitaria, sin mejoría tras un mes de tratamiento con antibióticos y corticoides tópicos. Como antecedente personal destaca que es portador de lentes de contacto blandos desechables de un mes. A la exploración se observa un infiltrado anular desepitelizado por la parte inferior con limbitis importante, así como ausencia de tyndall (Figura 1). La exploración de polo posterior es normal. La agudeza visual (AV) es de percepción y proyección de luz. Ante la sospecha de queratitis por Acanthamoeba se toman muestras para cultivo y frotis y se inicia tratamiento con clorhexidina 0.02% (CHX, Ashton Chemicals Ltd., Aylesbury, Reino Unido) 1 gota cada hora día y noche 48 horas y luego solo durante el día, así como una combinación de neomicina sulfato + gramicidina + polimixina B sulfato (Oftalmowell®) cada hora, ciclopléjico, flurbiprofeno (Froben®) e itraconazol (Canadiol®) oral, y se solicita isetionato de propamidina al 0,1% (Brolene®) como medicación extranjera, asociándolo al tratamiento en régimen horario a los 7 días. Los resultados de microbiología confirman el crecimiento de la ameba (Figura 2). Tras un mes de tratamiento antiamebiano, iniciamos corticoterapia sistémica y suspendemos Froben®. A los 6 meses, el paciente se encuentra estable, con un ojo bastante tranquilo, úlcera completamente epitelizada con leucoma central y adelgazamiento corneal (Figura 3). Para entonces, ya mantenemos dosis de 1 gota/8 h de Brolene® y CHX, así como corticoterapia sistémica a dosis bajas de 10 mg/ día. Se realiza microscopía confocal, que nos permite comprobar la ausencia de quistes. Un año después del inicio de la clínica, y ya sin tratamiento médico, dado la estabilidad del cuadro (persiste el leucoma y se observa una discreta opacificación capsular anterior y posterior del cristalino). Se decide incluir en lista de espera para queratoplastia penetrante. Ésta se practica a los 9 meses, sin complicaciones, siguiendo un tratamiento en el postoperatorio inmediato (Figura 4), con corticoides sistémicos, así como con antibioterapia, corticoterapia, midriáticos tópicos y Brolene® 1 gota 3veces/día. En la actualidad, tras siete meses de la queratoplastia, presenta una evolución satisfactoria, con el injerto epitelizado y transparente. Discusión La queratitis por Acanthamoeba inicialmente, se caracteriza por queratopatía punteada, pseudodendritas, infiltrados epiteliales y subepiteliales difusos o focales Figura 2. A) Trofozoito de Acanthamoeba con vacuola digestiva en su interior. B) Quistes de Acanthamoeba con la típica pared poligonal. Se introdujeron las muestras en salino de Page hasta su cultivo en agar no nutriente y posterior cultivo monoxenico. e infiltrados perineurales (queratoneuritis radial). Más adelante, se observan ulceración, infiltrados anulares y uveítis anterior (a menudo con hipopion). La limbitis es común tanto en etapas tempranas como avanzadas. Pueden producirse abscesos, escleritis, glaucoma, catarata e infección microbiana secundaria con hipotonía. En los estadios finales, el epitelio aparece íntegro, sobre un leucoma denso y vascularizado, a menudo con sinequias anteriores.1 Entre los factores predisponentes se destacan los traumatismos corneales, el contacto con cuerpos extraños2 o la exposición a aguas contaminadas (piscinas, por ejemplo); pero el factor de riesgo más importante para contraer esta infección es el uso de lentes de contacto. El diagnóstico se establece al ver las amebas en los frotis teñidos o cultivando los microorganismos obtenidos en los raspados corneales. Las amebas se ven en los frotis teñidos con Giemsa, ácido peryódico-Schiff (PAS), calcoflúor blanco o naranja de acridina. El agar sin nutrientes con una cepa de E. coli o E. aerogenes es el medio de cultivo preferido.3 Para demostrar la presencia de los microorganismos, en especial de las formas quísticas, se recurre también al microscopio confocal in vivo.4 PAN-AMERICA 23 CASE REPORT Figura 3. A) Leucoma residual corneal. B) Práctica completa resolución del defecto epitelial. medio, las consecuencias pueden ser devastadoras. Se asocian a un mal pronóstico: el diagnóstico tardío, un tratamiento antimicrobiano inadecuado, el empleo de corticoides tópicos antes del diagnóstico o la presencia de microorganismos resistentes. De ahí que sea importante un diagnóstico precoz, clínico y microbiológico, como se realizó en nuestro caso, pues un tratamiento inicial poco acorde da lugar al enquistamiento, el cual deriva, a su vez en resistencia y dificultades para erradicar la infección. Figura 4. Aspecto 9 días posqueratoplastia. La reacción en cadena de la polimerasa (PCR) detecta el ADN amebiano y también puede ser de utilidad.5 El diagnóstico precoz es el indicador pronóstico más importante del éxito del tratamiento. Las biguanidas y las diamidinas son los antiamebianos más eficaces y son quisticidas. Las diamidinas más usadas son el isetionato de propamidina (Brolene®) y la hexamidina al 0.1% (Desomedine®). Como biguanidas, polihexametileno biguanida (polihexamida) al 0.02% (PHMB, Avecia HQ, Manchester, Reino Unido), y Clorhexidina al 0.02% (CHX, Ashton Chemicals Ltd., Aylesbury, Reino Unido). La mayoría de estos fármacos sólo son eficaces frente a la forma libre del trofozoíto, con eficacia menor contra los quistes.3,6 Otros antiamebianos pueden ser aminoglucósidos e imidazoles por vía