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Volumen VIII

No.1

Marzo 2009

ESTUDIO DEL DONANTE DE CÓRNEA / THE CORNEA DONOR STUDY Alandra Powe; Robin L. Gal MSPH; Roy W. Beck MD PhD; Mark J. Mannis MD; Edward J. Holland MD

STEM CELL TRANSPLANTATION Raneen Shehadeh Mashor MD; Mark Shapiro; Allan R. Slomovic MD FRCSC

INTRAVITREAL BEVACIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: ONE YEAR RESULTS Joyce Kuntz MD; Mário J. Nóbrega MD; Fernando J. Novelli MD; João G. O. Moraes MD; Evandro L. Rosa MD; Thaís B. Berti MD; Samuel A. Coral MD

RESULTS AFTER SILICONE OIL REMOVAL IN COMPLEX RETINAL DETACHMENT Mário J. Nóbrega MD; Denise C. Souza MD; Sarah L. Weber MD; Juliana M. Viesi MD; Fernando J. Novelli MD

NATURAL HISTORY OF MACULAR HOLE ASSOCIATED WITH ELECTRICAL INJURY: AN OCT STUDY F. Ryan Prall MD; Antonio P. Ciardella MD; Jeffrey Olson MD; Naresh Mandava MD

SUCCESSFUL CONSERVATIVE MANAGEMENT OF AN ATRAUMATIC DIRECT INTERNAL CAROTID-CAVERNOUS FISTULA IN AN INFANT: CASE REPORT Paul M.J. Cheevers MD; Alejandra A. Valenzuela MD; Timothy J. Sullivan FRANZCO

SPONTANEOUS SCLERAL PERFORATION IN OCULAR ROSACEA Ana Carolina Vieira MD; Mark J Mannis MD

EVALUATION OF EARLY CHORIORETINAL ABNORMALITIES IN HYPERCHOLESTEROLEMIC RABBITS SUBMITTED TO THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR)-GAMMA AGONIST TREATMENT (ROSIGLITAZONE): HISTOLOGICAL AND HISTOMORPHOMETRIC STUDY Rogil José de Almeida Torres; Maurício Maia MD; Cristina Muccioli MD; Lucia Noronha; Michel Eid Farah; Andréa Luchini; Dalton Bertolin Précoma


ORGANIZAN

Sociedad Peruana de Oftalmología

CONFERENCISTAS INVITADOS Richard L. Abbott - USA / J. Fernando Arévalo - Venezuela / Rubens Belfort, Jr. - Brasil Ana Luisa Höfling-Lima - Brasil / Cristián Luco - Chile / Stephen A. Obstbaum - USA / Peter A. Quiros - USA Lihteh Wu - Costa Rica / Andrea Araujo Zin - Brasil PRECIOS DE INSCRIPCIÓN Hasta el 31 de Enero 2009

Miembro Titular PAAO NO Miembro PAAO Residentes Acompañantes

US$ 200 US$ 350 US$ 100 US$ 100

Después del 31 de Enero 2009

US$ 250 US$ 400 US$ 120 US$ 100

Fecha limite para inscripción de Temas Libres y Posters 31 de Enero del 2009 INSCRIPCIONES: www.paaoregional2009.org / www.spo.org.pe paao.peru@gmail.com Telf.: (511)365-0937 INFORMES: GRUPO MILENIUM Av. Rivera Navarrete 451 - Of. 601, SanIsidro Telf.: (511)440-8171 / (511)421-4977 • Fax: (511)222-3679 • e-mail: difusion@grupomilenium.com.pe


Febrero Marzo 2009

Mark J. Mannis, MD University of California, Davis Sacramento, California Editor-in-Chief Cristian Luco, MD Santiago, Chile Associate Editor

Teresa J. Bradshaw Arlington, Texas Managing 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

José Benítez del Castillo Sánchez, MD Madrid, Spain

J. Fernando Arévalo, MD Caracas, Venezuela

Allan Slomovic, MD Toronto, Ontario, Canada

José A. Roca Fernández, MD Lima, Perú

Luciene Barbosa de Sousa, MD São Paulo, Brazil

Denise de Freitas, MD São Paulo, Brazil

Lihteh Wu, MD San José, Costa Rica

Marian Macsai, MD Chicago, Illinois USA

Paulo Dantas, MD São Paulo, Brazil

David E. Pelayes, MD PhD Buenos Aires, Argentina OFFICERS Richard L. Abbott, MD San Francisco, USA President, Pan-American Association of Ophthalmology Rubens Belfort, MD São Paulo, Brazil Chairman of the Board, Pan-American Ophthalmological Foundation PRODUCTION STAFF Juan Pablo Cuervo Graphic Design Eliana Barbosa Director of Production and Distribution PAOF INDUSTRY SPONSORS

Special thanks to Ana Carolina Vieira, Enrique Graue Hernández, Citlali Gurrusquieta, Mapy Padilla, and Cristián Luco for assistance in translation to Spanish and Portuguese.

Advanced Medical Optics Inc. Alcon Inc. • Allergan Inc. • Bausch & Lomb Inc. • Carl Zeiss Meditec Inc. • •

Johnson & Johnson Vision Care Latin America • Merck & Co Inc. • Novartis International AG. • Santen Inc. •

Prepress Creative Latin Media. Printed in Printer Colombiana - Colombia

CREATIVE LATIN MEDIA, LLC. P.M.B 117 2901 Clint Moore, Boca Raton, FL 33496 Tel.: (561) 495 4728 Fax: (561) 865 1934 E-mail: editorial@clatinmedia.com info@clatinmedia.com

: B PAN-AMERICA PAN-AMERICA


MENSAJE DEL EDITOR MESSAGE FROM THE EDITOR MENSAGEM DO EDITOR

Mark Mannis MD Editor en Jefe Editor-in-Chief Editor Chefe

Banco de Ojos y Ceguera Corneal en Latino América Iniciamos el primer volumen 2009 de Visión Pan-América con una serie de interesantes trabajos, el primero de los cuales es un resumen de un muy importante Estudio de Donación de Córneas (EDC) de los Estados Unidos. Este ensayo clínico (clinical trial) de 5 años, auspiciado por el Instituto Nacional de Oftalmología de los Estados Unidos (US National Eye Institute), fue diseñado para responder en forma definitiva la pregunta si las córneas de donantes de mayor edad eran tan seguras y eficaces para trasplante como las córneas de donantes jóvenes. El resultado de este estudio, a 5 años, ha sido publicado y debiera tener un impacto a largo plazo en los banco de ojos de todo el mundo. Como uno de los co-investigadores principales del EDC, he analizado este impacto y me ha llevado a pensar acerca del estado actual de la organización de los bancos de ojos de los países miembros de la Asociación Pan-Americana de Oftalmología. La ceguera corneal es un problema mayor en América Latina. Los cirujanos de córneas de Latino América saben desde hace algún tiempo, que los tejidos corneales de donantes mayores trabajan muy bien y pueden

ser usados en forma muy efectiva. El EDC ha validado esta observación en forma científica. Sin embargo, el valor del EDC será verdaderamente realidad en Latino América cuando las naciones miembros de la Asociación Panamericana de Oftalmología empiecen a organizar sus bancos de ojos en forma efectiva. La poca organización de los bancos de ojos, obviamente no es uniforme a través de Latino América. Diferentes países encaran circunstancias muy divergentes: limitaciones económicas, dilemas sociales, barreras institucionales políticas y religiosas y niveles de educación muy variables. Por lo tanto, las soluciones que son aplicables en un país, pueden no serlo en el país vecino. Por esta razón, como países miembros de la Asociación Panamericana de Oftalmología debemos trabajar en forma colectiva y compartir información en el esfuerzo para hacer efectivos los bancos de ojos. Este esfuerzo colectivo se conseguirá a través de la Asociación Panamericana de Banco de Ojos (APABO) una organización dedicada a la educación y conservación de estándares y a conseguir recursos para bancos de ojos a través de Latino América.

Los cirujanos de córnea, hospitales y el personal técnico y administrativo de los bancos de ojos van finalmente a reconocer, como se hizo en varios estados de Estados Unidos hace más de 50 años, que el esfuerzo de regionalizar los bancos de ojos es la clave para el éxito en la adquisición de tejido corneal. La regionalización también lleva a una mejor educación y a una distribución de córneas más equitativa a pacientes que esperan una cirugía. Cada banco de América Latina debiera ser miembro de la APABO, la cual puede servir como recurso principal del desarrollo. Así, analizando el EDC, también debemos pensar cómo generar, de la mejor manera, tejido para trasplante en Latino América, liberando a los países de Centro y Sud América y del Caribe de la dependencia de córneas de los Estados Unidos. El EDC aumentará la cantidad de donantes, pero, sin nuestro esfuerzo concertado para trabajar en bancos de ojos en nuestros propios países, éste no tendrá un impacto duradero en la disponibilidad de tejidos para aquellos con ceguera corneal.

Eye Banks and Corneal Blindness in Latin America We begin the 2009 volume of Vision PanAmerica with an interesting series of papers, the first of which is a summary of the very important Cornea Donor Study (CDS) from the United States. This five-year clinical trial, sponsored by the National Eye Institute, was designed to answer definitively the question of whether older donor corneas are as safe and efficacious as younger donors for transplantation. The five year results of this study have now been published and should have a lasting impact on eye banking the world over. As one of the co-principal investiga-

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tors for the CDS, I have given a great deal of thought to the impact of these findings on eye banking in Latin America. It has led me to muse over the current status of organized eye banking among our member nations. Corneal blindness is a major problem in Latin America. Indeed, Latin American corneal surgeons have long known that older corneal tissue works very well and have used these tissues effectively. The CDS has now validated this observation scientifically. However, the value of the CDS will only truly be realized in Latin America when the mem-

ber nations of the PAAO begin to organize their eye banking efforts more effectively. The disarray in eye banking is, of course, not uniform across Latin America. Different nations face widely divergent circumstances: economic limitations, social dilemmas, political and religious institutional barriers, and varying levels of education. Thus, solutions that are applicable in one country may not apply at all to the nation next door. For this reason, as member nations of the PAAO, we need to work collectively and share informational resources in the eye banking effort.


Marzo 2009

This collective effort will be best achieved through the Pan-American Association of Eye Banks (APABO), an organization dedicated to education, maintenance of standards, and the provision of resources to eye banks throughout Latin America.

Regionalization also leads to better public education and more equitable distribution of tissue to patients waiting for surgery. Every bank in Latin America should be a member bank of APABO which can serve as a major resource for development.

Corneal surgeons, hospitals, and eye bank administrative and technical personnel will ultimately recognize, as did the many states in the U.S.A. over 50 years ago, that regionalization of eye banking efforts is the key to success in the acquisition of tissue.

So, in thinking about the CDS, we also need to ponder how we can best generate tissue for transplant in Latin America, freeing the countries of Central and South America and the Caribbean from dependence on tissue imported from the United States. The

CDS will increase the eligible donor pool, but without our concerted effort to make eye banking work in our home countries, this will not have a lasting impact on the availability of tissue for those with corneal blindness.

Bancos de Olhos e Cegueira Corneana na América Latina Iniciamos o primeiro volume de 2009 da Vision Pan-America com uma série de artigos interessantes. O primeiro é um resumo do importante estudo americano “Cornea Donor Study (CDS)”. Este estudo clínico realizado ao longo de cinco anos, sob o patrocínio do National Eye Institute, foi desenvolvido com o objetivo de esclarecer definitivamente se córneas obtidas de doadores idosos são tão seguras e eficazes para transplante quanto as de doadores mais jovens. O resultado dos cinco primeiros anos deste estudo, há pouco publicado, deve gerar um impacto decisivo nos bancos de olhos de todo o mundo. Como um dos co-investigadores principais do CDS, tenho pensado muito nos grandes efeitos que tais achados terão nos bancos de olhos da América Latina. Tenho refletido também sobre a atual organização e eficiência dos bancos de olhos das nações que são membros da Associação Pan-Americana de Oftalmologia (PAAO). A cegueira corneana é um enorme problema na América Latina. Cirurgiões latinoamericanos especialistas em córnea observam há muito tempo que transplantes de córneas obtidas de doadores idosos possuem bons resultados e já as utilizam com

sucesso. O CDS vem fornecer as evidências científicas para tal observação. Porém, o valor do CDS só será verdadeiramente compreendido na América Latina quando as nações membros da Associação Pan-Americana de Oftalmologia (PAAO) começarem a organizar seus bancos de olhos mais efetivamente. Naturalmente, a desordem no sistema de bancos de olhos não é uniforme em todos os países da América Latina. Os diferentes países lidam com circunstâncias bastante diversas: limitações econômicas, dilemas sociais, barreiras religiosas, políticas, e desníveis educacionais. Portanto, soluções aplicáveis em um determinado país podem não o ser em um país vizinho. Por isso, como nações membros da PAAO, precisamos trabalhar em conjunto e compartilhar nossos conhecimentos. Este esforço coletivo será melhor alcançado se feito através da Associação Pan-Americana de Bancos de Olhos (APABO), uma organização dedicada à educação, controle de qualidade e fornecimento de recursos para bancos de olhos em toda a América Latina. Assim como aconteceu nos vários estados americanos há mais de 50 anos, cirurgiões especialistas em córnea, hospitais,

funcionários administrativos e técnicos dos bancos de olhos irão por fim entender que a regionalização dos bancos de olhos é o caminho para o sucesso na captação de tecidos. Além disso, a regionalização permite uma melhor educação e conscientização da população e uma distribuição mais justa para os pacientes que aguardam um transplante. Todo banco de olhos na América Latina deve afiliar-se à APABO, que pode atuar como uma excelente fonte de recurso para o seu desenvolvimento. Precisamos usar os resultados do CDS para conseguirmos uma melhor e mais eficiente captação e distribuição de córneas dentro da própria América Latina, permitindo, assim, que os países das Américas do Sul, Central e do Caribe não dependam de córneas importadas dos Estados Unidos. O CDS permitirá que um número maior de pessoas sejam qualificadas como doadoras. Todavia, sem um esforço concentrado de todos nós para aperfeiçoarmos o funcionamento dos bancos de olhos em nossos países, não haverá impacto significativo na disponibilidade de córneas para pacientes portadores de cegueira corneana.

PAN-AMERICA: 131


MENSAJE DEL PRESIDENTE MESSAGE FROM THE PRESIDENT

Richard L. Abbott MD Presidente PAAO PAAO President

Español No se pierda nuestro Congreso Conjunto con la Academia Americana en San Francisco este octubre…No se Arrepentirá! Ahora que iniciamos el 2009, los planes para nuestro Congreso Conjunto con la Academia Americana de Oftalmología comienzan a tomar forma; y estamos muy entusiasmados con la extraordinaria calidad y amplitud de nuestro programa educativo. El comité del programa científico de la Panamericana, bajo el liderazgo de Steve Obstbaum en estrecha colaboración con los miembros del Comité Ejecutivo, Peter Quiros, Lihteh Wu, Fernando Arévalo, Paulo Dantas y Andrea Zin han venido trabajando diligentemente para crear un programa educativo verdaderamente memorable y valioso para todos los asistentes. Habrá Simposios, Cursos y trabajos libres; muchos de ellos en Español y Portugués. Además, tendremos sesiones de posters o paneles integrados con la Academia, permitiendo a nuestros miembros Panamericanos una excelente oportunidad para presentar información científica. Se presentarán 3 Simposios Conjuntos AAO/PAAO en Diabetes, Imagen Ocular y Cirugía de Catarata/LIO. Estos tópicos fueron elegidos no solo por su valor educativo, sino aún más importante, por su impacto inmediato en la práctica clínica. Estos simposios destacarán la más reciente información en estas áreas clínicas y participarán líderes expertos tanto de Norte América como de Latino América. Finalmente, el programa de nuestro Congreso Panamericano terminará con la siempre popular y bien concurrida sesión de Lo Mejor de la Academia en Español. Esta es una gran oportunidad para todos los miembros Panamericanos de participar

activamente en esta reunión enviando un resumen o abstract para un tema libre o poster. Esperamos asista una gran cantidad de oftalmólogos de Latino América y la reunión brindará un extraordinario escenario para el aprendizaje e intercambio de ideas. Sírvase tomar nota que la fecha límite para el envío de resúmenes de trabajos libres y posters es el 14 de abril del 2009. Los exhortamos a tomar ventaja de esta única oportunidad de participar activamente en este emocionante programa. El Congreso Conjunto con la Academia en San Francisco este octubre será una gran oportunidad para reunirse con muchos amigos, visitar una de las ciudades más hermosas de los Estados Unidos y acompañarnos a celebrar el 70 Aniversario de la Panamericana. Con la Academia, estamos organizando una Ceremonia de Inauguración muy especial para reconocer este importante hito para la Asociación Panamericana de Oftalmología. Además, estamos planificando un crucero magnífico el viernes en la noche alrededor de la Bahía de San Francisco con música de DJ en vivo, comida y bebidas alcohólicas para los miembros de la Panamericana. Las entradas son limitadas y estarán a disposición de los miembros a medida se vendan. Es por esto que los animamos a que reserven en cuanto salga el anuncio de la venta de entradas que se hará próximamente. Los fondos de este evento serán a beneficio de la Fundación Panamericana. Para mayor información sobre este evento, así como los detalles del programa científico, fechas para envíos y cualquier otra información importante de este evento, sírvase visitar la página web: www.PAAO.ORG Espero verlos en San Francisco en octubre!!

