Informe sobre procedimiento de terapia fotodinámica en

Informes valorativos 2001
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Terapia
fotodinámica en
oftalmología
Degeneración macular
asociada a la edad
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GENERALITAT
VALENCIANA
febrero 2001
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
I.-
PREÁMBULO Y PLANTEAMIENTO SEGUIDO..............................................1
II.-
EXTRACTO DE LA INFORMACIÓN RECOPILADA.......................................3
II.I.- DATOS MANEJADOS ..........................................................................3
II.II.- EVIDENCIAS Y CONCLUSIONES .......................................................7
III.-
RECOMENDACIONES Y SUGERENCIAS....................................................10
APÉNDICES .......................................................................................................................13
APÉNDICE A
Criterios de indicación, Criterios de no indicación ..........................................13
APÉNDICE B
Procedimientos e instrumentación, Modo de administración y
reintervención.................................................................................................14
APÉNDICE C
Guía de conocimientos clínicos......................................................................15
APÉNDICE D
Datos a recoger y documentar (susceptibles de mecanizar y tratar)..............16
APÉNDICES E
prevalencias poblacionales referidas o estimadas a partir de datos de
los estudios de prevalencia/incidencia poblacional seleccionados.................17
APÉNDICE F
escenarios de costes previsto ........................................................................19
ANEXOS
.......................................................................................................................20
1.-
febrero 2001. ANEXO DOCUMENTAL DE EXPLOTACIÓN DE DATOS DE
CONCIERTOS ............................................................................................................... 21
2.-
febrero 2001. ANEXO DOCUMENTAL DE LA BÚSQUEDA BIBLIOGRÁFICA EN
LA CDR (en sus bases de datos DARE, NHS EED y HTA)........................................... 29
3.-
febrero 2001. ANEXO DOCUMENTAL DE LA BÚSQUEDA BIBLIOGRÁFICA EN
MEDLINE A TRAVÉS DE LA NATIONAL LIBRARY OF MEDICINE (bajo criterios:
“photodynamic therapy degeneration macular”) ............................................................ 31
4.-
febrero 2001. ANEXO DOCUMENTAL DE LA BÚSQUEDA BIBLIOGRÁFICA EN
MEDLINE A TRAVÉS DE LA NATIONAL LIBRARY OF MEDICINE (bajo criterios:
“prevalence blindness older” or “epidemiology maculopathy” or “prevalence aged
macular”) ........................................................................................................................ 36
5.-
marzo 2000. SMM-REPORT NR.3/2000 THE NORWEGIAN CENTRE FOR
HEALTH TECHNOLOGY ASSESSMENT Photodynamic therapy for age-related
macular degeneration..................................................................................................... 57
6.-
1.994: GUIDE CANADIEN DE MEDICINE CLINIQUE ET PRÉVENTIVE.
Dépistage de la deficience visuelle chez les personnes âgées ..................................... 68
7.-
enero 2000. NATIONAL HORIZON SCANNING CENTRE. Photodynamic therapy
for age-related macular degeneration. ........................................................................... 83
8.-
Issue 1, 2001. Oxford. THE COCHRANE LIBRARY (COCHRANE REVIEW).
Photodynamic therapy for neovascular age-related macular degeneration................... 90
9.-
enero 2001. Irveng Arons in OCULAR SURGERY NEWS. Visudyne looks
promising for treating wet AMD .................................................................................... 108
10.-
febrero 2001: Información registrada en la FDA sobre el verteporfin .......................... 113
11.-
febrero 2001: Información registrada en la EMEA sobre el verteporfin ....................... 126
INDICE
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
INFORME VALORATIVO A DEMANDA
I.-
PREAMBULO Y PLANTEAMIENTO SEGUIDO
En fecha 12-II-2001 se recibe en estas dependencias solicitud de informe valorativo
relativo a la aplicación de la técnica de terapia fotodinámica que se viene realizando
por el servicio de oftalmología del hospital Universitario La Fe y de manera derivada
en centros asistenciales privados.
Ya en el seno del grupo de trabajo de “Organización de la Investigación médico-clínica: Usos Tutelados”, y por parte del Dr. José Luis Rey (jefe del Área de asistencia sanitaria), se comentaron las dudas que para el servicio de Conciertos se
planteaban, acerca de la efectividad y eficacia de la citada técnica.
A pesar de que este tipo de teapia se utiliza en otros campos especializados (dermatología y oncología) y dado lo requerido en la solicitud, nos ceñiremos en el presente informe a la utilización de la citada técnica en el campo oftalmológico. En
concreto se analizarán las indicaciones dirigidas a la resolución de problemas visuales derivados de la degeneración macular asociada a la edad [DMAE (acrónimo en
español), ARM, ARMD (acrónimos en inglés), DMLA (acrónimo en francés)].
La solicitud de informe valorativo recibida abarca un amplio campo prospectivo (utilidad, nivel de adecuación, guía de uso, optimización de recursos, previsión de demanda y análisis de escenarios, entre otros). Por ello se ha recurrido para la elaboración de este trabajo, a diversos servicios y organismos que pudieran aportarnos
datos o informaciones relevantes para el tema y los campos a evaluar. Así pues y
por dicho motivo se ha recabado información de diversos servicios de la Conselleria
de Sanidad, en un intento de recopilar toda aquella pertinente para el tema de análisis. Así pues mencionaremos ahora las peticiones de datos efectuadas a los servicios de Epidemiología, de Conciertos, de Actividad Asistencial y de Prestación Farmaceútica. Tras la recepción de lo solicitado, (cuando ésto se ha producido) se ha
procedido en este Servicio de Evaluación de Tecnologías al cotejo y análisis de los
datos, y al extracto y confección de indicadores ajustados a las necesidades que el
informe requería.
Pá gina 1 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Así mismo se ha procedido a solicitar información en el propio hospital Universitario
La Fe. Pareció prudente sin embargo, prescindir de recabar datos de otros servicios
asistenciales públicos o privados de la Comunidad Valenciana ralacionados con esta
técnica, dado que este informe no es sino un primer intento de acercamiento sistemático al tema. Por ello se consideró que debiera huirse de alentar espectativas innecesarias en esta fase evaluativa inicial.
También se ha recogido información de las diversas agencias de evaluación de tecnologías tanto nacionales (autonómicas y española), como de las extranjeras.
Igualmente se han sondeado bases de datos del campo asistencial especializado oftalmológico, así como aquellas obrantes y accesibles divulgadas por las sociedades
científicas y profesionales en relación con el campo de análisis. Del mismo modo se
ha reclutado información relevante de institutos y centros oftalmológicos nacionales
y extranjeros con competencia en el tema abordado.
Pá gina 2 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
II.-
REF.: ACEMSA/SET/AC/ac
febrero-2001
EXTRACTO DE LA INFORMACIÓN RECOPILADA
(En este apartado se reseñarán diversos datos considerados como elocuentes y representativos de la información global contenida en todo el informe. Se ha pretendido que de la lectura de este cuerpo del informe, se puedan obtener elementos de
juicio claros para las decisiones a acometer. En el material anexado a este informe,
se reflejan diversas explotaciones, análisis y referencias de forma más exhaustiva a
lo sintetizado en este apartado).
II.I.-
1.-
DATOS MANEJADOS
En contacto con el servicio de conciertos, se constata la presentación de un
total de 190 casos propuestos para la realización de la técnica reseñada. Diversas características de los casos para los que se dispone información en el
mencionado servicio, pueden observarse en la siguiente tabla. Lo presentado
en los anexos, permite un más amplio y exhaustivo conocimiento de las solicitudes de terapia fotodinámica que han sido registradas hasta la fecha en el
servicio de conciertos.
DATOS EXISTENTES EN CONCIERTOS SOBRE:
SOLICITUDES DE TERAPIA FOTODINÁMICA: AÑO Y MES DE ESTIMACIÓN POR
CONCIERTOS
% por AÑO – MES
DE ESTIMACIÓN
Recuento
ACEPTA
CONCIERTOS
SI
NO
2000-01
2000-02
2000-03
2000-04
2000-05
2000-06
2000-07
2000-08
2000-09
2000-10
2000-11
2000-12
2001-01
2001-02
TOTAL
10
10
16
13
10
10
13
13
3
1
2
1
7
1
110
1
1
3
10
7
18
25
11
1
1
1
1
80
TOTAL
10
11
17
16
20
17
31
38
14
2
3
2
7
2
190
ACEPTA
CONCIERTOS
SI
NO
100.0%
90.9%
94.1%
81.3%
50.0%
58.8%
41.9%
34.2%
21.4%
50.0%
66.7%
50.0%
100.0%
50.0%
57.9%
9.1%
5.9%
18.8%
50.0%
41.2%
58.1%
65.8%
78.6%
50.0%
33.3%
50.0%
50.0%
42.1%
TOTAL
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
% por MES
ESTIMACION
ACEPTA
CONCIERTOS
SI
NO
9.1%
9.1%
14.5%
11.8%
9.1%
9.1%
11.8%
11.8%
2.7%
.9%
1.8%
0.9%
6.4%
0.9%
100.0%
1.3%
1.3%
3.8%
12.5%
8.8%
22.5%
31.3%
13.8%
1.3%
1.3%
1.3%
1.3%
100.0%
TOTAL
POR
MES
5.3%
5.8%
8.9%
8.4%
10.5%
8.9%
16.3%
20.0%
7.4%
1.1%
1.6%
1.1%
3.7%
1.1%
100.0%
Pá gina 3 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
2.-
Puestos
en
REF.: ACEMSA/SET/AC/ac
febrero-2001
contacto
con el hospital Universitario La Fe se obtuvieron
informaciones
relativas al número de
pacientes
tratados,
técnica de abordaje y
resultados
obtenidos
hasta la fecha. Durante los meses de enero
y
febrero
del
año
2001, 54 pacientes han sido analizados en el citado hospital ante propuestas
de aplicación de Terapia Fotodinámica. La aplicación de la técnica parece
adaptarse en líneas generales a lo
estipulado en la autorización vigente
para el Verteporfin ®, en USA, Unión
Europea y Suiza. No obstante, el
protocolo de aceptación de técnica
empleado en la Fe se ha ampliado
así mismo para la miopia degenerativa (actualmente y todavía en fase
de estudio –ensayo VIP multicéntrico).
3.-
Mediante contacto con los servicios de Epidemiología, de Análisis de la Actividad asistencial y con el de Protocolarización, Alternativas Asistenciales y
Evaluación Económica se pretendía recoger información relativa al alcance
de la patología oftalmológica intervenible con la técnica citada, de aquella
otra cercana a la misma y de los costes imputables a dicha actividad asistencial. De ninguno de los servicios se nos refiere información específica de
la patología a estudio. Únicamente se toman en consideración datos relativos a incidencia atendida o prevalencia poblacional para patologías cercanas
o “competidoras asistenciales” de la analizada. Ésta información se ha tenido
Pá gina 4 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
en cuenta de cara a proyectar escenarios y calibrar mejor las estimaciones y
recomendaciones que posteriormente se presentan.
4.-
En la misma fecha del recibo de la solicitud, se procede a realizar búsquedas
dirigidas en diversas bases de datos de evaluación de tecnologías y científicas a las que desde este servicio se tiene acceso pleno o parcial: INAHTA,
ISTAH, AEETSA, CDR-NHS, MEDLINE, COCHRANE LIBRARY. En dichos procesos indagatorios, se han empleado métodos de sondeo aproximativos recursivo-selectivos al tema buscado. Los criterios últimos de búsqueda, se expresan en las diversas tablas que se adjuntan en el informe. Así mismo en
información anexada se presentan los artículos o resúmenes de las referencias más relevantes y que dan soporte a las recomendaciones que se plantean en el informe.
5.-
Mediante las búsquedas dirigidas empleadas, se han localizado una serie de
análisis evaluativos efectuados por diversas agencias de evaluación nacionales y extranjeras. La existencia y posibilidad de acceso a revisiones sistemáticas, metaanálisis y diversos ensayos clínicos controlados han permitido
aumentar la base científica en la que se apoyan los elementos de juicio, así
como las recomendaciones y sugerencias que se plantean.
6.-
Tras los procesos de búsqueda dirigida, las referencias halladas de forma
inmediata han sufrido un cotejo selectivo previo a su análisis y consideración definitiva. En dicho sentido los criterios ponderados de selección empleados han sido:
1.-
Relevancia de la información aportada para la indagación
2.-
Robustez del diseño y método científico empleado
3.-
Entornos socioeconómicos comparables o análogos a nuestro
entorno
4.-
Información accesible
Las referencias han sido analizadas en su versión íntegra siempre que ha sido posible acceder a ellas, no desdeñándose aquella que sólo ha podido ser
accesible en su formato resumido.
Pá gina 5 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
7.-
REF.: ACEMSA/SET/AC/ac
febrero-2001
En una segunda etapa se han sondeado como registros específicos, (aparte
de las bases antes descritas), las de la FDA americana y la EMEA europea,
dado que la técnica a analizar precisa de la utilización de productos farmacológicos de reciente incorporación al mercado farmacológico. En dicho sentido
y como ya ha sido reseñado, también se ha solicitado la información obrante
en diversos servicios dependientes de la D.G. para la Prestación Farmaceútica, en búsqueda de información respecto a la adquisición, uso, conservación
y reacciones adversas a los fármacos involucrados en la técnica analizada.
Desde esa dirección, no se nos ha comunicado hasta la fecha reacciones al
producto. No obstante hay una prolija descripción de las mismas en referencias procedentes de la FDA o EMEA, así como en otras de las fuentes manejadas.
Pá gina 6 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Tras la lectura, extracto y análisis de la profusa información final seleccionada, se
pueden avanzar ciertas conclusiones:
II.II.-
1.-
EVIDENCIAS Y CONCLUSIONES
La relativamente reciente finalización del ensayo clínico controlado a doble
ciego para el uso del Verteporfin® (Visudyne) en fase II y posterior fase III
(TAP 1 y 2, VIP 1 y 2 en proceso), y los datos aportados por el mismo, han
servido como elemento de juicio científico para la autorización de dicho producto y unas indicaciones precisas para la realización de la Terapia Fotodinámica en el caso de la degeneración macular asociada a la edad para su
forma exudativa con degeneración neovascular retrofoveal visible (presentación clásica). Dichas autorizaciones se realizaron en abril del 2000 en USA y
en junio del 2000 para los países de la Unión Europea. Actualmente no se
han obtenido evidencias formales que permitan la autorización para la miopía degenerativa, para la DMAE no exudativa, ni para la DMAE exudativa no
visible.
2.-
Para los casos en los que existe degeneración neovascular con característica
geográfica extrafoveal, la técnica de la fotocoagulación con láser es la de
elección. No así en los casos en donde se invade francamente mácula y fóvea. En estos casos, la nueva técnica pudiera presentar una cierta ventaja
comparativa ante los malos resultados obtenida con la anterior, a pesar de
que el estudio TAP no contemplaba dicha comparación.
3.-
Las diversas evaluaciones realizadas por las agencias coinciden en no recomendar la terapia fotodinámica en lesiones cuasi-asintomáticas y/o muy incipientes, en las no visibles y la desaconsejan en las variantes secas, constituyendo estas últimas casi el 90% de las degeneraciones maculares asociadas a la edad.
4.-
La técnica empleada es meramente protectora de la mala evolución pronóstica, no abordando en absoluto las causas y factores desencadenantes de la
degeneración macular. La terapia fotodinámica en la DMAE, como técnica
estabilizadora que trata de ser, y para el tipo de pacientes indicado en el es-
Pá gina 7 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
tudio TAP (base de la autorización), ostenta una eficacia comparativa menor
del 28%. De los datos manejados en el propio estudio TAP se desprende un
NNT=6’7 para todos los individuos tratados (se necesitan tratar 6’7 pacientes para que uno muestre el efecto mejorador). El NNT obtenido en el ensayo TAP es de 2, si en el análisis únicamente se consideran a los pacientes
que cumplen las condiciones extrictas (DMAE, clásica con vasos visibles retrofoveales: presentación clásica). A parte del ensayo TAP, la aplicación de la
técnica sobre el terreno, hace augurar a algunos expertos una efectividad inferior al 20%. Existen ahora mismo en marcha estudios y ensayos clínicos
controlados que investigan la acción de ciertas substancias de la dieta o
fármacos inhibidores de la neovascularización, que inhibirían o protegerían
de la aparición de esta degeneración desencadenante de la enfermedad clínica. Ninguno de los finalizados hasta ahora, ha obtenido resultados concluyentes.
5.-
En línea con las recomendaciones efectuadas por el gobierno canadiense en
su guía: “Déspistage de la déficience visuelle chez les personnes âgées”, así
como otros informes realizados en países nórdicos, en donde se analizan las
oportunidades de priorizar actividades eficaces sobre catarata, glaucoma y
degeneración macular asociada a la edad, sería preciso analizar con rigor,
elementos tales como coste-utilidad, coste-efectividad, seguridad, NNT efectivo, así como medidas de impacto asistencial y social derivadas de la ponderación de unas alternativas de forma prioritaria sobre otras. Máxime en
escenarios con recursos limitados y para los que se comparte (y compite) en
recursos destinados a la asistencia de otras patologías oculares en población
mayor (glaucoma, catarata, retinopatía diabética. Esta última se presenta en
el 15.7% de los casos de diabetes según datos de la Red centinela sanitaria
de la Comunidad Valenciana).
6.-
La prevalencia de esta enfermedad, el aumento de longevidad en los paises
de nuestro entorno socioeconómico, el mal pronostico visual para estos pacientes, el aparente casi nulo riesgo vital de la técnica y la presión del propio
mercado sanitario, aventuran una rapidísma expansión de la citada técnica,
como de hecho ya se está produciendo.