tópica. El uso de corticoesteroides tópico es controvertido.6 La queratoplastia penetrante puede ser necesaria en caso de cicatrices corneales o astigmatismo corneal irregular. Es recomendable esperar hasta haber conseguido la inactivación de la enfermedad, pues el pronóstico del injerto es mejor. No obstante, el riesgo de recurrencias es muy alto.1,3 Como conclusión, destacar, que aunque la queratitis por Acanthamoeba es poco frecuente en nuestro 24 PAN-AMERICA Por otra parte, el conocimiento por parte de los usuarios de lentes de contacto de sistemas eficaces de desinfección, como el calor o el peróxido de hidrógeno en dos pasos y empleo de soluciones comerciales de suero fisiológico,7 así como la evitación de situaciones de riesgo es fundamental en la prevención de esta enfermedad. REFERENCIAS 1. Juan A. Durán de la Colina. Queratitis por Acanthamoeba. En: Complicaciones de las lentes de contacto. Madrid: Tecnimedia; 1998:263-274 2. Abreu Reyes JA, Aguilar Estévez J, Rodríguez Martín FJ, Díaz Alemán VT, Abreu González R. Queratitis por acanthamoeba en paciente no portador de lentes de contacto. Arch Soc Canar Oftal 2003; 14:77-80 3. Thomas J. Liesegang, Gregory L. Skuta. Enfermedades infecciosas del exterior del ojo. En: Enfermedades externas y córnea. American Academy of Ophthalmology. Barcelona: Elsevier; 2008:187-189 4. Matsumoto Y, Dogru M, Sato EA, Katono Y, Uchino Y, Shimmura S et al. The application of in vivo confocal scanning laser microscopy in the management of Acanthamoeba keratitis. Mol Vis. 2007; 13:1319-26. 5. Zamfir O, Yera H, Bourcier T, Batellier L, Dupouy-Camet J, Tourte-Schaeffer C.Diagnosis of Acanthamoeba spp. keratitis with PCR. J Fr Ophtalmol. 2006; 29:1034-40 6. Ueki N, Eguchi H, Oogi Y, Shiota H, Yamane S, Umazume H. Three cases of Acanthamoeba keratitis diagnosed and treated in the early stage. J Med Invest. 2009; 56:166-9 7. López L, de Fernando S, Gaztelurrutia L, Vilar B, Pérez-Irezábal J, Barrón J. Queratitis por Acanthamoeba spp.: presentación de diez casos. Enferm Infecc Microbiol Clin. 2000; 18:229-33 Marzo 2010 Multilayered folded dehydrated amniotic membrane graft for scleral delle management Folded dehydrated AMT for scleral delle Jay C. Bradley MD Department of Ophthalmology & Visual Sciences, Texas Tech University Health Sciences Center Corresponding author/reprint requests: Jay C. Bradley MD 3601 4th St, STOP 7217 Lubbock, TX 79430-7217 Office: (806) 743-2020 Fax: (806) 743-2671 Email: jay.bradley@ttuhsc.edu No funding or support was provided for this study. The author does not have any financial or proprietary interests to disclose. Abstract Purpose: Report technique utilizing multilayered folded dehydrated amniotic membrane for refractory scleral delle management. Methods: A 3 x 2 centimeter dehydrated amniotic membrane was folded four times onto itself, with the basement membrane side on the exterior, to yield a 7.5 x 10 millimeter graft. This was sutured into the delle using four 9-0 vicryl sutures. Once adequate fixation of the multilayered folded graft was obtained, a primary conjunctival closure was performed using five 9-0 vicryl sutures. Total surgical time was fifteen minutes. Results: This technique was utilized on one patient with a refractory scleral delle after undergoing pterygium excision outside of my institution with bare sclera technique and intra-operative mitomycin C application. No post-operative complications or recurrence of the delle occurred after 9 months of followup. Conclusion: This technique provides an alternative efficient management of refractory scleral dellen while avoiding use of donor corneal or scleral tissue. Key words: multilayered, folded, dehydrated, amniotic membrane, scleral delle Introduction Scleral dellen occur due to various causes and are sometimes refractory to medical management.1-4 The association between sclera dellen and bare sclera pterygium excision with concomitant mitomycin C use is well known.2-3 Techniques for surgical management of scleral dellen, which generally involve a lamellar tectonic graft with overlying amniotic membrane and/or conjunctival closure, have been previously described.1,3 A few prior reports describe the use of fresh frozen amniotic membrane but, if multiple layers were used, separate grafts were cut and placed in a stepwise fashion.1,3-4 Dissection and manipulation of fresh frozen amniotic membrane for multilayered closure can be tedious due to the thin nature of the graft and the tendency of the Figure 1: Intra-operative anterior segment photographs demonstrating nasal scleral delle without perforation (upper, left), folded multilayered dehydrated amniotic membrane prior to suturing (upper, right) and after suturing (bottom, left), and immediate post-operative appearance after amniotic membrane graft and primary conjunctival closure (bottom, right). amniotic membrane to fold and inappropriately stick to itself or the ocular surface. Dehydrated amniotic membrane is also thin but can be easily folded and manipulated using forceps prior to wetting of the graft and is fixated in a single step. To the author’s knowledge, this report provides the first description of the use of folded multilayered dehydrated amniotic membrane with overlying conjunctival flap for the treatment of an acute scleral delle. Case Report The patient was a 78 