2009 Abstract Submitter Estará disponible el ‘2009 Abstract Submitter’ a partir del miércoles, 11 de marzo y culminará el martes, 14 de abril, para enviar abstractos de trabajos libres, posters y videos para el Congreso Conjunto de San Francisco, Octubre 2009. Si desea presentar un video, el plazo de entrega del video completo vence el viernes, 24 de abril de 2009. Asegúrese de verificar los requisitos antes de presentar un trabajo libre. Sírvase entrar a la página Presenter Central para mayor información. (http://www.aao.org/meetings/annual_meeting/program/presenter_central.cfm).

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Marzo 2009

English Don’t Miss our Joint Congress in San Francisco with the AAO in October…You Will Not be Disappointed! Now that we are at the beginning of 2009, the plans for our Joint Congress with the American Academy of Ophthalmology are beginning to take shape; and we are very excited with the outstanding quality and breadth of our educational program. The Pan-American scientific program committee, under the leadership of Steve Obstbaum, and working closely with our Executive Committee members, Peter Quiros, Lihteh Wu, Fernando Arévalo, Paulo Dantas, and Andrea Zin have been diligently working to create a truly memorable and valuable educational program for all attendees. There will be Symposia, Courses, and free papers; many given in Spanish and Portuguese. In addition we will have integrated poster sessions with the Academy, allowing an excellent opportunity for presentation of scientific information by our Pan-American members. There will be 3 Joint AAO/PAAO Symposia on Diabetes, Ocular Imaging, and Cataract/IOL Surgery. These topics were chosen not only because of their educational value, but more importantly, because of their immediate impact on clinical practice. These Symposia will feature the latest information in these clinical areas and will have leading experts from both North and Latin America participating. Finally, our Pan-American Congress program will close with the always popular and well attended session on the Best of the Academy in Spanish. This is a great opportunity for all PanAmerican members to actively participate

in this meeting by submitting an abstract for a free paper or a poster. We are expecting a very large number of ophthalmologists to attend from Latin America and the meeting should provide an outstanding venue for learning and exchange of ideas. Please note the deadline date of April 14, 2009 for submission of abstracts for free papers / posters and videos. We strongly encourage you to take advantage of this unique opportunity to actively participate in this exciting program. The Joint Congress with the Academy in San Francisco this October should be a great opportunity for seeing many friends, visiting one of the most beautiful cities in the U.S., and helping us to celebrate the 70th Anniversary of the PAAO. With the Academy, we are planning a very special Opening Ceremony to recognize this important milestone for the Pan-American Association of Ophthalmology. In addition, we are also planning a very unique boat cruise on Friday evening around San Francisco Bay with live DJ music, food, and libations for Pan-American members. This will be a ticketed event that will benefit our Pan-American Foundation and will be available to members on a first-come basis when ticket sales are announced later this year. The boat has a limited capacity, so we encourage everyone to sign up early! Look for more information about this event, as well as scientific program details, submission deadlines, and other important meeting information on the PAAO website: www. PAAO.ORG. I look forward to seeing you in San Francisco in October!

2009 Abstract Submitter For paper/posters and videos, the online submitter opens on Wednesday, March 11 and closes on Tuesday, April 14. If you plan to submit a video abstract, the deadline to submit the actual video is Friday, April 24. Be sure to review the abstract guidelines before making your submission. See Presenter Central for details (http://www.aao.org/meetings/annual_meeting/program/presenter_central.cfm).

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REVIEW

Estudio del Donante de Córnea Alandra Powe, Robin L. Gal MSPH, Roy W. Beck MD PhD, Mark J. Mannis MD y Edward J. Holland MD a nombre del Grupo Investigador del Estudio del Donante de Córnea Financiamiento/Apoyo: Financiado por convenios de cooperación con el Instituto Nacional de Oftalmología de los Estados Unidos, los Institutos Nacionales de Salud, el Departamento de Salud y Servicios Humanos EY12728 y EY12358. Se recibe apoyo adicional de: Asociación de Bancos de Ojos de América, Bausch & Lomb Inc., Tissue Banks International, Vision Share Inc., San Diego Eye Bank, The Cornea Society, Katena Products Inc., ViroMed Laboratories Inc., Midwest Eye-Banks (Michigan Eye-Bank, Illinois Eye-Bank), Konan Medical Corp., Eye Bank for Sight Restoration, SightLife, Sight Society of Northeastern New York (Lions Eye Bank of Albany), Lions Eye Bank of Oregon. Autor Correspondiente: Roy W. Beck MD PhD, Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, Teléfono: 813-975-8690, Fax: 813-975-8761, email: cds@jaeb.org

Contexto Por muchos años se ha debatido sobre el impacto de la edad del donante en el éxito del trasplante de córnea. A pesar de la falta de evidencia científica de esta relación, muchos cirujanos de córnea en los Estados Unidos han estado reacios de utilizar tejidos de donantes de edad avanzada y como resultado, muchos bancos de ojos de los Estados Unidos han limitado su abastecimiento de córneas de donantes de 65 años de edad o más. Para obtener la información requerida para la asociación de la edad del donante y la supervivencia del injerto, se desarrolló el Estudio del Donante de Córnea (CDS).1

Métodos Entre enero del 2000 y agosto del 2002, 105 cirujanos de 80 localidades de los Estados Unidos registraron en el Estudio CDS a 1.090 sujetos elegibles (la edad media era 70 + años, dentro del rango de 40 a 80 años de edad). Para evaluar en forma óptima la asociación entre la edad del donante y el fracaso del injerto, el grupo del estudio estuvo limitado a sujetos con una condición corneal asociada con riesgo moderado de fracaso, principalmente distrofia de Fuchs y edema seudofáquico corneal. Condiciones con una elevada tasa de éxito, tales como el queratocono, fueron excluídas debido a la baja probabilidad de fracaso independiente de la edad del donante, así como condiciones con una tasa baja de éxito, tales como los reinjertos y las córneas vascularizadas fueron excluídas debido a que los fracasos del injerto probablemente serían causados por factores no relacionados con la edad del donante. Solo se podía registrar un ojo por paciente en el estudio. Se ha publicado anteriormente un listado completo del criterio de la elegibilidad del paciente.2 Los donantes de córneas, en un rango de 12 a 75 años (La edad media del donante 134 :

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(SD) era 58 (14) años) fueron asignados por 43 bancos de ojos utilizando un proceso computarizado que evita la selección de un donante de córnea para un paciente dado basado en cualquier factor del donante o del beneficiario. Las córneas donadas cumplían los criterios establecidos por la Asociación de Bancos de Ojos de América3 y tenían recuento de células endoteliales entre 2300 y 3300 células/mm2. Se ha publicado un listado completo de criterios de elegibilidad de donantes.4 El fracaso del injerto se definió como un reinjerto o una córnea nubosa que estaba lo suficientemente opaca como para comprometer la visión por un mínimo de tres meses consecutivos.5,6

aumentó el riesgo de fracaso del trasplante debido a rechazo del injerto.10

Resultados Fracaso del Injerto

Las imágenes microscópicas especulares del endotelio central fueron obtenidas de 6 a 12 meses luego del trasplante y luego anualmente por 5 años, considerando que no se haya realizado un reinjerto.

La tasa de éxito a cinco años fue de 86% para ambos casos, los 707 injertos realizados con córneas de donantes de 12 a 65 años de edad y los 383 injertos realizados con córneas de donantes de 66 a 75 años de edad (diferencia = 0%, límite más alto de un intervalo confiable de 95% de un lado = 4%).7 Independientemente de la edad del donante, el riesgo de fracaso del injerto fue considerablemente mayor en ojos con un diagnósitco preoperatorio de edema corneal seudofáquico o afáquico comparado con Distrofia de Fuchs (27% vs 7%).8 También se asoció la cirugía previa de glaucoma con uso de medicamentos preoperatorios de glaucoma con un significativo aumento del riesgo de fracaso del injerto (58% versus 11% sin historia de glaucoma). La edad del beneficiario no estuvo asociada con el fracaso del injerto. Ningún factor del donante, incluyendo la densidad de las células endoteliales, fue asociada con un mayor riesgo.9 La incompatibilidad ABO no

Densidad de las Células Endoteliales La Densidad de las Células Endoteliales (ECD), medidas en microscopio especular, sirven como indicador de la salud de la córnea. Para evaluar el efecto de la edad del donante y otros factores de pérdida de células endoteliales con el tiempo, un grupo de 347 sujetos participaron en el Estudio Auxiliar de Microscopía Especular (SMAS). Las imágenes especulares, tomadas por el banco de ojos del donante de córnea y la sede clínica luego de la cirugía, fueron evaluadas por un Centro de Lectura de Microscopía Especular central (SMRC) para determinar el ECD.11,12

Entre los sujetos que tuvieron un trasplante exitoso a quienes se le realizó microscopía especular por 5 años luego de la cirugía, la pérdida de células endoteliales fue importante, independientemente de la edad del donante, aunque los 108 sujetos que recibieron una córnea de un donante entre 66 y 75 años de edad tuvieron una ligera mayor pérdida de células comparada con los 239 sujetos que recibieron una córnea de un donante entre 12 y 65 años de edad (P ajustada para línea basal ECD = 0.04). Aquellos en el grupo de donantes de mayor edad experimentaron una pérdida celular media de 75%, resultando en una media ECD en 5 años de 654 (rango de intercuartiles 538 a 986) células/mm2, mientras que aquellos de donantes más jóvenes tuvieron una pérdida celular media de 69%, resultando en una media ECD en 5 años de 824 (rango de intercuartiles 613 a 1342) células/mm2.13


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Conclusiones Para las condiciones corneales con un riesgo moderado de fracaso del trasplante, el riesgo por 5 años de fracaso del injerto no está relacionado a la edad del donante, a otros factores del donante o a la edad del beneficiario. El riesgo es considerablemente mayor en casos de edema corneal seudofáquico o afáquico (comparado con el riesgo en casos de distrofia de Fuchs) y cuando hay una historia previa de cirugía de glaucoma. En los casos en los cuales el trasplante es exitoso luego de 5 años, hay una ligera

asociación entre la edad del donante y la pérdida de células endoteliales. Sin embargo, la importancia clínica de esta ligera asociación no es conocida y sería importante evaluar luego de un mayor seguimiento. De gran importancia, quizás, es el hallazgo que independientemente de la edad del donante, la pérdida de células endoteliales es considerable más allá de los primeros cinco años del trasplante aún cuando el injerto haya sido exitoso. Queda aún información importante por aprender de este cohorte. En este sentido,

continuaremos evaluando el éxito de los trasplantes de cinco años por cinco años más. Además de determinar la tasa de éxito del injerto a los 10 años, un mayor seguimiento permitirá una determinación de cómo el ECD de 5 años es predictivo de un posterior fracaso de injerto.

The Cornea Donor Study Alandra Powe, Robin L. Gal MSPH, Roy W. Beck MD PhD, Mark J. Mannis MD and Edward J. Holland MD, on behalf of the Cornea Donor Study Investigator Group Funding/Support: Supported by cooperative agreements with the National Eye Institute, National Institutes of Health, Department of Health and Human Services EY12728 and EY12358. Additional support provided by: Eye Bank Association of America, Bausch & Lomb, Inc., Tissue Banks International, Vision Share, Inc., San Diego Eye Bank, The Cornea Society, Katena Products, Inc., ViroMed Laboratories, Inc., Midwest Eye-Banks (Michigan Eye-Bank, Illinois Eye-Bank), Konan Medical Corp., Eye Bank for Sight Restoration, SightLife, Sight Society of Northeastern New York (Lions Eye Bank of Albany), Lions Eye Bank of Oregon Corresponding Author: Roy W. Beck MD PhD, Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, Phone: 813-975-8690, Fax: 813-975-8761, Email: cds@jaeb.org

Background The impact of donor age on the success of a cornea transplant has been debated for many years. Despite the lack of scientific evidence of an association, many corneal surgeons in the United States have been reluctant to use tissue from older donors, and as a result, many United States eye banks have limited their procurement of corneas from donors 65 years and older. To provide the requisite data on the association of donor age and graft survival, the Cornea Donor Study (CDS) was developed.1

Methods Between January 2000 and August 2002, 1,090 eligible subjects (Mean age was 70 + 9 years, range 40 to 80 years old) were enrolled in the CDS by 105 surgeons at 80 sites in the United States. To optimally evaluate the association between donor age and graft failure, the study cohort was limited to subjects with a corneal condition associated with moderate risk of graft failure, principally Fuchs’ dystrophy and pseudophakic corneal edema. Conditions with a very high success rate, such as keratoconus, were excluded because of the low likelihood of failure irrespective of donor age, and conditions with a

low success rate, such as regrafts and vascularized corneas, were excluded because graft failures were likely to be caused by factors unrelated to donor age. Only one eye per subject could be enrolled in the study. A complete listing of the subject eligibility criteria has been previously published.2 Donor corneas, ranging in age from 12 to 75 years (Mean (SD) donor age was 58 (14) years) were assigned by 43 eye banks using a computerized process that prevented selection of a donor cornea for a given subject based on any donor or recipient factors. The donor corneas met criteria established by the Eye Bank Association of America3 and had endothelial cell counts between 2300 to 3300 cells/ mm2. A complete listing of the donor eligibility criteria has been published.4 Graft failure was defined as a regraft or a cloudy cornea that was sufficiently opaque as to compromise vision for a minimum of three consecutive months.5,6

Results Graft Failure The five-year success rate was 86% for both the 707 grafts performed with corneas

from donors 12 to 65 years old and the 383 grafts performed with corneas from donors 66 to 75 years old (difference = 0%, upper limit of one-sided 95% confidence interval = 4%).7 Irrespective of donor age, the risk of graft failure was substantially greater in eyes with a preoperative diagnosis of pseudophakic or aphakic corneal edema compared with Fuchs’ dystrophy (27% vs. 7%).8 Prior glaucoma surgery with preoperative glaucoma medication use also was associated with a substantially increased risk of graft failure (58% versus 11% with no history of glaucoma). Recipient age was not associated with graft failure. No donor factors, including the donor endothelial cell density were associated with increased risk.9 ABO incompatibility did not increase the risk of transplant failure due to graft rejection.10

Endothelial Cell Density Corneal endothelial cell density (ECD), measured by specular microscopy, serves as an indicator of the health of the cornea. To evaluate the effect of donor age and other factors on endothelial cell loss over time, a subset of 347 subjects participated in the Specular Microscopy Ancillary Study PAN-AMERICA : 135


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(SMAS). Specular images, taken by the eye bank on the donor cornea and the clinical site following surgery, were evaluated by a central Specular Microscopy Reading Center (SMRC) for ECD determination.11,12 Specular microscopic images of the central endothelium were obtained 6 and 12 months after transplant and then annually through 5 years, provided that a regraft had not been performed. Among subjects who had a successful transplant for whom specular microscopy was performed 5 years after surgery, endothelial cell loss was substantial, irrespective of donor age. though the 108 subjects who received a cornea from a donor 66 to 75 years old had slightly greater cell loss compared with the 239 subjects who received a cornea from a donor 12 to 65 years old (P adjusted

for baseline ECD = 0.04). Those in the older donor age group experienced a median cell loss of 75%, resulting in a median 5-year ECD of 654 (interquartile range 538 to 986) cells/mm2 while those in the younger donor age had a median loss of 69%, resulting in a 5-year median ECD of 824 (interquartile range 613 to 1342) cells/mm2.13

Conclusions For corneal conditions with a moderate risk for transplant failure, the 5-year risk of graft failure is not related to donor age, other donor factors, or recipient age. The risk is substantially greater in cases of pseudophakic/aphakic corneal edema (compared with the risk in cases of Fuchs’ dystrophy) and when there is a prior history of glaucoma surgery.

In cases in which the transplant is successful after 5 years, there is a slight association between donor age and endothelial cell loss. However, the clinical importance of this slight association is not known and will be important to evaluate after longer follow up. Of greater importance, perhaps, is the finding that irrespective of donor age, endothelial cell loss is substantial over the first five years after transplant even when the graft has been successful. Important information is still to be learned from this cohort. In this regard, we will be continuing to evaluate the transplants successful at five years for an additional five years. In addition to determining the 10-year graft success rate, further follow up will allow for a determination as to whether the 5-year ECD is predictive of subsequent graft failure.

