Actualizacion de Terapia Anti-VEGF en Enfermedades de La Retina y Coroides

ActualizaciN
de Terapia Anti-Vegf
en Enfermedades
de la Retina y Coroides
Actualizacin
de Terapia Anti-Vegf
en Enfermedades
de la Retina y Coroides
Luis Arias Barquet
Profesor asociado de Oftalmologa,

Universidad de Barcelona,
Hospital Universitario de Bellvitge,
LHospitalet de Llobregat;
Institut de la Mcula i de la Retina,
Centro Mdico Teknon, Barcelona
2010 Elsevier Espaa, S.A.

Travessera de Grcia, 17-21
08021 Barcelona (Espaa)
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El editor
ndice de captulos
Autores.......................................................................................................
vii
Prlogo.......................................................................................................
xi
Prefacio.......................................................................................................
xv
Frmacos anti-VEGF (vascular endothelial growth factor)...........
Captulo 2 Principales ensayos clnicos con frmacos anti-VEGF

en la DMAE exudativa.........................................................
Captulo 3 Pautas de seguimiento y retratamiento en pacientes

con degeneracin macular tratados con ranibizumab
(Lucentis)............................................................................
15
Captulo 4 Gentica del VEGF en la degeneracin macular asociada

a la edad...............................................................................
25
Papel de la angiografa en la era anti-VEGF...........................
29
Captulo 6 Tomografa de coherencia ptica en el seguimiento

del tratamiento anti-VEGF....................................................
39
Captulo 7 Tratamientos combinados: terapia fotodinmica

y anti-VEGF.........................................................................
49
Captulo 8 Tratamiento combinado: anti-VEGF y corticoides.................
55
Captulo 9 Anti-VEGF en combinacin con fotocoagulacin lser..........
61
Captulo 1
Captulo 5
vi
ndice de captulos
Captulo 10 Uso de radioterapia en la neovascularizacin coroidea
secundaria a degeneracin macular asociada a la edad...........
65
Captulo 11 Anti-VEGF en las lesiones polipoideas y la proliferacin

angiomatosa de la retina........................................................
69
Pacientes no respondedores a anti-VEGF...............................
81
Captulo 13 Tratamiento de la neovascularizacin coroidea

en el miope magno con inyeccin intravtrea
de antiangiognicos...............................................................
95
Captulo 12
Captulo 14 Anti-VEGF en las enfermedades inflamatorias....................... 101

Captulo 15
Frmacos anti-VEGF en el edema macular diabtico............. 107
Captulo 16 Anti-VEGF en retinopata diabtica proliferativa................... 115

Captulo 17 Anti-VEGF en las oclusiones venosas retinianas.................... 121
Captulo 18 Anti-VEGF en las distrofias maculares.................................. 131
Captulo 19 Antiangiognicos en las enfermedades tumorales................... 135
Captulo 20
Retinopata de la prematuridad y antiangiognicos................. 141
Captulo 21
Seguridad ocular del tratamiento anti-VEGF......................... 145
Captulo 22
Seguridad sistmica del tratamiento anti-VEGF..................... 155
Captulo 23
Relacin coste-eficacia del tratamiento anti-VEGF................. 163
Captulo 24
Organizacin de una unidad de tratamiento anti-VEGF......... 167
Captulo 25 Tratamiento combinado farmacolgico

en la DMAE exudativa: ms all de la monoterapia
antiangiognica..................................................................... 173
Autores
Santiago Abengoechea Hernndez

Oftalmlogo,
Departamento de Vtreo-retina,
Centro de Oftalmologa Barraquer,
Barcelona
Alfredo Adn Civera
Profesor titular de Oftalmologa,
Departamento de Ciruga y Especialidades
Quirrgicas,
Facultad de Medicina,
Universidad de Barcelona;
Director de Instituto,
Instituto Clnico de Oftalmologa,
Hospital Clnico,
Barcelona
Javier Araiz Iribarren
Profesor Titular de Oftalmologa,
Facultad de Medicina. Universidad del Pas
Vasco,
Instituto Clnico Quirrgico de Oftalmologa
(ICQO),
Bilbao
Luis Arias Barquet
LHospitalet de Llobregat,
Barcelona;
Centro Mdico Teknon,
Barcelona
Flix Armad Maresca

Servicio de Oftalmologa,
Hospital Universitario La Paz,
Madrid
Carolina Arruabarrena Snchez
Doctora en Medicina,
Vissum Corporacin Oftalmolgica,
Hospital Universitario Prncipe de Asturias,
Alcal de Henares,
Madrid
Jos Antonio Buil Calvo
Profesor Asociado,
Universidad Autnoma de Barcelona,
Jefe del Servicio de Oftalmologa,
Hospital de la Santa Creu i Sant Pau,
Barcelona
Francisco Cabrera Lpez
Profesor Asociado,
Universidad de Las Palmas de Gran Canaria;
Oftalmlogo,
Seccin de Vtreo-retina,
Hospital Universitario Insular de Gran Canaria,
Las Palmas de Gran Canaria
Josep M. Caminal Mitjana
Profesor Asociado,
Universidad de Barcelona;
Adjunto del Equipo de Retina y coordinador
de la Unidad de Tumores Intraoculares,
Hospitalet de Llobregat,
Barcelona
viii
Autores
Joaqun Castro Navarro
Seccin de Retina,
Hospital Universitario Central de Asturias,
Oviedo
Jaume Catal Mora
Barcelona;
Instituto Oftalmolgico del Pilar,
Clnica del Pilar,
Barcelona
Enrique Cervera Taulet
Profesor,
Universidad Catlica de Valencia,
Jefe de Servicio de Oftalmologa,
Hospital General Universitario,
Valencia
Ins Contreras Martn
Hospital Universitario Ramn y Cajal,
Madrid
Jaume Crespi Vilimelis
Mdico Adjunto,
Hospital de la Santa Creu i Sant Pau,
Barcelona
M. Carmen Desco Esteban
Unidad de Retina,
Fundacin Oftalmolgica del Mediterrneo,
Valencia
Juan Donate Lpez
Departamento de Patologa Macular,
Hospital Clnico San Carlos,
Madrid
Eduardo Esteban Gonzlez
Jefe de la Unidad de Mcula,
Hospital Universitario Virgen Macarena,
Coordinador de Oftalmologa,
Facultad de Medicina,
Universidad de Sevilla,
Sevilla
lvaro Fernndez-Vega Sanz

Especialista en Oftalmologa,
Fellow en Retina (Eye Foundation UMKC);
Jefe del Servicio de Retina,
Instituto Oftalmolgico Fernndez-Vega,
Oviedo
Maribel Fernndez Rodrguez
Instituto Tecnolgico de Oftalmologa,
Instituto Gallego de Oftalmologa,
Santiago de Compostela,
A Corua
Marta Fonoll Gil
Seccin de Retina,
Hospital Universitario Central
de Asturias,
Oviedo
Ana Mara Garca Alonso
Seccin de Retina,
Hospital Universitario Central
de Asturias,
Oviedo
Jos Garca Arum
Instituto de Microciruga Ocular;
Catedrtico de Oftalmologa,
Universidad Autnoma de Barcelona;
Jefe de Servicio,
Hospital Universitario Vall dHebron,
Barcelona
Alfredo Garca Layana
Doctor en Medicina,
Departamento de Oftalmologa,
Clnica Universidad de Navarra,
Pamplona
Mara Garca Pous
Unidad de Retina,
Fundacin Oftalmolgica
del Mediterrneo,
Valencia
Autores
Francisco Gmez-Ulla de Irazazbal
Presidente de la Sociedad Espaola de Retina
y Vtreo;
Universidad de Santiago de Compostela;
Doctor en Medicina,
Complejo Hospitalario Universitario
de Santiago,
Universidad de Santiago de Compostela,
Santiago de Compostela
Maribel Lpez Glvez
Facultativo Especialista de Oftalmologa,
Hospital Clnico,
Valladolid;
Profesor Asociado en Ciencias de la Visin,
Universidad de Valladolid;
Investigador clnico del Instituto de
Oftalmobiologa Aplicada (Ioba),
Universidad de Valladolid
Jos Luis Olea Vallejo

Jefe de Seccin Vtreo-Retina,
Hospital Son Dureta,
Palma de Mallorca
Elena Palacios Pozo
Unidad de Retina,
Fundacin Oftalmolgica
del Mediterrneo,
Valencia
Natalia Pastora Salvador
Madrid
Laura Pelegrn Cols
Especialista,
Instituto Clnico de Oftalmologa,
Hospital Clnico,
Barcelona
Jorge Mataix Boronat