year-old Hispanic male who underwent pterygium excision using bare sclera technique and mitomycin C by a surgeon outside Texas Tech University Health Sciences Center. After the surgery, delayed ocular surface healing was encountered which was refractory to medical therapy (including topical steroids, non-preserved artificial tears, and lubricating ointments). Almost three months after the surgery, the patient was referred to my institution for evaluation and a sceral delle adjacent to the nasal limbus was found (Figure 1). The scleral wall was thinned to approximately 20% normal thickness (estimated using anterior segment optical coPAN-AMERICA 25 CASE REPORT herence tomography) with a large overlying epithelial defect. The scleral bed surrounding the delle appeared avascular but no evidence of active melt or infection was noted. Since patient was refractory to prior medical management, surgical intervention was recommended. Methods/Results All necrotic material was removed to provide a smooth surface in the scleral delle. The scleral delle was measured and found to be 6 by 8 millimeters. A 3 x 2 centimeter dehydrated amniotic membrane (AmbioDry 2, IOP, Inc., Costa Mesa, California, USA) was used to fill the scleral delle and provide a substrate to allow revascularization and healing of the area postoperatively. The dry amniotic membrane was folded, using non-toothed forceps, four times onto itself, with the basement membrane side on the exterior, to yield a 7.5 x 10 millimeter graft. This was sutured into the delle using four 9-0 vicryl sutures. Once adequate fixation of the multilayered graft was obtained, a primary conjunctival closure was performed to close the defect overlying and adjacent to the scleral delle (Figure 1). This was performed using five 9-0 vicryl sutures being sure to eliminate any tension on the conjunctival closure. Total surgical time was fifteen minutes. Anterior segment optical coherence tomography was performed at 1 and 6 weeks post-operatively (Figure 2). After 9 months of additional follow-up, no complication or recurrence of the sclera delle was experienced. Discussion Sceral dellen can complicate pterygium surgery especially when bare scleral technique and mitomycin C are utilized.2-3 If perforation occurs or is imminent, a corneal or scleral graft with overlying amniotic membrane and/or conjunctival closure is likely the best option for surgical intervention.1 In cases with significant scleral thinning but without active melt or infection, my technique can be utilized effectively. This technique is simple to perform and can be performed under topical anesthesia. It does not require donor corneal or scleral tissue and can be performed more quickly than previously reported techniques. Folding of a single dehydrated amniotic membrane was performed to obtain the multilayered graft, as opposed to numerous single layered grafts stacked on one another, and the resultant graft had many more layers than previously reported techniques.1,3-4 The dehydrated amniotic membrane, prior to wetting, can be easily folded numerous times as desired using non-toothed forceps in a matter of seconds. This technique avoids some of the difficulty in manipulating fresh frozen amniotic membrane during multilayered closure and may decrease overall surgical time. By utilizing the folding technique, the amount of 26 PAN-AMERICA Figure 2: 1 week post-operative anterior segment optical coherence tomography (AS-OCT) testing (left) showing scleral delle with multi-layered folded amniotic membrane graft with overlying conjunctival closure. A space between the amniotic membrane graft and overlying conjunctival closure was noted. 6 week post-operative AS-OCT (right) showing thickening of scleral wall with incorporation of amniotic membrane graft. Resolution of space between amniotic membrane and overlying conjunctival closure was noted. graft material and associated costs are significantly decreased. Another advantage is that if this surgical intervention fails, a corneal or scleral graft can still be performed as previously described.1 Multilayered amniotic membrane has been reported for use in corneal ulcers, corneal perforations, and scleral dellen.1,3-5 There is some debate whether the amniotic membrane dissolves over time or if it adds thickness to the stroma in these cases. This case illustrates that folded multilayered amniotic membrane can also be used for thinning associated to scleral dellen and that the amniotic membrane appears to act as a tectonic graft, thickening the scleral wall. I utilized a graft of 8 layers (approximately 320 micrometers) in thickness based on single layer thickness of 40 microns. In the future, the optimal number of folds to use depending on the extent of the scleral thinning will need to be determined. Although additional study is needed, multilayered folded dehydrated amniotic membrane appears to be a valid alternative to previously reported techniques in the management of sclera dellen. BIBLIOGRAFÍA 1. Casas VE, Kheirkhah A, Blanco G, Tseng SC. Surgical approach for sclera ischemia and melt. Cornea. 2008;27(2):196:201. 2. Tsai YY, Lin JM, Shy JD. Acute sclera thinning pterygium excision with intraoperative mitomycin C: a case report of sclera dellen after bare sclera technique and review of the literature. Cornea. 