Estudo do Doador de Córnea Alandra Powe, Robin L. Gal MSPH, Roy W. Beck MD PhD, Mark J. Mannis MD, and Edward J. Holland MD, em nome do Cornea Donor Study Investigator Group Patrocinadores: National Eye Institute, National Institutes of Health, Department of Health and Human Services EY12728 and EY12358. Demais patrocinadores: Eye Bank Association of America, Bausch & Lomb Inc., Tissue Banks International, Vision Share Inc., San Diego Eye Bank, The Cornea Society, Katena Products Inc., ViroMed Laboratories Inc., Midwest Eye-Banks (Michigan Eye-Bank, Illinois Eye-Bank), Konan Medical Corp., Eye Bank for Sight Restoration, SightLife, Sight Society of Northeastern New York (Lions Eye Bank of Albany), Lions Eye Bank of Oregon. Para correspondencia: Roy W. Beck, M.D., Ph.D. - Jaeb Center for Health Research - 15310 Amberly Drive, Suite 350, Tampa, FL 33647- Telefone: 813- 975-8690 Fax: 813-975-8761 Email: cds@jaeb.org.

Histórico O impacto da idade do doador no sucesso do transplante de córnea tem sido tema de debate há muitos anos. Apesar da falta de evidências científicas sobre tal associação, muitos cirurgiões americanos têm colocado obstáculos para usar córneas de doadores idosos. Como conseqüência, vários bancos de olhos nos Estados Unidos têm limitado sua procura de doadores de córnea a indivíduos com até 65 anos de idade. O Cornea Donor Study (CDS) foi desenvolvido com o objetivo de fornecer os dados científicos necessários para esclarecer a associação entre a idade do doador de córnea e a sobrevida do enxerto.

Métodos Entre Janeiro 2000 e Agosto 2002, 1,090 pacientes qualificados (idade media 70 + 9 anos, entre 40 e 80 anos de idade) foram inscritos no CDS por 105 cirurgiões de 80 centros dos Estados Unidos. 136 :

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Para avaliar, da melhor maneira possível, a associação entre a idade do doador e a falência do enxerto, o grupo de estudo foi limitado apenas a pacientes com condições corneanas associadas a risco moderado de falência, principalmente distrofia de Fuchs e edema corneano do pseudofácico. Foram excluídas do estudo: condições associadas a alto índice de sucesso, como ceratocone, devido à baixa probabilidade de falência independente da idade do doador; condições associadas a baixo índice de sucesso, como retransplantes e córneas vascularizadas, pois é provável que a falência do enxerto seja causada por outros fatores, nãorelacionados à idade do doador. Somente um olho por paciente pode ser inscrito no estudo. Os critérios para a qualificação dos pacientes no estudo foram previamente publicados.2 Córneas de doadores entre as idades de 12 e 75 anos (idade média 58 + 14 anos) foram designadas por 43 bancos de olhos usando um processo computadorizado que

não permitia a seleção de uma determinada córnea para um determinado paciente baseada em qualquer fator relacionado ao doador ou ao receptor. As córneas doadas obedeceram critérios estabelecidos pela Eye Bank Association of America3 e tinham contagem celular endotelial entre 2300 e 3300 cels/ mm2. Uma lista completa dos critérios de elegibilidade dos doadores foi previamente publicada.4 Falência de enxerto foi definida como retransplante ou opacificação corneana suficiente para comprometer a visão por um mínimo de três meses consecutivos.5,6

Resultados Falência do enxerto O percentual de sucesso em cinco anos foi de 86% tanto para os 707 transplantes realizados com córneas de doadores de 12 a 65 anos de idade quanto para os 383 transplantes realizados com córneas de doadores de 66 a 75 anos de idade (diferença = 0%,


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limite superior do intervalo de confiança de 95% = 4%).7 Independente da idade do doador, o risco de falência foi consideravelmente maior em olhos com diagnóstico pré-operatório de edema corneano do pseudofácico ou afácico quando comparado a distrofia de Fuchs (27% vs 7%).8 Assim como em casos de cirurgia de glaucoma prévia com uso de medicação antiglaucomatosa no pré-operatório (58% vs 11% em pacientes sem historia de glaucoma). A idade do receptor não foi associada à falência do enxerto. Quanto ao doador, nenhum fator, incluindo densidade celular endotelial, foi associado a maior risco de falência.9 Incompatibilidade ABO também não aumentou o risco de falência do transplante devido à rejeição do enxerto.10

Densidade celular endotelial A densidade celular endotelial (DCE), medida pela microscopia especular, serve como um indicador da saúde corneana. A fim de avaliar o efeito da idade do doador e outros fatores na perda celular endotelial, 347 pacientes participaram do Specular Microscopy Ancillary Study (SMAS). Imagens especulares da córnea doadora obtidas, tanto pelo banco de olhos quanto apos a cirurgia, foram avaliadas por uma central de Micros-

copia Especular, o Specular Microscopy Reading Centre (SMRC), para determinação da DCE.11,12 Nos casos em que não houve necessidade de retransplante, microscopias especulares da área central do endotélio foram realizadas 6 e 12 meses apos o transplante e, após esse período, anualmente por 5 anos. Entre os pacientes cujos transplantes foram bem-sucedidos, a microscopia especular realizada 5 anos após a cirurgia mostrou perda celular endotelial substancial, independente da idade do doador. Porém, os 108 pacientes que receberam córneas de doadores entre 66 e 75 anos apresentaram perda celular ligeiramente maior que os 239 que receberam córneas de doadores entre 12 e 65 anos (P ajustado para DCE basal = 0.04). Os pacientes no grupo que recebeu córneas de doadores com idade mais avançada apresentaram perda celular media de 75%, resultando em DCE media em 5 anos de 654 (intervalo interquartil 538 a 986) cels/mm2. Aqueles no grupo de doadores mais jovens apresentaram perda media de 69%, resultando em DCE media em 5 anos de 824 (intervalo interquartil 613 to 1342) cels/mm2.13

Conclusão Para condições corneanas com risco moderado de falência do enxerto, o risco de

falência em 5 anos não esta relacionado a idade do doador, outros fatores do doador ou idade do receptor. O risco é significativamente maior em casos de edema corneano do pseudofácico/afácico (se comparados ao risco em casos de distrofia de Fuchs) e em casos de historia prévia de cirurgia antiglaucomatosa. Nos casos em que o transplante foi bem-sucedido após 5 anos, há uma pequena associação entre idade do doador e perda celular endotelial. Entretanto, a importância clínica desta ligeira associação não é ainda conhecida e deverá ser avaliada após um acompanhamento por um período mais longo. Talvez o achado de maior importância seja o fato de que, independente da idade doadora, a perda endotelial é substancial nos primeiros cinco anos após o transplante, mesmo nos casos de sucesso. Outras informações importantes ainda serão extraídas deste estudo. Por isso, os transplantes bem-sucedidos nos primeiros cinco anos serão acompanhados e avaliados por mais cinco anos. Além de determinar a taxa de sucesso em dez anos, esse acompanhamento mais prolongado nos permitirá determinar se a DCE nos primeiros cinco anos fornece uma previsão para uma subseqüente falência do enxerto.

BIBLIOGRAFÍA - REFERENCES - REFERÊNCIAS 1. Beck RW, Gal RL, Mannis MJ, et al. Is donor age an important determinant of graft survival? Cornea 1999; 18:503-510. 2. Cornea Donor Study Group. Clinical profile and early surgical complications in the Cornea Donor Study. Cornea 2006; 25:164-70. 3. Eye Bank Association of America. Medical Standards. EBAA 2000; Washington, DC. 4. Cornea Donor Study Group. Baseline donor characteristics in the Cornea Donor Study. Cornea 2005; 24:389-96. 5. Collaborative Corneal Transplantation Studies Research Group. The Collaborative Corneal Transplantation Studies (CCTS): effectiveness of histocompatibility matching in high-risk corneal transplantation. Arch Ophthalmol 1992; 110:1392-403. 6. Collaborative Corneal Transplantation Studies Research Group. Design and methods of the Collaborative Corneal Transplantation Studies. Cornea 1993; 12:93-103. 7. Cornea Donor Study Investigator Group. The effect of donor age on corneal transplantation outcome: results of the cornea donor study. Ophthalmology 2008; 115:620-626. 8. Cornea Donor Study Investigator Group. Recipient risk factors for graft failure in the cornea donor study. Submitted. 9. Cornea Donor Study Investigator Group. Donor factors predictive of graft failure in the cornea donor study. Submitted. 10. Cornea Donor Study Investigator Group. The effect of ABO blood type compatibility on corneal graft failure in the cornea donor study. Am J Ophthalmol. In press. 11. Benetz BA, Gal RL, Ruedy KJ, et al. Specular Microscopy Ancillary Study methods for donor endothelial cell density determination of Cornea Donor Study images. Curr Eye Res 2006; 31:319-27. 12. Cornea Donor Study Group. An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study. Ophthalmology 2005; 112:431-40. 13. Cornea Donor Study Investigator Group. Donor age and corneal endothelial cell loss five years after successful cornea transplantation: specular microscopy ancillary study results. Ophthalmology 2008; 115:627-632. PAN-AMERICA : 137


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Stem Cell Transplantation Raneen Shehadeh Mashor MD, Mark Shapiro, Allan R. Slomovic MD FRCSC Toronto Western Hospital, University of Toronto, Toronto,Ontario, Canada Corresponding author: Raneen Shehadeh Mashor, 2515 Bathurst Street, Toronto M6B 2Z1, ON, Canada E-mail: raneen_sh_mash@hotmail.com None of the authors have proprietary or financial interest

Resumen El tratamiento de la enfermedad de la superficie ocular (OSD por sus siglas en inglés, Ocular Surface Disease) se ha beneficiado debido a los grandes avances en los últimos años. Anteriormente, los pacientes afectados con la enfermedad de la superficie ocular presentaban un mal pronóstico. Los avances en la técnica del tratamiento micro quirúrgico y la compresión del importante papel que juegan las células madres del limbo han demostrado una mejoría en la agudeza visual y la calidad de vida del paciente por el uso del trasplante de células limbares.

Abstract The management of severe ocular surface disease (OSD) has benefited from major breakthroughs in recent years. Previously, patients with severe ocular surface disease had a poor prognosis. Advances in microsurgical techniques and understanding the role of limbal stem cells have led to great improvements in both of visual acuity and quality of life of these patients by using limbal cell transplantation techniques. The management of severe ocular surface disease (OSD) has benefited from major breakthroughs in recent years. Previously, patients with severe ocular surface disease had a poor prognosis. Advances in microsurgical techniques and understanding the role of limbal stem cells have led to great improvements in both of visual acuity and quality of life of these patients by using limbal cell transplantation techniques.

Limbal Stem Cell Theory Stem cells (SC) are progenitor cells that are responsible for cellular replacement and tissue regeneration. The single most important breakthrough in managing severe OSD was the understanding of the location and function of limbal stem cells. In 1971, Davenger and Evinson speculated that the source of replacing the corneal epithelium lay at the 138 :

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limbus when they observed that pigmented limbal cells moved centrally. Later on, basic research has identified a number of characteristics that are unique to the limbal basal epithelial cells and set them apart from the rest including high mitosis rates.1-2

Limbal Stem Cell Deficiency Causes of Limbal Stem Cell Deficiency

Stem-cell deficiency can be congenital or acquired. Congenital SC deficiency occurs as a result of hereditary aplasia of limbal stem cells as occurs in aniridia and congenital erythrokeratodermia. More often, stem cell deficiency is acquired as a result of chemical or thermal injuries (figure 1), ultraviolet and ionizing radiation, StevensJohnson syndrome, advanced ocular cicatricial pemphigoid (figure 2), multiple surgery or cryotherapy, contact lens wear, or extensive/chronic microbial infection such as trachoma.

Effects of Limbal Stem Cell Deficiency The hallmark of limbal SC deficiency is ‘conjunctivalisation’ of the cornea (figure 3) and the most significant clinical manifestation is a persistent corneal epithelial defect.3 The clinical features of SC deficiency, in increasing severity, include the following: loss of limbal anatomy, irregular thin epithelium with stippled fluorescein, unstable tear film, superficial and deep vascularisation, persistent epithelial defects leading to ulceration, melting and perforation, or fibrovascular pannus, scarring, keratinisation and calcification.4-5

Diagnosis of Stem Cell Deficiency The diagnosis of SC deficiency remains essentially clinical. On slit lamp examination, the conjunctivalised cornea presents a dull reflex. Conjunctival epithelium on the cornea appears to be more permeable than

corneal epithelium and takes up fluorescein stain. Loss of architecture of the limbal palisades of Vogt and vascularisation are other common features. The presence of goblet cells on impression cytology specimens taken from the corneal surface or in biopsy specimens of the fibrovascular pannus covering the cornea is pathogenomonic of conjunctivalisation of the cornea.6

Management of stem cell deficiency The management of limbal SC deficiency depends on several factors with the extent of the deficiency being the most important. In patients with partial loss, there is an opportunity for ocular surface rehabilitation without the need for SC transplantation such as Sector Conjunctival Epitheliectomy7 and amniotic membrane transplantation.8 Patients with more extensive SC deficiency cannot populate their corneal surface with remaining SC and most of them require limbal SC transplantation. If no healthy sector of limbus is available in the affected eye and if the other eye is completely normal with a positively documented absence of involvement in the original injury, autologous limbal transplantation should be considered. If the other eye is also affected, the underlying condition is a systemic illness such as Stevens-Johnson syndrome or bilateral such as contact lens wear, allografts from a living related donor or a cadaver donor should be considered. A variety of techniques have been reported for limbal transplant surgery. Although the different techniques have similar goals, they vary based on the source of the donor tissue and on the carrier tissue used for the transfer of the limbal SC.

Transplantation Techniques The basic technique for a limbal SC transplantation, upon which all variations are derived consists of:


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(1) Preparation of the ocular surface. A 360° peritomy is first performed in the recipient eye and the fibrovascular pannus covering the corneal surface is dissected. (2) The donor tissue is harvested (refer to chart 1 for details pertaining to each type of transplant). The donor site is left open to heal (if applicable). Refer to the section on Ex vivo for details on the expansion of the biopsy. (3) Suitable beds are made on the recipient eye at the superior and inferior limbus. (4) The donor tissue is sutured onto the recipient eye using interrupted 10-0 nylon sutures at the corneal margin and nylon or vicryl sutures at the conjunctival margin. (5) A Bandage contact lens may be placed on the cornea .Antibiotics and corticosteroids are applied at the end of the procedure.

Complications

Figure 1

Possible early but reversible complications include graft edema or haemorrhage and dellen formation. Infection is also a possible early complication. Late complications include epithelial inclusion cyst in the graft and scarring at the donor site, which is more likely to present if tenon’s tissue is excised at the time of the graft harvesting. For limbal allografts there is a risk of rejection. Compared to conventional penetrating keratoplasty, limbal allografts are at significantly higher risk for rejection due to the vascularity of the limbal area, which allows greater access for the immune system. It is also due to the greater antigenicity of limbal tissue, which contains a significant number of Langerhans cells, hence, the importance of systemic immunosuppression following this procedure.

Results of Stem Cell Transplantation

Figure 2

Figure 3

Overall, the success rate of ocular surface transplantation has been reported to be between 0-80%. Kenyon and Tseng22 first described the technique of limbal autograft transplantation in a series of 26 patients. The mean follow-up was 18 months. In 10 (38.5%) patients with persistent epithelial defects for 3 weeks to 4 years, there was rapid reepithelialisation (1-4 weeks). Failure of epithelialisation was seen in 3 (11.5%) eyes. Substantial improvement was noted in vision and reduction in stromal vascularisation. Later Arora and colleagues23 described the outcome of limbal SC autografts in 77 patients with unilateral limbal stem cell deficiency. Amniotic membrane grafting, sequential keratoplasty, and conjunctival surgery were employed. The authors reported an 80% success rate in ocular surface reconstruction with fornix formation and improved corneal clarity and reduced neovascularisation at the 2-year follow-up period. Kenyon and Repoz19 a reported their results with living related conjunctival limbal allografts. Their patients had a 75% success rate with mean follow-up of 19.5 months. Ilari and Daya24 investigated the long-term outcome of keratolimbal allograft (KLAL) for the treatment of severe OSD in twenty patients (23 eyes). Oral or topical cyclosporine or both were used after surgery in 15 patients to prevent allograft rejection. The mean follow-up was 60 months eight eyes (24.2%) never reepithelialised and were considered primary failures. The remaining 25 grafts initially restored a phenotypic corneal epithelium, but at last follow-up only 7 (21.2%) were stable. Graft survival rate was 54.4% at 1 year, 33.3% at 2 years, and 27.3% at 3 years. Visual acuity improved or was unchanged in 19 eyes (82.6%) and decreased in 4 eyes (17.4%). Cyclosporine was used initially in high-risk PAN-AMERICA : 139


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Chart 1 Type of procedure

Indications

Contraindications

Size and Location of Explants

Conjunctival Limbal Autograft

In patients where total stem cell deficiency affects only one eye. Prior chemical or thermal injuries are the most common causes.9-12

The donor eye should be free of any condition that may predispose it to later limbal SC deficiency. In unilateral manifestations of systemic diseases, harvesting tissue from the apparently normal eye is not recommended.13-14

Living Related Conjunctival Allograft

When the two eyes are affected and a living related donor is available.

The donor eye should be free of any Two trapezoidal limbal grafts, condition that may predispose it to including 6mm of the limbus and later limbal SC deficiency. extending 5 to 8mm posterior to the limbus are harvested from the donor eye.