Unidad de Retina,
Valencia
Jess Peralta Calvo

Madrid
Jordi Mons Carilla

Barcelona
Antonio Piero Bustamante

Catedrtico de Oftalmologa;
Jefe de Servicio,
Hospital Universitario de Valme,
Sevilla
Javier A. Montero Moreno

Instituto de Oftalmologa Alicante VISSUM,
Alicante;
Hospital Po del Ro Hortega,
Universidad de Valladolid,
Valladolid
Amparo Navea Tejerina
Unidad de Retina,
Valencia
Susana Noval Martn
Vissum Corporacin Oftalmolgica,
Madrid
Vladimir Poposki
Licenciado en Medicina y Ciruga,
Seccin de Retina y Vtreo,
Hospitales Universitarios del Mar
y de LEsperana,
Barcelona
Octavio Pujol Goyta
Barcelona;
Clnica del Pilar,
Barcelona
ix
Autores
Marcos Javier Rubio Caso
Barcelona;
Clnica del Pilar,
Barcelona
Daniel Vilaplana i Blanch

Doctor en Medicina i Ciruga,
Seccin de Retina i Vtreo,
Hospitales Universitarios del Mar
y de LEsperana,
Barcelona
Jos Mara Ruiz-Moreno

Departamento de Oftalmologa,
Universidad Castilla-La Mancha,
Albacete;
Instituto de Oftalmologa Alicante,
VISSUM,
Alicante
Eva Villota Deleu

Especialista en Oftalmologa y FEBO,
Servicio de Retina,
Instituto Oftalmolgico Fernndez-Vega,
Oviedo
Marta Surez-Figueroa
VISSUM Corporacin Oftalmolgica;
Hospital Universitario Ramn y Cajal,
Madrid
Clemencia Torrn Fernndez-Blanco
Profesora Asociada,
Universidad de Zaragoza;
Jefa de Seccin de Mcula y Uvetis,
Hospital Universitario Miguel Servet,
Zaragoza
Snia Viver Oller

Oftalmloga,
Departamento de Vtreo-retina,
Centro de Oftalmologa Barraquer,
Barcelona
Miguel ngel Zapata Victori
Doctor en Medicina y Ciruga,
UniversidadAutnoma de Barcelona;
Adjunto de Oftalmologa,
Seccin de la Retina,
Hospital Universitario Vall dHebron,
Barcelona
PRLOGO
Probablemente, cuando Michaelson formul, hace ms de 60 aos, su famosa hiptesis

de la existencia de un factor vasoproliferativo liberado por los tejidos isqumicos y causante de neovascularizacin, no poda imaginarse las repercusiones teraputicas que esto
conllevara. Ni que, 41 aos ms tarde, Napoleone Ferrara lo lograra clonar e identificar
como un factor angiognico al que bautiz
con el nombre de factor de crecimiento del endotelio vascular (VEGF).
Desde este momento, al recordar la hiptesis formulada por Folkman 18 aos antes sobre el factor de angiognesis tumoral y la
demostracin de Dvorak en 1983 de la secrecin tumoral del factor de permeabilidad vascular (hoy conocido como VEGF), empieza
una autntica carrera para desarrollar tratamientos antiangiognicos que luchen contra
los tumores y, de esta manera, la oncologa experimenta una autntica revolucin. Como
ocurre en muchas parcelas de la medicina y la
investigacin, lo que se desarrolla para una
puede servir para otras y, en este caso, la oftalmologa ha ido de la mano de la oncologa
para ofrecer un avance importantsimo en la
batalla para combatir la ceguera.
Muchos son los adelantos que se han producido en el siglo pasado en el campo de la retina;
podramos citar el desarrollo de la angiografa
y de la tomografa de coherencia ptica como

mtodos exploratorios, y los sistemas de campo amplio o los lquidos perfluorocarbonados
como ayuda en el tratamiento quirrgico-vitrectoma. Pero el nuevo siglo nos ha trado
una autntica revolucin y un regalo impensable con el desarrollo de los antiangiognicos,
que han cambiado el curso de la historia natural y el tratamiento de muchas enfermedades
retinianas. Por primera vez, donde antes hablbamos de perder menos visin al tratar la
DMAE hmeda, hoy nos referimos a mejoras
de agudeza visual. En la neovascularizacin
coroidea del miope, esto todava es ms llamativo y con un menor nmero de retratamientos.
Tambin, por primera vez, los antiangiognicos nos ayudan a controlar la neovascularizacin retiniana en muchas enfermedades en las
que el lser o la ciruga vitreorretiniana tienen
que actuar, y se est estudiando su efecto real
como antiedematoso en enfermedades tales
como la retinopata diabtica, las oclusiones
venosas de la retina y el edema macular cistoide secundario a otras enfermedades.
La experiencia mundial en el uso de estos
frmacos en el mbito clnico es tan slo de
5 aos. Comenz como una forma de tratamiento de la DMAE hmeda con la aprobacin por la Food and Drug Administration del
pegabtanib sdico en 2004, y fue seguida pos-
xii
Prlogo
teriormente por el ranibizumab en el 2006.
Pero como los trmites administrativos son
lentos y el bevacizumab ya estaba aprobado
como antiangiognico para el tratamiento del
cncer de colon, y dada su molcula similar
aunque no igual al ranibizumab, los oftalmlogos, despus de escuchar y leer los primeros trabajos de Rosenfeld del Bascom Palmer
Eye Institute de Miami, empezamos a utilizarlo off label, bajo la frmula del uso compasivo,
para poder dar una oportunidad a nuestros pacientes hasta que llegase la comercializacin
de este ltimo, por lo que el uso del bevacizumab se ha extendido a otras indicaciones distintas de la DMAE, en donde no hay por el
momento ningn otro antiangiognico aprobado a la espera de los resultados de los mltiples ensayos clnicos que se estn realizando
con diferentes frmacos desarrollados especficamente para uso oftalmolgico.
Los que llevamos muchos aos dedicando
una parte muy importante de nuestra actividad clnica al tratamiento de la DMAE y otras
enfermedades exudativas y neovasculares de
la retina, vivimos ahora tiempos ms felices,
aunque con una gran sobrecarga de trabajo
pero con un futuro apasionante. Hace escasamente 10 aos, cuando hacamos fotocoagulaciones yuxtafoveales, no nos podamos imaginar que bamos a poder tratar lesiones
subfoveales respetando la retina sensorial
y que podramos llegar a tratar casi todas las
formas de DMAE hmeda slo con que los
pacientes llegasen a tiempo a nuestras consultas. La terapia fotodinmica a principios del
2000 fue el primer intento de tratamiento selectivo fisiopatolgico que buscaba el cierre de
los neovasos coroideos sin daar la retina suprayacente, pero sus resultados no fueron todo
lo buenos que se esperaba de ella y, adems,
no todos los pacientes eran susceptibles a este
tratamiento. Los antiangiognicos, con el ranibizumab a la cabeza, han sido la gran revolucin que ha significado para los oftalmlogos, y sobre todo para nuestros pacientes, un
grito de esperanza.
Pero todava queda mucho por hacer y muchas cuestiones por resolver. No debemos olvidar que los antiangiognicos actuales son
sustancias bloqueadoras y no inhibidoras del