Pá gina 8 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
7.-
REF.: ACEMSA/SET/AC/ac
febrero-2001
El bajo coste relativo de amortización de los equipos/intervención (que se sitúa en una posición de gran ventaja sobre otras técnicas novedosas y de auge en el campo oftalmológico, y por tanto con una posibilidad de rendimiento económico por intervención mayor que otras técnicas), y el carácter de
ser la única indicación viable para cierto grupo de pacientes (así considerado
por los especialistas), abunda todavía más en la generación de una floreciente oferta de este tipo de intervención en el mercado sanitario. Estos
hechos posiblemente presionen alentando prescripciones de dicha técnica
para gradientes de degeneración macular más amplios que el actualmente
indicado.
8.-
Por último se hace preciso indicar que las empresas que comercializan o comercializarán los productos farmaceuticos involucrados en la técnica [Verteporfin ® de Ciba-visión-Novartis (ya autorizado), SnET2 de Miravant and
Pharmacia & Upjohn (finalizando estudio), Optrin de Pharmacyclics (en estudio)], completarán probablemente estudios con potenciado poder estadístico
(grandes muestras), que atestigüen mejoras comparativas en el límite, para
fases de la DMAE incipientes. Bajo esta suposición, y dado el alto coste de
los tratamientos y las altas prevalencias de las fases incipientes, podemos
asistir a un componente de gasto importante para años venideros en los
servicios sanitarios, como ya auguran diversos especialistas acerca de dicho
fenómeno en el Medicare estadounidense.
Pá gina 9 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
III.-
REF.: ACEMSA/SET/AC/ac
febrero-2001
RECOMENDACIONES Y SUGERENCIAS
A la luz de los datos barajados en el informe y sus anexos, se plantean una serie de
ejes de actuación en la actuación de diversos servicios competentes para cada una
de las materias a abordar:
1.-
Parece necesaria la planificación con el máximo rigor (6 meses – 12 meses)
de una serie de líneas o medidas a poner en práctica de forma escalonada.
Para la elaboración de las mismas y su puesta en marcha, parece necesario
el consurso y asesoramiento de oftalmólogos o bien de institutos oftalmológicos con capacidad de ajustar de forma precisa y científica las diversas circunstancias inherentes a la propia técnica. A falta de lo anterior y como
planteamientos operativos previos, parece conveniente lo siguiente:
1.1.-
Generación de normativa clara respecto a la prescripción de la terapia, criterios de intervención y flujos procedimentales de la citada
técnica (Una serie de propuestas preliminares se ofrecen en páginas
subsiguientes: apéndices A y B).
1.2.-
Guía clínica de actuación e indicaciones para los pacientes con DMAE
franca. (Una serie de propuestas preliminares se ofrecen en páginas
subsiguientes: apéndice C).
1.3.-
Adecuación de un subsistema informativo para la captación de información asistencial de este tipo de patología. Conveniencia de generar
un registro específico para esta enfermedad, ligado o no a registro
poblacional de ceguera. (Una serie de propuestas preliminares se
ofrecen en páginas subsiguientes: apéndice D).
1.4.-
Pautas de anotación y registro específicas para la terapia fotodinámica (a modo de registro de intervención específica documentada).
(Una serie de propuestas preliminares se ofrecen en páginas subsiguientes: apéndice D).
Pá gina 10 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
1.5.-
REF.: ACEMSA/SET/AC/ac
febrero-2001
Estudio poblacional transversal sobre deficit visual y ceguera en personas de más de 50 años, con evaluación específica para este tipo de
degeneración asociada a la edad. (Una estimación proyectada se
ofrece en las tablas subsiguientes: apéndice E).
2.-
Autorización de la técnica citada por parte del servicio competente y establecimiento de los criterios de adquisición y registro del aparataje (en el sector
público) de forma reglada y centralizada. La homologación formal de centros
(referenciales o no), para la ejecución de esta técnica es una línea que debiera valorarse e impulsarse en su caso.
3.-
Estudio de alternativas y costes de asunción en el sector público de esta intervención para estadíos categóricamente planteados. Esto implicaría la planificación del número de unidades a georeferenciar para la Comunidad (una
por provincia, una central...) y adecuar recursos para las mismas de forma
que la repercusión de esta alternativa no lastrase la actividad que ya se realiza en dichos servicios de oftalmología (retinopatía diabética, cataratas ...).
(La opción de asumir de forma reglada este tipo de intervención en el sector
público posibilitaría que mediante negociación global con la/s empresa/s
proveedoras del fármaco se pudiera optimizar en grado sumo la adquisición
o cesión del aparataje. A su vez, la compra centralizada del fármaco para
uso hospitalario podría permitir una rebaja substancial en el precio unitario).
4.-
Estudio de la alternativas de asunción mediante externalización (concertada
o no) y estimación de costes. En este caso sería preciso el mejor aquilatamiento de los precios, estableciéndolos bien por sesión o bien por proceso
global. (Una estimación de escenarios se ofrece en las tablas subs¡guientes:
apéndice F).
5.-
En cualquiera de los escenarios de asunción de esta terapia con cargo al erario público, habría que sopesar y estimar mecanismos que solventasen la
posible llegada de pacientes de otros servicios autonómicos de salud o del
INSALUD en caso de que la terapia (bien con proveedor público o privado)
sólo fuera asumida en la Comunidad Valenciana. Por otro lado no se tiene
Pá gina 11 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
hasta la fecha información de reintegros o sentencias judiciales que dicten la
asunción del coste de este tratamiento por las arcas públicas (única terapia
considerada viable por los oftalmólogos para cierto tipo de pacientes). La
posibilidad en un futuro próximo de este tipo de circunstancias, sin duda debería ser tenida en cuenta de cara a los análisis económicos que convendría
realizar.
Valencia 1 de marzo del año 2001
Servicio de Evaluación de Tecnologías
Pá gina 12 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE A
Criterios de indicación
La terapia de la DMAE mediante terapia fotodinámica con Verteporfin podrá indicarse a criterio del
especialista oftalmólogo bajo las siguientes condiciones:
-
El diagnóstico de DMAE con NVC (neovascularización coroidal) retrofoveolar predominantemente visible (50%) debe haberse establecido de forma clara.
-
Se trata de una forma exudativa con lesión retrofoveolar en la que más del 50% esté constituida
por nuevos vasos visibles, demostrado por angiografía de fluorescencia (completada en caso de
necesidad con la angiografía con verde de indocianina) (un cliché de angiografía debe poder ser
consultado).
-
Debe respetarse un intervalo de noventa días entre dos sesiones de tratamiento.
Criterios de no indicación
Las formas predominantemente visibles son las menos frecuentes de las DMAE exudativas retrofoveolares. La terapia de la DMAE mediante terapia fotodinámica con Verteporfin® no está indicada
en el tratamiento:
-
de las NVC ocultas;
-
de la DMAE con NVC visibles respetando la mácula (extra o yuxta foveolares) susceptibles de
un tratamiento por fotocoagulación láser convencional;
-
de las NVC secundarias a una fuerte miopía para las cuales el beneficio terapéutico de Verteporfin® está todavía en evaluación
Otras indicaciones sólo deberían establecerse en el marco de ensayos clínicos, debidamente protocolorizados y autorizados. Para étos es preciso asegurar las condiciones metodológicas, éticas y
legales para su puesta en marcha.
Pá gina 13 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE B
Procedimientos e instrumentación
Para esta terapia, el oftalmólogo debe de haber realizado los siguientes exámenes en los 7 días
anteriores:
-
medida de la agudeza visual, completada eventualmente con la medida de sensibilidad a los
contrastes
-
angiografía con fluoresceína, comportando clichés a 1, 2, 5 y 10 minutos, eventualmente completada con angiografía con verde de indocianina
-
fotografía del fondo de ojo (equipo con agrandamiento recomendado de 2,4-2,6).
La mayor dimensión de la lesión coroidiana se estimará sobre angiografía y la fotografía del fondo
de ojo.
Equipo necesario:
•
angiografo de fluoresceína y si es necesario la posibilidad de realizar una angiografía con verde de indocianina
•
jeringa eléctrica
•
láser diodo (longitud de onda: 689 nm),
Las contraindicaciones y reservas respecto a la manipulación, reconstitución del Verteprofin, protección a la luz, tiempo de activación, área de incidencia y actuación lumínica, y protecciones lumínicas postintervención en tiempo y forma, deben ser respetadas.
El riesgo de interacción con medicamentos u otros agentes fotosensibilizantes debe ser investigado.
Modo de administración y reintervención
El tratamiento comprende dos etapas:
1. Perfusión intravenosa de Verteporfin® durante 10 minutos con una dosis de 6mg/m2 de superficie corporal, diluido en 30 ml. de solución glucosada.
2. Activación de Verteporfin® por la luz 15 minutos después del inicio de la perfusión por medio
de una luz roja no térmica (longitud de onda: 689 nm), proporcionada por un laser diodo con
ayuda de una fibra óptica, de una lámpara de hendidura y de una lentilla de contacto apropiada. Para la intensidad luminosa recomendada (600 mW/cm2), son necesarios 83 segundos
para proporcionar la dosis luminosa requerida de 50 julios/cm2.
Los pacientes deben ser reevaluados cada tres meses. En caso de recidiva, el tratamiento por
Verteporfin® puede ser administrado hasta cuatro veces por año.
Pá gina 14 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE C
Guía de conocimientos clínicos
La indicación de la terapia fotodinámica es muy precisa en la DMAE: los pacientes que presentan
una neovascularización coroidiana retrofoveolar predominantemente visible. En esta indicación, la
eficacia de Verteporfin® sólo ha sido demostrada en los pacientes en los que la agudeza visual
estaba comprendida entre 1/10 y 5/10.
Los pacientes deben ser reevaluados cada tres meses en caso de recidiva, el tratamiento por Verteporfin® debe ser administrado un máximo de cuatro veces por año.
El Verteporfin® es un derivado de una benzoporfirina (BDP-MA) cuyas propiedades fotosensibilizantes son utilizadas para limitar la pérdida de la agudeza visual ligada a la degeneración macular
asociada a la edad (DMAE) en su forma exudativa, en los pacientes que presentan una neovascularización coroidiana retrofoveolar predominantemente visible (50% de nuevos vasos
bien delimitados en la angiografía con fluoresceina).
Esta forma de DMAE es una patología con mal pronóstico que conduce en un breve plazo a un
déficit visual mayor. La fototerapia dinámica con Verteporfin® es una alternativa terapéutica cuyo
interés reside en que respeta el tejido retiniano macular.
La prescripción debe ser únicamente realizada por especialistas en oftalmología.
El coste particularmente elevado de Verteporfin® y el riesgo de una utilización para indicaciones no validadas o justificadas, teniendo en cuenta otras alternativas terapéuticas, hacen que la
utilización del mismo en la terapia fotodinámica sea sometido al mayor control posible y a asegurar la idoneidad de los casos a ser tratados y que por tanto puedan beneficiarse del citado tratamiento.
Contraindicaciones del Verteporfin:
-
pacientes afectos de porfiria; pacientes que presenten una insuficiencia hepática grave; hipersensibilidad al verteporfin o a alguno de sus excipientes
Reservas y precauciones de empleo:
-
en ausencia de estudios apropiados, Verteporfin® debe ser utilizado con precaución en los
pacientes afectos de insuficiencia hepática moderada o de obstrucción de las vías biliares
-
no se dispone de ninguna experiencia clínica en los pacientes que sufren de insuficiencia cardíaca no controlada (clases III y IV) ni en los afectos de HTA no controlada
-
en ausencia de datos clínicos y farmacológicos, conviene ser prudente al considerar un tratamiento con Verteporfin® bajo anestesia general
-
Verteporfin® no ha sido estudiado en la mujer embarazada o mujer que amamante
Después de tratamiento por Verteporfin®, los pacientes pueden desarrollar molestias visuales como visión anormal, disminución de la agudeza visual, alteración del campo visual. Mientras persistan las molestias los pacientes a los que su agudeza visual les permite habitualmente conducir, no
deben hacerlo ni utilizar máquinas.
Pá gina 15 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE D
Datos a recoger y documentar (susceptibles de mecanizar y tratar)
La unidad de registro será el paciente afecto de la DMAE detectado en los servicios de oftalmología. Para cada paciente registrado se anexarán los datos referentes a las valoraciones periódicas efectuadas, así como de las intervenciones oftalmológicas realizadas, indicando para cada uno de los datos la fecha de acopio real de la información. Una serie de
datos socio-epidemiológicos deberán consignarse para cada paciente.
A fin de permitir el seguimiento de la adecuación de este tipo de intervenciones y del resultado en el grupo de pacientes intervenidos, diversos datos deben ser recogidos en cada
sesión valorativa o terapeútica en la historia clínica del paciente y tenidas a disposición de
agentes evaluadores de la Conselleria de Sanidad:
-
afectación uni o bilateral
-
agudeza visual precisa del ojo (o de los dos ojos) afectados
-
naturaleza y extensión de las lesiones por imagen angiográfica (un cliché de angiografía
debe poder ser consultado)
-
datos relativos a la intervención (fecha, hora y minutos de la inyección de la droga, activación del verteporfin mediante láser, tiempo de iluminación y campo)
-
datos del seguimiento oftalmológico del paciente
Pá gina 16 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE E (1)
prevalencias poblacionales referidas o estimadas a partir
de datos de los estudios de prevalencia/incidencia poblacional seleccionados (datos referidos salvo otra indicación
expresa en porcentaje poblacional para las cohortes de
edad analizadas)
(agosto 2000: 2000) Australia >40 años
(pob. n=5147 Victoria, examen oftalm.)
(sept 1999: 1993-1995) Wisconsin 48-72 años
(pob. n=11532 North Carolina, examen oftalm. graduac. Wisconsin)
(sept 1999: 4 años) VECAT study 55 a 80 años
(Cas-control n=1204, examen oftalm., Int.Clasif. ARM-AMD)
(jun 1999) NHNES-III USA >40 años
(pob. n=8270 USA, examen oftalm.)
(jun 1999) Baltimore >70 años
(pob n=5308 Baltimore, exam. oftalm.)
(agosto 2000) Blue Mountain Eye Study
(pob n=3654 Australia examen oftalm) 50-59 años (uni-bilateral)
alteraciones
Degenerac.
maculares maculopatía
macular
tempranas
asociada a
ligada a la
la edad
drusas
edad
(>65 µm )
exudativa)
15’1
0’39
DMAE en
ciegos
DMAE en
ciegos o
con daños
visuales severos
5’6
32
9’4
15
2’1
0’4 - 2’7
(agosto 2000) Blue Mountain Eye Study
(pob n=3654 Australia examen oftalm) 60 – 69 años (uni-bilateral)
0’8 - 6’2
(agosto 2000) Blue Mountain Eye Study
(pob n=3654 Australia examen oftalm) 70 – 79 años (uni-bilateral)
4’1 - 15’37
(agosto 2000) Blue Mountain Eye Study
(pob n=3654 Australia examen oftalm) >80 años (uni-bilateral)
20’1 - 39’9
(feb 2000: final 1998) Israel >18 años
(registro nacional de ceguera n=15.937)
0’36
(ciegos)
(jun 2000) Salisbury 65-84 años
(pob Medicare, n=2520, examen oftalm)
(may 2000: 3 meses) Serv. Oftalmología Orleans (Francia)
(pob asistida, n=1172, examen oftalm)<60 años
(may 2000: 3 meses) Serv. Oftalmología Orleans (Francia)
(pob asistida, n=1172, examen oftalm) 60-79 años
(may 2000: 3 meses) Serv. Oftalmología Orleans (Francia)
(pob asistida, n=1172, examen oftalm) >80 años
(jun 1998) Irlanda >16 años
(registro nacional de ceguera, n=5002)
(agosto 1998:seguim 10 años) Depart. Oftalm. Pensilvamia >43 años
(seguim cohorte, n=?, examen oftalm.)
(may 1998) North London
(pob médica, n=1547, Londres, examen oftal.) >65 años
(may 1998) Rotterdam Study
(pob, n=6775, examen oftalm.) >85 años
(nov 1996) Baltimore >40 años
(pob, n=5308, examen oftalm.)
(abril 1995) Finlandia >70 años
(pob, n=500 hab Oulu, examen oftalm.)
12
1’2 (con daños severos)
0’48 (daños
severos)
2’32 (daños
seeros)
5’84 (daños
severos)
40
16
2’54 (con cegurera)
8
10’8
14’2
41
4’7
Pá gina 17 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE E (2)
prevalencias poblacionales referidas o estimadas a partir
de datos de los estudios de prevalencia/incidencia poblacional seleccionados (datos referidos salvo otra indicación expresa en porcentaje poblacional para las cohortes de edad analizadas)
(enero 2000) National Horizon Scanning Centre >75 años
alteraciones maculaDegeneración macures tempranas
lar
asociada a la edad
maculopatía ligada a
drusas (>65 )
(DMAE exudativa)
la edad
30
3
(proyecto de revisión sistemática.)
