estudio del donante de córnea / the cornea donor study stem cell
TRANSCRIPT
Volumen VIII No.1 Marzo 2009
Estudio dEl donantE dE CórnEa / thE CornEa donor studyAlandra Powe; Robin L. Gal MSPH; Roy W. Beck MD PhD; Mark J. Mannis MD; Edward J. Holland MD
stEm CEll transplantationRaneen Shehadeh Mashor MD; Mark Shapiro; Allan R. Slomovic MD FRCSC
rEsults aftEr siliConE oil rEmoval in ComplEx rEtinal dEtaChmEntMário J. Nóbrega MD; Denise C. Souza MD; Sarah L. Weber MD; Juliana M. Viesi MD; Fernando J. Novelli MD
spontanEous sClEral pErforation in oCular rosaCEaAna Carolina Vieira MD; Mark J Mannis MD
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
intravitrEal BEvaCizumaB in nEovasCular agE-rElatEd maCular dEgEnEration: One Year results
F. Ryan Prall MD; Antonio P. Ciardella MD; Jeffrey Olson MD; Naresh Mandava MD
natural history of maCular holE assoCiatEd with ElECtriCal injury: an OCt studY
Paul M.J. Cheevers MD; Alejandra A. Valenzuela MD; Timothy J. Sullivan FRANZCO
suCCEssful ConsErvativE managEmEnt of an atraumatiC dirECt intErnal Carotid-CavErnous fistula in an infant: Case repOrt
Rogil José de Almeida Torres; Maurício Maia MD; Cristina Muccioli MD; Lucia Noronha; Michel Eid Farah; Andréa Luchini; Dalton Bertolin Précoma
Evaluation of Early ChoriorEtinal aBnormalitiEs in hypErCholEstErolEmiC raBBits suBmittEd to thE pEroxisomE prolifErator-aCtivatEd rECEptor (ppar)-gamma agonist trEatmEnt (rosiglitazonE): HistOlOgiCal and HistOmOrpHOmetriC studY
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Mark J. Mannis, MDUniversity of California, Davis
Sacramento, CaliforniaEditor-in-Chief
Cristian Luco, MDSantiago, ChileAssociate Editor
Teresa J. BradshawArlington, TexasManaging Editor
Terri L. GrassiArlington, TexasProduction Editor
EDITORIAL BOARD
Eduardo Alfonso, MDMiami, Florida USA
Eduardo Arenas, MDBogotá, Colombia
J. Fernando Arévalo, MDCaracas, Venezuela
José A. Roca Fernández, MDLima, Perú
Denise de Freitas, MDSão Paulo, Brazil
Marian Macsai, MDChicago, Illinois USA
David E. Pelayes, MD PhDBuenos Aires, Argentina
Alfredo Sadun, MDLos Angeles, California USA
José Benítez del Castillo Sánchez, MDMadrid, Spain
Allan Slomovic, MDToronto, Ontario, Canada
Luciene Barbosa de Sousa, MDSão Paulo, Brazil
Lihteh Wu, MDSan José, Costa Rica
Paulo Dantas, MDSão Paulo, Brazil
OFFICERS
Richard L. Abbott, MDSan Francisco, USA
President, Pan-American Association of Ophthalmology
Rubens Belfort, MDSão Paulo, Brazil
Chairman of the Board,Pan-American Ophthalmological Foundation
PRODUCTION STAFF
Juan Pablo CuervoGraphic Design
Eliana BarbosaDirector of Production and Distribution
PAOF INDUSTRY SPONSORS
• 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 33496Tel.: (561) 495 4728Fax: (561) 865 1934
E-mail: [email protected]@clatinmedia.com
Special thanks to Ana Carolina Vieira, Enrique Graue Hernández, Citlali Gurrusquieta, Mapy Padilla, and Cristián Luco for assistance in translation to Spanish and Portuguese.
PAN-AMERICA130 : PAN-AMERICA
Iniciamos el primer volumen 2009 de Vi-sión Pan-América con una serie de intere-santes trabajos, el primeros de los cuales es un resumen de un muy importante Estudio de Donación de Corneas (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 mun-do. Como uno de los co-investigadores prin-cipales 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 Asocia-ción Pan-Americana de Oftalmologia.
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 do-nantes mayores trabajan muy bien y pueden
ser usados en forma muy efectiva. El EDC ha validado esta observación en forma cien-tífica. Sin embargo, el valor del EDC será verdaderamente realidad en Latino América cuando las naciones miembros de la Aso-ciación Panamericana de Oftalmologia em-piecen 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 paí-ses 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 Oftalmolo-gía 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 esfuer-zo de regionalizar los bancos de ojos es la clave para el éxito en la adquisición de teji-do 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, el 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 au-mentará 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.
We begin the 2009 volume of Vision Pan-America 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 trans-plantation. 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-
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 cor-neal 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 na-tions face widely divergent circumstances: economic limitations, social dilemmas, po-litical 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 informa-tional resources in the eye banking effort.
Mark Mannis MDEditor en Jefe Editor-in-ChiefEditor Chefe
MENSAJE DEL EDITOR MESSAGE FROM THE EDITOR MENSAGEM DO EDITOR
Banco de Ojos y Ceguera Corneal en Latino América
Eye Banks and Corneal Blindness in Latin America
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This collective effort will be best achieved through the Pan-American Association of Eye Banks (APABO), an organization dedi-cated to education, maintenance of stan-dards, and the provision of resources to eye banks throughout Latin America.
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.
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.
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 tis-sue 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.
Iniciamos o primeiro volume de 2009 da Vision Pan-America com uma série de arti-gos 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 decisi-vo 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 eficiên-cia dos bancos de olhos das nações que são membros da Associação Pan-Americana de Oftalmologia (PAAO).
A cegueira corneana é um enorme pro-blema na América Latina. Cirurgiões latino-americanos especialistas em córnea obser-vam há muito tempo que transplantes de córneas obtidas de doadores idosos pos-suem bons resultados e já as utilizam com
sucesso. O CDS vem fornecer as evidências científicas para tal observação. Porém, o va-lor do CDS só será verdadeiramente compre-endido na América Latina quando as nações membros da Associação Pan-Americana de Oftalmologia (PAAO) começarem a organi-zar 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 des-níveis educacionais. Portanto, soluções apli-cáveis em um determinado país podem não o ser em um país vizinho. Por isso, como nações membros da PAAO, precisamos tra-balhar em conjunto e compartilhar nossos conhecimentos. Este esforço coletivo será melhor alcançado se feito através da Asso-ciação Pan-Americana de Bancos de Olhos (APABO), uma organização dedicada à edu-cação, controle de qualidade e fornecimento de recursos para bancos de olhos em toda a América Latina.
Assim como aconteceu nos vários es-tados americanos há mais de 50 anos, ci-rurgiões 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 te-cidos. 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 efi-ciente captação e distribuição de córneas dentro da própria América Latina, permitin-do, 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 pes-soas sejam qualificadas como doadoras. To-davia, sem um esforço concentrado de todos nós para aperfeiçoarmos o funcionamento dos bancos de olhos em nossos países, não haverá impacto significativo na disponibili-dade de córneas para pacientes portadores de cegueira corneana.