Cadaver Conjunctival Limbal or Keratolimbal Allograft

In bilateral cases and when there is no available or willing living relative. Surgery should be performed within 72 hours as the cells are expected to be more vital.16

Donor Tissue Preparation: While harvesting the tissue, damage to the epithelium should be avoided, and a peripheral skirt of conjunctiva about 3-4mm wide should be included. Scleral rim should be 4-5mm wide. Holland and Schwartz15 described a technique in which two corneoscleral rims from the two donors eyes is required to have sufficient tissue to place around the recipient limbus without gaps. Tsubota17 described a similar technique except that tissue from one donor corneo-scleral rim is used. Lamellar dissection of the peripheral rim of tissue to 1/3-1/2 depth18 is carried out. If the whole globe is used, a vacuum trephine may be used centrally, and the dissection of the peripheral cornea and limbus may be carried out with a diamond knife.19 An alternate technique is to use a microkeratome-based limbal harvester.20

Ex Vivo

This technique uses ex vivo growing of limbal epithelial cells from a small biopsy. In unilateral SC deficiency, limbal epithelial SC is harvested from the contralateral eye. In total SC deficiency cells harvested from either a living relative's eye or cadaveric eye. These limbal epithelial SC are then grown in a laboratory to produce a transplantable sheet of limbal epithelial cells.21 The biopsy is much smaller than that needed for the other grafts. This diminishes the possibility of the donor eye becoming deficient in SC. As well, there is a reduced risk of allograft rejection because of the lack of Langerhans cells in ex vivo grown limbal epithelial cells21. Oral mucosal epithelial cells can be used to treat bilateral total SC deficiency. This technique utilizes the autologous cells so there is no risk of immune rejection and no need for immunosuppression.

The biopsy for ex vivo transplantation ranges in size from 1 mm2 to 6 mm2, extending 1 mm on each side of the corneo-scleral junction. To take an oral mucosal biopsy, a strict oral hygiene program must be followed. An oral mucosal epithelial cell biopsy is bigger than a limbal epithelial SC biopsy ranging from 2 mm2 to 9 mm2. The location of the biopsy is on the inner buccal mucosa.18 Two main methods of culturing cells in vitro, the explant culture system and the suspension culture system. In the explant culture system, the limbal epithelial stem cell biopsy is allowed to adhere onto the basement membrane surface of amniotic membrane. Once the limbal epithelial stem cells have adhered to the amniotic membrane, it is submerged in culture medium and left to grow for 14 to 28 days.21 The suspension culture system, uses the enzymes dispase and trypsin to break down the basement collagen membrane, to separate the epithelial cells from the stroma and to separate the clumps of limbal epithelial cells into a suspension of single cells. This suspension is then placed either on amniotic membrane or on a feeder layer of 3T3 and left to grow for 14-21 days.

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Two explants, corresponding to 2 clock hours (11–1 o’clock and 5–7 o’clock) and consisting of a very narrow strip (1 mm or less) of peripheral cornea, limbus and 3mm of bulbar conjunctiva.


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recipients and later in all recipients. Graft survival was longer in the cyclosporine-treated group compared with the untreated group. Holland and Schwartz25 suggested a coordinated team approach by a variety of medical specialists including corneal, oculoplastic and glaucoma specialists allied to a carefully calibrated programme of systemic immunosuppression managed by transplant immunologists to deliver higher success rates for stem cell transplantation. They established a sequential paradigm for the management of these patients, starting with aggressive management of elevated IOP followed by evaluation and management of the eyelid and lashes prior to ocular surface transplantation. If significant conjunctival inflammation is present, topical and systemic immunosuppression should begin weeks to months before transplantation to control the ocular inflammation. They emphasised the importance of immunosuppression. Compared to conventional penetrating keratoplasty, limbal allografts are associated with a significantly higher risk for rejection because the grafted tissue does not have the same immune privilege status as a central corneal graft. They suggested immunosuppression protocol that includes topical corticosteroids as well as topical cyclosporine. All patients receive systemic immunosuppression with three agents: (1) corticosteroids used 1mg/kg/day and tapered during a 6-month period; (2) tacrolimus, 1 to 4mg bid; and (3) mycophenolate, 500 to 1,000mg bid. The necessary duration of immunosuppression depends on a patient’s preoperative diagnosis, postoperative course,

and whether the rejection of a transplant has occurred. The drug regimen is continued for at least 12 to 18 months for the vast majority of patients, with the corticosteroids reduced to less than 1mg/kg/day for the first 3 months postoperatively. They presented the results of ninety-four eyes of 74 patients with severe OSD who underwent either KLAL or lr-CLAL according to this protocol. Follow-up ranged from 12 to 120 months with a mean follow-up of 4.7 years. Thirty-two eyes had a total of 47 failed keratoplasties before the limbal transplantation. Overall, 69 eyes (73.4%) achieved a stable ocular surface. Twenty-five eyes (26.6%) had recurrent epithelial disease and were categorized as having a failed ocular surface. For ex vivo transplantation ,after combining results from many different studies the overall success rate for ex vivo limbal stem cell transplantation was 75.7% (147 out of 194)21. This average must be interpreted with a grain of salt because the included studies varied in many categories. There was significant variation in the conditions treated, the type of graft (allograft or autograft), the different culture methods and the different carriers to transplant the cells. Also it is important to take into account that some patients underwent subsequent surgical procedures. For ex vivo transplantation of oral mucosal epithelium, the success rate was 82% (22 out of 27).21

BIBLIOGRAFÍA- REFERENCES 1. RM. Existence of slow-cycling limbal epithelial basal cells that can be

15. Edward J, Holland MD, Gary S, Schwartz MD. Ocular Surface Trans-

preferentially stimulated to proliferate: implications on epithelial stem cells. Cell, 1989; 57:201–209. 2. Friedenwald JSB, Buschke W. Some factors concerned in the mitotic and wound-healing activities of the corneal epithelium. Trans Am Ophthalmol Soc, 1944; 42:371–383. 3. Dua HS, Joseph A,Shanmuganathan VA, Jones RE. Stem cell differentiation and effects of deficiency. Eye,2003; 17:877–885 4. Huang AJ, Tseng SC. Corneal epithelial wound healing in the absence of limbal epithelium. Invest Ophthalmol Vis Sci,1991; 32:96–105. 5. Pfister RR. Corneal stem cell disease: concepts, categorization, and treatment by auto- and homotransplantation of limbal stem cells. CLAO J, 1994; 20:64–72. 6. Puangsricharern V, Tseng SC. Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology, 1995; 102:1476–1485. 7. Dua HS.Sequential sector conjunctival epitheliectomy. In: Holland EJ, Mannis MJ (eds) Ocular surface disease, medical and surgical management, Chap 14. Springer,New York, pp 168–174 (2001) 8. Anderson DF, Ellies P, Pires R, Tseng S.Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol 2001;85:567– 575 9. Dua HS,Azuara-Blanco A. Autologous limbal transplantation in unilateral stem cell deficiency. Br J Ophthalmol, 2000; 84:273–278. 10. Holland EJ, Schwartz GS. The evolution of epithelial transplantation for severe ocular surface disease and a proposed classification system. Cornea, 1996; 15:549–556. 11. Kenyon KR, Rapoza PA Limbal allograft transplantation for ocular surface disorders. Ophthalmology, 1995; 102 (Suppl):101–102 12. Kenyon KR, Tseng SC Limbal autograft transplantation for ocular surface disorders. Ophthalmology, 1989; 96:709–22; discussion 722–723 13. Tseng SCG, Chen JJY, Huang AJW, Kruse FE, Maskin SL, Tsai RJF. Classification of conjunctival surgeries for corneal disease based on stem cell concept. Ophthalmol Clin North Am, 1990; 3:595-610 14. Kinoshita S, Kiritoshi A, Ohji M, Ohashi Y, Manabe R. Disappearance of palisades of Vogt in ocular surface disease. Jpn J Clin Ophthalmol, 1986;40:363-66

plantation: An overview of techniques, indications, and postoperative management. Cataract & refractive surgery today, 2005; 76-79 16. Croasdale CK, Schwartz GS, Malling JV, Holland EJ. Keratolimbal allograft: Recommendations for tissue procurement and preparation by eye banks, and standard surgical technique. Cornea, 1999;18:52-58 17. Tsubota K, Satake Y, Ohyama M, Toda I, Takano Y, Ono M, Shinozaki N. Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol, 1996;122:38-52 18. Tsai RJF, Tseng SCG. Human allograft limbal transplantation for corneal surface reconstruction. Cornea, 1994; 13:389-400. 19. Dua HS, Azuara-Blanco A. Allo-limbal transplantation in patients with limbal stem cell deficiency. Br J Ophthalmol, 1999; 83:414-19. 20. Behrens A, Shah SB, Li L, Cote MA, Liaw LL, Sweet PM, McDonnell PJ, Chuck RS. Evaluation of a microkeratome-based limbal harvester device for limbal stem cell transplantation. Cornea, 2002; 21:51-55. 21. Shortt AJ, Secker GA, Notara MD, Limb GA, Khaw PT, Tuft SJ, Daneils JT. Transplantation of ex vivo cultured epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol, 2007; 52(5): 483-502. 22. Kenyon KR and Tseng SCG. Limbal autograft transplantation for ocular surface disorders. Ophthalmology, 1989; 96:709-23. 23. Arora R, Jain T, Raina UK, Ghosh B. Outcome of limbal autograft transplant with other modalities in the management of disorders with moderate to severe limbal deficiency. Program and abstracts of the American Academy of Ophthalmology 2007 Annual Meeting; November 10-13, 2007; New Orleans, Louisiana. Poster 56. 24. Ilari L and Daya SM.Long-term outcomes of keratolimbal allograft for the treatment of severe ocular surface disorders. Ophthalmology. 2002 Jul; 109(7):1278-84. 25. Holland E and Schwartz G.The Paton Lecture: Ocular Surface Transplantation: 10 Years’ Experience. Cornea, 2004; 23(5):425-431

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Intravitreal Bevacizumab in Neovascular Age-Related Macular Degeneration: One Year Results Joyce Kuntz MD1, Mário J. Nóbrega MD2,3, Fernando J. Novelli MD2, João G. O. Moraes MD1,4, Evandro L. Rosa MD2, Thaís B. Berti MD2, Samuel A. Coral MD2 1 Pontifícia Universidade Católica do Paraná, Curitiba, PR - Brazil 2 Hospital de Olhos Sadalla Amin Ghanem, Joinville, SC - Brazil 3 Universidade da Região de Joinville, Joinville, SC - Brazil 4 Oftalmoclínica, Curitiba, PR – Brazil

Corresponding author: Joyce Kuntz Address: Rua Dr. Pedrosa, 134, Curitiba, PR 80420-120 – Brazil e-mail: joycek001@yahoo.com.br Authors Disclosure Information: The authors of this article have no proprietary or financial interest in a product or lack thereof.

Resumen Objetivos: Avaliar em longo prazo a eficácia e segurança do bevacizumab intravítreo (Avastin, Genentech) para o tratamento da degeneração macular relacionada à idade (DMRI) exsudativa em dois serviços oftalmológicos de referência do sul do Brasil: Hospital de Olhos Sadalla Amin Ghanem (Joinville/SC) e Oftalmoclínica (Curitiba/PR). Métodos: Estudo retrospectivo de 36 pacientes com DMRI neovascular que receberam uma ou mais injeções intravítreas de bevacizumab e completaram pelo menos um ano de seguimento. Em cada consulta, a acuidade visual (AV) e exame oftalmológico eram realizados; tomografia de coerência óptica e angiografia fluoresceínica foram efetuadas na primeira visita e quando necessário. Foram excluídos os casos previamente submetidos à terapia fotodinâmica com verteporfirina, fotocoagulação e aplicações intravítreas de triancinolona ou outras drogas anti-angiogênicas. Após preenchimento do consentimento informado, os pacientes foram tratados com bevacizumab intravítreo com doses de 0,05ml (1,25mg) a 0,1ml (2,50mg). Reinjeções eram aplicadas caso houvesse indicação. Resultados: Trinta e nove olhos de 36 pacientes foram tratados, sendo 61,1% do sexo feminino; a média de idade foi de 75,2 anos (59-88 anos). No período médio de 17,3 meses (12-27) os pacientes receberam média de 3,3 injeções (1-8). Vinte e oito olhos (71,8%) tiveram melhora (38,5%) ou estabilização (33,3%) da AV, com variação média de 0,80 logMAR antes do tratamento para 0,82 logMAR na última consulta. Não se notou efeito colateral ocular ou sistêmico durante o acompanhamento. Conclusões: Os resultados observados sugerem que o bevacizumab intravítreo seja eficaz e seguro no tratamento da DMRI neovascular após um ano do início do tratamento

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como apresentado recentemente por Bashur et al5. Novos estudos são necessários para validação desses achados preliminares

Abstract Purpose: To evaluate the long term efficacy and safety of intravitreal bevacizumab (Avastin, Genentech) for treatment of age-related macular degeneration (AMD) in two eye clinics in southern Brazil. Methods: Retrospective chart review of 36 consecutive patients with neovascular AMD who received one or more intravitreal injections of bevacizumab and completed at least one year of follow-up. At each visit, visual acuity (VA) and ophthalmic examination was assessed; optical coherence tomography and fluorescein angiography were performed at first visit and then as needed basis. Cases with prior verteporfirin photodynamic therapy, photocoagulation and intravitreal or periocular injections of triamcinolone or other antiangiogenic drugs were excluded. After written informed consent was obtained, patients were treated with an intravitreal bevacizumab dose of 0.05ml (1.25mg) to 0.1ml (2.50mg). Reinjections were performed if necessary. Results: Thirty-nine eyes of 36 patients were included in this study (38.9% male, 61.1% female) with a mean age of 75.2 years-old (5988 years). In the mean period of 17.3 months (range 12-27), they received an average of 3.3 injections (range 1-8). Twenty-eight eyes (71.8%) had improved (38.5%) or stabilized (33.3%) VA with a mean variation from 0.80 logMAR before treatment to 0.82 logMAR at last follow-up visit. No significant ocular or systemic side effects were noted. Conclusions: This study suggests that bevacizumab appears to be a safe and effective treatment for neovascular AMD after one year of initial therapy as it has been shown recently by Bashur et al.5 Further studies are necessary to validate these preliminary findings.

Introduction Neovascular age-related macular degeneration (AMD) is the leading cause of blindness in elderly people in developed countries.1 Although only 10% of AMD is a neovascular form, it is the main cause of visual loss in these patients. Treatment with laser photocoagulation and photodynamic therapy has limitations.2,3 The use of antivascular endothelial growth factor inhibitors has shown better outcomes, with significant visual improvement in a large proportion of cases. One of these agents is bevacizumab, widely used as an off-label intravitreal therapy that demonstrates short-term efficacy with no obvious safety issues.4,5 The design of this study is to evaluate the long term efficacy and safety of intravitreal bevacizumab (Avastin, Genentech) for treatment of AMD in two eye clinics in southern Brazil, Sadalla Amin Ghanem (Joinville/SC) and Oftalmoclínica (Curitiba/PR).

Methods This is a retrospective chart review of 36 consecutive patients with neovascular AMD who received one or more intravitreal injections of bevacizumab and completed at least one year of follow-up. Patients underwent Snellen visual acuity (VA) testing (converted into logarithm of the minimal angle of resolution, logMAR) and ophthalmoscopic evaluation at baseline and at 1 to 2-month follow-up examinations. Optical coherence tomography (OCT) and fluorescein angiography were performed at the first visit and then if there was a clinical suspicion of choroidal neovascular (CNV) regrowth or recurrence in spite of a stable visual acuity. Cases with prior verteporfirin photodynamic therapy, photocoagulation and intravitreal or periocular injections of triamcinolone or other anti-angiogenic drugs were excluded. After written informed consent was obtained, patients were treated with an intrav-


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itreal bevacizumab dose of 0.05ml (1.25mg) to 0.1ml (2.50mg). At follow-up visits, Snellen visual acuity was considered stable if there was a variation of no more than 1 line between the first and the last ophthalmologic examination. Bevacizumab reinjection criteria included a visual acuity loss of 2 lines or more, ophthalmoscopic findings pointing out CNV regrowth or recurrence and, if OCT was indicated, a persistent fluid accumulation below or within the retina.

Results

A total of 39 eyes of 36 patients were included in this study (38.9% male, 61.1% female) with a mean age of 75.2 years-old (59-88 years). In the mean period of 17.3 months (range 12-27), they received an average of 3.3 injections (range 1-8). Most of the intravitreal injections included a Bevacizumab dose between 2.0 mg and 2.50 mg (65.4%). Twenty-eight eyes (71.8%) had improved (38.5%) or stabilized (33.3%) VA; these cases had a pre-treatment logMAR VA mean of 1.28 and a post-treatment logMAR VA mean of 0.8. The overall mean VA varied from 0.80 logMAR before treatment to 0.82 logMAR at last follow-up visit (figure 1). No significant ocular or systemic side effects were noted.