2002;21(2):227-9. 3. Sridhar MS, Bansal AK, Rao GN. Multilayered amniotic membrane transplantation for partial thickness sclera thinning following pterygium surgery. Eye. 2002;16:639-42. 4. Hanada K, Shimazaki J, Shimmura S, Tsubota K. Multilayered amniotic transplantation for severe ulceration of the cornea and sclera. Am J Ophthalmol. 2001;131(3):324-31. 5. Muller M, Meltendorf C, Mirshahi A, Kohnen T. Use of multilayer amniotic membrane as first therapy for penetrating corneal ulcers. Klin Monbl Augenheilkd. 2009;226(8):640-4. Marzo 2010 Truly Unilateral Keratoconus Associated with Orbital Fibrosis Alejandro Navas MD; Armando González-Gomar MD; Zoraida Espinosa MD; José Luis Tovilla-Canales MD; Tito Ramírez-Luquín MD; Enrique O. Graue-Hernández MD Affiliation: Department of Cornea and Refractive Surgery, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico The authors have no proprietary interest in the materials presented herein. RESUMEN Objetivo: Reportar el caso de un paciente con queratocono unilateral verdadero en el ojo derecho asociado a fibrosis localizada en la órbita ipsilateral. Métodos: Hombre de 25 años de edad con agudeza visual progresiva en el ojo derecho con diagnóstico de queratocono unilateral y fibrosis orbitaria unilateral. El ojo derecho con una agudeza visual de 20/800 que mejoraba a 20/40 con una refracción de -7.50 -6.00 x 175°, presentando signos clínicos de queratocono. Los movimientos oculares muestran limitaciones en la mirada hacia arriba en todas las posiciones. El ojo y órbita del lado izquierdo sin ninguna alteración con una agudeza visual de 20/20. Resultados: Se realizó tomografía computada, confirmando el diagnóstico de fibrosis orbitaria en la órbita derecha, las topografías corneales a través del tiempo mostraron progresión evidente del queratocono en el ojo derecho y estabilidad en el ojo izquierdo. Conclusiones: El queratocono unilateral verdadero es una condición rara. La asociación de queratocono unilateral con alteraciones unilaterales de párpados y órbita se ha descrito previamente. Sin embargo, según nuestro conocimiento, este es el primer reporte de fibrosis orbitaria asociado con queratocono. ABSTRACT Purpose: To report a case of a patient who presented with true unilateral keratoconus in his right eye associated to a localized fibrosis in his ipsilateral orbit. Methods: A 25-year old male with progressive visual acuity loss in the right eye was diagnosed with unilateral keratoconus and unilateral orbital fibrosis. Right eye visual acuity was 20/800 improving to 20/40 with a Corresponding authors and Reprints: Alejandro Navas MD Deparment of Cornea and Refractive Surgery Institute of Ophthalmology “Conde de Valenciana” Chimalpopoca #14, Col Obrera, Mexico City, DF 06800 Mexico e-mail: babesian@gmail.com refraction of -7.50 -6.00 x 175° and he presented with clinical signs of keratoconus. Eye movements showed limitations in the upper gaze of the right eye in all positions. The fellow eye and orbit were under normal limits and visual acuity was 20/20. Results: Computed Tomography scan confirmed the diagnosis of orbital fibrosis in the right orbit and corneal topographies during a time span showed evident keratoconus progression of the right eye and stability in the left eye. Conclusions: True unilateral keratoconus is a rare condition. Association of unilateral keratoconus with unilateral eyelid and orbital conditions has been previously reported. Nevertheless, to our knowledge, this is the first report of orbital fibrosis associated with keratoconus. Key words: Keratoconus; unilateral keratoconus; monocular keratoconus; orbital fibrosis; eye rubbing Keratoconus (KC) is usually a bilateral condition that affects the cornea, producing thinning and protrusion without inflammation.1, 2 The asymmetry of the disease is well accepted, nonetheless, confirmed truly unilateral KC cases are rare and remote.3, 4, 5, 6 KC has been associated with several ocular disorders1, 2 as well as some eyelid and lacrimal system alterations,7, 8, 9 but there are no previous associations with orbital fibrosis to the best of our knowledge. Congenital orbital fibrosis is a disease classified under the congenital fibrosis of extraocular muscles (CFEOM). CFEOM classification has still been useful, even though sometimes the clinical presentation can overlap the subtypes of CFEOM.10, 11 Recently, some authors proposed to consider orbital fibrosis as a different clinical disease.12, 13 We present a case of true unilateral keratoconus secondary to orbital fibrosis. PAN-AMERICA 27 CASE REPORT CASE REPORT A 25 year-old male complained of progressive visual acuity loss in the right eye. He also noted changes in the cosmetic appearance of his right eyelid since childhood. Under examination, we found uncorrected distance visual acuity of 20/800 in his right eye with 20/20 in the left eye. The refraction was -7.50 -6.00 x 175° with scissoring reflex in the right eye and -0.50 -0.50 x 15° in the left eye, improving to a best spectacle corrected visual acuity of 20/40 and 20/15 respectively. Slit-lamp examination showed corneal thinning, Vogt’s striae as well as Munson’s and Rizzutti’s signs in the right eye. He presented a mild blepharoptosis and an inferior palpebral retraction. Interestingly, we found a limitation in the upper gaze of the right eye in