Bancos de Olhos e Cegueira Corneana na América Latina
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Richard L. Abbott MDPresidente PAAO PAAO President
MENSAJE DEL PRESIDENTE MESSAGE FROM THE PRESIDENT
Español
No se pierda nuestro Congreso Conjunto con la Academia Americana en San Francis-co este Octubre…No se Arrepentirá!
Ahora que iniciamos el 2009, los planes para nuestro Congreso Conjunto con la Aca-demia Americana de Oftalmología comienzan a tomar forma; y estamos muy entusiasma-dos 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 ve-nido trabajando diligentemente para crear un programa educativo verdaderamente memo-rable y valioso para todos los asistentes.
Habrán Simposios, Cursos y trabajos libres; muchos de ellos en Español y Por-tugués. Además, tendremos sesiones de posters o paneles integrados con la Acade-mia, permitiendo a nuestros miembros Pa-namericanos una excelente oportunidad para presentar información científica. Se presen-tarán 3 Simposios Conjuntos AAO/PAAO en Diabetes, Imagen Ocular y Cirugía de Cata-rata/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 Congre-so Panamericano terminará con la siempre popular y bien concurrida sesión de Lo Me-jor 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 pos-ter. 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 acom-pañarnos a celebrar el 70 Aniversario de la Panamericana. Con la Academia, estamos organizando una Ceremonia de Inauguración muy especial para reconocer este importan-te 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 al-cohólicas para los miembros de la Paname-ricana. 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 even-to, así como los detalles del programa cien-tífico, fechas para envíos y cualquier otra in-formación importante de este evento, sírvase visitar la página web: www.PAAO.ORG
Espero verlos en San Francisco en Octubre!!
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).
2009 abstract submitter
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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 Commit-tee members, Peter Quiros, Lihteh Wu, Fer-nando 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 Sym-posia, 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 impor-tantly, because of their immediate impact on clinical practice. These Symposia will feature the latest information in these clini-cal 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 Pan-American 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 sub-mission 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 Anniver-sary 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 Ophthalmol-ogy. 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, submis-sion deadlines, and other important meet-ing information on the PAAO website: www.PAAO.ORG.
I look forward to seeing you in San Fran-cisco in October!
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).
2009 abstract submitter
REVIEW
PAN-AMERICA134 :
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 CórneaFinanciamiento/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: [email protected]
Estudio del donante de Córnea
ContextoPor muchos años se ha debatido sobre
el impacto de la edad del donante en el éxito del trasplante de córnea. A pesar de la fal-ta 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 resul-tado, 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
métodosEntre Enero del 2000 y Agosto del 2002,
105 cirujanos de 80 localidades de los Es-tados 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 ópti-ma 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 condicio-nes 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 an-teriormente 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
(SD) era 58 (14) años) fueron asignados por 43 bancos de ojos utilizando un proce-so 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 re-cuento de células endoteliales entre 2300 y 3300 células/mm2. Se ha publicado un lis-tado 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 compro-meter la visión por un mínimo de tres meses consecutivos.5,6
resultadosFracaso del Injerto
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 cór-neas de donantes de 66 a 75 años de edad (diferencia = 0%, límite más alto de un inter-valo confiable de 95% de un lado = 4%).7
Independientemente de la edad del do-nante, 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 glauco-ma con un significativo aumento del riesgo de fracaso del injerto (58% versus 11% sin historia de glaucoma).
La edad del beneficiario no estuvo aso-ciada con el fracaso del injerto. Ningún fac-tor del donante, incluyendo la densidad de las células endoteliales, fue asociada con un mayor riesgo.9 La incompatibilidad ABO no
aumentó el riesgo de fracaso del trasplante debido a rechazo del injerto.10
Densidad de las Células EndotelialesLa Densidad de las Células Endoteliales
(ECD), medidas en microscopio especular, sirven como indicador de la salud de la cór-nea. Para evaluar el efecto de la edad del do-nante 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 imáge-nes 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
Las imágenes microscópicas especula-res 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.
Entre los sujetos que tuvieron un tras-plante exitoso a quienes se le realizó mi-croscopía 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 en-tre 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 ajus-tada para línea basal ECD = 0.04).
Aquellos en el grupo de donantes de ma-yor 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 aque-llos 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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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 GroupFunding/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: [email protected]
the Cornea donor study
BackgroundThe 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 re-luctant 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 Stu-dy (CDS) was developed.1
methodsBetween 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 eva-luate 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 irres-pective of donor age, and conditions with a
low success rate, such as regrafts and vas-cularized 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 sub-ject 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 publis-hed.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
resultsGraft 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 glau-coma surgery with preoperative glaucoma medication use also was associated with a substantially increased risk of graft failure (58% versus 11% with no history of glauco-ma). Recipient age was not associated with graft failure. No donor factors, including the donor endothelial cell density were associa-ted with increased risk.9 ABO incompatibility did not increase the risk of transplant failure due to graft rejection.10
Endothelial Cell DensityCorneal 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
ConclusionesPara 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 seudofá-quico 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 embar-go, la importancia clínica de esta ligera aso-ciación 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 consi-derable 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 éxi-to del injerto a los 10 años, un mayor se-guimiento permitirá una determinación de cómo el ECD de 5 años es predictivo de un posterior fracaso de injerto.
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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 endothe-lium were obtained 6 and 12 months after transplant and then annually through 5 years, provided that a regraft had not been perfor-med.
Among subjects who had a successful transplant for whom specular microscopy was performed 5 years after surgery, endo-thelial 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
ConclusionsFor 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 pseudopha-kic/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 suc-cessful after 5 years, there is a slight asso-ciation 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 fo-llow up. Of greater importance, perhaps, is the finding that irrespective of donor age, en-dothelial 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 con-tinuing 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.
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 GroupPatrocinadores: 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: [email protected].
Estudo do doador de Córnea
históricoO impacto da idade do doador no suces-
so 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 indiví-duos com até 65 anos de idade.
O Cornea Donor Study (CDS) foi desen-volvido com o objetivo de fornecer os dados científicos necessários para esclarecer a as-sociação entre a idade do doador de córnea e a sobrevida do enxerto.
métodosEntre 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.
Para avaliar, da melhor maneira possí-vel, 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 su-cesso, como retransplantes e córneas vas-cularizadas, pois é provável que a falência do enxerto seja causada por outros fatores, não-relacionados 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 pu-blicados.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 base-ada em qualquer fator relacionado ao doador ou ao receptor. As córneas doadas obede-ceram 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 su-ficiente para comprometer a visão por um mínimo de três meses consecutivos.5,6
resultadosFalência 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 trans-plantes 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 ris-co de falência foi consideravelmente maior em olhos com diagnóstico pré-operatório de edema corneano do pseudofácico ou afáci-co quando comparado a distrofia de Fuchs (27% vs 7%).8 Assim como em casos de cirurgia de glaucoma prévia com uso de me-dicação 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 fa-lência.9 Incompatibilidade ABO também não aumentou o risco de falência do transplante devido à rejeição do enxerto.10
Densidade celular endotelialA 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 Mi-croscopy 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 ne-cessidade de retransplante, microscopias es-peculares 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 espe-cular realizada 5 anos após a cirurgia mos-trou 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 avan-çada 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
ConclusãoPara 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 significativa-mente 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 antiglau-comatosa.