0’21 con pérdida
(febrero 2000) Norwegian Centre for Health Technology Assessment
>45 años (evaluación de la terapia fotodinámica: diciembre 1999 – febrero 2000) (proyección de datos del Beaver, Dam Eye Study)
20
1’2
a PDT: 0’48
(febrero 2000) Norwegian Centre for Health Technology Assessment
(evaluación de la terapia fotodinámica: diciembre 1999 – febrero 2000)
(proyección de datos del Beaver, Dam Eye Study) 43-54 años
0’1
(febrero 2000) Norwegian Centre for Health Technology Assessment
>45 años (evaluación de la terapia fotodinámica: diciembre 1999 – febrero 2000) (proyección de datos del Beaver, Dam Eye Study) >75
años
7’5
(febrero 2000) Norwegian Centre for Health Technology Assessment
>45 años (evaluación de la terapia fotodinámica: diciembre 1999 – febrero 2000) (proyección de datos del Beaver, Dam Eye Study) >85
20
(enero 1994) Dépistage de la déficience visuelle chez les personnes
âgéesCanadá 55 años, (revisión sistemática y recomendaciones,
1
Ministre des Approvisionnements et Services Canada: Guide Canadien
de Medicine clinique et préventive, 1994 >80 años
15
Ministre des Approvisionnements et Services Canada: Guide Canadien
de Medicine clinique et préventive, 1994 64 años
35
Ministre des Approvisionnements et Services Canada: Guide Canadien
de Medicine clinique et préventive, 1994 85 años
50
ESTIMACIONES PARA LA COMUNIDAD VALENCIANA PROYECTANDO ESTUDIOS RECIENTES SOBRE LA
DMAE (los datos contenidos en el cuadro se refieren a número de personas)
Población susceptible de intervención
de más de 45 años tras examen oftalmológico
Demanda expresada (no alentada) por
importante pérdida visual (pacientes de
más de 45 años)
Población susceptible de intervención
de más de 70 años tras examen oftalmológico
Demenda expresada (no alentada) por
importante pérdida visual (pacientes de
más de 70 años)
Prevalencia estimada máxima actual
Incidencia estimada
8.000 pacientes
2.000 /pacientes-año
1.250 - 3.000 pacientes
400 – 1.000 /pacientes-año
4.000 pacientes
1.500 /pacientes-año
600 – 1.250 pacientes
350 – 650 /pacientes-año
Pá gina 18 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
APÉNDICE F
ESTIMACIÓN DE COSTES DE LOS PRODUCTOS, PROCEDIMIENTOS Y EQUIPOS INVOLUCRADOS EN LA
TÉCNICA A PESETAS CONSTANTES (2001) SEGÚN LOS ESTUDIOS REFERENCIADOS
BASE DEL ESTUDIO PARA LA PROYECCIÓN
(Los datos se expresan en pesetas)
Dosis de verteporfín
Equipo láser
(amortización ± 25 sesiones)
REINO UNIDO
NORUEGA
USA
195.000
5.500.000
263.000
2.000.000
(adaptación cabezal)
262.000
Angiógrafo
7.800.000
(compartido)
Otros equipos
1.500.000
(compartido)
260.000
195.000
Sesión láser
Estancia y personal
Sesión excepto fármaco
61.380 (reembolso Medicare)
Factura actual por sesión
ESTIMACIÓN
VALENCIA
175.000
6.000.000
8.000.000
(5’5 M revelado diferido; 14’5 M digital)
1.000.000
(compartido)
230.000
70.000
Posibilidad de ajustar a 1.000.000 para 4 sesiones
300.000
ESCENARIOS DE COSTES PREVISTOS PARA LA ASUNCIÓN DE LA PREVALENCIA EXISTENTE Y POSTERIOR
INCIDENCIA AL RITMO PREVISTO
ESTIMACIÓN CON FACTURACIÓN ACTUAL (300.000 pts por sesión)
COSTE ESTIMADO DE TRATAMIENTOS
EN MILLONES DE PESETAS
(DMAE uniocular o bilateral en la misma
sesión)
población diana potencial de más de 45
años
Demanda expresada (no alentada) para
más de 45 años
población diana potencial de más de 75
años
Demanda expresada (no alentada) para
más de 75 años
Coste primer
año
Coste segundo
año
9.600
4.800
14.400
1.500 - 3.600
750 - 1.800
2.250 - 5.400
4.800
2.400
7.200
720 - 1.500
360 - 750
1.080 - 2.250
Coste primer
año
Coste segundo
año
8.000
4.000
12.000
1.250 – 3.000
625 – 1.500
1.875 – 4.500
4.000
2.000
6.000
600 – 1.250
300 -625
900 – 1.875
Facturación total
ESTIMACIÓN CON FACTURACIÓN AJUSTADA
COSTE ESTIMADO DE TRATAMIENTOS
EN MILLONES DE PESETAS
(DMAE uniocular o bilateral en la misma
sesión)
población diana potencial de más de 45
años
Demanda expresada (no alentada) para
más de 45 años
población diana potencial de más de 75
años
Demanda expresada (no alentada) para
más de 75 años
Facturación total
Pá gina 19 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXOS
Relación de anexos:
1.-
febrero 2001. ANEXO DOCUMENTAL DE EXPLOTACIÓN DE
DATOS DE CONCIERTOS ........................................................ 21
2.-
febrero 2001. ANEXO DOCUMENTAL DE LA BÚSQUEDA
BIBLIOGRÁFICA EN LA CDR (en sus bases de datos DARE,
NHS EED y HTA) ................................................................... 29
3.-
febrero 2001. ANEXO DOCUMENTAL DE LA BÚSQUEDA
BIBLIOGRÁFICA EN MEDLINE A TRAVÉS DE LA NATIONAL
LIBRARY OF MEDICINE (bajo criterios: “photodynamic therapy degeneration macular”) ..................................................... 31
4.-
febrero 2001. ANEXO DOCUMENTAL DE LA BÚSQUEDA
BIBLIOGRÁFICA EN MEDLINE A TRAVÉS DE LA NATIONAL
LIBRARY OF MEDICINE (bajo criterios: “prevalence blindness
older” or “epidemiology maculopathy” or “prevalence aged
macular”) ............................................................................ 36
5.-
marzo 2000. SMM-REPORT NR.3/2000 THE NORWEGIAN
CENTRE FOR HEALTH TECHNOLOGY ASSESSMENT Photodynamic therapy for age-related macular degeneration.................. 57
6.-
1.994: GUIDE CANADIEN DE MEDICINE CLINIQUE ET
PRÉVENTIVE. Dépistage de la deficience visuelle chez les personnes âgées ....................................................................... 68
7.-
enero 2000. NATIONAL HORIZON SCANNING CENTRE. Photodynamic therapy for age-related macular degeneration. ............. 83
8.-
Issue 1, 2001. Oxford. THE COCHRANE LIBRARY (COCHRANE
REVIEW). Photodynamic therapy for neovascular age-related
macular degeneration. ........................................................... 90
9.-
enero 2001. Irveng Arons in OCULAR SURGERY NEWS. Visudyne looks promising for treating wet AMD ..............................108
10.-
Información registrada en la FDA sobre el verteporfin ...............113
11.-
Información registrada en la EMEA sobre el verteporfin .............126
Pá gina 20 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO
1
Pá gina 21 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO DOCUMENTAL DE EXPLOTACIÓN DE DATOS DE CONCIERTOS
CENTRO ORIGEN DE PROPUESTA
H. LA RIBERA
H. GENERAL DE VALENCI
H. ARNAU DE VILANOVA
H. GENERAL DE ELDA
H. FRANCESC DE BORJA
H. LLUIS ALCANYIS
H. LA FE
H. CLINICO UNIVERSITA
C.E. JUAN LLORENS
H. GENERAL DE CASTELL
H. DE ONTINYENT
H. DR. PESET
H. SAN JUAN DE ALICAN
H. VIRGEN LIRIOS
H. DE SAGUNT
C.E. MONTEOLIVETE
H. DE REQUENA
H. MARINA ALTA DE DEN
H. DE SAGUNTO
H. VALENCIA AL MAR
ESCA-VALENCIA AREA 7
H. MARINA BAJA
H. GENERAL DE ALICANT
Total
Frecuencia
porcentaje
30
23
23
18
15
12
10
10
7
6
5
5
5
4
3
3
3
2
2
1
1
1
1
15.8
12.1
12.1
9.5
7.9
6.3
5.3
5.3
3.7
3.2
2.6
2.6
2.6
2.1
1.6
1.6
1.6
1.1
1.1
.5
.5
.5
.5
190
100.0
Porcentaje
acumulado
15.8
27.9
40.0
49.5
57.4
63.7
68.9
74.2
77.9
81.1
83.7
86.3
88.9
91.1
92.6
94.2
95.8
96.8
97.9
98.4
98.9
99.5
100.0
Pá gina 22 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
CENTRO DESTINO
Frecuencia
porcentaje
CLINICA VIRGEN DEL CONSUELO
NO CONSIGNADO
INSTITUTO ALIO
INSTITUTO OFTALMOLOGICO DE
ALICANTE
CERE
INSTITUTO MICROCIRUGIA OCULAR
137
45
3
72.1
23.7
1.6
Porcentaje
acumulado
72.1
95.8
97.4
3
1.6
98.9
1
1
.5
.5
99.5
100.0
Total
190
100.0
ESTIMACION POR CONCIERTOS
Porcentaje
Frecuencia porcentaje
acumulado
SI ACEPTADO
110
57.9
57.9
NO ACEPTADO
80
42.1
100.0
Total
190
100.0
AÑO Y MES DE ESTIMACIÓN
Frecuencia
porcentaje
Porcentaje
acumulado
2000-01
2000-02
2000-03
2000-04
2000-05
2000-06
2000-07
2000-08
2000-09
2000-10
2000-11
2000-12
2001-01
2001-02
10
11
17
16
20
17
31
38
14
2
3
2
7
2
5.3
5.8
8.9
8.4
10.5
8.9
16.3
20.0
7.4
1.1
1.6
1.1
3.7
1.1
5.3
11.1
20.0
28.4
38.9
47.9
64.2
84.2
91.6
92.6
94.2
95.3
98.9
100.0
Total
190
100.0
MESGRUPO
de VII-2000 hasta hoy
de inicio 2000 a VI-2000
Total
Frecuencia
porcentaje
99
91
52.1
47.9
190
100.0
Porcentaje
acumulado
52.1
100.0
Pá gina 23 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 24 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 25 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 26 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ESTIMACION POR CONCIERTOS / tiempo de resolución
(tiempo de resolución dicotomizado:: hasta junio-2000, desde julio 2000)
MESGRUPO
de inicio 2000
a VI-2000
ESTIMACION
POR
CONCIERTOS
NO
ACEPTADO
SI
ACEPTADO
Total
Recuento
% de ESTIMACION
POR CONCIERTOS
% de MESGRUPO
Recuento
% de ESTIMACION
POR CONCIERTOS
% de MESGRUPO
Recuento
% de ESTIMACION
POR CONCIERTOS
% de MESGRUPO
Total
de VII2000 hasta
febrero
2001
22
58
80
27.5%
72.5%
100.0%
24.2%
69
58.6%
41
42.1%
110
62.7%
37.3%
100.0%
75.8%
91
41.4%
99
57.9%
190
47.9%
52.1%
100.0%
100.0%
100.0%
100.0%
Prueba de chi-cuadrado significativa para p<0’0001
Pá gina 27 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 28 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO
2
Pá gina 29 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO DOCUMENTAL DE LA BÚSQUEDA BIBLIOGRÁFICA
EN LA CDR (en sus bases de datos DARE, NHS EED y HTA)
CONSTRUCTO DEL SONDEO: criterios no restrictivos para cualquier campo: “photodynamic Y therapy”
RESULTADO: 11 referencias
TÍTULO
ORIGEN
Photodynamic therapy - Summary. Canadian Coordinating Office for Health Technology Assessment (CCOHTA) 1994.
Photodynamic therapy for skin and mucosal can- Medicare Services Advisory Committee (MSAC)
cer. 1999 (MSAC application 1008: Final Assessment
Report): pp.16.
Photodynamic therapy in gastroenterology and Comite de Evaluation et de Diffusion des InnovaENT (systematic review, expert panel).
tions Technologiques (CEDIT) 1999.
Photodynamic therapy for neovascular age- Wormald R, Evans J, Smeeth L. Wormald R, Evrelated macular degeneration.
ans J, Smeeth L. Photodynamic therapy for neovascular age-related macular degeneration.
(Cochrane Review). In: The Cochrane Library, Issue 4, 2000. Oxford: Update Software..
Multi-drug versus single agent chemotherapy for Huncharek M, Muscat J, Geschwind J F. Anticanhigh grade astrocytoma; results of a metacer Research 1998; 18(6B): 4693-4697.
analysis.
A systematic review of treatment modalities for
Thissen M R, Neumann M H, Schouten L J. Arprimary basal cell carcinomas. chives of Dermatology 1999; 135(10): 1177-1183.
Photodynamic therapy for age-related macular Seland JH, Bragadottir R, Hedels C, Syrdalen P,
degeneration. Holm S, Kjonniksen I. The Norwegian Centre for
Health Technology Assessment (SMM) 2000.
(SMM-Report 3/2000).
Photofrin(R) and photodynamic therapy of cancer
Agence d'Evaluation des Technologies et des
- systematic review (project).
Modes d'Intervention en Sante (AETMIS).
Photodynamic therapy of aged-related nuclear
Danish Institute for Health Technology Assessdegeneration (funded by DIHTA) - systematic rement (DIHTA).
view (project).
Photodynamic therapy (project). Medicare Services Advisory Committee (MSAC).
Photodynamic therapy for treatment of ageNational Horizon Scanning Centre (NHSC).
related macular degeneration - horizon scanning
review (project).
En gris: referencias electas
Pá gina 30 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO
3
Pá gina 31 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO DOCUMENTAL DE LA BÚSQUEDA BIBLIOGRÁFICA
EN LA NATIONAL LIBRARY OF MEDICINE
(a través de NLM el 15-II-2001 bajo criterios: “photodynamic therapy degeneration
macular”)
CONSTRUCTO DEL SONDEO: (("photochemotherapy"[TÉRMINOS MeSH] O photodynamic therapy[Texto]) Y ("macular degeneration"[TÉRMINOS MeSH] O degeneration macular[Texto]))
RESULTADO: 31 referencias
TÍTULO DEL ARTÍCULO
ORIGEN
Extracts from "clinical evidence": age re- Aberdeen Royal Hospilated macular degeneration. tals NHS Trust, Aberdeen. [email protected]
AUTORES
Arnold JJ;
Sarks SH;
Photodynamic therapy with verteporfin
(Visudyne) for macular degeneration.
IDIOMA
REFERENCIA DE REVISTA
eng
BMJ 2000 Sep 23;321(7263):741-4.
eng
Med Lett Drugs Ther 2000 Sep
4;42(1086):81-2.
Update on photodynamic therapy.
Wills Eye Hospital,
Philadelphia, Pennsylvania 19107, USA.
Regillo CD;
eng
Curr Opin Ophthalmol 2000
Jun;11(3):166-70.
Ophthalmology update for the primary
practitioner. Part II. Therapeutic management of age-related macular degeneration.
William Beaumont
Hospital, Royal Oak,
Michigan, USA.
Sarrafizadeh
R; Trese MT;
eng
Dis Mon 2000 Aug;46(8):533-43.
No efficacious treatment for age-related
macular degeneration.
Department of Ophthalmology, Algemeen
Ziekenhuis Sint-Jozef,
Turnhout, Belgium.
Roodhooft J;
eng
Bull Soc Belge Ophtalmol
2000;276(8):83-92.
Potocky M;
Trnavec B;
slo
Bratisl Lek Listy 2000;101(4):231-3.
eng
Mayo Clin Health Lett 2000
Feb;18(2):4.
[Etiopathogenesis of age-related macular
degeneration and present possibilities of
treatment]
New treatment for macular degeneration
being tested.
Age-related macular degeneration: update
for primary care.
Southern California
Permanente Medical
Group, Baldwin Park,
California, USA.
Fong DS;
eng
Am Fam Physician 2000 May
15;61(10):3035-42.
Photodynamic therapy for neovascular 'Glaxo' Department of
age-related macular degeneration. Ophthalmic Epidemiology, Institute of Ophthalmology (UCL) and
Moorfields Eye Hospital, City Road, London,
UK, EC1V 2PD.
Wormald R;
Evans J;
Smeeth L;
eng
Cochrane Database Syst Rev
2000;61(2):CD002030.
Indocyanine green angiography and retinal University Eye Hospital
sensitivity after photodynamic therapy of Luebeck, Medical Unisubfoveal choroidal neovascularization. versity, Luebeck, Germany.
SchmidtErfurth U;
eng
Semin Ophthalmol 1999 Mar;14(1):3544.
Department of Clinical Donati G; KaNeurosciences, Uni- petanios AD;
versity Hospitals of Pournaras CJ;
Geneva, Geneva,
Switzerland.
eng
Semin Ophthalmol 1999 Mar;14(1):210.
ger
Ophthalmologe 2000 Feb;97(2):154-6.
Principles of treatment of choroidal neovascularization with photodynamic therapy in age-related macular degeneration.
[Vitreoretinal Update Meeting 1999. Conference of the American Academy of Ophthalmology, Orlando, Florida, 2223/10/1999]
UniversitatsAugenklinik, Mainz.
Augustin AJ;
Pá gina 32 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
TÍTULO DEL ARTÍCULO
ORIGEN
Texaphyrins: new drugs with diverse clini- Department of Chemiscal applications in radiation and photodytry & Biochemistry,
namic therapy.
University of Texas,
Austin 78712, USA.
[email protected]
REF.: ACEMSA/SET/AC/ac
febrero-2001
AUTORES
IDIOMA
REFERENCIA DE REVISTA
Sessler JL;
Miller RA;
eng
Biochem Pharmacol 2000 Apr
1;59(7):733-9.
Photodynamic therapy with verteporfin
(Visudyne): impact on ophthalmology and
visual sciences.
Retinal Vascular Center, Wilmer Ophthalmological Institute,
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2010, USA.
Bressler NM;
Bressler SB;
eng
Invest Ophthalmol Vis Sci 2000
Mar;41(3):624-8.
Age-related macular degeneration.
Department of Ophthalmology, Scheie Eye
Institute, University of
Pennsylvania Health
System, Philadelphia
19104-2689, USA.
Fine SL; Berger JW; Maguire MG; Ho
AC;
eng
N Engl J Med 2000 Feb
17;342(7):483-92.
[Confocal indocyanine green angiography Augenklinik Universitat
Schmidtwith 3-dimensional topography. Results in
Lubeck.
Erfurth U;
choroid neovascularization (CNV)]
Noack J; Teschner S;
Birngruber R;
ger
Ophthalmologe 1999 Dec;96(12):797804.