all the eye movement positions (Fig. 1). We also performed a passive duction test that was positive upward and temporal in the right eye. The left eye slit-lamp examination was unremarkable. Computed Tomography (CT) scan, focused on the orbital region, showed thickening of the inferior and medial intraocular muscles and a mass with increased density both in the intraconal and extraconal areas that can correspond with fibrotic tissue (Fig. 2). We analyzed the Orbscan II (Bausch & Lomb, Rochester, NY) corneal topographies of the patient in both eyes finding throughout time, KC progression data in the right eye (Fig. 3) with no KC data and lack of progression in the left eye (Fig 4). We decided to treat the right eye with a rigid contact lens improving visual capacity to 20/25 and we strongly suggested for him to avoid eye rubbing. DISCUSSION Figure 2: Planar and contrast-enhanced CT scan images on coronal view showing a mass with thickening between the inferior and medial extraocular muscles, with increasing density corresponding to fibrotic tissue. We presented a case of true unilateral KC in a patient with orbital fibrosis on the right eye. The corneal topographic compilation during three years confirmed the progression of the disease in the right eye and inversely showed no significant change in the left eye. Some studies support that mechanical rubbing can affect the progression of KC.14, 15 We intentionally inquired of our patient about eye rubbing and he admitted a positive eye rubbing history in both eyes and more importantly in the right eye. Also, it is important to comment that he is a right-handed patient, which could have contributed with more force and intensity to this mechanical factor. Prior to videokeratoscopy studies unilateral KC was believed to occur in higher incidences of 14.3% and up to 41%,1 although at present, it is considered rare with ranges between 0.5 to 4%.4 Conversely some authors challenged that the possibility Figure 1: All gaze positions showing right eye limitation in the upper gaze. 28 PAN-AMERICA Marzo 2010 presented case and other diseases associated with KC, such as Leber congenital amaurosis, Down syndrome, atopic disease, contact lens wear and floppy eyelid syndrome,16 than to assume that all have a different associated factor that affects the cornea. In conclusion, this is a case of true unilateral KC secondary to mechanical trauma owed to orbital fibrosis. Further follow-up is recommended in order to rule out the possibility of keratoconus in the fellow eye, since KC can often present in a unilateral fashion with significant asymmetry for several years or even decades with development of keratoconus in the other eye in the future.4 These kinds of cases accentuate the role of eye rubbing as an etiologic or exacerbating factor in patients with KC. BIBLIOGRAFÍA Figure 3: Right eye topographic maps showing evident signs of progression in curvature, elevation and pachymetric maps during time: (A) three years ago, (B) one year ago and (C) most recent evaluation. Figure 4: Left eye topographic maps showing stability and lack of keratoconus data during time: (A) three years ago, (B) one year ago and (C) most recent evaluation. of true monocular KC can exist and even created some diagnosis criteria.5 In our case there is evidence of the presence of true unilateral or monocular KC during a significant time period that discards the involvement of the left eye. There are previous reports of unilateral or asymmetric KC associated with various clinical conditions that are associated with eye rubbing,3, 7, 8, 9 notwithstanding, to our knowledge, there are no previous associations of KC with unilateral orbital fibrosis. Krachmer suggested that there are some factors that control the changes induced by eye rubbing such as corneal thickness and biomechanics, as well as orbital structure.16 In this case, the orbital involvement can provide a role in the eye rubbing effect. Orbital fibrosis is a rare disease usually classified as a type of congenital fibrosis of the extraocular muscles, but recently some authors proposed to consider this entity as a different disease because it is unilateral, affects the orbit and not just the extraocular muscles, and apparently does not have a well established hereditary pattern.12,13 There is one report of congenital fibrosis of the inferior rectus developing high myopia in the ipsilateral eye in a child,11 yet authors did not mention any keratoconic data. In our case, the patient’s relatives noticed his ocular affection since he was 2 or 3 years old, but KC did not become evident until adolescence. Thus, we recommend performing corneal topographic analysis in cases with orbital fibrosis and myopia or anisometropia. This case suggests that a chronic habit of abnormal rubbing can be part of the pathogenesis of KC, or that it can contribute to the progression, as reported in previous studies.14, 15, 17 It is easier to deduce that eye rubbing is the shared factor in the 1. Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28:293-322. 2. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297-319. 3. Jafri B, Lichter H, Stulting RD. Asymmetric keratoconus attributed to eye rubbing. Cornea. 2004;23:560-564. 4. Li X, Rabinowitz YS, Rasheed K, et. al. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology. 