Nos casos em que o transplante foi bem-sucedido após 5 anos, há uma pe-quena associação entre idade do doador e perda celular endotelial. Entretanto, a impor-tância 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 acom-panhamento mais prolongado nos permitirá determinar se a DCE nos primeiros cinco anos fornece uma previsão para uma subse-qüente 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. Oph-thalmology 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.
REVIEW
Raneen Shehadeh Mashor MD, Mark Shapiro, Allan R. Slomovic MD FRCSCToronto Western Hospital, University of Toronto, Toronto,Ontario, Canada
Corresponding author: Raneen Shehadeh Mashor, 2515 Bathurst Street, Toronto M6B 2Z1, ON, Canada E-mail: [email protected]
None of the authors have proprietary or financial interest
stem Cell transplantation
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resumenEl tratamiento de la enfermedad de la su-
perficie 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 quirúr-gico 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.
abstractThe management of severe ocular sur-
face disease (OSD) has benefited from major breakthroughs in recent years. Previously, patients with severe ocular surface disease had a poor prognosis. Advances in micro-surgical 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 lim-bal cell transplantation techniques.
The management of severe ocular sur-face disease (OSD) has benefited from major breakthroughs in recent years. Previously, patients with severe ocular surface disease had a poor prognosis. Advances in micro-surgical 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 lim-bal cell transplantation techniques.
Limbal Stem Cell TheoryStem cells (SC) are progenitor cells that
are responsible for cellular replacement and tissue regeneration. The single most impor-tant breakthrough in managing severe OSD was the understanding of the location and function of limbal stem cells. In 1971, Dav-enger and Evinson speculated that the source of replacing the corneal epithelium lay at the
limbus when they observed that pigmented limbal cells moved centrally. Later on, basic research has identified a number of charac-teristics 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 DeficiencyCauses of Limbal Stem Cell Defi-ciency
Stem-cell deficiency can be congeni-tal 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, Stevens-Johnson syndrome, advanced ocular ci-catricial pemphigoid (figure 2), multiple surgery or cryotherapy, contact lens wear, or extensive/chronic microbial infection such as trachoma.
Effects of Limbal Stem Cell DeficiencyThe hallmark of limbal SC deficiency is
‘conjunctivalisation’ of the cornea (figure 3) and the most significant clinical manifesta-tion 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 epi-thelium with stippled fluorescein, unstable tear film, superficial and deep vascularisa-tion, persistent epithelial defects leading to ulceration, melting and perforation, or fibro-vascular pannus, scarring, keratinisation and calcification.4-5
Diagnosis of Stem Cell DeficiencyThe diagnosis of SC deficiency remains
essentially clinical. On slit lamp examina-tion, 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 pali-sades of Vogt and vascularisation are other common features.
The presence of goblet cells on impres-sion cytology specimens taken from the cor-neal 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 oppor-tunity for ocular surface rehabilitation without the need for SC transplantation such as Sec-tor Conjunctival Epitheliectomy7 and amni-otic membrane transplantation.8 Patients with more extensive SC deficiency cannot populate their corneal surface with remain-ing SC and most of them require limbal SC transplantation.
If no healthy sector of limbus is avail-able 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 transplan-tation 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 report-ed 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 TechniquesThe 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.
ComplicationsPossible early but reversible complications include graft edema or hae-
morrhage and dellen formation. Infection is also a possible early complica-tion. 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 TransplantationOverall, 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 per-sistent epithelial defects for 3 weeks to 4 years, there was rapid re-epithelialisation (1-4 weeks). Failure of epithelialisation was seen in 3 (11.5%) eyes. Substantial improvement was noted in vision and reduc-tion 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 con-junctival 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
Figure 1
Figure 2
Figure 3
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Type of procedure Indications ContraindicationsSize and Location
of ExplantsConjunctival Limbal Autograft
Living Related Conjunctival Allograft
Cadaver Conjunctival Limbal or Keratolimbal Allograft
Ex Vivo
In patients where total stem cell deficiency affects only one eye. Prior chemical or thermal injuries are the most common causes.9-12
When the two eyes are affected and a living related donor is available.
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
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 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
The donor eye should be free of any condition that may predispose it to later limbal SC deficiency.
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 corneo-scleral 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
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 sys-tem. 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.
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.
Two trapezoidal limbal grafts, including 6mm of the limbus and extending 5 to 8mm posterior to the limbus are harvested from the donor eye.
Chart 1
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BIBLIOGRAFíA
1. RM. Existence of slow-cycling limbal epithelial basal cells that can be 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 differentia-tion and effects of deficiency. Eye,2003; 17:877–8854. 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 treat-ment 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 transplanta-tion for partial limbal stem cell deficiency. Br J Ophthalmol 2001;85:567–5759. 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 sur-face disorders. Ophthalmology, 1995; 102 (Suppl):101–10212. Kenyon KR, Tseng SC Limbal autograft transplantation for ocular sur-face disorders. Ophthalmology, 1989; 96:709–22; discussion 722–72313. 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; 3:595-61014. Kinoshita S, Kiritoshi A, Ohji M, Ohashi Y, Manabe R. Disappear-ance of palisades of Vogt in ocular surface disease. Jpn J Clin Ophthalmol, 1986;40:363-66
15. Edward J, Holland MD, Gary S, Schwartz MD. Ocular Surface Trans-plantation: An overview of techniques, indications, and postoperative man-agement. Cataract & refractive surgery today, 2005; 76-7916. Croasdale CK, Schwartz GS, Malling JV, Holland EJ. Keratolimbal al-lograft: Recommendations for tissue procurement and preparation by eye banks, and standard surgical technique. Cornea, 1999;18:52-5817. Tsubota K, Satake Y, Ohyama M, Toda I, Takano Y, Ono M, Shino-zaki N. Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol, 1996;122:38-5218. 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 tech-niques 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 trans-plant 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 Trans-plantation: 10 Years’ Experience. Cornea, 2004; 23(5):425-431
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 immunolo-gists 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 fol-lowed 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 inflam-mation. 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 de-pends on a patient’s preoperative diagnosis, postoperative course,
and whether the rejection of a transplant has occurred. The drug regi-men 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 subse-quent surgical procedures. For ex vivo transplantation of oral mucosal epithelium, the success rate was 82% (22 out of 27).21
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resumen
Objetivos: Avaliar em longo prazo a eficácia e segurança do bevacizumab intravítreo (Avas-tin, Genentech) para o tratamento da degen-eração 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 pa-cientes com DMRI neovascular que rece-beram uma ou mais injeções intravítreas de bevacizumab e completaram pelo menos um ano de seguimento. Em cada consulta, a acui-dade 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, foto-coagulação e aplicações intravítreas de trian-cinolona ou outras drogas anti-angiogênicas. Após preenchimento do consentimento infor-mado, os pacientes foram tratados com be-vacizumab 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 pa-cientes 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 mé-dia de 3,3 injeções (1-8). Vinte e oito olhos (71,8%) tiveram melhora (38,5%) ou estabili-zação (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 neo-vascular após um ano do início do tratamento
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 (Avas-tin, Genentech) for treatment of age-related macular degeneration (AMD) in two eye clin-ics in southern Brazil.