Help for macular degeneration.
McDonald HR;
eng
Health News 1999 Dec 15;5(15):1-2.
Vision researchers seek to be armed
against damaging ARMD. Age-related
macular degeneration.
Voelker R;
eng
JAMA 1999 Nov 10;282(18):1711-2.
[Present and future treatment of agerelated macular degeneration]
Centres Hospitaliers Verougstraete
Universitaires BrugC;
mann et Saint-Pierre,
Bruxelles.
fre
Bull Soc Belge Ophtalmol
1999;273(18):79-101.
Photodynamic therapy: a new approach to
the treatment of choroidal neovascularization secondary to age-related macular degeneration.
Glaser-Murphy Retina Wu L; Murphy
Treatment Center,
RP;
Chevy Chase, Maryland 20815, USA.
eng
Curr Opin Ophthalmol 1999
Jun;10(3):217-20.
Photodynamic therapy with verteporfin is
effective for selected patients with neovascular age-related macular degeneration.
Fine SL;
eng
Arch Ophthalmol 1999
Oct;117(10):1400-2.
eng
Arch Ophthalmol 1999
Oct;117(10):1329-45.
Photodynamic therapy of subfoveal choroidal neovascularization in age-related
macular degeneration with verteporfin:
one-year results of 2 randomized clinical
trials--TAP report. Treatment of agerelated macular degeneration with photodynamic therapy
Pá gina 33 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
TÍTULO DEL ARTÍCULO
ORIGEN
REF.: ACEMSA/SET/AC/ac
febrero-2001
AUTORES
IDIOMA
REFERENCIA DE REVISTA
Photodynamic therapy with verteporfin for
choroidal neovascularization caused by
age-related macular degeneration: results
of retreatments in a phase 1 and 2 study.
Retina Department,
SchmidtUniversity Eye HospiErfurth U;
tal, Lubeck, Germany. Miller JW; Sicuschmidterkenberg M;
[email protected] Laqua H; Barluebeck.de
bazetto I;
Gragoudas
ES; Zografos
L; Piguet B;
Pournaras CJ;
Donati G;
Lane AM;
Birngruber R;
van den Berg
H; Strong HA;
Manjuris U;
Gray T; Fsadni M; Bressler
NM;
eng
Arch Ophthalmol 1999
Sep;117(9):1177-87.
Photodynamic therapy with verteporfin for
choroidal neovascularization caused by
age-related macular degeneration: results
of a single treatment in a phase 1 and 2
study.
Retina Service, MasMiller JW;
sachusetts Eye and
SchmidtEar Infirmary, Harvard Erfurth U; SicMedical School, Boskenberg M;
ton, USA. jwmil- Pournaras CJ;
[email protected] Laqua H; Barbazetto I;
Zografos L;
Piguet B; Donati G; Lane
AM; Birngruber R; van den
Berg H;
Strong A;
Manjuris U;
Gray T; Fsadni M; Bressler
NM; Gragoudas ES;
eng
Arch Ophthalmol 1999
Sep;117(9):1161-73.
SchmidtErfurth U;
ger
Klin Monatsbl Augenheilkd 1998
Dec;213(6):aA11-5.
Department of Clinical Chong NH; BiOphthalmology, Instird AC;
tute of Ophthalmology
(UCL), Moorfields Eye
Hospital, London.
eng
Br J Ophthalmol 1998
Dec;82(12):1441-3.
Age-related macular degeneration: a re- Indiana University Ma- Ciulla TA; Daview of experimental treatments. cular Degeneration Cli- nis RP; Harris
nic and Research CenA;
ter, Department of
Ophthalmology, Indiana University School
of Medicine,
eng
Surv Ophthalmol 1998 SepOct;43(2):134-46.
[Photodynamic therapy--a conservative al- Augenklinik, Medizinisternative in treatment of exudative macular che Universitat Lubeck.
degeneration]
Alternative therapies in exudative age related macular degeneration.
[Use of complex compression diagnostic
test for defining the indications for surgical
treatment of atherosclerotic chorioretinal
dystrophy]
Basinskii SN;
Krasnogorskaia VN; Solomina EV;
rus
Vestn Oftalmol 1998 JanFeb;114(1):36-8.
[New method of atherosclerotic macular
dystrophies treatment]
Basinskii SN;
Krasnogorskaia VN;
rus
Vestn Oftalmol 1997 NovDec;113(6):17-9.
Solberg Y;
Belkin M;
heb
Harefuah 1997 Oct 2;133(7-8):268-72,
335.
[Advances in ophthalmological photodynamic therapy]
Goldschleger Eye Research Institute, Tel
Aviv University.
Pá gina 34 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
TÍTULO DEL ARTÍCULO
ORIGEN
Photosensitizers in photodynamic therapy.
Quadra Logic Technologies, Inc, Vancouver,
British Columbia, Canada.
REF.: ACEMSA/SET/AC/ac
febrero-2001
AUTORES
Levy JG;
IDIOMA
eng
REFERENCIA DE REVISTA
Semin Oncol 1994 Dec;21(6 Suppl
15):4-10.
Pá gina 35 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO
4
Pá gina 36 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO DOCUMENTAL DE LA BÚSQUEDA BIBLIOGRÁFICA
EN LA NATIONAL LIBRARY OF MEDICINE
(a través de NLM el 22-II-2001 bajo criterios: “prevalence blindness older” or “epidemiology maculopathy” or “prevalence aged macular”)
CONSTRUCTO DEL SONDEO:
CRITERIO A: (((((("epidemiology"[Subheading] OR "prevalence"[MeSH Terms])
OR "epidemiology"[MeSH Terms]) OR "Prevalence"[MeSH Terms]) OR
PREVALENCE[Text Word]) AND ("blindness"[MeSH Terms] OR BLINDNESS[Text
Word])) AND OLDER[All Fields])
CRITERIO B: ((("epidemiology"[Subheading] OR "epidemiology"[MeSH Terms])
OR EPIDEMIOLOGY[Text Word]) AND MACULOPATHY[All Fields])
CRITERIO C: (((((("epidemiology"[Subheading] OR "prevalence"[MeSH Terms])
OR "epidemiology"[MeSH Terms]) OR "Prevalence"[MeSH Terms]) OR prevalence[Text Word]) AND ("aged"[MeSH Terms] OR aged[Text Word])) AND macular[All Fields])
RESULTADO: 126 referencias para A; 128 referencias para B; 471 para C
224 referencias electas para su lectura, cotejo y análisis:
CRITERIO A CRITERIO B CRITERIO C
CRITERIO A
CRITERIO B
CRITERIO C
6
1
12
TITULO
1
5
14
ORIGEN
12
14
186
AUTORES
IDIOMA
TOTAL
CRITERIOS
19
20
215
REVISTA
CRIT.
Visual acuity in a population aged 70
Department of Oph- Hirvela H; Layears or older; prevalence and causes thalmology, University
atikainen L;
of visual impairment.
of Oulu, Finland.
eng
Acta Ophthalmol Scand 1995
Apr;73(2):99-104.
A
Knowledge and beliefs about common
Department of Opheye diseases. thalmology and Public
Health, University of
Sydney, New South
Wales, Australia.
Attebo K;
Mitchell P;
Cumming R;
Smith W;
eng
Aust N Z J Ophthalmol 1997
Nov;25(4):283-7.
A
Dana Center for Preventive Ophthalmology, Johns Hopkins
School of Medicine,
Baltimore, MD 212879019, USA.
[email protected]
West SK;
eng
Epidemiol Rev 2000;22(1):64-70.
A
Visual impairment in nursing home
Department of Ophresidents: the Blue Mountains Eye thalmology, University
Study.
of Sydney, NSW.
[email protected]
u
Mitchell P;
Hayes P;
Wang JJ;
eng
Med J Aust 1997 Jan 20;166(2):73-6.
A
Looking forward to 20/20: a focus on
the epidemiology of eye diseases.
Pá gina 37 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
TITULO
ORIGEN
Functional blindness and visual imEpidemiology, Depairment in older adults from three mography and Biomecommunities. try Program, National
Institute on Aging, National Institutes of
Health, Bethesda
20892.
AUTORES
REF.: ACEMSA/SET/AC/ac
febrero-2001
IDIOMA
REVISTA
CRIT.
Salive ME;
Guralnik J;
Christen W;
Glynn RJ;
Colsher P;
Ostfeld AM;
eng
Ophthalmology 1992
Dec;99(12):1840-7.
A
Canavan YM;
Jackson AJ;
Stewart A;
eng
Ulster Med J 1997 Nov;66(2):92-5.
A
Department of Oph- Wang JJ; Fothalmology, the Uni- ran S; Mitchell
versity of Sydney,
P;
New South Wales,
Australia.
eng
Clin Experiment Ophthalmol 2000
Aug;28(4):268-73.
AB
Prevalence and visual consequences
Department of Oph- Laatikainen L;
of macular changes in a population thalmology, University
Hirvela H;
aged 70 years and older.
of Oulu, Finland.
eng
Acta Ophthalmol Scand 1995
Apr;73(2):105-10.
AC
A model of the incidence and conseScheie Eye Institute,
quences of choroidal neovascularizaDepartment of Ophtion secondary to age-related macular thalmology, University
degeneration. Comparative effects of
of Pennsylvania
current treatment and potential pro- Health System, Philaphylaxis on visual outcomes in highdelphia, USA.
risk patients.
Lanchoney
DM; Maguire
MG; Fine SL;
eng
Arch Ophthalmol 1998
Aug;116(8):1045-52.
AC
Age-specific prevalence and causes of Department of EpideKlaver CC;
blindness and visual impairment in an miology and BiostatisWolfs RC;
older population: the Rotterdam Study. tics, Erasmus Univer- Vingerling JR;
sity Medical School, Hofman A; de
Rotterdam, The NethJong PT;
erlands.
eng
Arch Ophthalmol 1998
May;116(5):653-8.
AC
Causes of blindness and visual im- Wilmer Eye Institute,
pairment in a population of older
The Johns Hopkins
Americans: The Salisbury Eye Evalua- University, 600 N Woltion Study. fe St, Room 116, Baltimore, MD 21287,
USA. [email protected]
Munoz B;
West SK; Rubin GS;
Schein OD;
Quigley HA;
Bressler SB;
BandeenRoche K;
eng
Arch Ophthalmol 2000
Jun;118(6):819-25.
AC
Prevalence of serious eye disease and Southampton General
visual impairment in a north London
Hospital, Southamppopulation: population based, cross
ton SO16 6YD.
sectional study.
Reidy A; Minassian DC;
Vafidis G; Joseph J; Farrow S; Wu J;
Desai P; Connolly A;
eng
BMJ 1998 May 30;316(7145):1643-6.
AC
Munier A;
Gunning T;
Kenny D; O'Keefe M;
eng
Br J Ophthalmol 1998 Jun;82(6):6303.
AC
Dept. of Ophthalmol- Hod Y; Corcia
ogy, Carmel Medical
Y; Yassur Y;
Center Haifa.
Geyer O;
heb
Harefuah 2000 Feb 15;138(4):276-8,
342.
AC
[Evaluation of moderate and severe
Centre Hospitalier Cohen D; Sarvisual impairments in patients attendRegional d'Orleans, tral M; Nounou
ing an ophthalmology clinic. A pros- Service d'Ophtalmolo- P; Hamar M;
pective study of 1,172 patients]
gie, BP 2439, 45032 Drouard ME;
Orleans Cedex 1.
El Alamy A;
Bendeddouche K;
fre
J Fr Ophtalmol 2000 May;23(5):43743.
AC
Visual impairment in Northern Ireland.
Age-specific prevalence and causes of
bilateral and unilateral visual impairment in older Australians: the Blue
Mountains Eye Study.
Causes of blindness in the adult population of the Republic of Ireland.
[Causes of blindness in Israel]
Department of Opthalmology, Royal Victoria Hospital, Belfast.
National Council for
the Blind of Ireland,
Dublin, Ireland.
Pá gina 38 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
TITULO
ORIGEN
AUTORES
REF.: ACEMSA/SET/AC/ac
febrero-2001
IDIOMA
REVISTA
CRIT.
The prevalence of blindness and vis- Department of InternaTielsch JM;
ual impairment among nursing home
tional Health, Johns Javitt JC; Coresidents in Baltimore.
Hopkins University leman A; Katz
School of Hygiene and J; Sommer A;
Public Health, Baltimore, MD 212052103, USA.
eng
N Engl J Med 1995 May
4;332(18):1205-9.
AC
Visual acuity and the causes of visual
Department of Oph- Attebo K; Mitloss in Australia. The Blue Mountains thalmology, University chell P; Smith
Eye Study. of Sydney, Australia.
W;
eng
Ophthalmology 1996 Mar;103(3):35764.
AC
The cause-specific prevalence of visual impairment in an urban population.
The Baltimore Eye Survey.
Dana Center for Preventive Ophthalmology, Johns Hopkins
University School of
Medicine, Baltimore,
USA.
Rahmani B;
Tielsch JM;
Katz J;
Gottsch J;
Quigley H;
Javitt J; Sommer A;
eng
Ophthalmology 1996
Nov;103(11):1721-6.
AC
Age-related macular degeneration.
Department of Ophthalmology, University
of Birmingham, UK.
O'Shea JG;
eng
Postgrad Med J 1998
Apr;74(870):203-7.
AC
Relationship of ocular factors to the
incidence of age-related maculopathy.
LeClaire JE;
eng
Arch Ophthalmol 1998
Oct;116(10):1404-5.
B
Cataract and age-related maculopathy: the Blue Mountains Eye Study.
University of Sydney, Wang JJ; MitDepartment of Ophchell PG;
thalmology, Sydney, Cumming RG;
Australia.
Lim R;
eng
Ophthalmic Epidemiol 1999
Dec;6(4):317-26.
B
Exposure to diagnostic x-rays and inDepartment of Ophcident age-related eye disease. thalmology and Visual
Sciences, University
of Wisconsin Medical
School, Madison,
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TITULO
REVISTA
CRIT.
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TITULO
Visible light and risk of age-related
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ORIGEN
AUTORES
REF.: ACEMSA/SET/AC/ac
febrero-2001
IDIOMA
REVISTA
CRIT.
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ANEXO
5
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Photodynamic therapy for age-related macular degeneration
SMM-report nr.3/2000 The Norwegian Centre for Health Technology Assessment
The Steering committee of the Norwegian Centre for Health Technology Assessment (SMM) decided in
December 1999 to assess photodynamic therapy for age-related macular degeneration. This is a new therapeutic modality and the Steering committee wished to perform an early evaluation before the method
become widespread in the Norwegian health system. SMM established an expert group that started their
work in February 2000.
The expert group was constituted by:
Professor Johan H. Seland (chairman), Haukeland University Hospital
Chief Departmental Physician Ragnheidur Bragadottir, Ullevål University Hospital
Senior Physician Christian Hedels, Vestfold County Hospital
Professor Per Syrdalen, The National Hospital
Dr. Søren Holm, Centre for Social Ethics and Policy, University of Manchester, was invited to make an
ethical consideration on the treatment of age-related macular degeneration. His contribution is found in
Chapter 10.
Medical consultant Inge Kjønniksen, SMM, has been project leader, assisted by medical consultant Krystyna Hviding. The report has been approved by the Steering committee for SMM.
Berit Mørland
Inge Kjønniksen
Director
Medical consultant
Content
1. Dictionary *
2. Summary *
3. Introduction *
4. Epidemiology *
5. Norwegian participation in clinical research *
6. Photodynamic treatment of subfoveal CNV *
7. Equipment, competence and resources needed in Norway *
8. Organisational consequences *
9. Cost analyses, social consequences *
10. Ethical considerations *
11. Alternative treatments *
12. Indication for photodynamic treatment in other eye diseases *
13. Conclusions *
14. References *
1. Dictionary
AMD Age-related macular degeneration
ARM Age-related maculopathy – precursor to AMD
CNV Choroidal neovascularisation/newly formed and pathological vessels constituting membranes in the area of the visual acuity centre.
DRG Diagnosis-related groups – system for calculating treatment costs in hospitals
Fovea Area in the retina responsible for visual acuity
ISF Activity-based funding – funding based on DRG
Classic Cluster of blood vessels that has penetrated the pigment epithelium
Mixed Mixture of "occult" and "classic"
NOK Norwegian monetary unit, 1 ECU = 8.2 NOK
Occult Cluster of blood vessels beneath the pigment epithelium
PDT Photodynamic therapy
RTV Rikstrygdeverket/The National Insurance Institution – funds all out-patient treatment except day-surgery
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TAP-study Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP)
trial (phase III study including patients with a mixture of classic and occult lesions)
VIP-study Verteporfin in Photodynamic Therapy (VIP) trial (phase III study with patients having only classic or occult lesions)
2. Summary
Age-related macular degeneration is a leading cause of loss of vision among elderly, and these
patients have previously lacked therapeutic options. The disease can be either nonexudative (dry)
or exudative. This report deals with photodynamic therapy, which is a new therapeutic modality
for the most serious exudative subform. Untreated these patients undergo rapid loss of their central vision due to uncontrolled blood vessel proliferation in a process called choroidal neovascularisation (CNV).
Several new therapeutic options are presently being tested to control the disease, and photodynamic therapy has so far proven most promising. The rationale is to inject photoreactive drugs,
which are concentrated in the abnormal blood vessels in the eye fundus. Subsequently, these
vessels are illuminated with light of a specific wavelength thereby transforming the drugs to become reactive and to exert local tissue toxicity. The aim is to destroy abnormal vessels and to
prevent further blood vessel proliferation.