Conclusions Intravitreal bevacizumab appears to be a safe and effective treatment for neovascular AMD after one year of initial therapy. Recently, Bashur et al5 were the first to report outcomes from a long prospective clinical trial. Their analysis disclosed visual

stability or improvement in 82.4% of eyes that had been injected with 2.50 mg of Bevacizumab. Although the present study showed 71.8% of treated eyes with improved or stabilized VA, it may not be compared to Bashur´s results because this is a retrospective case series with inherent limitations. But it shows a tendency to long-term results similar to a previous prospective analysis.5 Yogonathan el al6 observed patients who Figure 1 received intravitreal Visual acuity before and after treatment with bevacizumab. bevacizumab for AMD from 24 to 50 weeks. functional responses to the previous injecNaive eyes (28%) had a mean increase of tions and not on an initial monthly schedule. 14.2 letters. Conversely, the actual study has shown VA gain of at least 2 lines (6 to 10 ETBevacizumab was well tolerated and no DRS letters) in 38.5% of the eyes. serious drug-related adverse events were seen as it was described in other articles.5-8 In the present report, patients required a relative few number of injections of bevaciAlthough Bevacizumab is a promising zumab (average of 3.3 injections) during a drug that shows efficacy and safety in pamean follow-up of 17.3 months. It is almost tients with neovascular AMD, further studies the same frequency described by Bashur et al are necessary to warrant its advantages for a (average of 3.4 injections) during the period longer period of observation. of one year.5 Probably the low rate of intravitreal applications was due to the criteria used for reinjections: it was mainly based on the

REFERENCES 1. Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol, 2004; 122:564-572. 2. Macular Photocoagulation Study Group. Visual outcome after laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration: the influence of initial lesion size and initial visual acuity. Arch Ophthalmol, 1994; 112:480-488. 3. Blumenkranz MS, Bressler NM, Bressler SB, et al. Treatment of age-related macular degeneration with photodynamic therapy study group. Verteporfirin therapy for subfoveal choroidal neovascularization in age-related macular degeneration. Arch Ophthalmol, 2002; 120:1307-1314 4. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging, 2005; 36:270-271. 5. Bashur ZF, Haddad ZA, Schakal A, et al. Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: a one-year prospective study. Am J Ophthalmol, 2008; 142:249-256. 6. Yoganathan P, Deramo VA, Lai JC, et al. Visual improvement following intravitreal bevacizumab (Avastin) in exsudative age-related macular degeneration. Retina, 2006; 26(9):994-998. 7. Avey RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology, 2006; 113(3):363-372. 8. Rich RM, Rosenfeld PJ, Puliafito CA, et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina, 2006; 26(5):495-511.

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CLINICAL SCIENCES

Results After Silicone Oil Removal In Complex Retinal Detachment Mário J. Nóbrega MD1,2, Denise C. Souza MD1, Sarah L. Weber MD2, Juliana M. Viesi MD2, Fernando J. Novelli MD1 1. Hospital de Olhos Sadalla Amin Ghanem, Joinville, SC - Brazil 2. Universidade da Região de Joinville, Joinville, SC - Brazil

Author Disclosure Information: The authors of this article have no proprietary or financial interest in a product or lack thereof.

Corresponding Author: Mário Junqueira Nóbrega, MD Address: Rua Abdon Batista 172, Joinville, SC 89201-010 – Brazil e-mail: mjn@terra.com.br

Resumo Objetivo: Avaliar os resultados anatômicos e visuais após a retirada do óleo de silicone em pacientes operados de descolamento de retina e vitreorretinopatia proliferativa num centro oftalmológico de referência em Joinville, sul do Brasil. Métodos: Estudo retrospectivo e não-comparativo de casos consecutivos de descolamento de retina com vitreorretinopatia proliferativa posterior grau C examinados e operados pelo mesmo médico (MJN) de Janeiro de 1997 a Agosto de 2006. Foram excluídos os casos de descolamento de retina associados a trauma, ruptura gigante, retinite viral ou retinopatia diabética. A cirurgia inicial, realizada em todos os olhos, consistiu de vitrectomia via pars plana, introflexão escleral em 360 graus, endofotocoagulação retiniana ao redor das rupturas retinianas e colocação de óleo de silicone na cavidade vítrea. A fotocoagulação profilática em 360 graus na periferia retiniana também foi realizada um a três meses antes da remoção do óleo de silicone. Resultados: Vinte e sete pacientes foram submetidos à extração do óleo de silicone. Dezenove (70,4%) eram homens e a idade média foi 54,1 anos (variação de 24 a 79 anos). O tempo de seguimento médio foi 284 dias (73-988 dias). Vinte e seis olhos (96,3%) tinham a retina colada no último exame oftalmológico. Após a extração do óleo de silicone, a acuidade visual melhorou em 13 pacientes (48,2%), manteve-se estável em 9 pacientes (33,3%) e diminuiu em 5 pacientes (18,5%). Houve um caso de perda visual grave após a remoção do óleo de silicone (de 20/40 a 20/400), com atrofia óptica de causa indeterminada. Conclusões: A retirada do óleo de silicone propiciou bons resultados anatômicos e visuais na maioria dos pacientes. Entretanto, 5 casos tiveram evolução desfavorável, principalmente um com perda visual grave 144 :

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e inexplicável. Os cirurgiões precisam estar cientes dos resultados adversos associados à extração do óleo de silicone e os seus benefícios devem ser analisados perante os riscos de sua duração prolongada no interior do olho e da possibilidade de complicações com um novo procedimento cirúrgico.

Abstract Purpose: To evaluate anatomical and visual outcomes after silicone oil removal in patients operated on retinal detachment and proliferative vitreoretinopathy in a referential eye-care centre in Joinville, southern Brazil. Methods: Retrospective, non-comparative, consecutive case series. Cases included all patients with retinal detachment and grade C posterior proliferative vitreoretinopathy examined and operated on by the same physician (MJN) from January 1997 to August 2006. Cases of retinal detachment associated with trauma, giant tears, viral retinitis or diabetic retinopathy were excluded. The initial surgery, performed in all the eyes, included pars plana vitrectomy, 360-degree scleral buckling, laser endophotocoagulation around the retinal tears and silicone oil infusion in the vitreous cavity. A prophylactic 360-degree peripheral laser photocoagulation was applied one to three months before silicone oil removal. Results: Twenty-seven patients underwent silicone oil extraction. Nineteen (70,4%) were men and the mean age was 54,1 yearsold (range 24-79 yo). The median follow-up was 284 days (73-988 days). Twenty-six eyes (96,3%) had the retina attached at the last examination. After silicone oil extraction, visual acuity improved in 13 patients (48,2%), stabilized in 9 patients (33,3%) and decreased in 5 patients (18,5%). There was a case of severe visual loss after silicone oil extraction (from 20/40 to 20/400), with an indetermined optic disc atrophy. Conclusions: Silicone oil removal provided

good anatomical and visual results in most of the patients. Nevertheless, 5 cases had unfavorable outcomes, particularly one with a severe and unexplained vision loss. Surgeons must be aware of adverse results associated with silicone oil removal and its benefits must be outweighed against its extended duration in the eye and the possibility of complications with a new surgical procedure.

Introduction Silicone oil is an important adjunct in vitreoretinal surgery as a long-acting intraocular tamponade. It is used most commonly in the management of complex retinal detachments due to severe proliferative vitreoretinopathy and improves its prognosis. Complications due to its prolonged time in the eye include cataract, glaucoma and keratopathy. In most cases, silicone oil is removed from the vitreous cavity between 6 weeks and 6 months after the surgery. Variable anatomical and functional results after its extraction are described (Table 1), including risk of recurrent retinal detachment1-8 and sudden visual loss.9,10 Prophylactic peripheral 360-degree photocoagulation may decrease the incidence of retinal redetachment after silicone oil removal11-13 thus enhancing outcomes after the surgery. The purpose of this study is to evaluate anatomical and visual results after silicone oil removal in patients operated on retinal detachment and proliferative vitreoretinopathy in a referential eye-care center in Joinville, SC, southern Brazil.

Methods This is a retrospective, non-comparative, consecutive case series. Patients with retinal detachment and grade C posterior proliferative vitreoretinopathy were operated on by the


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same physician (MJN) from January 1997 to August 2006. Cases of retinal detachment associated with trauma, giant tears, viral retinitis or diabetic retinopathy were excluded. The initial surgery included pars plana vitrectomy, 360-degree scleral buckling, laser endophotocoagulation around the retinal tears and 5000-centistoke silicone oil infusion in the vitreous cavity. A prophylactic 360-degree peripheral laser photocoagulation was applied one to three months before silicone oil removal. Laser spots were delivered via slit lamp and were placed in two or three rows on the scleral buckle area.

Results A total of 27 eyes of 27 patients were treated. Nineteen were men (70,4%) and the mean age was 54 years-old (24-79 years-old). The median duration of intraocular silicone oil tamponade was 165 days (47-1141 days) and the median follow-up after removal of silicone oil was 284 days (73-988 days). Twenty-six eyes had attached retina at last examination (96,3%) and one eye had a recurrent retinal detachment (3,7%). After silicone oil extraction, visual acuity improved in 13 patients (48,2%), stabilized in 9 patients (33,3%) and decreased in 5 patients (18,5%). One patient had a severe

visual loss after silicone oil extraction (from 20/40 to 20/400), with unexplained optic disc atrophy (Figure 1).

Conclusions Silicone oil removal provided good anatomical and visual results in most of the patients. However, visual acuity decreased in five patients. One of them had a severe and unexplained visual loss following the surgery. Some hypothesis to elucidate this complication include macular dysfunction due to changes in retinal ionic environment after silicone oil extraction9, posterior ischemic optic neuropathy10 and other causes like optic nerve injury during periocular anesthesia or subconjuntival gentamycin.

Table 1 Previous studies showing number of eyes (and percentage with retinal redetachment after silicone oil removal.

Comparing to previous studies1-8, a low detachment rate was observed in the present report. It may be due to improved surgical management of complicated retinal detachments during the last decade, with more adequate removal of vitreous base, wide-field viewing systems and endophotocoagulation. Prophylactic 360-degree retinopexy may also have permitted better outcomes.11-13 Surgeons must be aware of adverse results associated with silicone oil removal and its benefits must be outweighed against its extended duration in the eye and the possibility of complications with a new surgical procedure.

Figure 1 Preoperative and postoperative visual acuity values.

REFERENCES 1. Falkner CI, Binder S, Kruger A. Outcome after silicone oil removal. Br J Ophthalmol, 2001; 85 (11): 1324- 1327 2. Flaxel CJ, Mitchell SM, Aylward GW. Visual outcome after silicone oil removal and recurrent retinal detachment repair. Eye, 2000; 14: 834- 838. 3. Bassat IB, Desatnik H, Alhalel A, Treister G, Moisseiev J. Reduced rate of retinal detachment following silicone oil removal. Retina, 2000; 20 (6): 597- 603. 4. Scholda C, Egger S, Lakits A, Walch K, von Eckardstein E, Biowski R. Retinal detachment after silicone oil removal. Acta Ophthalmol Scand, 2000; 78 (2): 182- 186.

5. Jonas JB, Knorr HL, Rank RM, Budde WM. Retinal redetachment after removal of intraocular silicone oil tamponade. Br J Ophthalmol, 2001; 85 (10): 12031207. 6. Jiang F, Krause M, Ruprecht KW, Hille K. Management and results of retinal detachment after silicone oil removal. Ophthalmologica, 2002; 216 (5): 341345. 7. Unlu N, Kocaoglan H, Acar MA, Sargin M, Aslan BS, Duman S. Outcome of complex retinal detachment surgery after silicone oil removal. Int Ophthalmol, 2004; 25 (1): 33- 36. 8. Lam RF, Cheung BTO, Yuen CYF, Wong D, Lam DSC, Lai WW. Retinal redetachment after silicone oil removal in proliferative vitreoretinopathy: a prognostic factor analysis. Am J Ophthalmol, 2008; 145: 527- 533. 9. Newsom RSB, Johnston R, Sullivan PM, Aylward GB, Holder GE, Gregor ZJ. Sudden visual loss after removal of silicone oil. Retina, 2004; 24: 871- 877. 10. Tavallali A, Soheilian M. Sudden visual loss after removal of silicone oil [letter]. Retina, 2005; 25: 806- 807. 11. Tufail A, Schwartz SD, Gregor ZJ. Prophylactic argon laser retinopexy prior to removal of silicone oil: a pilot study. Eye, 1997; 11: 328- 330. 12. Laidlaw DA, Karia N, Bunce C, Aylward GW, Gregor ZJ.Is prophylactic 360-degree laser retinopexy protective? Risk factors for retinal redetachment after removal of silicone oil. Ophthalmology, 2002; 109 (1): 153- 158. 13. Abu El-Asrar AM, Al-Bishi SM, Kangave D. Outcome of temporary silicone oil tamponade in complex rhegmatogenous retinal detachment. Eur J Ophthalmol, 2003; 13 (5): 474- 481.

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CASE REPORT

Natural History of Macular Hole Associated with Electrical Injury: An OCT Study F. Ryan Prall MD1, Antonio P. Ciardella MD2, Jeffrey Olson MD1, Naresh Mandava MD1 1 University of Colorado, Department of Ophthalmology, Denver, Colorado USA 2 Policlinico S.Orsola-Malpighi, Department of Ophthalmology, Via P. Palagi 9, 40137 Bologna, Italy

Figure 1

Corresponding author: F. Ryan Prall MD University of Colorado, Dept of Ophthalmology, 1675 N Ursula Street, Mail Stop F731, Aurora, CO 80045 Email: fprall@hotmail.com

Figure 2

Figure 3

present in the right eye. (figure 2) No treatment was suggested at the initial visit. When the patient returned three months later the vision had improved to 20/40 in the right eye and an OCT (figure 3) demonstrated persistence of a Stage 1 macular hole. One year later the vision was 20/30, the cataract had not progressed and the macular hole had resolved (figure 4) without treatment.

Figure 4

Comment

Abstract Electrical and lightning-induced injuries are common and have known ocular manifestations. We report the case of a man injured by power lines who demonstrated a macular hole associated with electrical injury. This is the first to our knowledge to document the natural history of a macular hole after electrical injury using OCT.

Case Report A 44 year-old man complained of blurred vision after suffering an electrical injury 3 weeks prior to presentation. While working near power lines an electric current passed through his right scalp causing extensive facial burns and 11% body burns. Visual acuity was 20/50 OD and 20/30 OS. There were fine anterior subcapsular specks (figure 1) and a partial thickness macular hole 146 :

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Electrical and lightning injury has been associated with cataract1-6, uveitis1,4-5, cystoid macular edema2-3,5, punctate keratitis1, retinal folds1, retinal detachment6, optic neuropathy5-6, and macular hole1-3,5,6,7. The exact mechanism is unknown but three theories have been proposed: 1) disruption of cellular membranes as the electric current passes through the eye; 2) damage from thermal injury; and 3) ischemia secondary to vasoconstriction.8-9 It has been proposed that macular hole is caused by thermal injury to the retinal pigment epithelium (RPE) as the electric current passes through this pigmented layer. As the amount of resistance across a circuit is increased the amount of energy released as heat is increased (Ohm’s law). Because the RPE has a high concentration of melanin granules that provide resistance to electric current this layer is most likely to suffer thermal damage.

This may lead to a macular hole as the pigmentation is concentrated in the macula.4 This case demonstrates by OCT the natural history of macular hole caused by electric injury. Because vitreous traction may not be involved in the pathogenesis of macular hole in electric injury, it may be reasonable to expect these to close spontaneously as it did in our case. We would suggest conservative management of macular holes associated with electrical injury.

REFERENCES 1. Noel L-P, Clarke WN, Addison. Ocular complications of lightning. J Pediatr Ophthalmol Strabismus. 1980;17:245-246. 2. Campo RV, Lewis RS. Lightning-induced macular hole. Am J Ophthalmol. 1984;97:792-794. 3. Handa JT, Jaffe GJ. Lightning maculopathy. Retina. 1994;14:169-172. 4. Lagreze WDA, Bomer TG, Aiello LP. Lightning-induced ocular injury. Arch Ophthalmol. 1995;113:1076-1077. 5. Lee MS, Gunton KB, Fischer DH, Brucker AJ. Ocular manifestations of remote lightning strike. Retina. 2002;22(6):808-810. 6. Espaillat A, Janigian R, To K. Cataracts, bilateral macular holes, and rhegmatogenous retinal detachment induced by lightning. Am J Ophthalmol. 1999;127(2):216-217. 7. Moon S, Kim J, Han D. Lightning-induced maculopathy. Retina. 2005;25(3):380-382. 8. Grover S, Goodwin J. Lightning and electrical injuries: neuro-ophthalmic aspects. Semin Neurol. 1995;15:335-341. 9. Cherington M. Central nervous system complications of lightning and electrical injuries. Semin Neurol. 1995;15:233-240.