Methods: Retrospective chart review of 36 consecutive patients with neovascular AMD who received one or more intravitreal injec-tions 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 periocu-lar injections of triamcinolone or other anti-angiogenic 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). Rein-jections were performed if necessary.
Results: Thirty-nine eyes of 36 patients were included in this study (38.9% male, 61.1% fe-male) 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). 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 be-vacizumab 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 de-generation (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 anti-vascular 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 treat-ment 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 injec-tions 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 resolu-tion, logMAR) and ophthalmoscopic evalua-tion at baseline and at 1 to 2-month follow-up examinations. Optical coherence tomography (OCT) and fluorescein angiography were per-formed at the first visit and then if there was a clinical suspicion of choroidal neovascular (CNV) regrowth or recurrence in spite of a sta-ble visual acuity. Cases with prior verteporfirin photodynamic therapy, photocoagulation and intravitreal or periocular injections of triam-cinolone or other anti-angiogenic drugs were excluded. After written informed consent was obtained, patients were treated with an intrav-
intravitreal Bevacizumab in neovascular age-related macular degeneration: One Year resultsJoyce 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 - Brazil2 Hospital de Olhos Sadalla Amin Ghanem, Joinville, SC - Brazil3 Universidade da Região de Joinville, Joinville, SC - Brazil4 Oftalmoclínica, Curitiba, PR – Brazil
Corresponding author: Joyce KuntzAddress: Rua Dr. Pedrosa, 134, Curitiba, PR 80420-120 – Brazile-mail: [email protected]
Authors Disclosure Information: The authors of this article have no proprietary or financial interest in a product or lack thereof.
: 143PAN-AMERICA
Febrero 2009
itreal bevacizumab dose of 0.05ml (1.25mg) to 0.1ml (2.50mg). At follow-up visits, Snel-len 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 crite-ria 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 be-low or within the retina.
resultsA 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 aver-age 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 cas-es 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 improve-ment in 82.4% of eyes that had been injected with 2.50 mg of Beva-cizumab. Although the present study showed 71.8% of treated eyes with improved or sta-bilized VA, it may not be compared to Bashur´s results be-cause this is a retro-spective case series with inherent limita-tions. But it shows a tendency to long-term results similar to a previous prospective analysis.5
Yogonathan el al6 observed patients who received intravitreal bevacizumab for AMD from 24 to 50 weeks. Naive eyes (28%) had a mean increase of 14.2 letters. Conversely, the actual study has shown VA gain of at least 2 lines (6 to 10 ET-DRS letters) in 38.5% of the eyes.
In the present report, patients required a relative few number of injections of bevaci-zumab (average of 3.3 injections) during a mean follow-up of 17.3 months. It is almost the same frequency described by Bashur et al (average of 3.4 injections) during the period of one year.5 Probably the low rate of intravit-real applications was due to the criteria used for reinjections: it was mainly based on the
functional responses to the previous injec-tions and not on an initial monthly schedule.
Bevacizumab was well tolerated and no serious drug-related adverse events were seen as it was described in other articles.5-8
Although Bevacizumab is a promising drug that shows efficacy and safety in pa-tients with neovascular AMD, further studies are necessary to warrant its advantages for a longer period of observation.
Figure 1Visual acuity before and after treatment with bevacizumab.
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; 120:1307-13144. 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 degenera-tion. Retina, 2006; 26(5):495-511.
CLINICAL SCIENCES
PAN-AMERICA144 :
resumo
Objetivo: Avaliar os resultados anatômicos e visuais após a retirada do óleo de silicone em pacientes operados de descolamento de reti-na e vitreorretinopatia proliferativa num centro oftalmológico de referência em Joinville, sul do Brasil.
Métodos: Estudo retrospectivo e não-compa-rativo de casos consecutivos de descolamen-to 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 trau-ma, ruptura gigante, retinite viral ou retinopa-tia 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 exa-me 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 pacien-tes (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 silico-ne propiciou bons resultados anatômicos e visuais na maioria dos pacientes. Entretan-to, 5 casos tiveram evolução desfavorável, principalmente um com perda visual grave
e inexplicável. Os cirurgiões precisam estar cientes dos resultados adversos associados à extração do óleo de silicone e os seus bene-fícios 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 vi-sual 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 exam-ined 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 sur-gery, performed in all the eyes, included pars plana vitrectomy, 360-degree scleral buck-ling, laser endophotocoagulation around the retinal tears and silicone oil infusion in the vitreous cavity. A prophylactic 360-degree peripheral laser photocoagulation was ap-plied 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 years-old (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 extrac-tion, 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 un-favorable 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 vit-reoretinal 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 re-sults after its extraction are described (table 1), including risk of recurrent retinal detach-ment1-8 and sudden visual loss.9,10
Prophylactic peripheral 360-degree pho-tocoagulation may decrease the incidence of retinal redetachment after silicone oil re-moval11-13 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 de-tachment 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 prolifera-tive vitreoretinopathy were operated on by the
results after silicone oil removal in Complex retinal detachmentMário 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 - Brazil2. Universidade da Região de Joinville, Joinville, SC - Brazil
Corresponding Author: Mário Junqueira Nóbrega, MDAddress: Rua Abdon Batista 172, Joinville, SC 89201-010 – Brazile-mail: [email protected]
Author Disclosure Information: The authors of this article have no proprietary or financial interest in a product or lack thereof.
REFERENCES
1. Falkner CI, Binder S, Kruger A. Outcome after silicone oil removal. Br J Ophthalmol, 2001; 85 (11): 1324- 13272. 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): 1203- 1207.6. Jiang F, Krause M, Ruprecht KW, Hille K. Management and results of retinal detachment after silicone oil removal. Ophthalmologica, 2002; 216 (5): 341- 345.7. 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 Ophthal-mol, 2003; 13 (5): 474- 481.
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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 dia-betic retinopathy were excluded.
The initial surgery included pars plana vitrectomy, 360-degree scleral buckling, la-ser endophotocoagulation around the retinal tears and 5000-centistoke silicone oil infu-sion 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 treat-ed. 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 de-tachment (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 ana-tomical and visual results in most of the pa-tients. 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 compli-cation 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.
Comparing to previous studies1-8, a low detachment rate was observed in the pres-ent report. It may be due to improved surgical management of complicated retinal detach-ments during the last decade, with more ad-equate 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 as-sociated with silicone oil removal and its ben-efits must be outweighed against its extended duration in the eye and the possibility of com-plications with a new surgical procedure.
Table 1Previous studies showing number of eyes (and percentage with retinal redetachment after silicone oil removal.
Figure 1Preoperative and postoperative visual acuity values.
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146 : PAN-AMERICA
abstract
Electrical and lightning-induced injuries are common and have known ocular manifes-tations. 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 electri-cal 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 (fig-ure 1) and a partial thickness macular hole
present in the right eye. (figure 2)
No treatment was suggested at the ini-tial 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 treat-ment.