Several photoreactive drugs are being developed, but published results from clinical phase-III
trials are only available for Verteporfin. Recently, the 2-year results were published at a symposium. The overall results showed that after 24 months of therapy had 47% of the treated patients
a loss of vision of three reading lines (Snellen lines) or more, whereas corresponding number for
the control group was 62%. Thus, 15% of the patients received benefit from the treatment. Thirteen percent of the patients experienced an improvement in visual acuity. Sub-group analysis indicated that beneficial effects were mainly confined to patients having predominantly "classic"
lesions, of which 28% were treated with positive results. The therapy resulted in few adverse effects.
Long term efficiency beyond 2-year of treatment is not known, and the therapy do not benefit
patients with advanced disease. In Norway, approximately 800 new patients having mainly
"classic" lesions are yearly eligible for the treatment. Possibly, these patients will need on average 3-4 and approximately 2 sessions during the first and second year of treatment, respectively.
The report also contains simplified evaluations of cost-analyses and social consequences together with descriptions of alternative treatment regimens. It is advocated that many elderly have
a reduced level of physical activity that benefits from adequate vision (reading etc.). Even with
small therapeutic gains, improved vision could therefore be very important for these patients.
The main conclusions are that photodynamic therapy is so far the most effective treatment for
exudative age-related macular degeneration. The therapy is only effective on a subset of the patients. More data is needed on long-term efficiency before conclusions whether the therapy
should be widely implemented or not.
3.
Introduction
Macular degeneration is a retinal disease involving the macula (yellow spot). Central in this area
is a pit called the fovea, which is responsible for visual acuity. The illness affects two age
groups: 1) A rarely seen and hereditary juvenile form, and 2) the age-related form mainly affecting people above 60 years and increasing in frequency with age. The underlying cause of macular degeneration is unknown. The exact number of people in Norway with the disease is uncertain, but estimates have been made that about 20% of the population above 85 years are more or
less affected.
Age-related macular degeneration (AMD) can be either nonexudative (dry) or exudative. The
nonexudative form involves a variety of presentations and develops slowly over years with gradual visual impairment. The condition constitutes about 90% of all cases of macular degeneration,
and lacks efficient treatment. It is important that patients with the dry form are regularly examined since the condition can progress to the more serious exudative form.
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Patients having the exudative form rapidly undergo loss of their central vision. Small, but leaky
and abnormal blood vessels form under the macula in a process called choroidal neovascularisation (CNV). These vessels constitute membranes, they leak fluid and may rupture. The result is
scar formation and macular damage. Untreated the process will lead to marked visual impairment over a period of 3 – 24 months. Peripheral vision will be intact, but the ability for example,
to read, drive cars and to recognise faces will be lost. The exudative form constitutes only 10%
of the patients, but is responsible for about 90% of all cases of severe visual impairment in patients with age-related macular degeneration. This report deals with a new therapy for this, the
most serious subform.
Many therapies have been tried for age-related macular degeneration, but few have been effective. Despite an unknown pathogenesis, control of neovascularisation is important. This can be
done with laser photocoagulation (using "hot" laser), however, this treatment has been shown
also to destroy the light-sensitive cells in the retina and can only be used on lesions outside the
fovea (that is, only about 10% of all patients with exudative form). The other 90% of the patients
have subfoveal damage (see Figure 1) and can therefore not be treated with traditional laser.
Thus, other treatment regimens have been tried including X-radiation, surgery, angiostatic drugs
and photodynamic therapy (see Chapter 11).
Figure 1(A): Fovea is centrally localised in the macula (circle). The localisation of CNV can be
completely or partly covered by the fovea (B) or outside the fovea (C). Conventional laser can be
used in alternative C. In B photodynamic therapy can be a therapeutic option.
4.
Epidemiology
The epidemiology of age-related macular degeneration has been poorly studied in Norway, and
data must therefore be extrapolated from population studies in Europe, USA and Australia (1-3).
The reported prevalences vary somewhat, but the differences can partly be explained with the
different methods and criteria used in the studies. The incidence and prevalence in Norway, probably, do not differ strongly from that reported in these countries.
The Beaver Dam Eye Study from USA (4) used their own classification system for the evaluation of retinal photographs and gave data for both prevalence and incidence. The study estimated
that the prevalence of exudative age-related macular degeneration is 1.2% in people 43 – 86
years of age. The 5-year incidence for the same group was 0.6%. Prevalence correlated strongly
with age increasing from 0.1% in people being 43-54 years and 7.5% for people over 75 years.
In people older than 85 years the prevalence is about 20%. Extrapolating the data found in The
Beaver Dam Eye Study to the Norwegian society (4.5 million inhabitants) gives a prevalence of
20 400 patients with exudative age-related macular degeneration in people older than 45 years
(incidence about 2,000 new patient per year). Of these 2,000 about 40% would meet the criteria
for photodynamic treatment, i.e., 800 new patients each year.
5.
Norwegian participation in clinical research
Haukeland Sykehus participates in a multi-center study together with eight European universities. The purpose is to investigate the prevalence of ARM and AMD (see dictionary) and to correlate the UV irradiation on the different latitudes, nutritional and antioxidative status. The study
has recently begun and is expected to enrol about 5-6,000 subjects. It is co-ordinated by Prof.
Fletcher, London School of Hygiene and Tropical Medicine, and data collection and analyses
will be finished by 2002/2003.
Presently in Norway three hospitals are involved in photodynamic trials (VIP- and TAP- studies,
see dictionary). These are The National Hospital, Vestfold County Hospital and Vest-Agder
County Hospital. The trials are partly funded by a drug company (Ciba Vision).
6.
Photodynamic treatment of subfoveal CNV
The premise of photodynamic therapy is to inject an inactive drug (prodrug) which accumulates
in diseased tissues. Irradiation with light of a specific wavelength activates the drug, and a selective release of free radicals leads to local cellular damage. The principle is known from other
medical specialities including cancer treatment.
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Table 1 summarises the different drugs in clinical trials and which clinical phase the drugs have
reached (5):
Table 1
Verteporfin
Visudyne
690nm, 150 J/cm2
2-year data from phase
III clinical studies
known
SnET2
Purlytin
664nm, 36-126 J/cm2
Currently in phase III
trial
Lutetium taxaphyrin
Lutex/Optrin
732nm, 75-125 J/cm2
Currently in phase I/II
trial
Mono-L-aspartyl chori- Npe6
664nm, 2,3-7,5 J/ cm2
In preclinical studies
ne e-6
ATX-S10
670nm, 7,4 J/ cm2
In preclinical studies
In case of photodynamic treatment of macular degeneration the drug is injected intravenously,
and the drug concentrates in endothelial cells in the CNV. After a washout-time the CNV is illuminated with nonthermal laser light. As opposed to traditional "hot" laser, nonthermal light
does not result in retinal damage. The light-activated drug selectively destroys CNV without
harming the overlying sensory retina, expectantly, to reduce vascular leakage and to stabilise or
increase visual acuity. Initial experience has shown that CNV can reappear, and that the treatment must be repeated several times per year.
Adverse effects
Adverse effects have been best studied and published for Verteporfin (6). Extravasal injection of
Verteporfin will lead to serious and painful skin lesions including necrosis. Such effects are difficult to avoid completely, but the incidence can be kept to a minimum by maintaining strict to
guidelines and thorough training. Transient visual disturbances and back pain can be experienced
by some during injection. Allergic reactions are rarely seen for Verteporfin (6).
Clinical phase III-studies
Twelve-month data from the TAP–study with subgroup analyses were published October 1999
(6). Two-year results from this study were presented at The Association for Research in Vision
and Ophthalmology (ARVO) yearly conference in Florida held in May this year (7). Notably, the
results sited below have not been subjected to publication in international peer-review journals.
A total of 403 patients with age-related macular degeneration were treated with photodynamic
therapy using Verteporfin and compared to 207 sham treated placebo patients. Mean age of participating patients was 75 years and the groups were comparable at the start of treatment. During
the first year the patients needed 3.4 treatments, reducing in frequency to 2.1 treatments in the
second year. The overall results showed that after 24 months 47% of the treated patients had a
visual loss of three lines or more of best corrected distant visual acuity measured on a standard
visual acuity chart, whereas the corresponding numbers from the control group was 62%. Thus,
15% of the patients received benefit from the treatment. Thirteen percent of the treated patients
had improvement in their visual acuity. The results showed a significant difference of the two
groups in favour of active treatment. The subgroup that showed best therapeutic response had
mainly classic lesions (Figure 2). Twenty-eight percent of these patients received beneficial
treatment effects. It is not known at the present stage if the treatment permanently will stop disease progression thereby resulting in better vision outcome compared to no treatment.
Only about 40% of the patients with exudative age-related macular degeneration have predominantly classic CNVs. The other 60% have fluorescein angiograms characterised as predominantly "occult" lesions. These patients receive no benefit from the treatment and in reality, still
lack a therapeutic option. Figure 2 illustrates the different types of CNV lesions. The 1-year results from another and related study (VIP-study) were released in May this year. Similarly, the
results indicate that patients with only occult lesions do not benefit from the treatment (8).
Figure 2
Figure 2 shows fluorescein angiographic subtypes of different CNV types: classic, occult and
mixed lesions containing both classic and occult components. The term "predominantly classic"
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is used to describe the latter subtype if the classic component is equal to or greater than 50% of
the area of the entire CNV lesion.
7.
Equipment, competence and resources needed in Norway
Ophthalmologists diagnose age-related macular degeneration after clinical examination. For
this the ophthalmologists usually have all necessary equipment.
Opticians meet potential patients with age-related macular degeneration in their daily practice
and evaluate their visual function. However, they do not have the expertise to diagnose and select patients for treatment, but they can be an important source of referral to specialists.
Selection of eligible patients requires standard diagnostic equipment in addition to camera to
perform fluorescein angiograms (= investigations of the blood circulation) of the eye retina.
Laser: Standard laser employed in other eye treatments cannot be used for photodynamic treatment. Each photodynamic drug requires a special wavelength generated by dedicated lasers.
These lasers must be bought or leased, and a 689 nm laser costs approximately (Nov. 1999):
NOK 101,000 (VAT excluded).
Competence: There will be a need to increase the interest for diagnostic services and therapy of
macular diseases. However, with the availability of new therapeutic options this interest might
be stimulated. The treatment can be performed in an outpatient setting, and can therefore be performed by qualified ophthalmologists outside hospitals. Economic incentives will also determine
whether this therapeutic modality will be available outside hospitals.
Resources: To perform necessary diagnosis and treatment in Norway there are 21 eye departments in public hospitals and 320 ophthalmologists. In addition there will be a need for personnel responsible for performing angiographies, intravenous drug administration, patient surveillance and laser treatment. Few eye departments have photographers in full-time positions. Each
patient will need a photographic investigation of his or her fundus and fluorescein angiographic
examination in addition to photodynamic treatment approximately every third month. Each examination/treatment will require about 2-4 hours spent by health care personnel.
Drug cost will, however, represent the major part of the medical expenses (see below).
8.
Organisational consequences
There is still lacking long-term evidence (exceeding two years) proving that photodynamic therapy results in significantly better visual acuity compared to placebo. Until such evidence has
been provided it would be natural to offer the treatment in a limited scale. If this treatment modality gives long-term benefits, it would be natural to offer the treatment and follow-up in all eye
departments in the country comparable to other eye diseases. The treatment could also be offered
by ophthalmologists outside hospitals.
In hospitals photodynamic therapy would increase the demand for diagnostic services, and
would thereby also influence the capacity of ophthalmologists and other departmental resources
for traditional tasks.
The diagnostic steps and principles of photodynamic therapy are not very different from other
eye procedures, and the need for special training should be moderate. If photodynamic therapy
should be offered widely, there will be a need to inform general practitioners and opticians.
9.
Cost analyses, social consequences
Exudative macular degeneration tapers off after 2-5 years if no treatment is given. In the end
most patients have permanently lost their central vision (9). This loss creates a need for assistive
devices (optical and electronoptical) and reduces the degree of independence in daily activities
of the involved patients.
Costs
Present costs
Patients with age-related macular degeneration have had limited therapeutic options, and most
public expenses have been connected to medical consultations and assistive devices. Patient in
the final phase of the illness will often need training and courses for blind people, home help or
need to be institutionalised. Central for Assistive Devices in Oslo informs that patients with agerelated macular degeneration constitute about 95% of all patients that receive assistive devices
for visual impairment, and that this probably is representative for the whole nation.
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Patients with age-related macular degeneration need both optical devices (magnifying glasses,
telescopes etc.) and electron optical devices (magnifying video-systems, reading machines). The
National Insurance Institution informs that in 1998 about NOK 49.4 million was given in support
for these kind of assistive devices, whereas NOK 57 million was given to the whole group of patients with visual handicaps. Electron optical devices, mainly magnifying video-systems constitutes about 80% of all expenses for this patient group (personal communication).
Cost of treatment with photodynamic therapy
Photodynamic therapy is a new modality and can lead to considerable changes in expenses in
this patient group, which today only receives practical support. Of the therapeutic agents that today are in clinical trials, only Verteporfin is commercially available.
Verteporfin is available in Norway only on named patient use, and a marketing authorisation has
been submitted. Drug needed for each treatment costs about NOK 13,000 from the pharmacies.
The initial results from the clinical trials show that each patient needs in average 5.5 treatments
during the first two years of treatment (TAP-study).
Table 2. Estimated drug expenses for the treatment of one eye with Verteporfin based on data from the TAP-study.
1. year
3.4
44,200
44,200
2. year
2.1
27,300
71,500
In addition, early costs of hospitals and personnel time are estimated to be NOK 5-10,000. Available data from the clinical trials do not allow more accurate calculation of treatment costs.
The costs described above are calculated per eye. While age-related macular degeneration is often a bilateral disease, the disease progression rarely follows the same time course in both eyes.
The majority of the patients will require separate treatment for each eye and the minority could
have their eyes treated simultaneously at a reduced cost. We have not included the latter scenario
into our calculations.
The hospitals fund these treatment costs through ordinary financial channels (ISF/DRG 36). Corresponding RTV-funding (see dictionary) for ophthalmologist in private practice does not exist.
With drug and personnel costs reaching about NOK 85,000 over a 2-year period few patients are
able to pay for the treatment themselves.
The yearly incidence in Norway is about 800 eligible patients available for photodynamic treatment. These patients will need in average 5.5 treatments during the first two years, i.e., 4,400
treatments, representing a yearly price of NOK 44 million in medical costs only. Drug costs dominate and changes in drug pricing will strongly influence overall costs.
Social consequences
As stipulated above the total treatment costs approximately NOK 85,000 per patient per eye during the first two years of treatment. In addition comes the continued need for assistive devices
for people with reduced vision due to the disease, and the treatment will probably not result in
overall savings.
This is a group of patients at relatively advanced age, and the greatest health gain will be an increased quality of life experienced by the patients. Savings due to the new treatment are difficult
to estimate. If photodynamic therapy saves visual acuity for longer times, overall savings may in
the end be reached. Preliminary results are promising, and in the future the patients may need
less home help and postponed institutionalisation.
Quality of life
A study of 86 elderly patients with age-related macular degeneration found that the illness had a
negative influence on their quality of life, functional status and psychological welfare. The patients conducted several well-recognised tests (Quality of Well-being Scale, the Instrumental Activities of Daily Living Index, Self-rated General Health Status, Profile of Mood Scale), and the
results showed a significant difference between the patients and a comparable group of patients
without macular degeneration. The different quality of life parameters could be compared with
chronic diseases such as rheumatoid artrithis and chronic obstructive lung disease (10).
The greatest health gain achieved with photodynamic therapy is probably an increased quality of
life. Patients with sustained vision have increased chances to manage themselves without help
for a longer period of time. Collection of quality of life data is ongoing in several clinical stud-
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ies, but the results have not yet been published. Thus, we have no results that can be expressed in
QALYs.
High treatment costs implicate that social costs, ethics and the treatments long-term efficiencies
are included in an overall assessment.
10.
Ethical considerations
Every treatment of age-related macular degeneration raises difficult questions concerning allocation of resources, because the outcomes, both concerning health and quality of life, are limited
by the advanced age of the patients.
Several of the patients treated with photodynamic therapy will die due to natural causes during a
relative short time span. It follows that despite the method being proven effective, the involved
health economics can be difficult to compare to other treatments used in health care. One ethical
consideration is to measure the value to preserve vision in an older patient. How does loss of vision influence the quality of life of elderly people?
On one hand it can be advocated that loss of vision in the elderly is more difficult to handle than
corresponding loss among younger persons. Elderly patients may have major problems with adjustments and often the health care given to this group isn’t as good as that given to younger patients. Loss of vision is an important reason for elderly to abandon their own housing and seek
institutionalisation, and gives a loss in social function and status (and thereby resulting in considerable increased social costs).
On the other hand, age-related vision loss can be advocated to be generally less straining because
the elderly already have a reduced level of physical activity. The argument, however, is not very
good since many elderly perform activities dependent on reasonable vision (e.g., reading). The
short expected life span of the patients should therefore not be too strongly emphasised when resources are to be allocated to the treatment. The yield gained by the treatment is so important
that the patients should get as much as possible out of it, in spite of the fact that the improvement
might be incremental.
Another approach for performing ethical considerations could be to do a real cost-utility analysis. It might be possible that treatment of age-related macular degeneration does not end up being worse than other treatments used in health care. Loss of vision leads to a considerable loss in
quality of life. Elderly cannot be expected to adjust to the situation, thereby causing a permanent
loss in quality of life. Therefore, in the terms of e.g., QALYs, there will be a considerable gain in
QALYs each year that loss of vision is avoided. In a calculation of QALY per capital invested,
probably the short-term result of the treatment (partly due to the need for repeated treatments,
partly to short expected life span) could probably be compensated.
Another problem related to theoretical decision-making that also has ethical components, raised
by new treatments for age-related macular degeneration is how to handle the uncertainty regarding the long-term efficiency beyond two years. This is especially emphasised by the fact that the
treatment requires special apparatuses. However, even if the effect should be limited to a 2-year
postponement of the disease, would this result in a rather important health gain for the patients?
