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