2004;111:440-446. 5. Phillips AJ. Can true monocular keratoconus occur? Clin Exp Optom. 2003;86:399-402. 6. Zadnik K, Steger-May K, Fink BA, et. al. Between-eye asymmetry in keratoconus. Cornea. 2002;21:671-679. 7. Ioannidis AS, Speedwell L, Nischal KK. Unilateral keratoconus in a child with chronic and persistent eye rubbing. Am J Ophthalmol. 2005;139:356-357. 8. Lindsay RG, Bruce AS, Gutteridge IF. Keratoconus associated with continual eye rubbing due to punctual agenesis. Cornea. 2000;19:567-569. 9. Diniz CM, Tzelikis PF, Rodrigues Júnior A, et. al. Unilateral keratoconus associated with continual eye rubbing due to nasolac- rimal obstruction –case report. Arq Bras Oftalmol. 2005;65:122-125. 10. Shivaram SM, Engle EC, Petersen RA, et.al. Congenital fibrosis syndromes. Int Ophthalmol Clin. 2001;41:105-113. 11. Bagheri A, Naghibozakerin J, Yazdani S. Management of congenital fibrosis of the inferior rectus muscle associated with high myopia: a case report. Strabismus. 2007;15:157-163. 12. Athanasiov PA, Prabhakaran VC, Selva D. Unilateral orbital fibrosis with blepharoptosis and enophthalmos. Ophthal Plas Reconstr Surg. 2008;24:156-158. 13. Mavrikakis I, Pegado V, Lyons C, et al. Congenital orbital fibrosis: a distinct clinical entity. Orbit. 2009;28:43-49. 14. McMonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea. 2009;28:607615. 15. McMonnies CW. The evidentiary significance of case reports: eye rubbing and keratoconus. Optom Vis Sci. 2008;85:262-269. 16. Krachmer JH. Eye rubbing can cause keratoconus. Cornea. 2004;23:539-540. 17. Carlson AN. Keratoconus. Ophthalmology. 2009;116:2036-2037. PAN-AMERICA 29 Marzo 2011 New Publication Oftalmogeriatría Marcela Cypel and Rubens Belfort Jr Creative Latin Media, LLC Boca Raton, FL 440 pp. + Index Ha ssido sid idoo pu publ publicada blic icad adaa la eedi edición dici ción ón een español de Oftalmogeriatría. Todos los que nos ddedicamos a la oftalmología clínica reconocemos qu que los viejos son el centro de nuestra actividad. Marce Marcela Cypel y Rubens Belfort Jr., de la Universidad Federal de São Paulo, han producido un texto de gran importa importancia y que tendrá gran valor para los oftalmólogos de hhabla hispana. Este libro tiene un enfoque único, pues tra trata el diagnóstico y tratamiento de enfermedades que afectan todas las edades, desde el punto de vista geriátrico. Hace especial énfasis en el impacto que tienen varias entidades oftalmológicas en la población de edad avanzada y como el factor etario afecta el manejo de la enfermedad. Con más de 40 autores de los centros más importantes de Brasil, los 27 capítulos del libro cubren una gran gama de alteraciones oftalmológicas que afectan a la población de la tercera edad. Reviewed by Mark J. Mannis MD Geriatric Ophthalmology The Spanish language edition of Oftalmogeriatría has now been published. All of us who practice ophthalmology clinically recognize that the elderly are at the very center of what we do. Marcela Cypel and Rubens Belfort Jr. from the Federal University of São Paulo have produced a very important text that will be of great value to Spanish and Portuguese speaking ophthalmologists. The unique approach of this book is that it treats the diagnosis and management of entities that affect all ages from the special viewpoint of the elderly. The book emphasizes the specific impact that the wide variety of eye diseases have on the aging population and how the age factor specifically affects disease management. With over 40 contributing authors from the major ophthalmology programs in Brazil, the 27 chapters in the book cover the broad range of ophthalmic disorders and their impact on the aging population. Reviewed by Mark J. Mannis MD 30 PAN-AMERICA Marzo 2010 VISION PAN-AMERICA Instructions to Authors Vision Pan-America is the official publication of the PanAmerican Association of Ophthalmology (PAAO). The publication is particularly interested in receiving manuscripts that are short state-of-the-art review papers that will be of interest to the practicing PAAO member ophthalmologist. In addition to review articles, the publication is interested in articles on new surgical techniques, medical therapies, and case reports that emphasize clinicopathologic correlations. Submission information Manuscripts should be submitted electronically to the Editor-in-Chief, Mark J. Mannis MD at mjmannis@ucdavis.edu or can be sent via mail to: Mark J. Mannis MD Department of Ophthalmology University of California, Davis 4860 Y Street, Suite 2400 Sacramento, CA 95817, U.S.A. All submissions must be provided in electronic form as well as written manuscript form if mailed. All submissions must be original publications that have not been published elsewhere. Submissions can be in Spanish, English, Portuguese or French. All papers should be preceded by an abstract in either English or Spanish. Submission Format Papers submitted should be no longer than 1500 words (six double –spaced type-written pages) plus references. References should be included as a list on a separate page at the end of the manuscript with cited references keyed to the text in the order of appearance. The following format should be used for referenced papers: Jones JS, Garcia TL, Perrero M. Diabetic retinopathy in Bolivia. Cornea, 1996; 26 (2): 341- 343. Smith DJ, Caldera