VEGF y que, por tanto, su efecto desaparece
con el tiempo, y nos obliga a realizar inyecciones intravtreas repetidas, lo que significa una
gran sobrecarga asistencial. Esto tiene un efecto directo sobre la necesidad de reorganizar
las consultas y los servicios de oftalmologa,
tanto en el aspecto de dotacin tecnolgica
como de recursos humanos y administrativos, optimizando los recursos disponibles.
Todava desconocemos los efectos de la inhibicin del VEGF a largo plazo y, adems,
debemos aprender a identificar a los no respondedores y a poner en marcha nuevas dianas teraputicas. Lo que se ve no es ms que la
punta del iceberg y debajo se encuentran un
sinfn de molculas en investigacin y dispositivos de liberacin sostenida. Sera tedioso
enumerar todas las molculas que hoy da
estn en diferentes fases de estudio; simplemente podramos recordar como ejemplo el
VEGF-Trap, los agentes inmunomoduladores, los inhibidores de la va mTOR, de las integrinas o de la proteintirosincinasa, entre
otros muchos.
De todo esto, de lo que se conoce en el apasionante mundo de los anti-VEGF y de lo que
viene, se habla en este libro pleno de actualidad. En l escriben los ms destacados oftalmlogos de nuestro pas expertos en retina.
Han sido seleccionados por su experiencia
en los diferentes temas de los que se ocupan
y han conseguido hacer una autntica puesta
al da repasando todas las enfermedades retinianas susceptibles de ser tratadas mediante
estos frmacos. En este libro nada se ha dejado al azar o en el olvido, por muy escabroso
que pudiese resultar, y as, no slo se tratan las
diferentes enfermedades y pacientes, como los
peditricos, sino que tambin se dedican captulos a otras cuestiones, como la relacin coste-eficacia del tratamiento y la organizacin
de una unidad de tratamiento anti-VEGF, haciendo de este libro un autntico manual
que nos permitir a todos consultarlo en nuestro quehacer diario.
El editor y coordinador de esta obra es Luis
Arias Barquet y esto, por s solo, es ya una garanta que, unida a la de los numerosos auto-
Prlogo
res, aade un plus de calidad. Luis Arias tiene
una formacin slida como retinlogo e investigador cimentada en una extensa experiencia
clnica que se refleja en sus conferencias y publicaciones en el campo de la enfermedad macular, que ya han sido referenciadas por otros
muchos colegas en sus artculos internacionales. Esto no le impide ser una persona modesta
que ha irrumpido de puntillas en el mundo oftalmolgico pero que ya se ha labrado un presente indiscutible y un futuro prometedor. Su
natural generosidad hace que todos los que
hemos tenido la suerte de trabajar con l apreciemos estas virtudes, y desde este prlogo
quisiera agradecerle su trabajo y esfuerzo para
aunar y coordinar a tantas personas para hacer posible este libro que hoy, amigo lector,
tienes entre tus manos, y que estoy seguro de
que leers con gran inters y que te ayudar a

despejar dudas en tu ejercicio diario de la oftalmologa.
Un libro se escribe para que se lea y, adems,
retrata a su autor, que cuando me solicit que
escribiera este prlogo me dijo que era un libro
para todos hecho entre todos. Estoy seguro de
que este deseo se va a cumplir y de que el juicio
postrero de los lectores har justicia al esfuerzo,
rigor cientfico, claridad de exposicin y seleccin iconogrfica de los diferentes captulos de
esta obra. Alea jacta est.
Francisco Gmez-Ulla de Irazazbal
Presidente de la Sociedad Espaola
de Retina y Vtreo;
Universidad de Santiago de Compostela
xiii
PRefacio
Este libro pretende ser una puesta al da del

uso de los frmacos anti-VEGF (vascular endothelial growth factor) en las distintas enfermedades de
la retina y coroides en las que pueden estar indicados. Estos frmacos empezaron a usarse para
el tratamiento de la degeneracin macular asociada a la edad (DMAE) exudativa hace tan slo
cuatro aos. Su notable eficacia y buen perfil de
seguridad han difundido su aplicacin a otras
patologas retinianas tales como la retinopata
diabtica y las oclusiones venosas, en las que
tambin se estn obteniendo buenos resultados.
Los dos primeros captulos de la obra estn
dedicados a revisar la estructura molecular de
los distintos frmacos anti-VEGF y los ensayos
clnicos que han avalado su aprobacin por las
autoridades sanitarias, en el caso de pegaptanib
y ranibizumab. En los siguientes captulos se
revisan las pautas de seguimiento y retratamiento de los pacientes, aspectos genticos
y las pruebas complementarias ms relevantes
a la hora de tomar decisiones teraputicas con
estos frmacos. Posteriormente, se estudian posibles terapias de combinacin entre agentes
anti-VEGF y terapia fotodinmica, esteroides,
lser y radioterapia. Tambin se analiza el tratamiento de formas atpicas de DMAE, como
la vasculopata coroidea polipoidal idioptica
y la proliferacin angiomatosa de la retina y el
abordaje de los pacientes no respondedores.
Los siguientes captulos estn dedicados al tratamiento con terapia anti-VEGF de enfermedades distintas a la DMAE que tambin cursan
con neovascularizacin coroidea, como la miopa patolgica, y al tratamiento de enfermedades que cursan con edema macular y que tambin se pueden tratar con estos frmacos. En
los ltimos captulos del libro se revisa la seguridad ocular y sistmica de esta terapia, su rentabilidad y el reto que supone la organizacin
de una unidad de tratamiento y seguimiento de
estos pacientes. Finalmente, se revisan los futuros tratamientos que estn en estudio.
Esta obra ha sido posible gracias al apoyo de
gran parte de los ms prestigiosos retinlogos
de Espaa. Su trabajo, enriquecido con su experiencia, queda plasmado en los distintos captulos del libro. Les doy mi ms sincero agradecimiento a todos ellos por su esfuerzo y dedicacin.
Barcelona, febrero de 2010
Luis Arias Barquet
Profesor asociado de Oftalmologa,
Universidad de Barcelona,
LHospitalet de Llogregat;
Barcelona
Captulo 1
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entre la
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cristalizable.
Bibliografa recomendada
Bakri SJ, Snyder MR, Reid JM, et al. Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology.
2007;114:855-9.
Bauelos Bauelos J, Garca Saenz MC, Gil Manzanero P, Arias Puente A. Farmacologa ocular. Ponencia Oficial
LXXXIII de la Sociedad Espaola de Oftalmologa. 2007. p. 307-13.
Campochiaro P. Retinal and choroidal neovascularization. J Cell Sci. 2000;184:301-10.
Costa RA, Jorge R, Calucci D, et al. Intraviteal bevacizumab for choroidal neovascularization caused by AMD (IBeNA
Study): results of a phase 1 dose-escalation study. Invest Ophthalmol Vis Sci. 2006;47:4569-78.
Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161:851-8.
Frmacos anti-VEGF (vascular endothelial growth factor)
Ferri F, Fine S, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch
Ophthalmol. 1984;102:1640-2.
Folkman J. Anti-angiogenesis; new concepts for therapy of solid tumors. Ann Surg. 1972;175:409-16.
Gaudreault J, Fei D, Beyer JC, et al. Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody
fragment directed against VEGF-A, following intravitreal administration in rabbits. Retina. 2007;27:1260-6.
Gragoudas ES, Adamis AP, Cunningham ET Jr, et al. Pegaptanib for neovascular age-related macular degeneration.
N Engl J Med. 2004;351:2805-16.
Green W, Enher C. Age-related macular degeneration histopathology studies: the 1992 Lorenz Zimmermann lecture.
Ophthalmology. 1993;100:1519-35.
Jaeger RD, Aliello LP, Patel SC, Cunningham ET Jr. Risk of intravitreous injection: a comprehensive review. Retina.
2004;24:676-98.
Kohler G, Milstein C. Continuous cultures of fussed cells secreting antibodies of determined specificity. Nature.
1975;256:495-7.
Michelson IC. The mode of development of the vascular system of the retina: with some observations on its significance for certain retinal diseases. Trans Ophthalmol Soc UK. 1948;68:137-80.
Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of
bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Laser Imaging.
2005;36:331-5.
Ruckman J, Green L, Beeson J. 2-fluopyrimidine RNA-based aptamers to the 165 aminoacid form of vascular endothelial growth factor-VEGF 165: inhibition of receptor binding and VEGF-induced vascular permeability through
interaction requiring the exon 7encoded domain. J Biol Chem. 1998;273:20556-67.
Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGFA) receptor system and its role under physiological and pathological conditions. Clin Sci. 2005;109:27-241.
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ranibizumab (n = 61)
0,5 mg ranibizumab
Inyecciones
mensuales (3)
simuladas (n = 63)
simuladas
NVC subfoveal asociada a DMAE y espesor foveal

central 300 m (OCT) (n = 40)
3 inyecciones mensuales 0,5 mg ranibizumab
D PrONTO
Nueva inyeccin ranibizumab si:

- Prdida AV > 5 letras y uido macular (OCT)
- Incremento grosor foveal > 100 m
- Hemorragia macular
- Nueva neovascularizacin
- Persistencia uido macular 1 mes postinyeccin
Figura 2-1. Diseo de los principales ensayos clnicos con ranibizumab. A, MARINA.
B, ANCHOR. C, PIER. D, PrONTO.
AV, Agudeza visual; DMAE, degeneracin macular asociada a la edad; NVC,
neovascularizacin coroidea; TFD, terapia fotodinmica; OCT, tomografa de
coherencia ptica.
10