The question is therefore:
"Should the treatment be implemented despite the uncertainties regarding the long-term effects?"
If "yes", the uncertainties regarding the long-term effects consequently are of no concern.
If "no", an approach could be to make estimates of duration and magnitude of the possible effects. The probability of these estimates should also be assessed. The estimates could then be
used in modelling to help decision-making.
11.
Alternative treatments
Conventional laser treatments
Previously, only conventional laser treatment has been the only proven therapeutic modality for
exudative macular degeneration. However, the Macular Photocoagulation Study, MPS (11)
showed that this treatment could only be used by 15% of the patients having small and well confined lesion. Of these 15% nearly one-half of them have lesions covered by the fovea and where
the use of conventional laser would result in immediate reduction in vision. Of those patients
that originally have lesions outside the fovea, above 50% experience recurrence after the first
treatment. These recurrences often have a subfoveal location, and repeated laser treatment would
thus lead to further reduction of vision.
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Other treatment modalities
In addition to photodynamic therapy several other treatment modalities have been tried. Previous, but small studies have been promising regarding both radiation therapy and treatment with
interferon alfa-2a. Recently, the results from larger, prospectively randomised studies were published, but unfortunately, without showing positive effects (12,13). Transpupillary thermotherapy (TTT) is a new treatment under investigation for occult subfoveal membranes (14). The latter technique is now under evaluation at The National Hospital, and it is too early to draw conclusions about clinical effects.
Advanced retinal surgery gives possibilities today to remove CNV and coagulated tissues beneath the retina. In case of age-related macular degeneration the CNV is located under the pigment epithelium, a cell-layer necessary for the function of the photoreceptors. When the membrane is removed, concurrently the pigment epithelium is removed, and this leads to an inferior
result of the surgery.
Several clinics perform experimental transplantation of pigment epithelium (15). In addition to
submacular surgery there are ongoing pilot studies where the retina is removed (translocation
surgery) resulting in CNV-membranes that originally were located subfoveally. After translocation the membranes can be treated with conventional laser. Coagulation in CNV can also be treated with injection of gas and anticoagulative drugs given by intraocular administration (16). The
patient can thereafter lie in a face down position that allows the gas to press the blood away from
the macula to prevent central vision loss.
Approaches to inhibit angiogenesis are also investigated. Animal studies with angiostatic substances e.g., thalidomide have been shown to inhibit vessel growth (17). Age-related macular
degeneration has probably a multifactorial causality. Theories have been proposed that prophylactic supplementation of antioxidants could prevent the disease. These theories could be difficult to assess since this would require very large and long-lasting studies. One such study has
been ongoing for several years, and the results have not yet been published (18).
Soft drusen (ARM) represent retinal changes that increase the risk exudative age-related macular
degeneration. These drusen are often reduced in number and area after laser treatment (19).
Studies are underway to investigate if such treatment also reduce the risk for developing CNV.
12.
Indication for photodynamic treatment in other eye diseases
Pathological blood vessels can also be formed in the eye fundus in diseases other than agerelated macular degeneration. Examples of such conditions are severe myopia, ocular histoplasmosis syndrome, "angioid streaks" and von Hippel Lindau syndrome. It is possible that photodynamic treatment could be effective since the pathological blood vessels are both limited and localised. Several studies are ongoing to investigate the effectiveness of photodynamic therapy in
these conditions.
13. Conclusions
• Photodynamic therapy is so far the most effective treatment described for exudative subfoveal
age-related macular degeneration.
• In cases where the macular lesions are located outside the fovea, conventional laser should still
be the treatment of choice.
• Photodynamic therapy only works in the early stages of the illness.
• The therapy is very costly and requires careful selection of the patients.
• More data is needed on long-term efficiency before conclusions whether the therapy should be
widely implemented or not.
1.
References
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M, Kramer CF, de Jong PT. The prevalence of age-related maculopa-
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thy in the Rotterdam Study. Ophthalmology. 1995;102(2):205-10.
2. Klein R, Klein BE, Moss SE, Linton KL. The Beaver Dam Eye
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3. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related
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4. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992;99(6):93343.
5. Blumenkranz, M.S. Status of photodynamic drugs and photodynamic trials, Vitreoretinal update/subspeciality day. San Francisco.
1999; Amer.Acad.Ophthalmol.
6. Photodynamic therapy of subfoveal choroidal neovascularization in
age-related macular degeneration with verteporfin: one-year results of
2 randomized clinical trials--TAP report. Treatment of age-related
macular degeneration with photodynamic therapy (TAP) Study
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7. Blumenkranz, M. S. TAP 24-month topline data. 5-3-2000. Internet
Communication: http://www.visudyne.wwwebposium.com/pw/html/
index.html
8. Singerman, L. VIP 12-month topline data. 5-3-2000 Internet
Communication:
http://www.visudyne.wwwebposium.com/pw/html/index.html
9. Fine SL, Berger JW, Maguire MG, Ho AC. Age-related macular
degeneration. N.Engl.J.Med.2000.Feb.17.;342.(7.):483.-92.
342(7):483-92.
10. Williams RA, Brody BL, Thomas RG, Kaplan RM, Brown SI.
The psychosocial impact of macular degeneration. Arch Ophthalmol
1998;116(4):514-20.
11. Argon laser photocoagulation for neovascular maculopathy. Fiveyear results from randomized clinical trials. Macular Photocoagulation Study Group. Arch.Ophthalmol. 1991;109(8):1109-14.
12. Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a prospective randomized placebo-controlled clinical trial.
Pharmacological Therapy for Macular Degeneration Study Group.
Arch.Ophthalmol. 1997;115(7):865-72.
13. A prospective, randomized, double-masked trial on radiation therapy for neovascular age-related macular degeneration (RAD Study).
Radiation Therapy for Age-related Macular Degeneration. Ophthalmology 1999;106(12):2239-47.
14. Reichel E, Berrocal AM, Ip M, Kroll AJ, Desai V, Duker JS,
Puliafito CA. Transpupillary thermotherapy of occult subfoveal chor-
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oidal neovascularization in patients with age-related macular
degeneration. Ophthalmology 1999;106(10):1908-14.
15. Crafoord, S. Experimental transplantation of retinal and iris pigment epithelial cells into the subretinal space. Linköping University
Medical Dissertations No. 629 2000; Linköping University;
16. Hassan AS, Johnson MW, Schneiderman TE, Regillo CD, Tornambe PE, Poliner LS, Blodi BA, Elner SG. Management of submacular hemorrhage with intravitreous tissue plasminogen activator
injection and pneumatic displacement. Ophthalmology
1999;106(10):1900-6.
17. D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is
an inhibitor of angiogenesis. Proc.Natl.Acad.Sci.U.S.A.
1994;91(9):4082-5.
18. VandenLangenberg GM, Mares-Perlman JA, Klein R, Klein BE,
Brady WE, Palta M. Associations between antioxidant and zinc intake and the 5-year incidence of early age-related maculopathy in the
Beaver Dam Eye Study. Am J Epidemiol. 1998;148(2):204-14.
19. Frennesson IC, Nilsson SE. Effects of argon (green) laser treatment of soft drusen in early age-related maculopathy: a 6 month prospective study. Br.J Ophthalmol 1995;79(10):905-9.
Senter for medisinsk metodevurdering (SMM)
The Norwegian Centre for Health Technology Assessment, SINTEF Unimed, Forskningsveien
1, Postboks 124 Blindern, 0314 OSLO
Direktørr Berit Mørland
Informasjonskonsulent Berit Kolberg Rossiné
Tlf: 47 22 06 79 61 Faks: 47 22 06 79 79 E-post: [email protected]
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ANEXO
6
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REF.: ACEMSA/SET/AC/ac
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Pá gina 69 de 170
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REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 70 de 170
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REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 71 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 72 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 73 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 74 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 75 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 76 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 77 de 170
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REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 78 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 79 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 80 de 170
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REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 81 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 82 de 170
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ANEXO
7
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Pá gina 84 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 85 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 86 de 170
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REF.: ACEMSA/SET/AC/ac
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Pá gina 87 de 170
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Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 88 de 170
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REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 89 de 170
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REF.: ACEMSA/SET/AC/ac
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ANEXO
8
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REF.: ACEMSA/SET/AC/ac
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Photodynamic therapy for neovascular age-related macular
degeneration
Wormald R, Evans J, Smeeth L
This review should be cited as: Wormald R, Evans J, Smeeth L.
Photodynamic therapy for neovascular age-related macular
degeneration (Cochrane Review). In: The Cochrane Library, Issue 1,
2001. Oxford: Update Software.
A substantive amendment to this systematic review was last made on
22 February 2000. Cochrane reviews are regularly checked and
updated if necessary.
Background: In neovascular age-related macular degeneration, new
vessels grow under the retina, distorting vision and leading to
scarring. This is further exacerbated if the blood vessels leak.
Photodynamic therapy, originally used in cancer treatment, has
been investigated as a way to treat the neovascular membranes
without affecting the retina.
Objectives: The aim of this review is to examine the evidence for
the safety and effectiveness of photodynamic therapy in the
treatment of neovascular age-related macular degeneration.
Search strategy: We searched for trials in the Cochrane Eyes and
Vision Group specialised register (available in CENTRAL), the
Cochrane Controlled Trials Register - CENTRAL, MEDLINE and EMBASE.
We used the Science Citation Index to search for reports that
cited identified relevant study reports. We contacted experts in
the field for further trials information, and we searched the
reference lists of identified relevant studies for further trial
reports.
Selection criteria: We included randomised trials of photodynamic
therapy in people with choroidal neovascularisation due to
age-related macular degeneration.
Data collection and analysis: Two reviewers extracted the data
independently. Meta analysis was not performed.
Main results: One published trial was identified. Outcome data
were available at 12 months after the first treatment. Patients
received an average of 3.7 treatments. The relative risk of losing
three or more lines of visual acuity at 12 months comparing the
intervention with the control group was 0.72 (95% confidence
interval 0.61 to 0.86). The relative risk of losing six or more
lines of visual acuity at 12 months comparing the intervention
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with the control group was 0.62 (95% confidence interval 0.44 to
0.87). Subgroup analyses suggest that the benefits may be confined
to people with no occult choroidal neovascularisation.
Reviewers' conclusions: Photodynamic therapy in people with
classic choroidal neovascularisation due to age-related macular
degeneration is effective in preventing visual loss. This evidence
is drawn from a subgroup analysis of 143 participants in one
trial. Outcomes and potential adverse effects of this treatment
should be monitored closely. There is no evidence that
photodynamic therapy is beneficial for people with evidence of
occult choroidal neovascularisation. These people should be
offered treatment in the context of a randomised trial.
Background
Age-related macular degeneration (ARMD) is a disease affecting the
macula, the central area of the retina. The disease is defined as
degeneration of the macula in older people (aged over 50) with no
other apparent cause for the degeneration.
There are several signs in the retina that are associated with
increasing age and increased risk of developing age-related
macular degeneration. These signs, known as age-related
maculopathy, include the presence of drusen (yellow spots
maculopathy, include the presence of drusen (yellow spots beneath
the retina) and pigmentary disturbance. In general age-related
maculopathy is not associated with visual loss. Some people with
age-related maculopathy will go on to develop age-related macular
degeneration.
There are two main types of age-related macular degeneration. In
geographic atrophy or dry age-related macular degeneration, the
retinal pigment epithelium is lost completely in localised areas.
In neovascular or wet age-related macular degeneration,
sub-retinal neovascular membranes (new blood vessels) develop
beneath the retina. These are associated with scarring of the
retina that affects vision. The new vessels can leak, causing
haemorrhage that leads to larger scars, or macular oedema and
significant loss of vision. This review is concerned with
treatment for neovascular age-related macular degeneration.
Subretinal neovascular membranes are defined as classic or occult
according to their appearance on fluorescein angiography, in which
fluorescent dye is injected intravenously and imaged as it passes
through the blood vessels of the eye. Classic membranes are
clearly delineated and leak fluorescein uniformly. Occult
membranes are often hidden or their extent is hard to delineate,
and fluorescein leakage is patchy. Some lesions may have classic
and occult components.
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Trials have shown that early laser photocoagulation of classic
extra-foveal membranes (those not directly underneath the fovea at
the centre of the macula) could delay the loss of vision in a
small number of patients (MPS 1994). However, most patients
present with sub-foveal membranes, and whilst photocoagulation can
limit the extent of the subsequent visual loss, it causes
immediate loss of central vision due to the concurrent destruction
of the overlying retina.
Photodynamic therapy, originally used in the treatment of cancer,
has been investigated as a way to treat the neovascular membranes
without affecting the retina. Photoreactive chemicals are injected
into the patient and irradiated with light as they pass through
the neovascular membranes. This light is strong enough to activate
the chemicals, causing them to emit free radicals that destroy the
blood vessels, but is not strong enough to cause damage to the
overlying retina.
Objectives
The aim of this review is to examine the evidence for the safety
and effectiveness of photodynamic therapy in the treatment of
neovascular age-related macular degeneration.
Criteria for considering studies for this review
Types of studies
We included randomised controlled trials.
Types of participants
Participants were people with neovascular age-related macular
degeneration as defined by the study investigators.
Types of intervention
We included any study in which photodynamic therapy was compared
to another treatment, placebo or no treatment.
Types of outcome measures
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We included the following outcomes:
(1)
(2)
(3)
(4)
prevention of visual loss
new vessel growth
quality of life measures
any adverse outcomes as reported in trials
We used the following definitions:
Visual loss: Any well-defined outcome based on visual acuity was
used depending on the way in which authors presented trial data.
Other validated measures of visual loss, such as contrast
sensitivity, were used where available.
Quality of life: Any validated measurement scale which aims to
measure the impact of visual function loss on quality of life of
participants.
Search strategy for identification of studies
See: Collaborative Review Group search strategy
We searched for trials in the Cochrane Controlled Trials Register
- CENTRAL, the Cochrane Eyes and Vision Group specialised register
(available in the CENTRAL), MEDLINE and EMBASE.
We used the following strategy to search the CENTRAL Issue 4 1999:
#1 MACULAR-DEGENERATION:ME
#2 RETINAL-DEGENERATION:ME
#3
#3 NEOVASCULARIZATION-PATHOLOGIC*:ME
#4 (MACULA or MACULAR) or RETINA or RETINAL or CHOROID or
CHOROIDAL near (DEGENERATION or NEOVASCULARIZATION))
#5 MACULOPATHY
#6 #1 or #2 or #3)or #4 or #5
#7 PHOTOCHEMOTHERAPY*:ME
#8 PHOTOSENSITIZING-AGENTS*:ME
#9 (PHOTOSENSITIZING or PHOTOSENSITISING) or PHOTODYNAMIC or PDT
or VERTEPORFIN or VISUDYNE
#10 #7 or #8 or #9
#11 #6 and #10
We used the following strategy to search Medline 1966 to October
1999:
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SilverPlatterASCII 3.0DOSNSelected Databases
#1 "MACULAR-DEGENERATION"/ all subheadings
#2 "RETINAL-DEGENERATION"/ all subheadings
#3 "CHOROIDAL-NEOVASCULARIZATION"/ all subheadings
#4 (MACUL* or RETINA* or CHOROID*) near (DEGENER* or NEOVASC*) in
TI,AB
#5 MACULOPATHY in TI,AB
#6 #1 or #2 or #3 or #4 or #5
#7 explode "PHOTOCHEMOTHERAPY"/ all subheadings
#8 explode "PHOTOSENSITIZING-AGENTS"/ all subheadings
#9 (PHOTOSENSITI?ING?AGENTS or 'PHOTOSENSITI?ING AGENTS' or
PORPHYRIN* or BENZOPORPHYRIN) in NM,TI,AB
#10 (PHOTODYNAMIC or PDT) in TI,AB
#11 VERTEPORFIN or VISUDYNE in TI,AB
#12 #7 or #8 or #9 or #10 or #11
#13 #6 and #12
We used the following strategy to search Embase 1980 to September
1999:
SilverPlatterASCII 3.0DOSNSelected Databases
#1 explode "RETINA-MACULA-DEGENERATION"/ all subheadings
#2 "RETINA-DEGENERATION"/ all subheadings
#3 "NEOVASCULARIZATION-(PATHOLOGY)"/ all subheadings
#4 "SUBRETINAL-NEOVASCULARIZATION"/ all subheadings
#5 (MACUL* or RETINA* or CHOROID*) near (DEGENER* or NEOVASC*) in
TI,AB
#6 MACULOPATHY in TI,AB
#7 #1 or #2 or #3 or #4 or #5 or #6
#8 "PHOTODYNAMIC-THERAPY"/ all subheadings
#9 explode "PHOTOSENSITIZING-AGENT"/ all subheadings
#10 (PHOTODYNAMIC or PDT) in TI,AB
#11 (PHOTOSENSITI?ING AGENT* or VERTEPORFIN or VISUDYNE) in
RN,TI,AB
#12 #8 or #9 or #10 or #11
#13 #7 and #12
We used the Science Citation Index to search for reports that
cited identified relevant study reports. We contacted experts in
the field for information about further trials, and we searched
the reference lists of identified relevant studies for further
trial reports.
Methods of the review
Selection of trials
Two reviewers independently scanned the titles and abstracts
resulting from the electronic searches. We obtained full copies of
all potentially or definitely relevant articles. Two reviewers
assessed the full copies according to the 'Criteria for
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considering studies for this review'. Only articles meeting these
criteria were assessed for quality.
Assessment of methodological quality
Two reviewers independently assessed study quality according to
methods set out in the Section 6 of the Cochrane Reviewer's
Handbook. Reviewers were not masked to any trial details during
the assessment. Four parameters of quality were considered:
allocation concealment and method of allocation to treatment,
masking of providers and recipients of care, masking of outcome
assessment, and completeness of follow-up. Each parameter of trial
quality was graded: A - adequate; B - unclear; C - inadequate.