MC, Chang N, Ferrer RJ. Managing Ocular Trauma. Hofstra and Kennimore Publishers, London, 1989. Color figures are encouraged and should be submitted in PICT or JPEG format. Powerpoint format is not acceptable, and images embedded in word documents are not acceptable. The title page should include the following: (1) each author’s full name (i.e., first name, middle initial if used, and last name) and highest degree (i.e. MD, PhD); (2) city, state, and country in which work was carried out; (3) name and address of author to receive reprint requests; (4) statement about the authors’ proprietary or financial interest in a product or lack thereof. Vision Pan-America es la publicación oficial de la Asociación Panamericana de Oftalmología (PAAO). La publicación está particularmente interesada en recibir manuscritos que sean cortas revisiones de materias novedosas de interés para los oftalmólogos miembros de la Asociación. Además de las revisiones, la publicación está interesada en artículos acerca de nuevas técnicas quirúrgicas, nuevas terapias médicas y casos de correlación clínico-patológica. Información de presentación Los manuscritos deben enviarse electrónicamente al jefe de redacción, Mark J. Mannis, MD a mjmannis@ucdavis.edu o puede enviarse vía correo a: Mark J. Mannis, MD, Departamento de Oftalmología Universidad de California, Davis 4860 Y Street, Suite 2400 Sacramento, CA 95817, U.S.A. Si se envía el trabajo por correo, este debe ir tanto impreso (a máquina, etc.) y en forma electrónica (CD, etc.). Todas las presentaciones deben ser publicaciones originales que no se hayan publicado en otra parte. Las presentaciones pueden ser escritas en idioma español, inglés, portugués o francés. Todos los trabajos deben tener un resumen en inglés y en español. Formato de presentación Los trabajos presentados no deben sobrepasar las 1500 palabras (seis páginas escritas a doble espacio) más las referencias. Las referencias deben ser incluidas como una lista en una página separada al final del manuscrito con referencias citadas codificadas al texto en el orden de aparición. El siguiente formato debe usarse para las referencias: Jones JS, García TL, Perrero M. Retinopatía Diabética en Bolivia. Córnea, 1996; 26 (2): 341 - 343. Smith DJ, Caldera MC, Chang N, Ferrer RJ. Managing Trauma Ocular. Hofstra y Publicadores de Kennimore, Londres, 1989. Se aceptan figuras de color y deben enviarse en PICT o formato de JPG. El formato de Powerpoint no es aceptable. La página del título debe incluir lo siguiente: (1) el nombre completo de cada autor (es decir, nombre(s) y apellido(s)) y el grado académico más alto (ej. MD PhD); (2) la ciudad, estado, y país en que el trabajo se llevó a cabo; (3) el nombre y dirección del autor para recibir pedidos de separata; (4) declaración de los autores si existe o no interés financiero en un producto citado o utilizado en el trabajo. PAN-AMERICA 31 2011 Pre ARVO PanAmerican Research Day April 30, 2011 Renaissance Fort Lauderdale Hotel Atlantic Ballroom Sponsored by Registration 11:00 am - 12:30 pm Working Session Co-Sponsored by 12:30 pm- 5:30 pm Keynote Speakers Renaissance Fort Lauderdale Hotel 1617 SE 17th Street Fort Lauderdale, FL 33316 www.renaissancehotels.com Phone : 954-626-1700 Cocktail reception (light buffet will be served) Garden Terrace 6:00-9:00 pm 16 Travel Scholarships to be awarded on site! www.paao.org Preserva la visión alcanzando las menores presiones-objetivo en más pacientes Investigadores de diversos estudios, (AGIS, Shirakashi, Shields) han comprobado que alcanzar y mantener la PIO entre 14 y 15 mmHg reduce la progresión de pérdida del campo visual1,2,3. Lumigan® alcanza la PIO-objetivo de 14/15 mmHg en un mayor número de pacientes: ® vs. timolol 4 ® vs. dorzolamida/ timolol 5 ® vs. latanoprost 6 Porcentaje de Pacientes que alcanzaron la PIO-Objetivo ≤14 21% 9% 17% 2% 19% 9% Porcentaje de Pacientes que alcanzaron la PIO-Objetivo ≤15 31% 16% 24% 9% 29% 14% Lumigan ® (bimatoprost) Forma farmacéutica y pr esentación. Composición. Cada ml contiene: 0,3 mg de bimatoprost. Vehículo: cloreto de sódio, fosfato de sódio presentación. esentación.Frascos cuenta-gotas conteniendo 5 ml de solución oftalmológica estéril de bimatoprost a 0,03%. USO ADULTO.Composición. hepta-hidratado, ácido cítrico mono-hidratado, ácido clorídrico y/o hidróxido de sódio, cloruro de benzalconio y agua purificada qsp. Indicaciones. LUMIGAN® (bimatoprost) es indicado para la reducción de la presión intra-ocular elevada en pacientes con glaucona o hipertensión ecauciones y Adver tencias. Advertencias. Fueron relatados aumento gradual del crescimiento Contraindicaciones. LUMIGAN® (bimatoprost) está contraindicado en pacientes con hipersensibilidad al bimatoprost o cualquier otro componente de la fórmula del producto. Pr Precauciones Advertencias. ocular.Contraindicaciones. de las pestañas en el largo y espesura, y oscurecimiento de las pestañas (en 22% de los pacientes después 3 meses, y 36% después 6 meses de tratamiento), y, oscurecimiento de los párpados (en 1 a <3% de los pacientes después 3 meses y 3 a 10% de los pacientes después 6 meses de tratamiento). También fue relatado oscurecimiento del íris en 0,2% de los pacientes tratados durante 3 meses y en 1,1% de los pacientes tratados durante 6 meses. Algunas de esas alteraciones pueden ser permanentes. Pacientes