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Successful Conservative Management Of An Atraumatic Direct Internal Carotid-Cavernous Fistula In An Infant: Case Report Paul M.J. Cheevers MD1, Alejandra A. Valenzuela MD1,2, Timothy J. Sullivan FRANZCO2 1 Department of Ophthalmology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Canada 2 Department of Ophthalmology, Division of Surgery, Royal Brisbane Children’s Hospital and the University of Queensland Medical School, Brisbane, Australia The study has been presented as a poster during the Fall annual meeting of the American Society of Ophthalmic Plastic and Reconstructive Surgery meeting in New Orleans, November 9-10th 2007. The study was rejected for publication with the affiliated meeting’s journal (OPRS).

The authors have received no financial support, and don’t have any proprietary interests in any of the products mentioned in the manuscript. Corresponding Author: Assistant Professor Alejandra A. Valenzuela Room 2035, 2W Victoria Bldg., 1278 Tower Road, Halifax, NS, B3H 3Y9 Canada Tel : 1 (902) 473 3700 Fax: 1 (902) 473 2839 Email: AA.Valenzuela@dal.ca

Resumen Las fistulas Carótido - Cavernosas (Carotid cavernous fistulae - CCF) son conecciones anormales arterio-venosas dentro del seno cavernoso. Ellas están típicamente asociadas a trauma, pero pueden ocurrir espontáneamente. La pérdida progresiva de visión ha sido clásicamente la indicación para terapia intervencional. Nosotros presentamos un caso de un bebé varón de 18 semanas de edad con una CCF y pérdida de visión secundaria a ambliopía por una parálisis de VI par. El paciente fue exitosamente tratado con terapia oclusiva para la ambliopía. Un caso similar ha sido previamente reportado en la literatura, y fue manejado con técnicas intervencionales endovasculares. Nosotros presentamos un manejo conservador cuando la funciones intraoculares y del nervio óptico son estables.

Introduction Carotid cavernous fistulas (CCF) in children are rare and typically associated with trauma. We present the first reported case of a spontaneous direct CCF in an infant that was successfully managed conservatively.

Case Report An 18 week-old child presented with a two-week history of right proptosis, bruit and esotropia. He was developmentally normal with no history of trauma or connective tissue disorder. Examination showed swelling and purple discoloration of the right upper lid with injection and tortuosity of the temporal conjunctiva (Fig. 1). There was evidence of right amblyopia with sixth nerve palsy. Intra-ocular pressure and dilated funduscopic examination was unremarkable.

Figure 1 Clinical photograph of an 18-week old infant demonstrating twenty degrees of esotropia. The patient presented with swelling and purple discoloration of the right upper lid and associated enlargement of the temporal conjunctival vessels secondary to a cavernous carotid fistula..

Head-orbit CT-scan demonstrated a dilated right superior ophthalmic vein with an enlarged right cavernous sinus (Fig. 2A-2B). Subsequent MRI/MRA confirmed it, showing drainage via the angular vein with no overtly enlarged external carotid artery supply, consistent with an internal CCF. The treatment of choice was to use detachable balloons, but this was deemed unsuitable given the patient’s size and the balloon delivery system required. Given the risks of cerebral angiography and intervention, the parents elected for conservative management in the form of patching. A cup/disc asymmetry was noted at 17-months with an otherwise stable exam. At the age two, he presented with cross-fixation and improvement in the vascular congestion. At age three, his cup/disc ratio remained stable, intra-ocular pressures were normal and the bruit disappeared. Vision continued deve-

loping despite cross-fixation with no evidence of anisometropia.

Discussion CCFs are abnormal arteriovenous connections with the venous plexus of the cavernous sinus. They could be classified based on their arterial supply, but can also divided into spontaneous, traumatic and iatrogenic.1 A breach of the internal carotid artery within the cavernous sinus has been postulated to arise from the differential accelerations of the brain vasculature and the calvarium during blunt trauma or from tearing by fractures.2,3 Spontaneous CCFs are common in hypertensive, post-menopausal women4 or connective tissue diseases.5 Ophthalmic findings are based on the underlying raised venous pressure and decreased arterial perfusion including: proptosis, ocular bruit, glaucoma, ophthalmoplePAN-AMERICA : 147


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gia, anterior segment ischemia, neovascular glaucoma, retinal ischemia and vision loss. In childhood, glaucoma is associated with buphthalmos, corneal opacification, and refractive errors. This is the first reported case of a spontaneous direct vision threatening CCF that was treated conservatively. While no specific indications for treatment have been established in children, progressive vision loss is regarded as an indication for intervention in all patients.5,6 Prior reports have also supported intervention with progressive proptosis and concomitant ocular hypertension or abducens palsy, who underwent angiographically guided procedures.7,8 Rai et al. reported an 11-month-old patient with a spontaneous direct CCF who underwent embolization for elevated intra-ocular pressure and concern regarding long-term intra-cranial venous hypertension.6 In our case, intervention may have resolved the VI-nerve palsy; however, patching remained the definitive treatment for amblyopia. While most authors consider intervention to be the gold standard when vision loss is present, we present an option for management when all other intra-ocular and optic nerve functions are stable.

Figure 2 A. Axial contrast enhanced CT scan demonstrating an enlarged superior ophthalmic vein and mild right hypoglobus. B. Axial contrast enhanced CT scan in the same patient demonstrating an enlarged right cavernous sinus.

REFERENCES 1. Barrow DL, Spector RH, Braun IF, Landman JA, Tindall SC, Tindall GT. Classification and treatment of spontaneous carotid-cavernous sinus fistulas. J Neurosurg 1985;62(2):248-56. 2. Arseni C, Horvath L, Ciurea V, Simionescu N. Carotid-cavernous fistula in the child. Neurol Psychiatr (Bucur) 1978;16(1):29-32. 3. Ringer AJ, Salud L, Tomsick TA. Carotid cavernous fistulas: anatomy, classification, and treatment. Neurosurg Clin N Am 2005;16(2):279-95, viii. 4. Jayanta Kr Das, Jnanankar Medhi et al. Clinical Spectrum of spontaneous carotid-cavernous fistula. Indian J Ophthalmol 2007;55:310-312 5. Lau F., Lam D. Spontaneous Carotid Cavernous Fistula in a Pediatric Patient: Case Report and Review of the Literature. Journal of AAPOS. 2005. 9 (3) 292-294 6. Rai A, Marano G. Direct Carotid Cavernous Fistula in Infancy: Presentation and Treatment. Am J Newroradiol 25:1083-1085 7. Gossman MD, Berlin AJ, Weinstein MA, Hahn J, Price RL. Spontaneous direct carotid-cavernous fistula in childhood. Ophthal Plast Reconstr Surg 1993;9(1):62-5. 8. Biglan AW, Pang D, Shuckett EP, Kerber C. External carotid-cavernous fistula in an infant. Am J Ophthalmol 1981;91(3):351-6.

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Spontaneous Scleral Perforation In Ocular Rosacea Ana Carolina Vieira MD1,2, Mark J Mannis MD2 1 Department of Ophthalmology, Federal University of São Paulo, Brazil 2 Department of Ophthalmology & Vision Science, University of California, Davis

No funding was received for this work.

Corresponding author: Mark J. Mannis MD, Professor and Chair, Department of Ophthalmology & Vision Science, University of California, Davis, 4860 Y St, Suite 2400, Sacramento, CA 95817 Voice: 916-734-6957 Fax: 916-703-5076 E-mail: mjmannis@ucdavis.edu

Figure 1 Small round scleral perforation with protruding vitreous in a patient with ocular rosacea.

Resumo Objetivo: Relatar um caso raro de perfuração escleral espontânea em paciente com rosácea ocular tratado cirurgicamente com enxerto escleral. Métodos: Relato de caso. Resultados: Paciente feminina, 52 anos, com diagnóstico prévio de rosácea ocular há 9 anos procurou atendimento oftalmológico apresentando perfuração escleral espontânea no olho esquerdo. Ao exame, notavase eritema facial e pápulas eritematosas. A biomicroscopia do olho esquerdo revelou disfunção meibomiana, hiperemia conjuntival, afinamento corneano periférico, neovascularização e depósitos lipídicos na região temporal da córnea. Na região temporal da esclera, observava-se área de perfuração escleral, medindo aproximadamente 1 mm de diâmetro, através da qual se percebia protrusão vítrea. A perfuração escleral foi tratada cirurgicamente com um enxerto homólogo de esclera fixado com cola de fibrina e 4 suturas com fio de mononylon 10-0. Um mês apos o procedimento cirúrgico, a acuidade visual corrigida era 20/25.

Conclusão: Esclerite pode ser uma complicação rara das formas graves de rosácea ocular. O enxerto escleral homólogo mostrou-se eficaz no tratamento da perfuração escleral secundária a rosácea ocular. Pacientes portadores de rosácea ocular e esclerite requerem tratamento sistêmico e acompanhamento frequente por um oftalmologista. Palavraschave: rosácea ocular, esclera, perfuração, enxerto homólogo.

asuring approximately 1 mm in diameter, with protruding vitreous was present. The scleral perforation was repaired with a homologous scleral patch graft sealed into position with fibrin glue and 4 sutures of 10-0 monofilament nylon. One month postoperatively, her best corrected visual acuity was 20/25.

Purpose: To report a rare case of spontaneous scleral perforation in a patient with ocular rosacea and its surgical management.

Conclusion: Scleritis can be a rare complication of severe ocular rosacea. A homologous scleral patch graft proved successful in treating this condition. Patients with ocular rosacea severe enough to induce scleritis require systemic therapy and close monitoring. Key words: ocular rosacea, sclera, perforation, homologous graft.

Methods: Case report.

Introduction

Results: A 52 year-old woman with a history of ocular rosacea diagnosed 9 years earlier presented with a spontaneous scleral perforation in the left eye. On examination, axial facial redness with erythematous papules was present. Slit lamp examination of the left eye revealed meibomian gland dysfunction, conjunctival injection, marked peripheral corneal thinning, neovascularization and lipid deposition in the cornea temporally. A discreet round scleral perforation temporal to the limbus me-

Rosacea is a chronic progressive cutaneous disorder that affects approximately 13 million Americans.1 It is characterized by persistent erythema, telangiectases, papules and pustules that involve primarily the convexities of the central face (cheeks, chin, nose and central forehead). If left untreated, it can be disfiguring and the ocular form has the potential to compromise vision.

Abstract

The etiology of the disease is still unknown. Many factors have been implicated in PAN-AMERICA : 149


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its pathogenesis. Several studies confirm an inflammatory mechanism.2,3 An elevated concentration of interleukin-1alpha and a greater activity of gelatinase B (MMP-9) were found in tear fluids of patients with ocular rosacea. Recently cathelicidin, an antimicrobial peptide with pro-inflammatory action, was found to be expressed in greater levels in the skin of individuals with rosacea than in normal facial skin. These peptides promote leukocyte chemotaxis, angiogenesis, and extracellular matrix component expression.4 Vascular dilation and incompetence may also contribute to the signs and symptoms of rosacea.5 Microbial organisms such as Helicobacter pylori and Demodex folliculorum have been identified as possible causative factors in exacerbation of the disease.6-8 H. pylori is frequently found in rosacea patients and its eradication has been shown to influence the clinical outcome of this disease.9 Ocular manifestations occur in half or more of rosacea patients and are potentially blinding.10,11 The diagnosis can be challenging, given that up to 90% of patients with ocular rosacea may not show charateristic or obvious roseatic skin changes. The most common ocular complaints include foreign body sensation, pain, burning, photophobia, itchy/watery eyes and redness. The disease usually affects both eyes, and the most frequent ocular findings include anterior and posterior blepharitis, meibomian gland dysfunction, recurrent chalazia and chronic conjunctivitis. Episcleritis and, less commonly, scleritis, have been documented in more severe ocular rosacea patients. Ghanem et al found episcleritis in 4.5% and scleritis in 1.2% of rosacea patients seen in an ophthalmology clinic.11 Gracner et al reported a case of a corneoscleral perforation in an ocular rosacea patient.12 We report a case of a spontaneous scleral perforation in a patient with severe ocular rosacea. To the best of our knowledge, no similar case has been previously described.

Case Report A 52 year-old woman with a history of ocular rosacea diagnosed 9 years earlier presented with a spontaneous scleral perforation in the left eye (OS). Her best corrected visual acuity was 20/20 in the right eye (OD) and 20/50 OS. Examination demonstrated axial facial red150 :

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ness with erythematous papules. Slit lamp examination revealed meibomian gland dysfunction and an area of marked peripheral corneal thinning and scar with neovascularization inferotemporally suggestive of previous keratitis in OD. The remainder of the examination in the right eye was normal. The left eye revealed meibomian gland dysfunction, 1+ conjunctival injection, marked peripheral corneal thinning, neovascularization and lipid deposit in the cornea temporally and a discreet round scleral perforation temporal to the limbus measuring approximately 1 mm in diameter, with protruding vitreous (figure 1). The anterior chamber was shallow, with 1+ flare. A fibrinous membrane was noted in the pupillary region. Intraocular pressure in the right eye was normal, while the left eye was hypotonous. The posterior segment in both eyes was normal. Her past ocular history was positive for rosacea with significant peripheral corneal involvement. There had been peripheral corneal thinning in both eyes (OU) and recurrent episodes of very persistent nodular scleritis temporally in the left eye. Inflammation slowly responded to systemic corticosteroids but would subsequently recur. Diagnostic testing included ANA, rheumatoid factor, angiotensin converting enzyme, sedimentation rate, serum calcium, ANCA, C-reactive protein and surface cultures, all of which were within the normal limits. Her past medical history was significant for acne rosacea, obesity and asthma. Her past surgical history included knee arthroscopy for a lateral meniscus tear correction and tonsillectomy. She had been on regular therapy with prednisolone acetate 1% twice daily OU, methotrexate 15 mg/week and folic acid for 6 years. In the past, she had tried a variety of medications including topical and oral corticosteroids, oral non-steroidal anti-inflammatory agents, oral doxycycline, and topical antibiotics. We repaired the scleral perforation with a homologous scleral patch graft under general anesthesia. The conjunctiva around the area of perforation was mobilized and recessed to allow direct access to the scleral perforation site. After carefully removing the extruded vitreous with Vannas scissors, a 3 mm scleral patch formed from eye bank sclera with a dermatologic punch was placed over the perforation and sealed into position with fibrin glue (TisseelTM, Baxter AG Industries, Inc). Four

sutures of 10-0 monofilament nylon were then placed to secure the patch graft to the surrounding sclera. The conjunctiva was closed over the graft using 10-0 vicryl sutures. There were no surgical complications. The patient was started on topical tobramycin/dexamethasone drops four times daily and cyclopentolate twice daily postoperatively. One day after surgery, there was improvement of best-corrected visual acuity to 20/40 OS. Slit-lamp examination showed 3+ temporal conjunctival injection, thinning and lipid deposit in peripheral cornea at 3 o’clock, a well-positioned scleral patch graft covered by conjunctiva. The anterior chamber was deep, with 1+ cell. Intraocular pressure was 27 mmHg. The posterior segment was normal. On the fifth postoperative day the intraocular pressure was 16. The tobramycin/dexamethasone drops were tapered to twice daily. One month postoperatively, best corrected visual acuity was 20/25, 90% corneal thinning peripherally at temporal limbus unchanged from pre-operatively, 1+ conjunctival injection overlying a well-positioned scleral patch graft and a deep anterior chamber with no inflammatory reaction (figure 2). The intraocular pressure was 9 mmHg. The patient maintained the ocular medication twice daily. The patient is currently stable on prednisolone acetate 1% twice daily OU, methotrexate 15 mg/week and folic acid.

Discussion Although rare, rosacea has been shown to cause scleritis and episcleritis.11,12 Our patient had a history of rocasea, keratitis and recurrent nodular scleritis. Other more common causes of scleritis were investigated. However, cultures and serologies were negative, ruling out infection and autoimmune disease. We considered rosacea to be the underlying cause of the ocular inflammation. The persistence of her scleritis was atypical for a rosacea patient. Despite significant efforts to control the inflammatory process with high-dose oral corticosteroids and methotrexate, the patient developed active scleritis. Spontaneous scleral perforation occurred secondary to long-term inflammation. Various surgical techniques for sealing scleral perforations have been reported and include the use of tissue glue, conjunctival patches, and both autologous and homologous scleral grafts.13 In our case, there was a punched out scleral perforation with vitreous


Marzo 2009

Figure 2 Scleral perforation repaired with a homologous scleral patch graft. On examination one month post-operatively, deep anterior chamber with no inflammatory reaction.

prolapse so that tissue glue and a conjunctival patching were not suitable. The use of a homologous scleral patch graft is the most frequently reported method in the surgical repair of scleral perforations.13 General anesthesia provides optimal akinesia minimizing the risk of increased intraocular pressure and further vitreous prolapse. Although retrobulbar anesthesia provides excellent regional anesthesia and akinesia, with minimal cardiac and respiratory stress, increased pressure and further vitreous prolapse are risks. A homologous scleral patch graft was the chosen method for the surgical treatment of our patient’s scleral perforation. The recipient

bed was prepared by performing conjunctival dissection and debridement of necrotic tissue from the scleral margins. The donor sclera was then cut to the appropriate size with a dermatologic punch and then thinned to 50% normal scleral thickness. We oversized the graft to allow for good coverage of the perforation. Fibrin glue was used both to secure the graft as well as to ensure a tight seal of the perforation. We then sutured the graft in place using 4 10-0 monofilament nylon sutures with buried knots to provide a smooth bulbar surface. Conjunctiva was then pulled over the graft and closed with 10-0 vicryl sutures.

cations demonstrate its utility.14,15,16 Batman et al compared the use of tissue glue and vicryl sutures for closing scleral and conjunctival wounds after conventional 20-gauge vitrectomy and found no adverse effects and fewer postoperative patient symptoms in the tissue glue group.17 Apart from providing less discomfort, fibrin glue reduces time of surgery. This case demonstrates a rare complication of chronic acne rosacea with ocular involvement and its successful surgical management. Patients with ocular rosacea severe enough to induce scleritis require systemic therapy and close monitoring.