Comment
Electrical and lightning injury has been associated with cataract1-6, uveitis1,4-5, cys-toid macular edema2-3,5, punctate keratitis1, retinal folds1, retinal detachment6, optic neu-ropathy5-6, and macular hole1-3,5,6,7. The exact mechanism is unknown but three theories have been proposed: 1) disruption of cellular mem-branes 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 pig-ment epithelium (RPE) as the electric current passes through this pigmented layer. As the amount of resistance across a circuit is in-creased 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 pig-mentation is concentrated in the macula.4
This case demonstrates by OCT the natu-ral 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 ex-pect these to close spontaneously as it did in our case. We would suggest conservative management of macular holes associated with electrical injury.
natural history of macular hole associated with Electrical injury: an OCt studyF. Ryan Prall MD1, Antonio P. Ciardella MD2, Jeffrey Olson MD1, Naresh Mandava MD1
1 University of Colorado, Department of Ophthalmology, Denver, Colorado USA2 Policlinico S.Orsola-Malpighi, Department of Ophthalmology, Via P. Palagi 9, 40137 Bologna, Italy
Corresponding author:F. Ryan Prall MDUniversity of Colorado, Dept of Ophthalmology, 1675 N Ursula Street, Mail Stop F731, Aurora, CO 80045Email: [email protected]
REFERENCES
1. Noel L-P, Clarke WN, Addison. Ocular com-plications of lightning. J Pediatr Ophthalmol Strabismus. 1980;17:245-246.2. Campo RV, Lewis RS. Lightning-induced mac-ular 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. Light-ning-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 electri-cal injuries: neuro-ophthalmic aspects. Semin Neurol. 1995;15:335-341.9. Cherington M. Central nervous system com-plications of lightning and electrical injuries. Semin Neurol. 1995;15:233-240.
Figure 1
Figure 4
Figure 2 Figure 3
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resumen
Las fistulas Carótido - Cavernosas (Ca-rotid cavernous fistulae - CCF) son conec-ciones anormales arterio-venosas dentro del seno cavernoso. Ellas están típicamente asociadas a trauma, pero pueden ocurrir es-pontáneamente. La pérdida progresiva de vi-sión 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 amblio-pía 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 en-dovasculares. Nosotros presentamos un ma-nejo conservador cuando la funciones intrao-culares y del nervio óptico son estables.
introduction
Carotid cavernous fistulas (CCF) in chil-dren 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 con-junctiva (Fig. 1). There was evidence of right amblyopia with sixth nerve palsy. Intra-ocular pressure and dilated funduscopic examination was unremarkable.
Head-orbit CT-scan demonstrated a di-lated 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, con-sistent 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 angiogra-phy 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 sta-ble, 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 con-nections with the venous plexus of the caver-nous 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 hyperten-sive, post-menopausal women4 or connective tissue diseases.5
Ophthalmic findings are based on the underlying raised venous pressure and de-creased arterial perfusion including: propto-sis, ocular bruit, glaucoma, ophthalmople-
successful Conservative management of an atraumatic direct internal Carotid-Cavernous fistula in an infant: Case reportPaul 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, Canada2 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. ValenzuelaRoom 2035, 2W Victoria Bldg., 1278 Tower Road, Halifax, NS, B3H 3Y9 CanadaTel : 1 (902) 473 3700Fax: 1 (902) 473 2839Email: [email protected]
Figure 1Clinical 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..
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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 re-fractive errors.
This is the first reported case of a spon-taneous direct vision threatening CCF that was treated conservatively. While no specific indications for treatment have been establis-hed in children, progressive vision loss is re-garded as an indication for intervention in all patients.5,6 Prior reports have also supported intervention with progressive proptosis and concomitant ocular hypertension or abdu-cens 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 manage-ment when all other intra-ocular and optic nerve functions are stable.
Figure 2A. 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;55:310-3125. 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) 292-2946. Rai A, Marano G. Direct Carotid Cavernous Fistula in Infancy: Presentation and Treatment. Am J Newroradiol 25:1083-10857. 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 rosaceaAna Carolina Vieira MD1,2, Mark J Mannis MD2
1 Department of Ophthalmology, Federal University of São Paulo, Brazil2 Department of Ophthalmology & Vision Science, University of California, Davis
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 95817Voice: 916-734-6957Fax: 916-703-5076E-mail: [email protected]
No funding was received for this work.
resumo
Objetivo: Relatar um caso raro de perfuração escleral espontânea em paciente com rosá-cea ocular tratado cirurgicamente com enxer-to 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 espontâ-nea no olho esquerdo. Ao exame, notava-se eritema facial e pápulas eritematosas. A biomicroscopia do olho esquerdo revelou disfunção meibomiana, hiperemia conjunti-val, afinamento corneano periférico, neovas-cularização 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 pro-trusão 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 compli-cação rara das formas graves de rosácea ocu-lar. O enxerto escleral homólogo mostrou-se eficaz no tratamento da perfuração escleral secundária a rosácea ocular. Pacientes por-tadores de rosácea ocular e esclerite reque-rem tratamento sistêmico e acompanhamento frequente por um oftalmologista. Palavras-chave: rosácea ocular, esclera, perfuração, enxerto homólogo.
abstract
Purpose: To report a rare case of spontaneous scleral perforation in a patient with ocular ro-sacea and its surgical management.
Methods: Case report.
Results: A 52 year-old woman with a history of ocular rosacea diagnosed 9 years earlier presented with a spontaneous scleral perfo-ration 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, con-junctival injection, marked peripheral corneal thinning, neovascularization and lipid deposi-tion in the cornea temporally. A discreet round scleral perforation temporal to the limbus me-
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 fi-brin glue and 4 sutures of 10-0 monofilament nylon. One month postoperatively, her best corrected visual acuity was 20/25.
Conclusion: Scleritis can be a rare complication of severe ocular rosacea. A homologous scleral patch graft proved successful in treating this con-dition. Patients with ocular rosacea severe enou-gh to induce scleritis require systemic therapy and close monitoring. Key words: ocular rosacea, sclera, perforation, homologous graft.
introduction
Rosacea is a chronic progressive cuta-neous disorder that affects approximately 13 million Americans.1 It is characterized by per-sistent 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 poten-tial to compromise vision.
The etiology of the disease is still unk-nown. Many factors have been implicated in
Figure 1Small round scleral perforation with protruding vitreous in a patient with ocular rosacea.
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its pathogenesis. Several studies confirm an inflammatory mechanism.2,3 An elevated con-centration 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 pepti-de 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 che-motaxis, angiogenesis, and extracellular ma-trix 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 challen-ging, 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 fre-quent ocular findings include anterior and posterior blepharitis, meibomian gland dys-function, recurrent chalazia and chronic con-junctivitis.
Episcleritis and, less commonly, scleritis, have been documented in more severe ocular rosacea patients. Ghanem et al found episcle-ritis 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 corneoscle-ral perforation in an ocular rosacea patient.12
We report a case of a spontaneous scleral perforation in a patient with severe ocular ro-sacea. To the best of our knowledge, no simi-lar case has been previously described.