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Tabla 2-1. Ensayo MARINA: resultados a 12 y 24 meses
Tiempo Tratamiento Ranibizumab

(meses)
simulado
0,5 mg
(n = 238)
(n = 240)
Ranibizumab
0,3 mg
(n = 238)
Prdida <15 letras

de agudeza visual
ETDRS (%)*
12
62%
94,6%
94,5%
24
52,9%
90%
92%
Ganancia 15 letras
de agudeza visual
ETDRS (%)*
12
5%
33,8%
24,8%
24
3,8%
33,3%
26,1%
Cambio medio de
agudeza visual ETDRS:
letras
12
10,5
+7,2
+6,5
24
14,9
+6,6
+5,4
Tabla 2-2. Ensayo ANCHOR: resultados a 12 y 24 meses
Prdida <15 letras de agudeza visual ETDRS (%)*
Ganancia 15 letras de
agudeza visual ETDRS (%)*
Cambio medio de agudeza

visual ETDRS: letras (desviacin estndar)*
*p <0,01.
TFD, Terapia fotodinmica.
Tiempo
(meses)
TFD
(n = 143)
Ranibizumab Ranibizumab
0,5 mg
0,3 mg
(n = 140)
(n = 140)
12
64,3%
96,4%
94,3%
24
65,7%
89,9%
90%
12
5,6%
40,3%
35,7%
24
6,3%
41%
34,3%
12
9,5 (16,4)
+11,3 (14,6)
+8,3 (14,6)
24
9,8 (17,6)
+10,7 (16,5)
+8,1 (16,2)

Inyeccin simulada Ranibizumab 0,3 mg
(n = 238)
(n = 238)
Ranibizumab 0,5 mg
(n = 240)
Cambio de agudeza visual media (letras)

10
+7,2
+6,6
+5,4
+6,5
Diferencia
21,4 letras ***
0
2
10
12
14
16
18
20
22
24
-5
Diferencia
20,3 letras ***
-10,4
-10
-15
-14,9
Visita (meses)
***p < 0,0001 frente a inyeccin simulada
Rosenfeld et al. N Engl J Med. 2006;355:1419-31.
Figura 2-2. Cambio en la agudeza visual media (MARINA).
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12

Tabla 2-3. Ensayo PIER: resultados a 12 meses
Tiempo Tratamien- Ranibizumab Ranibizumab

(meses) to simula0,5 mg
0,3 mg
do
(n = 61)
(n = 60)
(n = 63)
Prdida <15 letras de agudeza visual ETDRS (%)*
12
49,2%
90,2%
83,3%
Ganancia 15 letras de
agudeza visual ETDRS (%)*
12
9,5%
13,1%
11,7%
Cambio medio de agudeza

visual (letras ETDRS) desde
la inicial
12
16,3
0,2
1,6
*p <0,01.
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Antoszyk AN, Toumi L, Chung CY, Singh A. Ranibizumab combined with verteporfin photodynamic therapy
in neovascular age-related macular degeneration. FOCUS: year 2 results. Am J Ophthalmol. 2008;145:
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Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009;116:1731-9.
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intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol.
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17
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DE, Desviacin estndar; MAVC, mejor agudeza visual corregida.
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Lesin inactiva
Lucentis
Control 6 semanas
Control 4 semanas
Lesin inactiva
Control 8 semanas
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flexible de
visitas de
seguimiento y
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en el estudio
del Hospital de
Bellvitge.
Tabla 3-1. Principales estudios en el tratamiento con Lucentis de pacientes con DMAE neovascular en la prctica clnica diaria
Autor
Estudio
Tratamiento
previo
Protocolo Criterios Medicin Edad me- Composide trata- de retraAV

dia (aos) cin NVC
miento tamiento
124 ojos
(122 pacientes)
Retrospec- No (nave)
tivo
3+PRN
(32%)
1+PRN
(68%)
AV
FO
OCT
Letras
ETDRS
Dadgostar 131 ojos

(124 pacientes)
Retrospec- No (nave)
tivo
1+PRN
AV
FO
OCT
Arias
90 ojos
(88 pacientes)
Prospectivo
No (nave)
3+PRN
Rothenbuehler
138 ojos
(138 pacientes
Prospectivo
No (nave)
1+PRN
78
Localizacin NVC
Clsica:
25%
Oculta:
75%
No definido
Snellen
81
(logMAR)
PC: 16%
MC: 16%
Oculta:
66%
Subfoveal:
75%
Yuxtafoveal:
20%
Extrafoveal:
5%
AV
FO
OCT
Letras
ETDRS
76
Subfoveal:
PC: 33%
83%
MC: 10%
YuxtafoOculta:
45%
veal:17%
RAP: 12%
AV
FO
OCT
Letras
ETDRS
76
PC: 4%
MC: 31%
Oculta:
65%
Subfoveal
AV, Agudeza visual; ETDRS, Early Treatment Diabetic Retinopathy Study; FO, fondo de ojo; MC, mnimamente clsica; NVC, neovascularizacin coroidea; OCT, tomografa de coherencia ptica; PC, predominantemente clsica; PRN, pro re nata (a demanda); RAP, proliferacin
angiomatosa de la retina.
Cohen
Nmero
de casos
19
20
Autor
AV basal
media
AV final
media
Cambio de AV Nmero medio Nmero medio

de inyecciones
de visitas
Seguimiento
(meses)
Cohen
56,1 letras
(20/80+1)
56,8 letras
(20/80+1)
+0,7 letras
3,7
8,0
12
Dadgostar
20/110
20/90
+1 lnea
5,2
No definido
12
Arias
53,0 letras
(20/80-2)
(mediana)
60,0 letras
(20/63)
(mediana)
+5,0 letras
4,4
8,0
12
Rothenbuehler
49,7 letras
(20/100-1)
56 letras
(20/80+1)
+6,3 letras
9,9
No definido
19
AV, Agudeza visual.
Tabla 3-2. Principales resultados de los estudios con Lucentis en la prctica clnica diaria
Figura 3-4. Mujer de 80 aos con neovascularizacin coroidea clsica secundaria a DMAE
tratada con una dosis de carga de tres inyecciones intravtreas mensuales
consecutivas de ranibizumab. La agudeza visual mejora de 20/125 a 20/50.
Basal: retinografa (A), fase precoz de angiografa fluorescenica (AGF) (B), fase
tarda AGF (C), autofluorescencia y tomografa de coherencia ptica (OCT) (D).
Tras las tres inyecciones de ranibizumab: retinografa (E), fase precoz de AGF (F),
fase tarda de AGF (G), autofluorescencia y OCT (H).
21
22
Figura 3-5. Mujer de 70 aos con degeneracin macular asociada a la edad (DMAE)
neovascular en situacin basal (A, retinografa. B, fase precoz de angiografa
fluorescenica [AGF]). C, fase tarda de AGF. D, tomografa de coherencia ptica
[OCT]). En esta paciente se produce una reactivacin de la lesin con nuevo
cmulo de fluido subretiniano cada 12 semanas (E-G, OCT separadas por 12
semanas en las que la paciente recibe su 7., 8. y 9. inyecciones intravtreas de
ranibizumab, respectivamente).
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SXHGHQREWHQHUFRQ/XFHQWLVILJ
Arias L. Del ensayo clnico a la prctica clnica diaria en DMAE neovascular. Simposio: Cmo podemos optimizar an
ms los resultados conseguidos con ranibizumab? 85 Congreso de la Sociedad Espaola de Oftalmologa. Santander, 25 de septiembre de 2009.
Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-44.
Cohen SY, Dubois L, Tadayoni R, et al. Results of one-years treatment with ranibizumab for exudative age-related
macular degeneration in a clinical setting. Am J Ophthalmol. 2009;148:409-13.
Dadgostar H, Ventura A, Chung JY, et al. Evaluation of injection frequency and visual acuity outcomes for ranibizumab monotherapy in exudative age-related macular degeneration. Ophthalmology. 2009;116:1740-7.
Eldem B, Bartz-Schmidt KU, Schlingemann RO, et al. Visual acuity response profiles in patients with neovascular agerelated macular degeneration treated quarterly with ranibizumab in the EXCITE trial. Association for Research
in Vision and Ophthalmology: Abstract no. D1107. 2009.
Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with
intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol.
2007;143: 566-83.
Holz FG, Meyer C, Eter N, et al. Safety and efficacy of ranibizumab treatment in patients with neovascular age-related
macular degeneration: 12-month results of the SUSTAIN study. Association for Research in Vision and Ophthalmology: Abstract no. 3095. 2009.
Lalwani GA, Rosenfeld PJ, Fung AE, et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular
age-related macular degeneration: year 2 of the PrONTO study. Am J Ophthalmol. 2009;148:43-58.
Mitchell P, Korobelnik JF, Lanzetta P, et al. Ranibizumab (Lucentis) in neovascular age-related macular degeneration:
evidence from clinical trials. Br J Ophthalmol. 2009. Disponible en: doi:10.1136/bjo.2009.159160.
Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for
neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008;145:239-48.
Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J
Med. 2006;355:1419-31.
Rothenbuehler SP, Waeber D, Brinkmann CK, et al. Effects on ranibizumab in patients with subfoveal choroidal
neovascularization attributable to age-related macular degeneration. Am J Ophthalmol. 2009;147:831-7.
Schlingemann RO, Schmidt-Erfurth U, Eldem B, et al. Safety and efficacy of quarterly versus monthly ranibizumab
injections in patients with neovascular age-related macular degeneration: 12-month results of the EXCITE study. Association for Research in Vision and Ophthalmology: Abstract no. D1115. 2009.
Spaide RF. Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol.
2007;143:679-80.
23
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Boekhoorn SS, Isaacs A, Uitterlinden AG, Van Duijn CM, Hofman A, De Jong PT, et al. Polymorphisms in the vascular
endothelial growth factor gene and risk of age-related macular degeneration: the Rotterdam Study. Ophthalmology. 2008;115:1899-903.
Brantley MA Jr, Edelstein SL, King JM, Plotzke MR, Apte RS, Kymes SM, et al. Association of complement factor H and
LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy. Eye. 2009;23:626-31.
Brantley MA Jr, Fang AM, King JM, Tewari A, Kymes SM, Shiels A. Association of complement factor H and LOC387715
genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. Ophthalmology. 2007;114:2168-73
Churchill AJ, Carter JG, Lovell HC, Ramsden C, Turner SJ, Yeung A, et al. VEGF polymorphisms are associated with
neovascular age-related macular degeneration. Hum Mol Genet. 2006;15:2955-61.
De la Fuente M, Blanco MJ, Pazos B, Fernndez MI, Carracedo A, Snchez-Salorio M, et al. Complement factor H.
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Papel de la angiografa en la era anti-VEGF
Figura 5-1. Desprendimiento del epitelio pigmentado secundario a vasculopata coroidal