Biologic adhesives (fibrin-based adhesives) have been widely used in ophthalmology, and many studies on its ophthalmic appli-

REFERENCES 1. Zuber TJ. Rosacea. Prim Care. 2000; 27 (2): 309-18. 2. Sobrin L, Liu Z, Monroy DC et al. Regulation of MMP-9 activity in human tear fluid and corneal epithelial culture supernatant. Invest Ophthalmol Vis Sci. 2000; 41 (7): 1703-9. 3. Afonso AA, Sobrin L, Monroy DC et al. Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea. Invest Ophthalmol Vis Sci. 1999; 40 (11): 2506-12. 4. Yamasaki K, Di Nardo A, Bardan A et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 2007; 13(8): 975-8. 5. Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and sbtype classification. J Am Acad Dermatol 2004; 51: 327-341. 6. Georgala S, Katouis AC, Kylafis GD et al. Increased density of Demodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea. J Eur Acad Dermatol Venereol 2001; 15 (5): 441-444. 7. Lacey N, Delaney S, Kavanagh K et al. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol 2007; 157 (3): 474-481. 8. Diaz C, O’Callaghan CJ, Khan A et al. Rosacea: a cutaneous marker of Helicobacter pylori infecton? Results of a pilot study. Acta Derm Venereol 2003; 83 (4): 282-286. 9. Utas S, Ozbakir O, Turasan A et al. Helicobacter pylori eradication

treatment reduces the severity of rosacea. J Am Acad Dermatol 1999; 40: 433-435. 10. Alvarenga LS, Mannis MJ. Ocular Rosacea. Ocul Surf. 2005; 3 (1): 41-58. 11. Ghanem VC, Mehra N, Wong S et al. The prevalence of ocular signs in acne rosacea: comparing patients from ophthalmology and dermatology clinics. Cornea 2003; 22 (3): 230-3. 12. Gracner B, Pahor D, Gracner T. Repair of an extensive corneoscleral perforation in a case of ocular rosacea with a keratoplasty. Klin Monatsbl Augenheilkd 2006; 223 (10): 841-3. 13. M. Bowes Hamill. Management of Scleral Perforation. In Krachmer, Mannis & Holland, Cornea – Volume Two: Surgery of the cornea and conjunctiva. Philadelphia: Elsevier Inc., 2005: 1863-1870. 14. Kaufman HE, Insler MS, Ibraim-Elzembely HA. Human fibrin tissue adhesive for sutureless lamellar keratoplasty and scleral patch adhesion. Ophthalmology 2003; 110: 2168–2172. 15. Bahar I, Kaiserman I, Slomovic A et al. Fibrin glue for opposing wound edges in “top hat” penetrating keratoplasty – A laboratory study. Cornea 2007; 26: 1235-1238. 16. Kahook MY, Noecker RJ. Fibrin glue-assisted glaucoma drainage device surgery. Br J Ophthalmol 2006; 90: 1486-1489. 17. Batman C, Ozdamar Y, Mutevelli S et al. A comparative study of tissue glue and vicryl suture for conjunctival and scleral closure in conventional 20-gauge vitrectomy. Eye 2008 Sep 5. [Epub ahead of print]. PAN-AMERICA : 151


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Evaluation of Early Chorioretinal Abnormalities in Hypercholesterolemic Rabbits Submitted to the Peroxisome Proliferator-Activated Receptor (PPAR)Gamma Agonist Treatment (Rosiglitazone): Histological and Histomorphometric Study Rogil José de Almeida Torres1, Maurício Maia MD2, Cristina Muccioli MD3, Lucia Noronha4, Michel Eid Farah5, Andréa Luchini6, Dalton Bertolin Précoma7 1 Doctoral student at the Department of Ophthalmology, Universidade Federal de São PauloSP 2 Graduate Program Advisor at the Department of Ophthalmology, Universidade Federal de São Paulo – São Paulo - SP 3 Associate Professor at the Department of Ophthalmology, UNIFESP/EPM 4 Associate Professor at the Department of Pathology, Pontifícia Universidade Católica do Paraná - Curitiba - PR 5 Associate Professor at the Department of Ophthalmology, Universidade Federal de São Paulo - São Paulo – SP 6 Physician at the Centro Oftalmológico de Curitiba- Paraná 7 Associate Professor at the Department of Cardiology, Pontifícia Universidade Católica do Paraná - Curitiba - PR

Resumo Objetivos: Avaliar, de forma experimental em coelhos, as anormalidades histológicas degenerativas na esclera e coróide após administração diária de alta dosagem de colesterol tão bem quanto possível prevenção destas anormalidades degenerativas com administração sistêmica de rosiglitazona, um agonista dos receptores Gama Ativados pelo Proliferador de Peroxissomo (PPAR gama). Método: 55 coelhos New Zealand foram divididos em 4 grupos: Grupo controle (GC) (06 coelhos) recebeu dieta normal durante 6 semanas. Grupo 1 (G1) (13 coelhos) recebeu dieta de colesterol a 1% por 02 semanas e após dieta de colesterol a 0,5% por mais 4 semanas. Grupo 2 (G2) (18 coelhos) recebeu dieta de colesterol a 1% por 02 semanas e após dieta de colesterol a 0,5% por mais 4 semanas. Adicionalmente este grupo recebeu 3 mg de rosiglitazona diariamente a partir da 3ª semana do início do experimento. Grupo 3 (G3) recebeu dieta de colesterol a 1% por 02 semanas e após dieta de colesterol a 0,5% por mais 4 semanas. Adicionalmente este grupo recebeu 3 mg de rosiglitazona diariamente a partir do início do experimento. Dados foram analisados pelo teste de ShapiroWilks-Testand e valores abaixo de 0,05 foram considerados estatisticamente significantes. Resultados: Nenhuma alteração foi observada no GC. No entanto o G1 mostrou um significativo aumento da espessura da esclera e coróide (301,48 ± 50,12) comparados com 152 :

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Participating Institutions: Angelina Caron Hospital - Campina Grande do Sul/ Paraná/ Brazil; Federal University of São Paulo (UNIFESP - EPM) Corresponding author: Rogil José de Almeida Torres Praça Ruy Barbosa, 827 – Conj. 305, CEP 80010-030, São Paulo, SP Brazil Fax: (55-41) 3225-6349 E-mail: rjat@terra.com.br Financial Disclosure: The authors declare that they have no financial interests in this manuscript.

o GC (239,09 ± 24,33) ( p= 0,005). O G2 mostrou espessamento da esclera e coróide menor (282,08 micrometros/DP36,44) que G1 (301,48 ± 50,12); no entanto estes valores não foram estatisticamente significantes (p=0,222). O G3 mostrou espessamento de esclera e coróide menor (266,11 ± 47,94) que G1 (301,48 ± 50,12); este valor foi estatisticamente significante (p=0,02). Grande número de histiócitos foram observados na parede escleral do grupo submetido a dieta hipercolesterolêmica (G1) seguidos de forma decrescente por G2, G3 e GC. Conclusões: Este estudo revela que a hipercolesterolemia no modelo animal (coelho) pode conduzir a anormalidades degenerativas precoces na esclera e coróide e que a ativação dos receptores do PPAR gama oculares, através da dieta oral de rosiglitazona, demonstra ser efetivo na preservação anatômica destas estruturas. Este estudo pode ter relevância clínica visto que as glitazonas podem oferecer uma nova modalidade de tratamento para a degeneração macular seca e/ou úmida em olhos humanos.

Abstract Purpose: To evaluate in a rabbit model the degenerative histological abnormalities in the choroid and sclera following the daily administration of high cholesterol dosages as well as the possible prevention of these degenerative abnormalities following systemic administration of oral rosiglitazone, an activator

of agonist peroxisome proliferator-activated receptor (PPAR)-gamma receptors. Methods: Fifty-five New Zealand rabbits were studied and divided into four groups: Control Group (CG – 6 rabbits) received normal diet for six weeks; Group 1 (G1 – 13 rabbits) received 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks; Group 2 (G2 – 18 rabbits) received 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks. Additionally, this group also received 3 mg of rosiglitazone daily after the third week since the beginning of the experiment; and Group 3 (G3 – 18 rabbits) received 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks. Additionally, this group also received 3 mg rosiglitazone since the beginning of the experiments. The animals were euthanized and their eyes underwent histomorphometric analysis. Results: No histological abnormalities were observed in CG while G1 presented a significant increase in the scleral and choroidal thickness in relation to CG and G3. Conclusions: This study revealed that hypercholesterolemia may lead to early degenerative abnormalities of the choroid and sclera of rabbits and that the activation of agonist PPAR ocular gamma receptors, by means of oral administration of rosiglitazone, proved to be effective for the preservation of choroidal and scleral anatomy.


Marzo 2009

Purpose The objective of this study is to evaluate, in a rabbit model, the degenerative histological abnormalities in the choroids and sclera following the daily administration of high cholesterol dosages as well as the possible prevention of these degenerative abnormalities following systemic administration of oral rosiglitazone, an activator of agonist peroxisome proliferator-activated receptor (PPAR)gamma receptors. Peroxisome proliferator-activated receptors gamma is a nuclear receptor that acts in the systemic lipid and glucose metabolism as well regulates cellular functions including anti-inflammatory, anti-atherogenic and immunomodulatory actions. Reduction in progression of atherosclerosis with activation of PPAR by rosiglitazone (RGZ) is promising in animal models. This action is independent of its effects on metabolic control. The similarity in physiopathogeny between age macular degeneration and atherosclerosis was the main factor that motivated this study.

Methods The protocol was approved by the Animal Experimentation Ethics Committee of the Hospital Angelina Caron Hospital and the Federal University of SĂŁo Paulo. Fifty-five New Zealand rabbits were studied and divided into four groups according to the diet they were fed (normal diet or high cholesterol diet -Sigma-AldrichÂŽ - London, England). 1. Control Group (CG) (06 rabbits): normal diet for six weeks; 2. Second group (G1) (13 rabbits): 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks; 3. Third group (G2) (18 rabbits): 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks. Additionally, this group also received 3 mg of rosiglitazone daily after the 14th day; 4. Fourth group (G3) (18 rabbits): 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks. Additionally, this group also received 3 mg rosiglitazone since the beginning of the experiments. The animals were euthanized with an intravenous injection of 5 ml pentobarbital and their eyes were immediately fixed in 4% paraformaldehyde solution in 0.1M phosphate/

pH 7.4 for 4 hours for the histomorphometric analysis. One eye in each rabbit was randomly examined. Histomorphometry was performed with the purpose to evaluate the choroids as well as scleral thickness in several segments and to detect atypical cells in these structures. Data was analyzed by Shapiro-Wilks W Test and P values lower than 0.05 were considered statistically significant.

Results No histological abnormalities were observed in CG. However, G1 group showed a significant increase in sclerochoroidal thickness (301.48 micrometers/DP 50.12) compared with CG (239.09 micrometers/DP 24.33) (p=0.005). The G2 group, which received rosiglitazone since the third week, showed a sclerochoroidal thickness (282.08 micrometers/DP 36.44) lower than the hypercholesterolemic rabbit group (G1) (301.48 micrometers/DP 50.12); however, this value was not statistically significant (p = 0.222). The G3 group, which received rosiglitazone since the beginning of the experiment, showed a sclerochoroidal thickness (266.11 micrometers/ DP 47.94) lower than the hypercholesterolemic rabbit group (G1) (301.48 micrometers / DP 50.12). This value was statistically significant (p=0.02). Out of the studied groups of rabbits, G1 presented the highest number of histiocytes in the scleral wall, followed by groups G2, G3 and CG, respectively (Fig.1).

CG

Absence of histiocytes in the sclera

G1

A large number of histiocytes in the scleral wall Significant presence of collagen fibers Increase of choroidal thickness

G2

Discussion Lipid deposition in the sclera leads to an increase in the postcapillary resistance of the choroidal system, located between the progressively stiffened sclera and the noncompressable contents of the globe.1 The decrease in the choroidal blood flow and the increase in resistance lead to an increase in the choriocapillaris hydrostatic pressure,1 increasing leakage and extracellular protein and lipid deposition, specifically in the posterior pole, forming basal deposits on the Drusen and Bruch’s membrane,2 the earliest agerelated macular degeneration (AMD) clinical manifestation. This mechanism is similar to the atherosclerosis pathophysiology, an inflammatory process, in which the cholesterol (LDL) is deposited in the intima of the vessel wall leading to loss of arterial elasticity. Immunologic and inflammatory processes are also observed in AMD as the immunohistochemical analysis of drusen reveals

Decrease in the number of histiocytes and collagen fibers in the scleral wall

G3

Similar results to CG

Figure 1 SR - SENSORIAL RETINA C - CHOROID S - SCLERA * - HISTIOCYTES

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BASIC INVESTIGATION

the presence of apolipoproteins B and E, immunoglobulines, factor X, amyloid P component, C5 and C5b-9 complements, fibrinogen and vitronectin.3 Moreover, histological examination of the neovascular membrane or disciform scar has revealed macrophages adjacent to thin areas or ruptures in Bruch’s membrane.4,5,6 These aspects demonstrate that atherosclerosis and AMD share similar pathophysiologic mechanisms. Evidences of scleral and choroidal alterations due to hypercholesterolemia in rabbits have already been reported in the literature.7 A trial in which rabbits were fed a daily 0.75% and 2.5% cholesterol diet for 6 months revealed lipid deposition on the inner surface of the choroid as well as foam cells (histiocytes) and lipid drops in the connective tissue. This study has considered the possibility of a reduction in the ocular blood flow caused by hypercholesterolemia.8 Another experimental study has observed that cholesterol drops in the suprachoroid compress the vascular layers and cause hypertrophy of the endothelial and vascular smooth muscle cells.9 The same study observed an increase in the suprachoroid thickness in the rabbits which were fed a hypercholesterolemic diet due to abundance of collagen fibers. In this study it was also possible to perceive a significant increase in the scleral and choroidal thickness in the hypercholesterolemic rabbits (G1). It is important to point out that the studies that have been carried out until the present date, whose purpose was to evaluate the chorioretinal alterations in rabbit eyes, used 0.5 cholesterol diet for a minimum period of 6 months.9,10,11 Conversely, in this study the alterations could be perceived after 6 weeks of hypercholesterolemic diet. This fact provides useful information as it shows that alterations in the ocular wall in rabbits can be obtained in a short period of time, thus offering more opportunities for trials and reducing research costs. It is worth pointing out that ocular alterations in rabbits occur as early as the vascular alterations. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the 48 members of the ligand-activated nuclear receptor superfamily and regulates the gene expression in response to specific ligands.12 It is a modern group of drugs that can be used to improve the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus. 154 :

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In atherosclerosis, the treatment with glitazones (PPAR-gamma ligands) results in the reduction of the markers of atherosclerosis activity, suggesting an additional effect besides the one of metabolic control.13 It has been demonstrated that activation of PPAR-gamma inhibits the Matrix metaloproteinase-9 expression and activity.14 In macrophages, antiinflammatory and potentially anti-atherosclerotic activities have been observed, including: Inhibition of cytokine production, attenuation of cytokine-induced nitric oxide synthase expression, gelatinase B1 and scavenger receptors; and an antagonism of the activities of transcription factors NF-kB, AP-1, STAT.14 Moreover, the authors observed a reduction in the expression of the Cell Adhesion Molecules ICAM-1, VCAM-1 in the endothelial cells, as well as reduction in the transendothelial migration of monocytes due to the reduction in MCP-1 expression, and of their receptors CCR2 on monocytes.15,16,17 In 2000, MURATA and other researchers18 performed a study to determine the anti-angiogenic effect of PPAR-gamma agonists on the cells involved in the pathogenesis of choroidal neovascularization (CNV) in vitro and in vivo experimental models. It was observed that PPAR-gamma was expressed in both RPE and choroidal endothelial cells. Consequently, PPAR-gamma ligands played a significant role in the inhibition of VEGF-induced proliferation and migration in both types of cells and in the vein formation by choroidal endothelial cells. The authors concluded that inhibition of choroidal angiogenesis by PPAR-gamma ligands is also possible in the exsudative AMD of humans. In the present study, anatomic preservation of the choroid and sclera was statistically significant in G3 and statistically non-significant in G2. Thus, oral rosiglitazone proved to be effective in reducing reduce the degenerative damage of the choroid-scleral complex, corresponding to dry AMD in humans.