Disagreement between the reviewers on assessments was resolved by
discussion. We contacted the trial authors for clarification on
any parameter graded B - unclear, and we excluded any trial
scoring C - inadequate on allocation concealment.
We constructed an overall score of quality for each trial as
follows:
1 - Low risk of bias - All parameters graded A - adequate
2 - Moderate risk of bias - One parameter graded C - inadequate
3 - High risk of bias - Two or more parameters graded C inadequate
Data collection
Two reviewers independently extracted data using a form developed
for use by the Cochrane Eyes and Vision Group (available from the
editorial base). We resolved discrepancies by discussion. Two
reviewers independently entered data into RevMan 4.0.4 and we
checked any inconsistencies between the two against the study
report.
Data synthesis
Our original data analysis plan was to
Our original data analysis plan was to summarise data from studies
collecting similar outcome measures with similar follow-up times
using the Peto method, after testing for heterogeneity between
trial results using a standard chi-square test. At present only
one trial is included in this review so no data synthesis was
necessary. The main outcome analysed, loss of 3 or more lines of
visual acuity at 12 months follow-up, occurred relatively
frequently in the trial cohort. The odds ratio, therefore, does
not approximate to the relative risk. We present relative risks in
this review. We planned to conduct sensitivity analyses to
determine the effect of excluding studies given an overall grade
of 3 - high risk of bias but this has not been necessary to date.
Description of studies
The electronic searches identified 76 reports. We found one
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randomised controlled trial (TAP 1). This multicentre study
investigated the safety and effectiveness of verteporfin
(Visudyne; CIBA Vision Corp, Dulth,GA) and was conducted in 22
ophthalmology practices in Europe and North America. Participants
were people with subfoveal choroidal neovascularisation (CNV)
caused by age-related macular degeneration. The majority of
participants were white (98%) with a mean age of 75 years.
Verteporfin (six milligrams per square meter of body surface area)
was compared to placebo (5% dextrose in water) administered via
intravenous infusion of 30 millilitres over 10 minutes. This was
followed after 15 minutes by application of eighty three seconds
of laser light at 689 nm delivered 50 Joules per square centimetre
at an intensity of 600 mW/cm squared using a spot size with a
diameter 1000 microns larger than the greatest linear dimension of
the CNV lesion. Participants in the trial were reviewed every
three months when visual acuity and repeat fluorescein angiography
performed. If the trial surgeon judged a recurrence of the
membrane to be present or a persistence of the previous lesion,
then repeat treatment was undertaken. In the phase 1 and 2
studies, it was concluded that up to five treatments were
necessary to stabilise the situation (Miller 1999; Schmidt-Erfurth
1999). A mean of 3.4 treatments were delivered to the treatment
group and 3.7 to the controls.
TAP 1 was originally devised as two concurrent trials in order to
comply with regulatory agency requirements. The study protocols
were identical. Ten of the clinical centres were assigned to study
A and 12 to study B. As the results of the trials were similar and
the investigators analysed and presented the data as one trial, we
have also assessed it as one trial.
Methodological quality
TAP 1 was a high quality study.
Allocation of treatment group was by opaque serially numbered
sealed envelopes. The baseline characteristics of the participants
by treatment group were published. The groups were well balanced
with respect to a variety of demographic and clinical variables.
Only one eye per person was treated.
Reasonable attempts were made to mask the ophthalmologist,
patient, vision examiner and Photograph Reading Center Personnel.
As verteporfin and placebo were different colours (green versus
colourless) the solutions and the intravenous tubing were covered
with foil. The fundus appearance does not change during treatment
to indicate whether verteporfin or placebo had been infused. There
is no other physical evidence of treatment as verteporfin dye is
excreted in the faeces and does not cause any colour change. Nor
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does it alter the colour of the skin or urine so that it was
unlikely the patient was aware of their treatment or control
status. The study investigators reported two instances where the
patients were unmasked having noted a green solution and a further
four cases where the ophthalmologists were unmasked.
Rates of follow-up were high (94%) and were similar between the
two treatment groups. The analysis was intention-to-treat and
subgroup analyses were planned a priori.
Results
The realistic aim of photodynamic therapy is to slow progression
of Age related macular degeneration (ARMD), not to produce normal
vision. Outcomes are therefore expressed as risks of a poor
outcome, rather than as improvements in vision. All results refer
to the TAP 1 study.
The relative risk of losing three or more lines of visual acuity
at 12 months comparing the intervention with the control group was
0.72 (95% confidence interval 0.61 to 0.86). The relative risk
reduction was therefore 0.28 (95% confidence interval 0.14 to
0.39). The relative risk of losing six or more lines of visual
acuity at 12 months comparing the intervention with the control
group was 0.62 (95% confidence interval 0.44 to 0.87). The
relative risk reduction was therefore 0.38 (95% confidence
interval 0.13 to 0.56).
The mean number of lines of vision lost at 12 months was 2.2 in
the intervention group and 3.5 in the control group. The
difference was 1.3 with fewer lines lost in the intervention
group. The P value for the difference in the mean number of lines
lost was given in the trial report as P <0.001 (Wilcoxon rank sum
test). The standard deviations for the mean numbers of lines lost
were not given in the published report and we therefore could not
calculate a confidence interval. We hope to include this in a
future version of this review.
Subgroup analyses
Subgroup analyses were specified a priori (Bressler N, personal
communication). Outcome data for these subgroups are only
available for the outcome 'risk of losing 3 or more lines'.
The proportion of the lesion comprised of classic choroidal
neovascularisation (CNV) was estimated as 0%, greater than 0% but
less than 50% and greater than 50%. The proportion was unknown in
four participants (three in the treatment group and one in the
control group). The sub-group analysis was therefore based on a
total of 399 eyes. The relative risks in these three groups of
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losing three or more lines of visual acuity at 12 months comparing
the intervention with the control group were: 0.54 for 0% CNV;
0.99 for greater than 0% but less than 50% CNV and 0.54 for
greater than 50%. These results suggest there was a reduction in
the risk of loss of vision when classic CNV was absent or when
greater than 50% of the lesion was comprised of classic CNV.
However there was no reduction in risk when between 0% and 50% of
the lesion was comprised of classic CNV. The test for effect
modification between these three sub-groups was highly significant
(chi-squared 10.74, 2 degrees of freedom, P <0.001). The
inconsistencies in these results are discussed below.
The other subgroup analysis was undertaken on the basis of the
presence or absence of occult CNV. The relative risks of losing
three or more lines of visual acuity at 12 months comparing the
intervention with the control group were 0.90 if occult CNV was
present (95% confidence interval 0.73 to 1.11) and 0.34 if occult
CNV was absent (95% confidence interval 0.22 to 0.51). The test
for effect modification between these two subgroups was highly
significant (chi-squared 17.63, 1 degree of freedom, P <0.001).
The 95% confidence intervals for these two sub-groups do not
overlap, nor do the 99% confidence intervals.
Numbers needed to treat
We calculated the numbers needed to treat (NNTs) to prevent one
person losing three or more lines and, where possible, one person
losing six or more lines of vision at 12 months. These NNTs are
derived from the study population, that is, people with subfoveal
CNV and a baseline visual acuity of between 20/40 and 20/200. They
refer to an average of 3.4 treatments of photodynamic therapy
using verteporfin over a 12 month period. The NNT to prevent one
person losing three or more lines of vision was 6.7 (95%
confidence interval 4.3 to 14.3). The NNT to prevent one person
losing six or more lines of vision was 11.1 (95% confidence
interval 6.3 to 50). Because of the inconsistencies in the results
of subgroup analysis for the proportion of the lesion comprised of
classic CNV, we did not
classic CNV, we did not calculate NNTs for these subgroups. For
the subgroup analysis according to the presence or absence of
occult CNV, the NNTs are as follows. The NNT to prevent one person
with occult CNV present losing three or more lines of vision was
20 (95% confidence interval number needed to benefit 7.1 to
infinity to number needed to harm 20). The NNT to prevent one
person with no occult CNV present losing three or more lines of
vision was two (95% confidence interval 1.6 to 3.3).
Summary of analyses
MetaView: Tables and Figures
The figures and graphs in Cochrane Reviews display the Peto Odds
Ratio and the Weighted Mean Difference by default. These are not
always the methods used by reviewers when combining data in their
review. You should check the text of the review for a description
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of the statistical methods used.
Discussion
Age related macular degeneration is the most common cause of
irreversible visual impairment in Western countries and the
population burden of the disease is increasing as the population
ages. Its incidence increases steeply after the age of 70 years,
but it also occurs in younger age groups and it is probably among
the most common causes of sight loss in people in their 50's and
60's. Its precise cause is unknown but both genetic and
environmental factors are thought to be relevant. The absence to
date of any effective treatment (except for the few in whom laser
photocoagulation works) means that there will be intense interest
in photodynamic therapy for the many millions of sufferers of the
disease worldwide. Unfortunately, photodynamic therapy, like
photocoagulation, can only be effective during the proliferative
stage of the disease while the neovascular process is active. It
cannot have any effect once sight is lost and the scarring process
is complete. Therefore, like so many other degenerative processes
of the neuroretina, once the damage is done, nothing can be done
to restore function. Most sufferers of the condition have
established sight loss and for these, the publicity surrounding
the launch of Visudyne (verteporfin) will have raised false hopes.
Nevertheless, the evidence presented in this review from the only
trial so far reported looks promising.
A key question is how long the effect of treatment will last and
whether repeated treatments would be required in the longer term.
Important information on this is awaited from the TAP studies and
from others.
Another important issue is how many presenting patients will
benefit or be treatable. Quite apart from the problem of accessing
specialist services in time is the question of the proportion of
lesions that will actually be treatable. The evidence reported
here clearly suggests that purely 'classic' neovascular membranes
do well. However when occult neovascular membranes are present,
then the outcome is much less certain and indeed, there is no
evidence of the treatment being effective in this circumstance.
'Occult' vessels mean that the extent of the membrane cannot be
clearly defined and so it is not surprising that treatment is
found to be less effective simply because the laser energy cannot
be reliably aimed at all of the membrane. We are not told in the
available reports the extent to which clinicians and indeed the
trial reading centre are able to agree about the subgroup
classification of 'classic' or 'occult' lesions. It is likely that
there is much variation in opinion on this. The necessary skill to
report on fluorescein angiograms and recognise different lesion
types is highly refined. Most experts assert that the stereo
images are required to be able to locate the position in depth of
staining or fluorescein leaks. Stereophotography requires either a
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dedicated camera equipped to take simultaneous stereo images or a
skilled photographer who takes sequential images slightly
laterally displaced from one another providing a non-simultaneous
or pseudo-stereo image.
The natural history of the growth of subretinal
The natural history of the growth of subretinal membranes varies
from individual to individual. They may be aggressive and rapidly
growing or indolent. This is the kind of individual factor that
will influence the likelihood of a patient being in a position to
benefit from this treatment. The trial report does not comment on
the proportion of patients presenting to the trial centres that
had treatable lesions. The verbal estimate from one trialist was
approximately 25% and of another expert, between 5 and 7%. This is
of crucial importance in estimating the impact of this new
treatment on health care budgets.
The first subgroup analysis (presence or absence of occult
choroidal neovascularisation (CNV)) provides some pointers to
which people will benefit from treatment, although any conclusions
can only be tentative. The effect of treatment on people with
occult CNV present was small and did not approach statistical
significance. There appeared to be a far greater beneficial effect
in people with no occult CNV present. However this finding was
based on a total of only 143 eyes (94 in the treatment group and
49 in the control group). There is a need for great caution in
interpreting a result based on this relatively small subgroup.
The second subgroup analysis (percentage of lesion comprised of
classic CNV) produced a somewhat surprising result. Whilst it is
difficult to think of a good biological explanation for the
observed results, there are two likely explanations for the
inconsistent results observed. Firstly the effects observed in the
subgroups could be a statistical artefact (Yusuf 1991). The
following factors could have contributed to this: the relatively
small numbers in the three subgroups; the multiple testing
inherent in such subgroup analyses; and the fact that even though
the subgroup analysis was specified a priori, the trial was not
specifically powered to explore effects in these subgroups.
Another explanation for the observed subgroup effects could be
misclassification bias. As discussed above, determining the
percentage of a lesion that is composed of classic CNV is unlikely
to be an exact science. Inter or intra-observer variation could
have contributed to the somewhat puzzling results obtained for the
subgroup analysis based on the percentage of the lesion comprised
of classic CNV. For example, some people with a small amount of
classic CNV (between 0% and 50%) could have been erroneously
judged to have no classic CNV or vice-versa. Because of the
relatively small numbers in the subgroups, misclassification
resulting in a different outcome would have been required in only
a small number of people to explain the inconsistencies observed.
In the 0% classic CNV subgroup, an alteration of 1 one in the
numbers of people losing less than three lines of vision at 12
months in both the treatment and control groups is sufficient to
make the result for the subgroup non-significant (i.e. if 15
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people in the treatment group and 12 people in the control group
lost three or more lines, the relative risk for the sub-group
would have been 0.63 (95% confidence interval 0.37 to 1.05,
P=0.09). This illustrates the fragility of this subgroup analysis
and the caution needed in its interpretation.
ARMD is a bilateral disease although one eye is usually affected
before the other. With a lesion present in one eye, the annual
cumulative incidence of a lesion in the second eye is estimated to
be about 15%. It is common practice now for clinicians to advise
patients already afflicted with a lesion in one eye to be watchful
for the onset of symptoms in the second eye and to present as soon
as those symptoms are noticed so that the chances of catching the
lesion in the second eye in time are improved. This often entails
the provision of an Amsler grid, a simple chart on which a number
of gridlines are printed around a central fixation spot. The
patient is instructed to examine the grid and to look for focal
distortion of the lines in the grid which would indicate local
elevation of the retina as a result of the growth of an underlying
membrane. This strategy
membrane. This strategy offers the best hope of saving sight with
this new treatment at least in places where access to a qualified
ophthalmologist can be slow.
It should also be recalled that this treatment does not restore
sight but rather, prevents further deterioration. Sustaining
numerous assessments which involve relative invasive treatments
may have an adverse effect on the patient. Without patient
orientated outcomes in this trial, we cannot comment on the
patient's perspective on the experience of Visudyne therapy. It is
likely that in most cases, especially where loss of sight of the
second eye is threatened, that patients will be willing to undergo
all the necessary interventions, even when the probability of
success is small.
The trial was too small to assess rare important adverse effects
although it does provide evidence that there are no common
short-term adverse effects of treatment.
This trial appears to have been performed to high standards and
was closely supervised by the Food and Drugs Administration of the
USA. The trial was sponsored by the manufacturers of the drug
(CIBA Vision) and declared potential conflicts of interest exist
for a number of the trialists who hold interests in the
manufacturer of the laser technology. This makes detailed scrutiny
of reports of the trial essential. That numerous protocol
revisions were registered with the Institutional Review Bodies
throughout the study and after completion of follow up is also of
concern. Although we have not yet had access to the main protocol
or the revisions, a CIBA representative has assured us that these
were not substantive and in particular, there were no changes to
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the a priori determinants of the primary outcomes.
Reviewers' conclusions
Implications for practice
This review provides evidence that photodynamic therapy in people
with classic choroidal neovascularisation due to age-related
macular degeneration is effective in preventing visual loss. This
evidence is drawn from a subgroup analysis of the results of one
trial (143 people). In our opinion, further trials should be
conducted to verify this finding. Given the current level of
interest in photodynamic therapy, and the fact that the effect was
strong (NNT of two to prevent a doubling of the visual angle) we
envisage that there will be little enthusiasm for further trials.
Policy makers and clinicians should be aware, if they introduce
this therapy, that the estimates of beneficial outcome are based
on treatment of 143 eyes only. Outcomes and potential adverse
effects of this treatment should be monitored closely. Clinicians
need to have the expertise and resources to exclude people with
occult choroidal neovascularisation.
There is no evidence that photodynamic therapy is beneficial for
people with evidence of occult choroidal neovascularisation. These
people should be offered treatment in the context of a randomised
controlled trial.
There are major implications for health services, both in terms of
potential expenditure and organisation, if photodynamic therapy is
to be introduced. Where referral to an ophthalmologist is through
a primary care network, facilities for the recognition of this
condition in its early stages are needed. There is potential for
an enormous increase in referral of people with early age-related
maculopathy for assessment, in case an early treatable lesion is
present. This could swamp already overstretched facilities at the
secondary care level. Extra resources will be required at the
secondary care level to manage increased referrals, for the
necessary technology to diagnose treatable lesions and to deliver
treatment.
Implications for research
Further independent trials of verteporfin are required to
establish that the effects seen in this study are consistent and
to determine important questions not yet addressed - particularly
relating to quality of life and cost. Longer term outcomes are
also needed both from the efficacy and safety perspective.
Descriptive epidemiology on the population at
Descriptive epidemiology on the population at risk and the numbers
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likely to benefit is essential to estimate the impact of this new
treatment on health service resources. We need to establish how
people in need of treatment can access it in time. Surveillance
for possible rare but severe adverse effects will be required.
Acknowledgements
We would like to thank Neil Bressler MD, Simon Harding FRCOphth
and Javed Bhatti (CIBA Vision) for providing information about the
TAP1 study. Usha Chakravarthy (Queens University, Belfast) and Bob
Thompson (Macular Disease Society) provided useful comments on the
review.
Potential conflict of interest
None known
Characteristics of included studies
Table: Characteristics of included studies
References
References to studies included in this review
TAP 1 {published and unpublished data}
Treatment of Age-related Macular Degeneration With Photodynamic
Therapy (TAP) Study Group. Photodynamic therapy of subfoveal
choroidal neovascularization in age-related macular degeneration
with verteporfin. Archives of Ophthalmology 1999;117:1329-1345.