polipoide. A, retinografa en color en la que se observan drusas con dispersin
pigmentaria macular. Levantamiento del polo posterior y una imagen
suavemente anaranjada en la porcin superior del haz papilomacular porcin
superior yuxtapapilar. B, retinografa aneritra. Las drusas y la dispersin se
visualizan mejor contrastadas. C, angiografa fluorescenica. Desprendimiento
del epitelio pigmentado en fases ms tempranas del angiograma. Inicia
hiperfluorescencia de la membrana neovascular oculta. D, angiografa
fluorescenica. Desprendimiento del epitelio pigmentado en fases ms tardas
del angiograma. Hiperfluorescencia acusada de la lesin. E, verde de
indocianina. Tiempos tempranos del angiograma, donde se inicia la
hiperfluorescencia de la lesin polipoidea yuxtapapilar. F, verde de indocianina.
Tiempos tardos del angiograma. Apreciamos bien definida la lesin polipoide
causal del desprendimiento del epitelio pigmentado. G, tomografa de
coherencia ptica. Visualizacin del desprendimiento del epitelio pigmentado
y del caracterstico dedo de guante yuxtapapilar correspondiente a la lesin
polipoide.
31
32
Figura 5-2. Proliferacin angiomatosa de la retina. Estadio II. A, retinografa en color.

Depsitos blanco-amarillentos intrarretinianos procedentes de la exudacin que se produce
en la proliferacin angiomatosa retiniana. Restos hemticos intrarretinianos extrafoveales.
B, retinografa aneritra. Los depsitos y la hemorragia se visualizan mejor contrastadas.
C, angiografa fluorescenica. Fases tempranas del angiograma donde se intuye la
proliferacin angiomatosa retiniana. La sangre produce un efecto pantalla sobre la lesin.
D, angiografa fluorescenica. Fases ms tardas del angiograma. Desprendimiento del
epitelio pigmentado con mancha caliente inferior. E, verde de indocianina. Tiempos
tempranos del angiograma, donde apreciamos la localizacin exacta de la proliferacin
angiomatosa sin efecto pantalla gracias a las propiedades del verde de indocianina. F, verde
de indocianina. Tiempos tardos del angiograma. Observamos la persistencia de la lesin
y no apreciamos ninguna hiperfluorescencia inferior como habamos sospechado con la
fluorescena.
OCLUSIONES VENOSAS
RETINIANAS
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UD$'
Figura 5-3. Retinopata diabtica proliferante. A, retinografa en color. Mnimos

microaneurismas en el polo posterior. B, angiografa fluorescenica. Neovasos en
la zona temporal a la mcula e hiperfluorescencia en la zona nasal secundaria a
neovasos no visibles en la retinografa.
Figura 5-4. Vasculitis (composicin). Tanto en las retinografas en color como en luz aneritra
apenas apreciamos signos. En las diferentes imgenes del polo posterior y
perifricas observamos la difusin del colorante secundario a la vasculitis con
edema macular y pequeas reas de isquemia en la periferia.
33
34
Figura 5-5. Obstruccin venosa, colateral secundaria del tronco principal temporal superior.
A, retinografa en color. Hemorragias prerretinianas en el polo posterior.
Obsrvese la esclerosis vascular de la colateral secundaria del tronco principal
temporal superior. B, retinografa en color. Siguiendo el trayecto de la colateral
secundaria del tronco principal temporal superior observamos hemorragias
intrarretinianas y unas pequeas reas de fibrosis. C, angiografa fluorescenica.
Hemorragias prerretinianas que provocan efecto en pantalla sin poder
determinar la etiologa. D, angiografa fluorescenica. Siguiendo el trayecto
de la colateral secundaria del tronco principal temporal superior observamos
las hemorragias intrarretinianas, una pequea rea de isquemia con amputacin
de la red capilar, telangiectasias y una mnima rea hiperfluorescente con
neovasos causantes de la hemorragia vtrea y del polo posterior.
TUMORES INTRAOCULARES
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CONCLUSIONES
7DQWROD$*)FRPRODDQJLRJUDItDFRQ9,
VLJXHQVLHQGRH[FHOHQWHVPpWRGRVGHGLDJQyV
WLFR\VHJXLPLHQWRSDUDODPD\RUtDGHODVHQ
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/D +'2&7 OD DXWRIOXRUHVFHQFLD \ RWURV
PpWRGRV H[SORUDWRULRV KDQ KHFKR GLVPLQXLU
Figura 5-6. Angioma coroideo. A, retinografa en color. Recidiva de un angioma coroideo

yuxtapapilar previamente tratado con fotocoagulacin lser (ms de 5 aos).
Apreciamos un desprendimiento de retina exudativa con la imagen yuxtapapilar
nasal del angioma hiperpigmentado secundario a la antigua fotocoagulacin
con lser. B, retinografa en color. Desprendimiento de retina inferior exudativa.
C, angiografa fluorescenica. Imgenes angiogrficas hiperfluorescentes activas
causantes de la exudacin crnica. D, tomografa de coherencia ptica de alta
definicin de dominio espectral (HD-OCT). Quistes intrarretinianos en el haz
papilomacular secundarios a la exudacin. E, composicin. Tumoracin inactiva
por la termoterapia. Retina adaptada despus de la ciruga vitreorretiniana.
Retinotoma de drenaje temporal superior. Resto de una bola de
perfluorocarbono retrorretiniano en el meridiano de las 6 h.
35
36