Case Report
A 52 year-old woman with a history of ocular rosacea diagnosed 9 years earlier pre-sented 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 red-
ness with erythematous papules. Slit lamp examination revealed meibomian gland dys-function and an area of marked peripheral corneal thinning and scar with neovasculari-zation inferotemporally suggestive of previous keratitis in OD. The remainder of the exami-nation in the right eye was normal. The left eye revealed meibomian gland dysfunction, 1+ conjunctival injection, marked periphe-ral 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 cor-neal 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, se-rum 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 arthrosco-py 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 cor-ticosteroids, oral non-steroidal anti-inflam-matory 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 vi-treous with Vannas scissors, a 3 mm scleral patch formed from eye bank sclera with a der-matologic punch was placed over the perfo-ration 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 clo-sed over the graft using 10-0 vicryl sutures. There were no surgical complications.
The patient was started on topical tobra-mycin/dexamethasone drops four times daily and cyclopentolate twice daily postoperatively.
One day after surgery, there was improve-ment of best-corrected visual acuity to 20/40 OS. Slit-lamp examination showed 3+ tem-poral 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/dexametha-sone drops were tapered to twice daily.
One month postoperatively, best correc-ted visual acuity was 20/25, 90% corneal thinning peripherally at temporal limbus un-changed from pre-operatively, 1+ conjuncti-val injection overlying a well-positioned scle-ral 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 predni-solone acetate 1% twice daily OU, methotre-xate 15 mg/week and folic acid.
discussion
Although rare, rosacea has been shown to cause scleritis and episcleritis.11,12 Our pa-tient had a history of rocasea, keratitis and re-current nodular scleritis. Other more common causes of scleritis were investigated. Howe-ver, 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 aty-pical for a rosacea patient. Despite significant efforts to control the inflammatory process with high-dose oral corticosteroids and me-thotrexate, the patient developed active scleri-tis. 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 homolo-gous scleral grafts.13 In our case, there was a punched out scleral perforation with vitreous
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prolapse so that tissue glue and a conjunc-tival patching were not suitable. The use of a homologous scleral patch graft is the most frequently reported method in the surgical re-pair of scleral perforations.13
General anesthesia provides optimal aki-nesia minimizing the risk of increased intrao-cular 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 pro-lapse 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 per-foration. 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 pla-ce 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.
Biologic adhesives (fibrin-based adhesi-ves) have been widely used in ophthalmolo-gy, and many studies on its ophthalmic appli-
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 vitrec-tomy and found no adverse effects and fewer postoperative patient symptoms in the tissue glue group.17 Apart from providing less dis-comfort, fibrin glue reduces time of surgery.
This case demonstrates a rare compli-cation of chronic acne rosacea with ocular involvement and its successful surgical ma-nagement. Patients with ocular rosacea seve-re enough to induce scleritis require systemic therapy and close monitoring.
Figure 2Scleral perforation repaired with a homologous scleral patch graft. On examination one month post-operatively, deep anterior chamber with no inflammatory reaction.
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 Oph-thalmol Vis Sci. 2000; 41 (7): 1703-9.3. Afonso AA, Sobrin L, Monroy DC et al. Tear fluid gelatinase B activ-ity 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, pathogen-esis, and sbtype classification. J Am Acad Dermatol 2004; 51: 327-341.6. Georgala S, Katouis AC, Kylafis GD et al. Increased density of De-modex 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 Ve-nereol 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 dermatol-ogy 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 tis-sue adhesive for sutureless lamellar keratoplasty and scleral patch adhe-sion. 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 con-ventional 20-gauge vitrectomy. Eye 2008 Sep 5. [Epub ahead of print].
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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 studyRogil 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 Paulo- SP2 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/EPM4 Associate Professor at the Department of Pathology, Pontifícia Universidade Católica do Paraná - Curitiba - PR5 Associate Professor at the Department of Ophthalmology, Universidade Federal de São Paulo - São Paulo – SP6 Physician at the Centro Oftalmológico de Curitiba- Paraná7 Associate Professor at the Department of Cardiology, Pontifícia Universidade Católica do Paraná - Curitiba - PR
Participating Institutions: Angelina Caron Hospital - Campina Grande do Sul/Paraná/ Brazil; Federal University of São Paulo (UNIFESP - EPM)
Corresponding author: Rogil José de Almeida TorresPraça Ruy Barbosa, 827 – Conj. 305, CEP 80010-030, São Paulo, SP BrazilFax: (55-41) 3225-6349E-mail: [email protected]
Financial Disclosure: The authors declare that they have no financial interests in this manuscript.
resumo
Objetivos: Avaliar, de forma experimental em coelhos, as anormalidades histológicas degenerativas na esclera e coróide após administração diária de alta dosagem de co-lesterol 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 di-vididos 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 diaria-mente a partir do início do experimento. Da-dos foram analisados pelo teste de Shapiro-Wilks-Testand e valores abaixo de 0,05 foram considerados estatisticamente significantes.
Resultados: Nenhuma alteração foi observa-da no GC. No entanto o G1 mostrou um sig-nificativo aumento da espessura da esclera e coróide (301,48 ± 50,12) comparados com
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 va-lores 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 es-tatisticamente 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 hiper-colesterolemia no modelo animal (coelho) pode conduzir a anormalidades degenerativas precoces na esclera e coróide e que a ativa-ção dos receptores do PPAR gama oculares, através da dieta oral de rosiglitazona, de-monstra ser efetivo na preservação anatômica destas estruturas. Este estudo pode ter rele-vância 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 admi-nistration of high cholesterol dosages as well as the possible prevention of these degene-rative abnormalities following systemic ad-ministration 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) re-ceived 1% cholesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks; Group 2 (G2 – 18 rabbits) received 1% cho-lesterol 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 ra-bbits) 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 signi-ficant increase in the scleral and choroidal thickness in relation to CG and G3.
Conclusions: This study revealed that hyper-cholesterolemia may lead to early degenera-tive 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.
: 153PAN-AMERICA
Febrero 2009
purpose
The objective of this study is to evaluate, in a rabbit model, the degenerative histolo-gical abnormalities in the choroids and scle-ra following the daily administration of high cholesterol dosages as well as the possible prevention of these degenerative abnormali-ties following systemic administration of oral rosiglitazone, an activator of agonist peroxi-some proliferator-activated receptor (PPAR)-gamma receptors.
Peroxisome proliferator-activated recep-tors 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 im-munomodulatory actions. Reduction in pro-gression 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 de-generation and atherosclerosis was the main factor that motivated this study.
methods
The protocol was approved by the Ani-mal Experimentation Ethics Committee of the Hospital Angelina Caron Hospital and the Fe-deral University of São 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 -Sig-ma-Aldrich® - 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% cho-lesterol diet for two weeks and then a 0.5% cholesterol diet for 4 weeks. Additionally, this group also received 3 mg of rosiglitazone dai-ly after the 14th day;
4. Fourth group (g3) (18 rabbits): 1% cho-lesterol 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 in-travenous injection of 5 ml pentobarbital and their eyes were immediately fixed in 4% pa-raformaldehyde 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 structu-res. Data was analyzed by Shapiro-Wilks W Test and P values lower than 0.05 were consi-dered statistically significant.
results
No histological abnormalities were obser-ved in CG. However, G1 group showed a sig-nificant 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 microme-ters/DP 36.44) lower than the hypercholeste-rolemic rabbit group (G1) (301.48 microme-ters/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 scle-rochoroidal thickness (266.11 micrometers/DP 47.94) lower than the hypercholesterole-mic rabbit group (G1) (301.48 micrometers / DP 50.12). This value was statistically sig-nificant (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).