* indicates the major publication for the study
Additional references
Fine 1999
Fine SL. Photodynamic therapy with verteporfin is effective for
selected patients with neovascular age-related macular
degeneration. Archives of Ophthalmology 1999;117(10):1400-1402.
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Miller 1999
Miller JW, Schmidt-Erfurth U, Sickenberg M, Pournaras CJ, Laqua H,
Barbazetto I, Zografos L, Piguet B, Donati G, Lane AM, Birngruber
R, van den Berg H, Strong A, Manjuris U, Gray T, Fsadni M,
Bressler NM, Gragoudas ES. Photodynamic therapy with verteporfin
for choroidal neovascularisation caused by age-related macular
degeneration. Results of a single treatment in a phase 1 and 2
study. Archives of Ophthalmology 1999;117(9):1161-1173.
MPS 1994
Macular photocoagulation study group. Laser photocoagulation for
juxtafoveal choroidal neovascularization: five year results from
randomized clinical trials. Arch Ophthalmol 1994;112:500-509.
Schmidt-Erfurth 1999
Schmidt-Erfurth U, Miller JW, Sickenberg M, Laqua H, Barbazetto I,
Gragoudas ES, Zografos L, Piguet B, Pournaras CJ, Donati G, Lane
AM, Birngruber R, Zografos L, van den Berg H, Strong A, Manjuris
U, Gray T, Fsadni M, Bressler NM. Photodynamic therapy with
verteporfin for choroidal neovascularisation caused by age-related
macular degeneration. Results of retreatment in a phase 1 and 2
study. Archives of Ophthalmology 1999;117(9):1177-1187.
Yusuf 1991
Yusuf S, Wittes J, Probstfield J, Tyroler HA. Analysis and
interpretation of treatment effects in subgroups of patients in
randomized clinical trials. JAMA 1991;266(1):93-98.
Coversheet
Title
Photodynamic therapy for neovascular age-related macular
degeneration
Reviewer(s)
Wormald R, Evans J, Smeeth L
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Contribution of Reviewer(s)
All three reviewers participated in protocol development, study
selection and assessment and writing up of the final review. Liam
Smeeth and Jennifer Evans abstracted data and entered it onto
Revman.
Issue protocol first published: Information not available
Issue review first published: 2000 Issue 2
Date of most recent amendment: 29 November 2000
Date of most recent substantive amendment: 22 February 2000
Most recent changes: Information not supplied by reviewer
Date new studies sought but none found: Information not supplied
by reviewer
Date new studies found but not yet included/excluded: Information
not supplied by reviewer
Date new studies found and included/excluded: Information not
supplied by
supplied by reviewer
Date reviewers' conclusions section amended: Information not
supplied by reviewer
Contact address:
Mr Richard Wormald MA MB MSc FRCS FRCOphth
Consultant Ophthalmologist and Honorary Senior Lecturer
Research and Development Department
Moorfields Eye Hospital and Institute of Ophthalmology (UCL)
City Road
London
UK
EC1V 2PD
Telephone: +44 20 7566 2818
Facsimile: +44 20 7608 6925
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E-mail: [email protected]
For information on the editorial group see: Cochrane Eyes and
Vision Group
Extramural sources of support to the review
NHS Exectutive London, Research and Development UK
Intramural sources of support to the review
Moorfields Eye Hospital NHS Trust UK
Synopsis
PHOTODYNAMIC THERAPY MAY REDUCE VISION LOSS CAUSED BY ONE TYPE OF
AGE-RELATED MACULAR DEGENERATION BUT MORE RESEARCH IS NEEDED
Age-related macular degeneration (ARMD) affects the macula, the
centre of the retina (the light-sensitive area inside the eye).
One type is called 'wet' or neovascular, as new blood vessels
develop in the macula. These can leak and scar the eye, causing
vision loss. Photodynamic therapy involves injecting chemicals,
then radiating light as they flow through these new blood vessels.
This aims to activate the chemicals enough to destroy the vessels,
but not enough to hurt the eye. The review found some evidence
that this may reduce vision loss caused by 'classic' neovascular
ARMD, but more research is needed.
Keywords
Human; Macular Degeneration/*drug therapy; Neovascularization,
Pathologic; *Photochemotherapy; Photosensitizing
Agents/*therapeutic use;
CRG Code: HM-EYES
Cochrane Library number: CD002030
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febrero-2001
ANEXO
9
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REF.: ACEMSA/SET/AC/ac
febrero-2001
Retina/Vitreous
Visudyne looks promising for treating
wet AMD
But will the new procedure break the Medicare bank? With 65,000
procedures performed in 2000, the question is apt.
by Irving J. Arons
Special to Ocular Surgery News
January 15, 2001
Last year at this time I reported that Visudyne photodynamic therapy (PDT), along with several other
PDT treatments in the pipeline, appeared promising for those afflicted with predominantly classic, wet
age-related macular degeneration. This year the technology has come to the market, and good results are
being reported but financial questions remain.
My earlier report was filed following the 1999 American Academy of Ophthalmology (AAO) meeting
(“Laser treatments for AMD show promise,” Jan. 15, 2000, issue), One question posed by industry analysts during that meeting was how, when these new techniques came to market, would the Health Care
Financing Administration (HCFA) handle the reimbursement issues without bankrupting Medicare?
Well, the inevitable has happened. Visudyne therapy (verteporfin for injection, marketed for QLT Inc. by
CIBA Vision) for predominantly classic wet AMD was approved for marketing by the Food and Drug
Administration in April 2000. Since then, thousands of AMD patients have flooded retinal surgeons’ offices seeking treatment.
The approval was based on the 12-month data from two 24-month randomized, double-masked, placebocontrolled phase 3 clinical trials known as the Treatment of AMD with Photodynamic therapy (TAP) Investigation. Results of the TAP studies were published in the October 1999 issue of Archives of Ophthalmology. The TAP 12-month findings showed that in 243 patients with predominantly classic wet choroidal neovascularization (CNV), vision remained stable or improved in 67% of patients treated with Visudyne therapy versus 39% of patients in the placebo arm of the study. Additional data released this past
summer showed that the beneficial effect and the favorable safety profile of Visudyne therapy that was
observed at the 12-month time point was maintained out to 2 years, with fewer treatments required in the
second year (see clinical results update below).
Market size and reimbursement
It is estimated that some 65,000 U.S. PDT treatments, both primary and retreatments, were done in 2000,
producing $90 million to $100 million in drug revenues for QLT/CIBA Vision. If analysts’ projections
continue to hold up, the drug could reach more than $200 million in sales in 2001 — and as high as $500
to $700 million by 2003.
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febrero-2001
But the picture isn’t all rosy. In November, HCFA issued its revised National Policy for Reimbursement,
calling Visudyne therapy a “medically reasonable and necessary treatment.” The agency also expanded
somewhat the number of patients who can receive treatment (those presenting with at least 50% classic
symptoms from a fluorescein angiogram) and how often retreatments can occur — up to 6 treatments
over 24 months, although recent field interviews/surveys show that fewer retreatments are occurring in
practice over an extended time. (The TAP inclusion criteria included having visual acuities between 20/40
and 20/200, and lesions greater in size than 0.5 mm. On average, 5.6 treatments were reported over the 2year period.)
However, the agency cut the expected physician reimbursement for the treatment — including infusion,
use of the laser and staff overheads — to $341 from the $500-to-$700 reimbursement figure expected
(and previously paid for laser photocoagulation). When added to the drug reimbursement ($1,458), Visudyne PDT therapy total reimbursement will be $1,799 in 2001. Taken against the cost to administer the
treatment, according to a Dain Rauscher Wessels analysis, a high-volume practice could expect a profit
per procedure of about $500, while a low-volume practice might only clear $135, not including the physician’s fee! This total is down from the $900 profit that high-volume practices could have expected under
the older laser photocoagulation rates, and about $550 for lower-volume practices.
With between 1,200 and 1,300 practicing retinal specialists in the United States, we estimate that there are
currently about 600 PDT activation lasers (from either Zeiss Humphrey or Coherent Medical) in use in
the United States, with an additional 600 in use worldwide.
In a poll of 67 retinal practices conducted by Leerink Swann & Company in November 2000, 82% of respondents stated that the new level of reimbursement from HCFA was below expectations and inadequate. At an AMD press conference held during this year’s AAO meeting before the HCFA announcement, Mark Blumenkranz, MD, noted that Visudyne treatment may end up being offered only at larger
medical centers or academic centers if the reimbursement issues are not satisfactorily resolved.
Medicare cost
I have attempted to calculate the potential cost to the Medicare system for PDT for the year 2000 and beyond. The cost for 2000 depends on how many people actually underwent the treatment, which in turn
depends on how many of the 200,000 to 350,000 of the current AMD pool met the acceptance criteria.
The wet form of AMD accounts for about 10% to 15% of the total AMD population, or 1.3 to 1.5 million
people in the United States, plus another 200,000 new cases diagnosed each year (and 400,000 more
worldwide). The predominantly classic form represents about 10% to 15% of the total wet form population, or approximately 130,000 to 250,000 people that could now be treated, with an additional 20,000 to
30,000 being diagnosed and entering the potential treatment pool each year, not taking into account additional patients with diseases such as pathological myopia, which should be added to the Visudyne labeling sometime in mid-2001.
The cost to Medicare for Visudyne PDT in 2000 could conceivably have ranged from $160 million to
$280 million, assuming that one-third of the current pool elected treatment, half of those were eligible
(many in the pool may have already lost too much vision to be treatable) and the cost to the system is
$1,799 per procedure ($1,458 for the drug — or less depending on the copay — plus $341 for treatment)
with an average of three treatments needed over the course of the first year. (This calculation assumes that
60% of recipients have Medicaid and Medicare pays 80% of the drug cost, with the recipient paying the
remaining 20% co-pay. The actual cost for 2000, based on 65,000 doses, was closer to $115 million.)
In subsequent years, with another third of those eligible entering treatment, along with additional retreatments for some of those already started on their initial course of treatment, Medicare costs could average
over $250 million a year. And when other eye diseases and treatment modalities are approved, the cost
can only rise. Another factor is the subjective nature of the diagnosis. Those patients with marginal classic symptoms may be included in the treatment class, as this might be their only hope for retaining vision.
Improved quality of life
On a more positive note, Dr. Sanjay Sharma of Queens University in Kingston, Ontario, presented a paper
during the AAO meeting on a decision-making model for measuring the impact of Visudyne therapy on
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febrero-2001
the quality of life of those with AMD. He concluded that PDT is a very effective treatment for AMD, and
that patients who are still able to drive could expect a 10.7% improvement in quality of life if they received the treatment, while patients who were legally blind could expect a 7.8% improvement. This compares to those who have lost significant vision, who are assessed as having a 40% reduction in their quality of life.
With the looming crisis in vision loss as baby boomers advance into their middle and senior years over
the next decade, more than 500,000 people a year will be diagnosed with AMD, and without treatment
will become more dependent on others (and possibly on the welfare system). As Dr. Sharma’s model suggests, “For one patient with macular degeneration to obtain one quality of life-adjusted year, PDT will
cost a managed care organization $86,721. If the treatment proves effective over the entire duration of a
patient’s life, this cost will fall dramatically.” Left unsaid is the potential cost to the system for legally
blind people unable to avail themselves of the treatment.
Clinical update — PDT trials
During the AAO Vitreoretinal Update meeting, Susan Bressler, MD, provided 24-month data for the TAP
study. The data reiterated the significant difference in eyes treated with PDT versus the placebo control,
with 53% of the Visudyne patients losing less than 15 letters (three lines) of visual acuity, compared to
38% for the placebo group. The subgroup results for predominantly classic patients showed even better
results, but they were not so good for those with minimally classic or nonclassic disease. For those with
predominantly classic lesions, 59% lost less than 15 letters, versus 31% of the placebo group; in the minimally classic group, 48% lost less than 15 letters, versus 44% getting the placebo; and 56% versus 30%
for the nonclassic disease group.
Dr. Bressler concluded that the results seen at 12 months were sustained at 24 months, with even more
compelling evidence to use Visudyne therapy for patients with classic wet AMD. The additional benefits
of the 24-month TAP trial were limited, but included slower lesion growth, reduced leakage and stable
contrast sensitivity. The average number of treatments of the group during the second year was 2.2 out of
a possible maximum of 4, resulting in an average number of treatments over the 2-year period of 5.6 out
of a maximum of 8.
Joan Miller, MD, reported on the 12-month results of the Verteporfin in Photodynamic Therapy (VIP)
study for pathologic myopia taking place at 28 clinical centers worldwide. In this case, 72% of those treated achieved less than 8 letter loss (less than 1.5 lines) compared to 44% in the placebo group. Dr. Miller
concluded that VIP treatment resulted in a significantly increased incidence of stability or improved visual acuity, with no evidence of ocular or systemic tissue risk. The VIP trial was focused on two groups
of patients; those with pathologic myopia and those with earlier stage AMD than in the TAP study (that
is, either those with occult lesions or those with classic lesions but better than 20/40 vision). While the
VIP trial was intended to expand the population for Visudyne-eligible patients, it was less definitive than
TAP. Statistical benefits were experienced among those in the pathologic myopia group, but there were
no statistically significant differences or advantages for those with earlier stage AMD treated with Visudyne compared to placebo.
At the AAO’s AMD press conference, Dr. Blumenkranz, coordinator for the Pharmacyclics/Alcon Labs
trials of Optrin (LuTex), said that the phase 1 and 2 clinical trials for that drug had been completed and
were being evaluated prior to recruiting patients for phase 3 trials. (It was also learned that a Zeiss diode
laser is being used for activation, not the Diomed system as reported in my article last year.)
Edgar Thomas, MD, head of the Miravant/Pharmacia & Upjohn trial of Photopoint (purlytin), said the
drug was completing phase 3 trials with nothing new to report.
Laser treatments
Elias Reichel, MD, reported on the results to date in the ongoing multicenter clinical trial to treat occult
wet AMD, the most prevalent form of the disease, with low-intensity laser energy, in the transpupillary
thermotherapy (TTT) for CNV trial. Unlike PDT, this trial used the Iridex Iris Medical SLx 810 nm diode
laser in its unique long-pulse mode to treat the lesions without the need for a photoactive drug. He reported that after 1 year, 80% of patients with occult wet AMD treated with the laser experienced a halt in
new vessel growth and that 70% had stable or improved vision, with no signs of damage to the photore-
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REF.: ACEMSA/SET/AC/ac
febrero-2001
ceptor cells of the retina. TTT appears to stop the evolution of the exudative process, and may avoid development of or progression to the classic form. (Traditionally, half of all cases of occult AMD move into
the classic form, with profound visual loss.)
Anecdotal evidence indicates that TTT is doing quite well in the field, but the reimbursement picture remains cloudy. According to Iridex, reimbursements for this treatment, which are left up to the discretion
of local Medicare carriers, range from a low of $127 to a high of $700. Until this discrepancy and confusion is cleared up, and published peer-reviewed studies on its success begin to appear, TTT will be slow
to be accepted by most retinal surgeons.
Clinical update — dry AMD
At the Iridex booth, a number of speakers provided updates on the ongoing work with both therapeutic
and prophylactic treatments for the dry form of AMD. In a pilot study their 810 nm diode laser was used
in a grid-pattern therapy on nonexudative soft drusen, with resorption of drusen seen in 68% of treated
eyes and visual acuity improvement in 24% of a subset of treated eyes after a single treatment. The company continues to sponsor additional work in both therapeutic and prophylactic trials.
In the therapeutic study, the 4-year follow-up of the original pilot study showed continued improvement
in 78% of treated eyes, defined as a reduction of 50% or more of drusen from baseline, versus only 8% of
eyes not treated but observed. This resulted in visual acuity improvement by two or more lines in 14% of
treated eyes, which suggests a therapeutic benefit for patients with dry AMD who have lost two or more
lines of acuity due to the presence of central soft drusen.
In the ongoing prophylactic study, Prophylactic Treatment of AMD, a total of 35 neovascular events have
occurred in 4 years in the 22% of eyes nonresponsive to treatment, with half occurring in the observed
eyes and half in the treated eyes, indicating no treatment harm or benefit. However, in the 78% of eyes
that responded to treatment with a significant reduction in drusen, only one eye developed CNV. The
study authors suggest that a prophylactic treatment that effectively promotes drusen resorption may be effective in reducing or delaying progression to CNV.
It is beginning to appear that the once-dreaded AMD disease, and the visual loss accompanying it in its
worst cases, will become treatable for the vast majority of those who contract it over the next decade.
This calculation assumes (or less, depending on the co-pay).
For Your Information:
•
Irving J. Arons is managing director of Spectrum Consulting with offices
at 4 Harvard St., Peabody, MA 01960; phone and fax: (978) 531-0939; email: [email protected]. Mr. Arons has no direct financial interest in any
of the products mentioned in this article, nor is he a paid consultant for
any companies mentioned.
Copyright 2001, SLACK Incorporated. Revised 5 January 2001.
Pá gina 112 de 170
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REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO
10
Pá gina 113 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 114 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 115 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 116 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 117 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 118 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 119 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 120 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 121 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 122 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 123 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 124 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 125 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
ANEXO
11
Pá gina 126 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 127 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 128 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 129 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 130 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 131 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 132 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 133 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 134 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 135 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 136 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 137 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 138 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 139 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 140 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 141 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 142 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 143 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 144 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 145 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 146 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 147 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 148 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 149 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 150 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 151 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 152 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 153 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 154 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 155 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 156 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 157 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 158 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 159 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 160 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 161 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 162 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 163 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 164 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 165 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 166 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 167 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 168 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 169 de 170
INFORME VALORATIVO A DEMANDA
Terapia Fotodinámica en el tratamiento de la
Degeneración Macular Asociada a la Edad
REF.: ACEMSA/SET/AC/ac
febrero-2001
Pá gina 170 de 170