VXV LQGLFDFLRQHV HQ OD SUiFWLFD FOtQLFD GLDULD
SHURQRSRUHOORGHEHPRVUHFKD]DUVXXWLOL]D
FLyQ\REWHQHUDVtXQPHMRUFRQRFLPLHQWRGH
PXFKDVHQIHUPHGDGHVFX\DFXUDFLyQHVWiD~Q
SRUOOHJDU
Augustin AJ, Puls S, Offermann I. Triple therapy for choroidal neovascularization due to age-related macular degeneration: verteporfin PDT, bevacizumab, and dexamethasone. Retina. 2007;27:133-40.
Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, et al. Three-year follow-up of a randomized trial
comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch
Ophthalmol. 2009;127:245-51.
Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, et al. Ranibizumab for macular edema due to retinal
vein occlusions: implication of VEGF as a critical stimulator. Molecular Therapy. J Am Soc Gene Ther. 2008;16:
791-9.
Chang LK, Sarraf D. Tears of the retinal pigment epithelium: an old problem in a new era. Retina. 2007;27:523-34.
Eandi CM, Ober MD, Freund KB, Slakter JS, Yannuzzi LA. Selective photodynamic therapy for neovascular age-related
macular degeneration with polypoidal choroidal neovascularization. Retina. 2007;27:825-31.
Early Treatment Diabetic Retinopathy Study Research Group. EDTRS. Report n. 1. Photocoagulation for diabetic macular edema. Arch Ohthalmol. 1985;103:1796-806.
Forooghian F, Yeh S, Faia LJ, Nussenblatt RB. Uveitic foveal atrophy: clinical features and associations. Arch Ophthalmol. 2009;127:179-86.
Freeman WR, Falkenstein I. Avastin and new tratments for AMD. Where we are? [editorial]. Retina. 2006;26:853-8.
Guyer DR, Yannuzzi LA, Krupsky S, Slakter JS, Sorenson JA, Orlock D, et al. Digital indocyanine-green videoangiography of intraocular tumors. Sem Ophthalmol. 2003;8:224-9.
Muller C, Spital G, Radermacher M, Dohrmann J, Lommatzsch A, Pauleikhoff D. Pigment epithelium detachments in
AMD (age-associated macular degeneration) and polypoid choroidal vasculopathy. A fluorescein and indocyanine green angiography study. Ophthalmologe. 2002;99:85-9.
Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, et al. Pathogenesis of macular edema with branch
retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am
J Ophthalmol. 2005;140:256-61.
Ohno-Matsui K, Tokoro T. The progression of lacquer cracks in pathologic myopia. Retina. 1996;16:29-37.
Otani A, Sasahara M, Yodoi Y, Aikawa H, Tamura H, Tsujikawa A, et al. Indocyanine green angiography: guided photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007;144:7-14.
Snyers B, De Potter P. Advantages of digital indocyanine green angiography for diagnosing choroidal tumors. J Francais Opthalmologie. 2002;25:212-20
Spaide RF, Donsoff I, Lam DL, Yannuzzi LA, Jampol LM, Slakter J, et al. Treatment of polypoidal choroidal vasculopathy
with photodynamic therapy. Retina. 2002;22:529-35.
Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina. 1995;15:100-10.
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Tong JP, Chang WM, Liu DT, Lai TY. Aqueus humor levels of VEGF and pigment epithelium-derived factor in polypoidal
choroidal vasculopathy and choroidal neovascularization. Am J Ophthalmol. 2006;141:456-62.
Vilaplana D, Castilla M, Poposki V. Fotocoagulacin lser en la vasculopata coroidal polipoidea idioptica. Seguimiento superior a un ao. Arch Soc Esp Oftalmol. 2005;80:597-602.
Vilaplana D, Poposki V, Martn D, Martnez-Palmer A, Castilla M. Idiopathic juxtapapillary polypoidal choroidal vasculopathy in the papillomacular bundle: treatment with photodynamic therapy: two years follow-up. Retinal Cases Brief Rep. 2008;2:325-7.
Weinberger AW, Thiel M, Mohammadi B, Theofylaktopoulos I, Thumann G, Walter P. Retinal pigment epithelium tears
after intravitreal bevacizumab in pigment epithelium detachment. Am J Ophthalmol. 2007;144:294-6.
Yanagi Y, Tamaki Y, Sekine H. Fluorescein angiography-guided indocyanine green angiography for the detection of
feeder vessels in subfoveal choroidal neovascularization. Eye. 2004;18:474-7.
Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 1990;10:1-8.
Yannuzzi LA, Sorenson JA, Guyer DR, Slakter JS, Chang B, Orlock D. Indocyanine green videoangiography: current
status. Eur J Ophthalmol. 1994;4:69-81.
Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodrguez-Coleman H, Slakter J, et al. Retinal angiomatous proliferation in
age-related macular degeneration. Retina. 2001;21:416-34.
37
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40

Espejo
de referencia
Onda de referencia
Ojo
Fuente
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con las medidas
(onda de medida)
Detector
Figura 6-1. Interfermetro ptico: tcnica para medir tiempo y distancia en alta resolucin
mediante la luz, comparando un haz de luz con otro. Una luz procedente de una
fuente se dirige a un espejo parcialmente reflejante y es dividida: una onda se
dirige a un espejo de referencia (onda de referencia) y otra hacia el tejido (onda
de medida). La onda de medida es reflejada por el tejido con diferentes retrasos
segn su estructura interna. La onda de referencia se refleja desde el espejo, sin
alterar, pero a un tiempo variable segn la distancia del espejo mvil. Los ecos
de la onda de medida (mltiples) y la onda de referencia (eco nico con retraso
conocido, pues conocemos la distancia del espejo en cada momento) se hacen
coincidir (interferencia) y se detectan. La estructura del eco mltiple de la onda
de medida se determina procesando electrnicamente los datos que llegan
al detector al variar la posicin del espejo de referencia para hacer coincidir un
determinado pulso de luz procedente del tejido, con el pulso de referencia de
retraso conocido.
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Figura 6-2. Seguimiento evolutivo de la degeneracin macular asociada a la edad (DMAE)

con tomografa de coherencia ptica Stratus OCT. A, paciente con
desprendimiento del epitelio pigmentario retiniano (DEP) y fluido subretiniano.
B, se instaura tratamiento con ranibizumab consiguindose una gran mejora.
C, al suspender el tratamiento se observa reactivacin de la neovascularizacin
coroidea.
41
42

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Arias Barquet L. Tomografa de coherencia ptica. En: Monografa de la SERV. Degeneracin Macular Asociada a la
Edad (DMAE) exudativa. 2008.
Bolz M, Michels S, Geitzenauer W, et al. Effect of systemic bevacizumab therapy on retinal pigment epithelial detachment. Br J Ophthalmol. 2008;91:785-9.
Brown DM, Kaiser PK, Michels M, et al, ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular agerelated macular degeneration. N Engl J Med. 2006;355:1432-44.
Brown DM, Regillo CD. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: applying
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Dadgostar H, Ventura AA, Chung JY, Sharma S, Kaiser PK. Evaluation of injection frecuency and visual acuity outcomes for ranibizumab monotherapy in exudative age related macular degeneration. Ophthalmology. 2009;
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Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, et al. An optical coherence tomography-guided,
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Holz F, Jorzik J, Schutt F, et al. Agreement among ophthalmologists in evaluating fluorescein angiograms in patients
with neovascular age-related macular degeneration for photodynamic therapy eligibility (FLAP-study).
Joeres S, Kaplowitz K, Brubaker JW, Updike PG, Collins AT, Walsh AC, et al. Quantitative comparison of optical coherence tomography after pegaptanib or bevacizumab in neovascular age-related macular degeneration.
Kaiser PK, Blodi BA, Shapiro H, et al, MARINA Study Group. Angiographic and optical coherente tomographic results
of the MARINA Study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology.
2007;114:1868-75.
Kashani AH, Keane PA, Dustin L, Walsh AC, Sadda SR. Quantitative subanalysis of cystoid spaces (ICS) and outer nuclear layer (ONL) using OCT in age related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50:3366-73.
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Keane PA, Liakopoulos S, Chag KT, Wang M, Dustin L, Walsh AC, et al. Relationship between optical coherence tomography retinal parameters and visual acuity in neovascular age-related macular degeneration. Ophthalmology.
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Kiernan DF, Hariprasad SM, Chin EK, Kiernan CL, Rago J, Mieler WF. Prospective comparison of cirrus and stratus optical coherence tomography for quantifying retinal thickness. Am J Ophthalmol. 2009;147:267-75.
Krebs I, Haas P, Zeiler F, Binder S. Optical coherence tomography: limits of retinal-mapping program in age-related
macular degeneration. Br J Ophthalmol. 2008;92:933-5.
Krebs I, Falkner-Radler C, Hagen S, et al. Quality of threshold algorithm in age-related macular degeneration: Stratus
versus Cirrus OCT. Invest Ophthalmol Vis Sci. 2009;50:995-1000.
Lommatzsch A, Heimes B, Gutfleisch M, Spital G, Zeimer M, Pauleikhoff D. Serous pigment epithelial detachment in
age related macular degeneration: comparison of different treatments. Eye. 2009 [Epub ahead of print].
Meyer CH, Helb HM, Eter N. Monitoring of AMD patients on antivascular endothelial growth factor treatment. Practical notes on functional and anatomical examination parameters from drug approval studies, specialist information and case series. Ophthalmologe. 2008;105:125-38 y 140-2.
Regillo CD, Brown DM, Abraham P, et al. PIER Study Group. Randomized, doubled-masked, sham-controlled trial of
ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol.
2008;145:239-48.
Sadda SR, Wu Z, Walsh AC, et al. Errors in retinal thickness measurements obtained by optical coherence tomography.
Sayanagi K, Sharma S, Yamamoto T, Kaiser P. Comparison of spectral-domain versus time-domain optical coherence
tomography in management of age-related macular degeneration with ranibizumab. Ophthalmology.
2009;116:947-55.
Schaal KB, Hh AE, Scheuerle A, Schtt F, Dithmar S. OCT based reinjections for anti-VEGF treatment for neovascular
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Witkin AJ, Vuong LN, Srinivasan VJ, et al. High-speed ultrahigh resolution optical coherence tomography before and
after ranibizumab for age-related macular degeneration. Ophthalmology. 2009;116:956-63.
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tratamiento personalizado con terapia fotodinmica (TFD) y bevacizumab.
Se observa que la mayora (95,2%) de los ojos evita la prdida grave de visin
(ms de 15 letras). El 79,3% mantiene la misma o una mejor visin que antes del
tratamiento y el 19% gana ms de 15 letras.
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tratamiento personalizado con terapia fotodinmica (TFD) y ranibizumab.
Se observa que la mayora (92,3%) de los ojos evita la prdida grave de visin
(ms de 15 letras). El 78,8% mantiene la misma o mejor visin que antes del
tratamiento y el 32,7% gana ms de 15 letras.
Tratamientos combinados: terapia fotodinmica y anti-VEGF
Figura 7-3. A, retinografa en color pretratamiento. Hemorragia submacular, alteracin