Conclusions This study revealed that hypercholesterolemia induced by high cholesterol diet may lead to early degenerative abnormalities of the choroid and sclera of rabbits. Moreover, the activation of agonist PPAR ocular gamma receptors, by means of oral administration of rosiglitazone, proved to be effective for the preservation of choroidal and scleral anatomy. These findings have clinical relevance

as the rosiglitazones may offer a new treatment modality for dry and/or exsudative AMD in human eyes.

REFERENCES 1. Friedman E, Krupsky S, Lane A, Oak S, Friedman ES, Egan K, Gragoudas E. Ocular blood flow velocity in age-related macular degeneration. Ophthalmology. 1995; 102:640-6. 2. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Age-related degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol. 2003;48:257-93. 3. Hageman GS, Luthert PJ, Victor Chong NH, et al: An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the rpe-bruch’s membrane interface in aging and agerelated macular degeneration. Prog Retin Eye Res. 2001; 20:705–32. 4. Killingsworth MC, Sarks JP, Sarks SH: Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye. 1990;4:613–21. 5. Penfold PL, Killingsworth MC, Sarks SH: Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol. 1985;223:69–76. 6. Van der Schaft TL, Mooy CM, de Bruijn WC, de Jong PT: Early stages of age-related macular degeneration: an immunofluorescence and electron microscopy study. Br J Ophthalmol.1993; 77:657–61. 7. Cogan DG, Kuwabara T. Ocular changes in the experimental hypercholesterolemia. Arch Ophthalmol. 1959;61:219-25. 8. Janes RG. Changes in the rabbit’s eye caused by cholesterol feeding. Am J Ophthalmol. 1964;58:81928. 9. Salazar JJ. Ramirez AI, Hoz R, Rojas B, Ruiz E, Tejerina T, Triviño A, Ramirez JM. Alterations in the choroid in hypercholesterolemic rabbits: Reversibility after normalization of cholesterol levels. Exp Eye Res. 2007;84:412-422. 10. Triviño A, Ramirez AL, Salazar JJ, de Hoz R, Rojas B, Padilla E, Tejerina T, Ramirez JM. A cholesterol-enriched diet induces ultrastructural changes in retinal and macroglial rabbit cells. Exp Eye Res. 2006;83:357-66. 11. Ramirez AI, JJ Salazar JJ, Hoz R, Rojas B, Ruiz E, Tejerina T, Ramirez JM, Triviño A. Macroglial and retinal changes in hypercholesterolemic rabbits after normalization of cholesterol levels. Expe Eye Res. 2006:83:1423-38. 12. Chawla, A; Repa, J J; Evans, R M; et al. Nuclear receptors and lipid physiology: opening the X-files. Science 2001; 294:1866-1870. 13. Minamikawa, J; Tanaka, S; Yamauchi, M; et al. Potent inhibitory effect of troglitazone on carotid artery wall thickness in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism 1998; 83:1818-1820. 14. Marx, N; Schonbeck, U; Lazar, M A; et al. Peroxissome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circulation Research 1998; 83:1097-1103. 15. Jackson, S M;Parhami, F;Xi,X;et al. Peroxissome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Atherosclerosis, Thrombosis, and Vascular Biology 1999; 19: 2094-2104. 16. Pasceri, V; Wu, H D; Willerson, J T; et al. Modulation of vascular inflammation in vitro and in vivo by peroxissome proliferator-activated receptor-gamma activators. Circulation 2000;101: 235-238. 17. Han, K H; Chang, M K; Boullier, A; et al. Oxidized LDL reduces monocyte CCR2 expression through pathways involving peroxissome proliferatoractivated receptor. J Clin Invest 2000; 106:793-802. 18. Murata T, He S, Hangai M, Ishibashi T, Xi XP, Kim S, Hsueh WA, Ryan SJ, Law RE, Hinton DR. Peroxisome Proliferator-Activated Receptor-y Ligands Inhibit Choroidal Neovascularization. Invest Ophthalmol Vis Sci 2000;41:2309-17.


Marzo 2009

PAAO’s next educational event is the VII Annual Pan-American Research Day. This course continues the tradition of highlighting the most important papers and posters to be presented at ARVO and creating a forum for leaders getting together. This exciting event will be held on Saturday, May 2, 2009, from 12 – 6 PM, in the Grand Ballroom of the Renaissance Hotel in Fort Lauderdale, Florida. Presentations will be made in the language of the presenter: English, Spanish and/or Portuguese. This course is free of charge. Seating is limited so we ask that you please pre-register before April 24, 2009. Please see www.paao.org for more details. We would like to take advantage of this opportunity to thank Allergan International, our industry partner, who is offering a generous educational grant to support this meeting. We would like to thank our other educational partners who provide research initiatives and travel awards to attend this event: • David & Julianna Pyott Foundation • Johnson & Johnson Inc. • Retina Research Foundation • Santen Inc. We hope that you will take advantage of this educational opportunity. Sincerely, The Organizing Committee PAN-AMERICA : 155


2008 Gillingham Fellow

I had been selected as one of the 2008 Gillingham Pan-American Fellows and it has not only been an honor, but also, one of the most wonderful opportunities I have ever had in my life. As a Colombian, I have always had a profound love for my country and an eternal commitment to work for its progress. There are different ways to accomplish this: the road I chose was to work hard to become a highly qualified professional surgeon so that I could offer the best care to my community. Since my childhood, this has been my goal and I have always tried to get the best education possible. When you are in a developing country, new knowledge and ideas are always the best ingredients to promote progress. Based on that thought, I decided to do a fellowship in a different country. I was fortunate to be accepted in the Kellogg Eye Center at the University of Michigan to accomplish this goal. This institution is categorized as one of the best in the country with a health system that has been rated as number 13 in the United States on the Honor Roll by the U.S. News and World Report ranking. Here, I have found an invaluable human resource with vast experience, the most advance technology on their hands and a very rich academic activity.

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Due to this institution’s prestige, it is one of the biggest referral centers in the region, allowing me to be exposed to a huge variety of pathologies, complex cases and surgeries. The Oculoplastic department is one of the busiest in the Kellogg Eye Center; it is composed by four outstanding oculoplastic surgeons and an ASOPRS fellow who have contributed in the best way to my learning. To have the opportunity of learning from the experience of Doctor Christine Nelson, Doctor Bartley Frueh, Doctor Victor Elner, Doctor Alon Kahana and Doctor Raymond Cho, has given me a broad variety of knowledge that will definitely leave a huge imprint on my formation and education. Due to the high complexity of different cases, I have participated in the multidisciplinary management they require. This has allowed me to interact with other services as Ear, Nose and Throat, Neurosurgery, Plastic Surgery, Dermatology, Oncology and Radiology. Being at the Kellogg Eye Center has enriched my profession as an ophthalmologist as well. I have participated in the clinical practice of other subspecialties, such as NeuroOphthalmology. I have also been part of the multiple academic activities this center has, like the Grand Rounds, Visiting Professors conferences, Fall Symposium, Neuro-Radiology Conference, Neurosurgery Tumor Board

and Head and Neck Tumor Board and other conferences. I have actively participated in teachig the resident suture workshop, Grand Rounds and other conferences which has helped me become a better teacher. Not only have the clinical and surgical experience contributed to my learning and progress but this experience has also allowed me to participate in clinical research. I am involved in several different research projects such as Ptosis, Orbital Fractures, Decompressions, Exophthalmometry and case reports. This activity has taught me a lot and has created in me the research spirit that we lack in a country like Colombia. I hope to continue to collaborate internationally on several projects that we have started. In summary, these six months have been a world wide experience that could never be possible without the financial aid I have received from this award. I will be eternally grateful to the Retina Research Foundation of Houston, Texas and the Pan-American Association of Ophthalmology. Sincerely yours,

Ángela María Sánchez Castellanos, M.D.


Marzo 2009

BOOK REVIEW

Mark Mannis MD Editor en Jefe Editor-in-Chief Editor Chefe

Oftalmogeriatría. Cypel M and Belfort Jr. R, Editora Roca, Ltd., São Paulo, Brasil, 2008. 428 pages; CD ROM Todos los que nos dedicamos a la oftalmología clínica reconocemos que los viejos son el centro de nuestra actividad. Marcela Cypel y Rubens Belfort Jr. de la Universidad Federal de São Paulo, han producido un texto de gran importancia y que tendrá gran valor para los oftalmólogos de habla hispana y portuguesa. Este libro tiene un enfoque único, pues 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 de libro cubren una gran gama de alteraciones oftalmológicas que afectan a la población de la tercera edad. Comenzando con un capítulo introductorio en geriatría y gerontología en oftalmología, el libro continua con la anatomía ocular del viejo y la epidemiología de las enfermedades oculares en este grupo etario. Los siguientes capítulos incluyen aspectos psico-sociales, percepción visual, error refractivo, y baja visión. Cuenta también con capítulos que tratan por separado el ojo seco, oculoplástica, enfermedades de la córnea, párpados, vía lagrimal, escleritis y epiescleritis, uveítis, los glaucomas, catarata, retinopatía diabética, enfermedades vasculares y degenerativas de la retina, desprendimiento de retina y consid-

eraciones especificas en neuro-oftalmología, oncología, estrabismo y toxicología. El texto cuenta con un gran número de tablas e ilustraciones a color, lo mismo que fotografías clínicas de gran calidad. Los autores han incluido un excelente CD con películas de procedimientos quirúrgicos estándar, que son narrados en portugués. El CD funciono sin problema alguno en la computadora Mac de este revisor. Como conclusión, este texto debería estar en la repisa de todo oftalmólogo que atienda a pacientes de la tercera edad. Es una contribución excepcional y de gran calidad a la biblioteca de nuestra especialidad. Esperamos que la editorial produzca una traducción para la comunidad oftalmológica de habla inglesa.

Oftalmogeriatría. Cypel M and Belfort Jr. R, Editora Roca, Ltd., São Paulo, Brasil, 2008. 428 páginas; DVD

gem as alterações oftalmológicas freqüentes na população de idosos e sua repercussão na qualidade de vida.

Todos nós que trabalhamos na área da oftalmologia reconhecemos que o envelhecimento está atualmente no centro de nossas atenções. Marcela Cypel e Rubens Belfort Jr. da Universidade Federal de São Paulo produziram uma importante obra que será de grande valor para oftalmologistas de língua Portuguesa e Espanhola. O enfoque diferenciado deste livro é a abordagem das doenças oftalmológicas do paciente idoso, com seus diagnósticos e tratamentos. O livro dá ênfase ao impacto das afecções oftalmológicas mais comuns nas populações idosas e como a idade interfere ou modifica a manifestação e conduta destas doenças. Juntamente com 40 colaboradores oftalmologistas de renome no Brasil, os 27 capítulos deste livro abran-

Iniciando com um capítulo sobre geriatria e gerontologia na oftalmologia, a obra descreve as alterações oculares anatômicas no processo do envelhecimento e segue apresentando dados epidemiológicos das doenças oculares mais freqüentes. Os capítulos subseqüentes incluem aspectos psicovisuais, percepção visual, erros refrativos e visão subnormal. Capítulos abordando doenças específicas incluem: olho seco; oculoplástica, pálpebra e doenças da córnea; alterações do canal lacrimal; esclerites e episclerites; uveítes; glaucoma; catarata; retinopatia diabética; doenças vasculares e degenerativas da retina; descolamento e considerações específicas sobre neuro-oftalmologia, oncologia ocular, estrabismo e toxicologia ocular.

O texto fornece ricas ilustrações, tabelas didáticas assim como imagens clínicas de alta qualidade. Os autores incluíram na obra um excelente DVD com filmes breves dos procedimentos cirúrgicos oftalmológicos mais comuns narrados em português. O DVD funcionou no computador (Mac) deste revisor que lhes escreve sem nenhuma dificuldade. Em resumo, este texto deveria estar na prateleira de todo oftalmologista que trata pacientes idosos. É uma obra única e de alta qualidade que vem acrescentar à biblioteca do especialista. A nossa esperança é que os autores realizem uma tradução para o inglês para que os oftalmologistas desta comunidade possam também usufruir desta obra.

PAN-AMERICA : 157


Oftalmogeriatria. Cypel M and Belfort Jr. R, Editora Roca, Ltd., São Paulo, Brasil, 2008. 428 pages; CD ROM 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. Beginning with an introductory chapter on geriatrics and gerontology in ophthalmology, the book goes on to cover ocular anatomy in the elderly and the epidemiology of ocular disease in the elderly. Subsequent chapters include psychophysical aspects, visual perception, refractive errors, and low vision. Disease entities to which chapters are devoted include dry eye; oculoplastic, lid and corneal diseases; lacrimal disease; scleritis and episcleritis; uveitis; the glaucomas; cataract; diabetic retinopathy; vascular and degenerative retinal diseases; retinal detachment; and age specific considerations in neuro-ophthalmology, oncology, strabismus, and toxicology. The text is generously supplied with clear color tables and illustrations as well as high quality clinical images. The authors have included an excellent CD with movies of the standard surgical procedures narrated in Portuguese. The CD worked on this reviewer’s Mac computer without any difficulty. Overall, this text is one that should be on the shelf of every ophthalmologist who treats elderly patients. It is a unique and high quality contribution to the library of our specialty. Our only hope is that the publisher will produce a translation for the English speaking community of practitioners.

Reviewer Acknowledgement Vision Pan-America gratefully acknowledges the contributors who provided peer review for articles during the past year. Eduardo Alfonso, USA

Lani Gurria Quintana, USA/Australia/Mexico

Christopher Rapuano, USA

Eduardo Arenas, Colombia

Luis Izquierdo, Peru

Ivan Schwab, USA

J. Fernando Arévalo, Venezuela

Lily Koo Lin, USA

Allan Slomovic, Canada

J. Bronwyn Bateman, USA

Chun Cheng (Luis) Lin Yang, Costa Rica

Suzana Tanimoto, USA

Hilda Capo, USA

Cristian Luco, Chile

David Telander, USA

Javier Córdoba, Costa Rica

Marian Macsai, USA

José Tovilla Canales, Mexico

Denise de Freitas, Brazil

Eduardo Marback, Brazil

Rupan Trikha, USA

Teodoro Evans, Canada/Costa Rica

Roberto Marback, Brazil

Daniel Weil, Argentina

José Gomes, Brazil

Mary O’Hara, USA

Lihteh Wu, Costa Rica

Enrique Graue Hernández, USA/Australia/Mexico

Susanna Park, USA

Enrique Graue Wiechers, Mexico

David Pelayes, Argentina

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Marzo 2009

SightLife ™ Global Eye Eye Bank and and Corneal Corneal Transplant Transplant Congress Come Ear ly to the 2009 EBAA Annual Meeting in Seattle

Is your Eye Bank a member of APABO?

¿Es su Banco de Ojos miembro de la APABO?

If not, you are missing out on the opportunity to increase both the quantity and quality of eye bank corneal tissue in your country/community.

Si no forma parte, está desaprovechando la oportunidad de enriquecer la cantidad y la calidad del banco de ojos de tejido ocular en su país o comunidad.

Join APABO now and enjoy the following important member benefits:

Forme parte de la APABO y disfrute de los siguientes beneficios de membresía:

1) Participation in annual courses in Spanish or Portuguese for your technicians and physicians 2) Participation in tissue sharing networks with high quality eye banks in the United States 3) Significant discounts on the purchase of corneal storage media 4) Annual Eye Banking Forum at the AAO/PAAO meetings. 5) Sharing of information with other member eye banks

1) La participación de los médicos o técnicos de su banco de ojos en cursos anuales en español o portugués. 2) La participación en programas de intercambio de tejido con bancos de ojos de gran calidad en los Estados Unidos. 3) Grandes descuentos en la compra del líquido de conservación para el tejido ocular. 4) El foro Anual Banco de Ojos en los congresos de la AAO/PAAO. 5) Compartir información con otros bancos de ojos miembros de la APABO.

To learn more about APABO membership, visit our web page and complete an APABO membership application at:

Para más información sobre la membresía, sírvase ingresar a nuestra página web y llene una solicitud de membresía:

www.apaboeyebanks.org

www.apaboeyebanks.org

or, e-mail mjmannis@ucdavis.edu for more information

Para más información, sírvase contactar a: mjmannis@ucdavis.edu

La Asociación Panamericana de Bancos de Ojos (APABO) ofrecerá becas por la cantidad de US$3.000 a cinco (5) candidatos Latino Americanos para que asistan y participen en el FORO MUNDIAL DE BANCOS DE OJOS en Seattle, Washington en Junio del 2009. Los solicitantes deberán ser técnicos o médicos afiliados a un banco de ojos miembro de la APABO y deberán presentar una solicitud al Dr. Mark Mannis mjmannis@ucdavis. edu antes del 1 de abril del 2009 para ser considerado. PAN-AMERICA : 159


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Febrero 2009

4 :

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PAN-AMERICA : B


Febrero 2008

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.

A :

PAN-AMERICA

PAN-AMERICA

: 5


Paao Marzo 2009