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 non-compressable 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 in-creasing 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 age-related macular degeneration (AMD) clinical manifestation. This mechanism is similar to the atherosclerosis pathophysiology, an in-flammatory process, in which the cholesterol (LDL) is deposited in the intima of the vessel wall leading to loss of arterial elasticity.
Immunologic and inflammatory proces-ses are also observed in AMD as the immu-nohistochemical analysis of drusen reveals
Absence of histiocytes in the sclera
A large number of histiocytes in the scleral wall Significant presence of collagen fibers Increase of choroidal thickness
Similar results to CG
Decrease in the number of histiocytes and collagen fibers in the scleral wall
Figure 1SR - SENSORIAL RETINA
C - CHOROID
S - SCLERA
* - HISTIOCYTES
CG
G1
G2
G3
BASIC INVEStIgAtIoN
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the presence of apolipoproteins B and E, immunoglobulines, factor X, amyloid P com-ponent, C5 and C5b-9 complements, fibrino-gen 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 altera-tions 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 reve-aled 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 re-duction 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 endo-thelial 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 per-ceive a significant increase in the scleral and choroidal thickness in the hypercholesterole-mic 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 re-ducing research costs. It is worth pointing out that ocular alterations in rabbits occur as early as the vascular alterations.
Peroxisome proliferator-activated recep-tor-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.
In atherosclerosis, the treatment with gli-tazones (PPAR-gamma ligands) results in the reduction of the markers of atherosclerosis activity, suggesting an additional effect besi-des the one of metabolic control.13 It has been demonstrated that activation of PPAR-gamma inhibits the Matrix metaloproteinase-9 ex-pression and activity.14 In macrophages, anti-inflammatory and potentially anti-atheroscle-rotic activities have been observed, including: Inhibition of cytokine production, attenuation of cytokine-induced nitric oxide synthase expression, gelatinase B1 and scavenger re-ceptors; 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 Molecu-les 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-an-giogenic effect of PPAR-gamma agonists on the cells involved in the pathogenesis of cho-roidal neovascularization (CNV) in vitro and in vivo experimental models. It was observed that PPAR-gamma was expressed in both RPE and choroidal endothelial cells. Consequen-tly, PPAR-gamma ligands played a significant role in the inhibition of VEGF-induced prolife-ration 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 li-gands is also possible in the exsudative AMD of humans.
In the present study, anatomic preserva-tion of the choroid and sclera was statistically significant in G3 and statistically non-signifi-cant in G2. Thus, oral rosiglitazone proved to be effective in reducing reduce the degenera-tive damage of the choroid-scleral complex, corresponding to dry AMD in humans.
Conclusions
This study revealed that hypercholestero-lemia 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 ana-tomy. These findings have clinical relevance
as the rosiglitazones may offer a new treat-ment modality for dry and/or exsudative AMD in human eyes.
REFERENCES1. Friedman E, Krupsky S, Lane A, Oak S, Fried-man ES, Egan K, Gragoudas E. Ocular blood flow velocity in age-related macular degeneration. Oph-thalmology. 1995; 102:640-6.2. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Ad-amis AP. Age-related degeneration: etiology, patho-genesis, and therapeutic strategies. Surv Ophthal-mol. 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 age-related macular degeneration. Prog Retin Eye Res. 2001; 20:705–32.4. Killingsworth MC, Sarks JP, Sarks SH: Macrophag-es related to Bruch’s membrane in age-related macu-lar degeneration. Eye. 1990;4:613–21.5. Penfold PL, Killingsworth MC, Sarks SH: Senile macular degeneration: the involvement of immuno-competent 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 degen-eration: an immunofluorescence and electron mi-croscopy study. Br J Ophthalmol.1993; 77:657–61.7. Cogan DG, Kuwabara T. Ocular changes in the experimental hypercholesterolemia. Arch Ophthal-mol. 1959;61:219-25.8. Janes RG. Changes in the rabbit’s eye caused by cholesterol feeding. Am J Ophthalmol. 1964;58:819-28.9. Salazar JJ. Ramirez AI, Hoz R, Rojas B, Ruiz E, Tejerina T, Triviño A, Ramirez JM. Alterations in the choroid in hypercholesterolemic rabbits: Reversibil-ity 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. Peroxis-some proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-en-dothelial cell interaction. Atherosclerosis, Thrombo-sis, and Vascular Biology 1999; 19: 2094-2104. 16. Pasceri, V; Wu, H D; Willerson, J T; et al. Modu-lation of vascular inflammation in vitro and in vivo by peroxissome proliferator-activated receptor-gam-ma activators. Circulation 2000;101: 235-238. 17. Han, K H; Chang, M K; Boullier, A; et al. Oxi-dized LDL reduces monocyte CCR2 expression through pathways involving peroxissome proliferator-activated 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 Li-gands Inhibit Choroidal Neovascularization. Invest Ophthalmol Vis Sci 2000;41:2309-17.
Febrero 2009
PAN-AMERICA : 155
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 Satur-day, 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: En-glish, 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-AMERICA156 :
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 accep-ted in the Kellogg Eye Center at the Universi-ty 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 invalua-ble human resource with vast experience, the most advance technology on their hands and a very rich academic activity.
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 surge-ries. 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, Doc-tor 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 for-mation and education.
Due to the high complexity of different ca-ses, I have participated in the multidisciplina-ry 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 enri-ched my profession as an ophthalmologist as well. I have participated in the clinical prac-tice of other subspecialties, such as Neuro-Ophthalmology. I have also been part of the multiple academic activities this center has, like the Grand Rounds, Visiting Professors conferences, Fall Symposium, Neuro-Radio-logy 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 hel-ped me become a better teacher.
Not only have the clinical and surgical ex-perience contributed to my learning and pro-gress but this experience has also allowed me to participate in clinical research. I am invol-ved in several different research projects such as Ptosis, Orbital Fractures, Decompressions, Exophthalmometry and case reports. This ac-tivity 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 collabo-rate 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 recei-ved from this award. I will be eternally grateful to the Retina Research Foundation of Hous-ton, Texas and the Pan-American Association of Ophthalmology.
Sincerely yours,
Ángela María Sánchez Castellanos, M.D.
2008 gillingham fellow
Febrero 2009
PAN-AMERICA : 157
Mark Mannis MDEditor en Jefe Editor-in-ChiefEditor Chefe
BOOK REVIEW
Oftalmogeriatria.
Oftalmogeriatria.
Cypel m and Belfort Jr. r, editora roca, ltd., são paulo, Brasil, 2008. 428 pages; Cd rOm
Todos los que nos dedicamos a la oftalmo-logía 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 oftal-mológicas 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 tra-tan 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 es-tándar, que son narrados en portugués. El CD funciono sin problema alguno en la computa-dora 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 con-tribución 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.