del epitelio pigmentario macular. B: angiografa con fluorescena pretratamiento.
Hemorragia con efecto pantalla, con hiperfluorescencia que la rodea, membrana
neovascular (MNV) evidente en la parte inferior. C, OCT pretratamiento.
Desprendimiento del epitelio pigmentario (DEP), desprendimiento del
neuroepitelio (DNE). D, OCT a los 3 meses del tratamiento. Desaparicin del DEP
y DNE; reflectividad subfoveal correspondiente a cicatrizacin de la MNV. E, OCT
a un ao. Disminucin de la reflectivad subfoveal. F, retinografa a un ao. Atrofia
del epitelio pigmentario macular; no se observa fibrosis. Progresin de la
esclerosis cristaliniana.
53
54
Augustin AJ, Puls S, Offermann I. Triple therapy for choroidal neovascularization due to age-related macular degeneration: verteporfin PDT, bevacizumab, and dexamethasone. Retina. 2007;27:133-40.
Benjamin LE, Golijanin D, Itin A, et al. Selective ablation of inmature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest. 1999;271:7788-95.
Ferrara N, Gerber H-P, Le Couter J. The Biology of VEGF and its receptors. Nat Med. 2003;9:660-76.
Fingar VH. Vascular effects of photodinamic therapy. J Clin Laser Med Surg. 1996;101:89-99.
Granville DJ, Jiang H, McManus BM, Hunt DW. Fas ligand and TRAIL augment the effect of photodynamic therapy on
the induction of apoptosis in JURKAT cells. Int Immunopharmacol. 2001;1831-40.
Heier JS, Boyer DS, Ciulla TA, Ferrone PJ, Jumper JM, Gentile RC, et al. FOCUS Study Group. Ranibizumab combined
with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the
FOCUS Study. Arch Ophthalmol. 2006;124:1532-42.
Kaiser PK, MD,1 for the Registry of Visudyne AMD Therapy Writing Committee. Verteporfin photodynamic therapy
combined with intravitreal bevacizumab for neovascular age-related macular degeneration. Ophthalmology.
2009;116:747-55.
Navea A, Mataix J, Desco MC, Garca-Pous M, Palacios E. One-year follow-up of combined customized therapy. Photodynamic therapy and bevacizumab for exudative age-related macular degeneration. Retina. 2009;29:13-9.
Schmidt-Erfurth U, Wolf S; PROTECT Study Group. Same-day administration of verteporfin and ranibizumab 0.5 mg
in patients with choroidal neovascularisation due to age-related macular degeneration. Br J Ophthalmol.
2008;92:1628-35.
Witmer AN, Vrensen GFJM, Van Noorden CJF, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye diseases. Prog Retin Eye Res. 2003;22:1-29.
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Figura 8-1. Paciente con lesin de tipo proliferacin angiomatosa de la retina.

A, retinografa previa al tratamiento. B, retinografa a mayor aumento previa al tratamiento
en la que se aprecian las caractersticas hemorragias retinianas de las lesiones tipo RAP.
C, angiografa (AGF) previa al tratamiento en la que se evidencia exudacin a partir
de la neovascularizacin coroidea (NVC) con edema macular asociado. D, tomografa de
coherencia ptica (OCT) previa al tratamiento con edema macular qustico.
(Contina)
57
58
Figura 8-1. (Cont.) E, retinografa posterior al tratamiento en la que se aprecia atrofia en la

zona macular. F, AGF posterior al tratamiento con tincin de la lesin, pero
sin exudacin. G, OCT posterior al tratamiento en la que se aprecia resolucin completa
del edema macular.
CONCLUSIONES
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Arias L, Garca-Arum J, Ramn JM, et al. Photodynamic therapy with intravitreal triamcinolone in predominantly
classic choroidal neovascularization: One-year results of a randomized study. Ophthalmology. 2006;113:
2243-50.
Arias L, Garca-Arum J, Ramn JM, et al. Optical coherence tomography analysis of a randomized study combining
photodynamic therapy with intravitreal triamcinolone. Graefes Arch Clin Exp Ophthalmol, 2008;246:245-254.
Augustin AJ, Puls S, Offermann I. Triple therapy for choroidal neovascularization due to age-related macular degeneration. Verteporfin PDT, bevacizumab, and dexamethasone. Retina. 2007;27:133-40.
Bradley J, Ju M, Robinson GS. Combination therapy for the treatment of ocular neovascularization. Angiogenesis.
2007;10:141-8.
Jonas JB, Libondi T, Golubkina L. Combined intravitreal bevacizumab and triamcinolone in exudative age-related
macular degeneration. Acta Ophthalmol. 2009. Epub ahead of print.
Schaal S, Kaplan HJ, Tezel TH. Is there tachyphylaxis to intravitreal anti-vascular endotelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology. 2008;115:2199-205.
Spaide RF. Perspectives. Rationale for combination therapies for choroidal neovascularization. Am J Ophthalmol.
2006;141:149-56.
Yip PP, Woo CF, Tang HHY, Ho CK. Triple therapy for neovascular age-related macular degeneration using single-session photodynamic therapy combined with intravitreal bevacizumab and triamcinolone. Br J Ophthalmol.
2008;93:754-8.
59
Captulo 9
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62
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una hemorragia vtrea subtotal
en una retinopata diabtica
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complet la PFCR, a medida
que se reabsorba la sangre.
Figura 9-2. Paciente de la figura 9-1,