que deben recibir el tratamiento ecauciones LUMIGAN® (bimatoprost) no fue estudiado en pacientes con insuficiencia renal o hepática y por lo tanto debe ser utilizado con cautela en tales pacientes.Las lentes de contacto deben Precauciones de apenas uno de los ojos, deben ser informados a respecto de esas reacciones. Pr ser retiradas antes de la instilación de LUMIGAN® (bimatoprost) y pueden ser recolocadas 15 minutos después. Los pacientes deben ser advertidos de que el producto contiene cloruro de benzalconio, que es absorvido por las lentes hidrofílicas.Si más que un medicamento de uso tópico ocular estuviera siendo utilizado, se debe respetar un intervalo de por lo menos 5 minutos entre las aplicaciones.No está previsto que LUMIGAN® (bimatoprost) presente influencia sobre la capacidad del paciente conducir vehículos u operar máquinas, sin embargo, así como para cualquier colírio, puede ocurrir visión borrosa transitoria después de la instilación; en estos casos el paciente debe aguardar que la visión se normalice antes de conducir u operar máquinas. Interacciones medicamentosas. medicamentosas.Considerando que las concentraciones circulantes sistemicas de bimatoprost son extremadamente bajas después múltiplas instilaciones oculares (menos de 0,2 ng/ml), y, que hay varias vías encimáticas envueltas en la biotransformación de bimatoprost, no son previstas interacciones medicamentosas en humanos. eacciones adversas. LUMIGAN® (bimatoprost) es bien tolerado, pudiendo causar eventos adversos oculares leves a moderados y no graves.Eventos adversos ocurriendo en 10-40% de los pacientes que recibieron doses únicas diarias, durante No son conocidas incompatibilidades. RReacciones 3 meses, en orden decreciente de incidencia fueron: hiperenia conjuntival, crecimento de las pestañas y prurito ocular.Eventos adversos ocurriendo en aproximadamente 3 a < 10% de los pacientes, en orden decreciente de incidencia, incluyeron: sequedad ocular, ardor ocular, sensación de cuerpo estraño en el ojo, dolor ocular y distúrbios de la visión.Eventos adversos ocurriendo en 1 a <3% de los pacientes fueron: cefalea, eritema de los párpados, pigmentación de la piel periocular, irritación ocular, secreción ocular, astenopia, conjuntivitis alérgica, lagrimeo, y fotofobia.En menos de 1% de los pacientes fueron relatadas: inflamación intra-ocular, mencionada como iritis y pigmentación del íris, ceratitis puntiforme superficial, alteración de las pruebas de función hepática e infecciones (principalmente resfriados e infecciones de las vías respiratorias).Con tratamientos de 6 meses de duración fueron observados, además de los eventos adversos relatados más arriba, en aproximadamente 1 a <3% de los pacientes, edema conjuntival, blefaritis y astenia. En tratamientos de asociación con betabloqueador, durante 6 meses, además de los eventos de más arriba, fueron observados en aproximadamente 1 a <3% de los pacientes, erosión de la córnea, y empeoramiento de la acuidad visual. En menos de 1% de los pacientes, blefarospasmo, depresión, retracción de los párpados, Posología y Administración. hemorragia retiniana y vértigo.La frecuencia y gravedad de los eventos adversos fueron relacionados a la dosis, y, en general, ocurrieron cuando la dosis recomendada no fue seguida.Posología Administración.Aplicar una gota en el ojo afectado, una vez al día, a la noche. La dosis no debe exceder a una dosis única diaria, pues fue demostrado que la administración más frecuente puede disminuir el efecto hipotensor sobre la hipertensión ocular.LUMIGAN® (bimatoprost) puede ser administrado concomitantemente con otros productos oftálmicos tópicos para reducir la hipertensión intra-ocular, respetándose el intervalo de por lo menos 5 minutos entre la administración de los medicamentos. VENTA BAJO PRESCRIPCIÓN MÉDICA.“ESTE PRODUCTO ES UM MEDICAMENTO NUEVO AUNQUE LAS INVESTIGACIONES HAYAN INDICADO EFICACIA Y SEGURIDAD, CUANDO CORRECTAMENTE INDICADO, PUEDEN SURGIR REACCIONES ADVERSAS NO PREVISTAS, AÚN NO DESCRIPTAS O CONOCIDAS, EN CASO DE SOSPECHA DE REACCIÓN ADVERSA, EL MÉDICO RESPONSABLE DEBE SER NOTIFICADO. 1. The AGIS Investigators: The Advanced Glaucoma Intervetion Study - The Relationship Between Control of Intraocular Pressure and Visual Field Deterioration. Am. J. Ophthalmol, 130 (4): 429-40, 2000. 2. Shirakashi, M. et al: Intraocular Pressure-Dependent Progression of Visual Field Loss in Advanced Primary Open-Angle Glaucoma: A 15-Year Follow-Up. Ophthalmologica, 207: 1-5, 1993. 3. Mao, LK; Stewart, WC; Shields, MB: Correlation Between Intraocular Pressure Control and Progressive Glaucomatous Damage in Primary Open-Angle Glaucoma. Am. J. Ophthalmol, 111: 51-55, 1991. 4. Higginbotham, EJ et al. One-Year Comparison of Bimatoprost with Timolol in Patients with Glaucoma or Ocular Hypertension. Presented at American Academy Ophthalmology, Nov 11-14, 2001. 5. Gandolfi, S et al. Three-Month Comparison of Bimatoprost and Latanoprost in Patients with Glaucoma and Ocular Hypertension. Adv. Ther, 18 (3): 110-121, 2001. 6. Coleman, AL et al: A 3-Month Comparison of Bimatoprost with Timolol/Dorzolamide in Patients with Glaucoma or Ocular Hypertension. Presented at American Acedemy of Ophthalmol, New Orleans, La, 2001. Mejor comodidad posológica: 1 vez al día. No requiere refrigeración. Presentación conteniendo 3 ml.