Cypel m and Belfort Jr. r, editora roca, ltd., são paulo, Brasil, 2008. 428 pági-nas; dVd
Todos nós que trabalhamos na área da oftalmologia reconhecemos que o envelheci-mento está atualmente no centro de nossas atenções. Marcela Cypel e Rubens Belfort Jr. da Universidade Federal de São Paulo pro-duziram uma importante obra que será de grande valor para oftalmologistas de língua Portuguesa e Espanhola. O enfoque diferen-ciado deste livro é a abordagem das doenças oftalmológicas do paciente idoso, com seus diagnósticos e tratamentos. O livro dá ênfa-se 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-
gem as alterações oftalmológicas freqüentes na população de idosos e sua repercussão na qualidade de vida.
Iniciando com um capítulo sobre geriatria e gerontologia na oftalmologia, a obra des-creve as alterações oculares anatômicas no processo do envelhecimento e segue apre-sentando dados epidemiológicos das doen-ças oculares mais freqüentes. Os capítulos subseqüentes incluem aspectos psicovisu-ais, percepção visual, erros refrativos e visão subnormal. Capítulos abordando doenças es-pecíficas incluem: olho seco; oculoplástica, pálpebra e doenças da córnea; alterações do canal lacrimal; esclerites e episclerites; uveí-tes; 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 comunida-de possam também usufruir desta obra.
PAN-AMERICA158 :
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 manage-ment. 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 gerontol-ogy in ophthalmology, the book goes on to cover ocular anatomy in the elderly and the epidemiology of ocular disease in the elderly. Sub-sequent 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; lacri-mal 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 illustra-tions as well as high quality clinical images. The authors have included an excellent CD with movies of the standard surgical procedures nar-rated 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 oph-thalmologist 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 commu-nity of practitioners.
Vision Pan-America gratefully acknowledges the contributors who provided peer review for articles during the past year.
Eduardo Alfonso, USA
Eduardo Arenas, Colombia
J. Fernando Arévalo, Venezuela
J. Bronwyn Bateman, USA
Hilda Capo, USA
Javier Córdoba, Costa Rica
Denise de Freitas, Brazil
Teodoro Evans, Canada/Costa Rica
José Gomes, Brazil
Enrique Graue Hernández, USA/Australia/Mexico
Enrique Graue Wiechers, Mexico
Lani Gurria Quintana, USA/Australia/Mexico
Luis Izquierdo, Peru
Lily Koo Lin, USA
Chun Cheng (Luis) Lin Yang, Costa Rica
Cristian Luco, Chile
Marian Macsai, USA
Eduardo Marback, Brazil
Roberto Marback, Brazil
Mary O’Hara, USA
Susanna Park, USA
David Pelayes, Argentina
Christopher Rapuano, USA
Ivan Schwab, USA
Allan Slomovic, Canada
Suzana Tanimoto, USA
David Telander, USA
José Tovilla Canales, Mexico
Rupan Trikha, USA
Daniel Weil, Argentina
Lihteh Wu, Costa Rica
reviewer acknowledgement
Febrero 2009
PAN-AMERICA : 159
SightLife™ Global Eye Bank and
Corneal Transplant Congress
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 op-portunity to increase both the quantity and quality of eye bank corneal tissue in your country/community.
Join APABO now and enjoy the follow-ing important member benefits:
1) Participation in annual courses in Spanish or Portuguese for your techni-cians and physicians
2) Participation in tissue sharing net-works 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
SightLife™ Global Eye Bank and
Corneal Transplant Congress
Come Early to the 2009 EBAA Annual Meeting in Seattle
Si no forma parte, está desaprovechan-do la oportunidad de enriquecer la can-tidad y la calidad del banco de ojos de tejido ocular en su país o comunidad.
Forme parte de la APABO y disfrute de los siguientes beneficios de membre-sía:
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 in-tercambio 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 ban-cos de ojos miembros de la APABO.
To learn more about APABO membership,
visit our web page and complete an APABO membership application at:
www.apaboeyebanks.org
or, e-mail [email protected] for more information
Para más información sobre la membresía, sírvase ingresar a nuestra página web y llene una solicitud de
membresía:
www.apaboeyebanks.org
Para más información, sírvase contactar a: [email protected]
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 [email protected] antes del 1 de abril del 2009 para ser considerado.
PAN-AMERICA160 :
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 VisualField 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 Bimatoprostand 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 ofOphthalmol, New Orleans, La, 2001.
Preserva la visión alcanzando las menorespresiones-objetivo en más pacientes
Mejor comodidad posológica:
1 vez al día.
No requiere refrigeración.
Presentación conteniendo 3 ml.
LLLLLumiganumiganumiganumiganumigan® ® ® ® ® (bimatoprost) Forma farmacéutica y prForma farmacéutica y prForma farmacéutica y prForma farmacéutica y prForma farmacéutica y presentación.esentación.esentación.esentación.esentación.Frascos cuenta-gotas conteniendo 5 ml de solución oftalmológica estéril de bimatoprost a 0,03%. USO ADULTO.Composición. Composición. Composición. Composición. Composición. Cada ml contiene: 0,3 mg de bimatoprost. Vehículo: cloreto de sódio, fosfato de sódiohepta-hidratado, ácido cítrico mono-hidratado, ácido clorídrico y/o hidróxido de sódio, cloruro de benzalconio y agua purificada qsp. Indicaciones.Indicaciones.Indicaciones.Indicaciones.Indicaciones. LUMIGAN®®®®® (bimatoprost) es indicado para la reducción de la presión intra-ocular elevada en pacientes con glaucona o hipertensiónocular.Contraindicaciones.Contraindicaciones.Contraindicaciones.Contraindicaciones.Contraindicaciones. LUMIGAN®®®®® (bimatoprost) está contraindicado en pacientes con hipersensibilidad al bimatoprost o cualquier otro componente de la fórmula del producto. Pr Pr Pr Pr Precauciones y Adverecauciones y Adverecauciones y Adverecauciones y Adverecauciones y Advertencias.tencias.tencias.tencias.tencias. Advertencias. Fueron relatados aumento gradual del crescimientode 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 después6 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 tratamientode apenas uno de los ojos, deben ser informados a respecto de esas reacciones. PrPrPrPrPrecaucionesecaucionesecaucionesecaucionesecauciones 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 debenser 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 medicamentode 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.Interacciones medicamentosas.Interacciones medicamentosas.Interacciones medicamentosas.Interacciones medicamentosas.Considerando que las concentracionescirculantes 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.No son conocidas incompatibilidades. R R R R Reacciones adversas.eacciones adversas.eacciones adversas.eacciones adversas.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, durante3 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 infeccionesde 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,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 y Administración.Posología y Administración.Posología y Administración.Posología y Administración.Posología y 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 oftálmicostópicos 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 HAYANINDICADO 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.
vs. timolol 4 vs. latanoprost6
Porcentaje de Pacientes quealcanzaron la PIO-Objetivo ≤≤≤≤≤14 21% 9% 17% 2% 19% 9%
Porcentaje de Pacientes quealcanzaron la PIO-Objetivo ≤≤≤≤≤15 31% 16% 24% 9% 29% 14%
dorzolamida/ timolol 5vs.
®®®
Lumigan® alcanza la PIO-objetivo de 14/15 mmHg en un mayor númerode pacientes:
Investigadores de diversos estudios, (AGIS, Shirakashi, Shields)han comprobado que alcanzar y mantener la PIO entre 14 y 15 mmHgreduce la progresión de pérdida del campo visual1,2,3.
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