5 meses despus, con la
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20/40.
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Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic
retinopathy. Ophthalmology. 2006;113:1695.e1-15.
Avitabile T, Longo A, Reibaldi A. Intravitreal triamcinolone compared with macular laser grid photocoagulation for
the treatment of cystoid macular edema. Am J Ophthalmol. 2005;140(4):695-702.
Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of Diabetic Retinopathy Study (DRS) findings. DRS Report Number 8. Ophthalmology.
1981;88:583-600.
DRCRNET. Diabetic Retinopathy Clinical Research Network. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology. 2007;114:1860-7.
Gillies MC, Sutter FKP, Simpson JM, Larsson J, Ali H, Zhu M. Intravitreal Triamcinolone for Refractory Diabetic Macular
Edema. Two-Year results of a double-masked, placebo-controlled, randomized clinical trial. Opthalmology.
2006;113:1533-8.
Gonzlez VH, Giulari GP, Bonda RM, Guel DA. Intravitreal injection of pegaptamib sodium for proliferative diabetic
retinopathy. Br J Ophthalmol. 2009;93(11):1474-8.
Huang YH, Yeh PT, Chen MS, Yang CH, Yang CM. Intravitreal bevacizumab and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage. Retina. 2009;29:1134-40.
Lam DS, Chan CK, Mohamed S, Lai TY, Lee VY, Liu DT, et al. Intravitreal triamcinolone plus sequential grid laser versus
triamcinolone or laser alone for treating diabetic macular edema: six-month outcomes. Ophthalmology.
2007;114(12): 2162-7.
Neubauer AS, Kook D, Haritoglou C, Priglinger SG, Kampik A, Ulbig MW. Bevacizumab and retinal ischemia. Ophthalmology. 2007;114:2096.
ODoherty M, Dooley I, Hickey-Dwyer H. Interventions for diabetic macular oedema: a systematic review of the literature. Br J Ophthalmol. 2008;92:1581-90.
Russo V, Barone A, Conte E, Prascina F, Stella A, Noci ND. Bevacizumab compared with macular laser grid photocoagulation for cystoid macular edema in branch retinal vein occlusion. Retina. 2009;29:511-5.
Soheilian M, Ramezani A, Obudi A, Bijanzadeh B, Salehipour M, Yaseri M, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.
Ophtalmology. 2009;116(6):1142-50.
The Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for macular edema in central
vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology. 1995;102:1425-33.
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from a feasibility study of intraocular, epiretinal radiation therapy for the treatment of subfoveal CNV secondary
to AMD. Retina. 2009;29:157-69.
Avila MP, Farah ME, Santos A, Duprat JP, Woodward BW, Nau J. Twelve-month short-term safety and visual-acuity results from a multicentre prospective study of epiretinal strontium-90 brachytherapy with bevacizumab for the
treatment of subfoveal choroidal neovascularisation secondary to age-related macular degeneration. Br J
Ophthalmol. 2009;93:305-9.
Brucker AJ, Spaide RJ. Supplement on combination therapy. Retina. 2009;29 Suppl:S1.
Chakravarthy U, Houston RF, Archer DB. Treatment of age-related subfoveal neovascular membranes by teletherapy:
a pilot study. Br J Ophthalmol. 1993;77:265-73.
Chan RC, Shukovsky LJ. Effects of irradiation on the eye. Radiology. 1976;120:673-5.
Finger Pt, Berson H, Sherr DA, et al. Radiation therapy for subretinal neovascularization. Opthalmology. 1996;103:
878-89.
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Moore RF. Choroidal sarcoma treated by intra-ocular insertion of radon seeds. Br J Ophthalmol. 1930;14:145-52.
Plowman PN, Harnett AN. Radiotherapy in benign orbital disease. I. Complicated ocular angiomas. Br J Ophthalmol.
1986;72:286-8.
Sivagnanavel V, Evans JR, Ockrim Z, Chong V. Radiotherapy for neovascular age-related macular degeneration [review]. Cochrane Database Syst Rev. 2004;(4):CD004004.
Spaide RF. Rationale for combination therapy in age-related macular degeneration. Retina. 2009;29 Suppl:S5-7.
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Figura 11-1. Caracterstico desprendimiento del epitelio pigmentario en paciente con

vasculopata coroidea polipoide idioptica (VCPI). La angiografa fluorescenica
muestra el desprendimiento con imagen de neovascularizacin coroidea
oculta. Se observa una lesin polipoidea peripapilar en la angiografa con
verde de indocianina.
Anti-VEGF en las lesiones polipoideas y la proliferacin angiomatosa de la retina

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neovascularizacin coroidea oculta en la angiografa fluorescenica. Se aprecia en la
retinografa la tpica hemorragia perilesional con edema intrarretiniano en la tomografa de
coherencia ptica. Con la angiografa con verde de indocianina se hace visible la
comunicacin retino-retiniana.
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Autor, ao
y referencia
bibliogrfica
Tipo
de estudio
N.o de ojos
Frmaco
Dosis
de inyeccin
Seguimiento
Reinyeccin
Lee, 200858
Retrospectivo
Bevacizumab
Dosis simple
17 semanas
A demanda
Lai, 200849
Retrospectivo
15
Bevacizumab
3 mensuales
12,8 meses
A demanda
Gomi, 200848
Retrospectivo
11
Bevacizumab
Dosis simple
3 meses
A demanda
Song, 200973
Retrospectivo
19
Bevacizumab
Dosis simple
3 meses
A demanda
Reche-Frutos,
200874
Prospectivo
13
Ranibizumab
3 mensuales
3 meses
A demanda
Kokame, 200947
Prospectivo
12
Ranibizumab
Mensuales
6 meses
Mensual
Tabla 11-1. Resultados de tratamiento anti-VEGF en la vasculopata coroidea polipoide idioptica
73
74

1.o RANIBIZUMAB
AV OI: 20/50
2.o RANIBIZUMAB
AV OI: 20/40
3.o RANIBIZUMAB
Lesiones polipoideas con verde de indocianina
AV OI: 20/40
Figura 11-3. Caso de neovascularizacin coroidea oculta en un paciente con degeneracin

macular asociada a la edad exudativa refractario al tratamiento con ranibizumab.
Tras tres inyecciones de ranibizumab intravtreo se realiza una angiografa con
verde de indocianina, aprecindose plipos subfoveales. Se realiz una sesin de
terapia fotodinmica con buena respuesta, tanto funcional como anatmica, con un
seguimiento a 12 meses.
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Tabla 11-2. Resultados de tratamiento con bevacizumab en la proliferacin angiomatosa de la retina
Autor, ao
y referencia
bibliogrfica
Tipo de estudio
N.o de ojos
Retrospectivo
Joeres, 200766
Prospectivo
16
Retrospectivo
23
67
Meyerle, 2007
Kang, 200768
Prospectivo
69
I-II-III
Dosis
de inyeccin
Seguimiento
Reinyeccin
Dosis simple
12 meses
A demanda
Dosis simple
3 meses
A demanda
I-II-III
Dosis simple
3 meses
A demanda
II-III
3 mensuales
6 meses
A demanda
II-III
3 mensuales
12 meses
A demanda
Montero, 2008
Retrospectivo
26
Ghazi, 200859
Retrospectivo
13
3 mensuales
3 meses
A demanda
Gharbiya, 200963
Prospectivo
17
3 mensuales
12 meses
A demanda
Tabla 11-3. Resultados de tratamiento con ranibizumab en la proliferacin angiomatosa de la retina
Autor, ao
y referencia
bibliogrfica
Tipo de estudio
Lai, 200770
Freund, 200827
71
N.o de
ojos
Revisin de casos
Revisin de casos
Estadio
Dosis
de inyeccin
Seguimiento
Reinyeccin
3 mensuales
3 meses
A demanda
Dosis simple
Variable
A demanda
Konstantinidis, 2009
Prospectivo
31
II-III
3 mensuales
13,4 meses
A demanda
Rouvas, 200972
Prospectivo
13
II-III
3 mensuales
6 meses
A demanda
Costagliola, 200765
Estadio
75
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35. Gomi F, Ohji M, Sayanagi K, Sawa M, Sakaguchi H, Oshima Y, et al. One-year outcomes of photodynamic therapy
in age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese patients. Ophthalmology. 2008;115:141-6.
36. Quaranta M, Mauget-Faysse M, Coscas G. Exudative idiopathic polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin. Am J Ophthalmol. 2002;134:277-80.
37. Spaide RF, Donsoff I, Lam DL, et al. Treatment of polypoidal choroidal vasculopathy with photodynamic therapy.
Retina. 2002;22:529-35.
38. Chan WM, Lam DS, Lai TY, et al. Photodynamic therapy with verteporfin for symptomatic polypoidal choroidal
vasculopathy. Ophthalmology. 2004;111:1576-84.
39. Lee SC, Seong YS, Kim SS, et al. Photodynamic therapy with verteporfin for polypoidal choroidal vasculopathy of
the macula. Ophthalmologica. 2004;218:193-201.
40. Silva RM, Figueira J, Cachulo ML, et al. Polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin. Graefes Arch Clin Exp Ophthalmol. 2005; 243:973-9.
41. Mauget-Faysse M, Quaranta-El Maftouhi M, De La Marnierre E, Leys A. Photodynamic therapy with verteporfin in the treatment of exudative idiopathic polypoidal choroidal vasculopathy. Eur J Ophthalmol. 2006;16:
695-704.
42. Otani A, Sasahara M, Yodoi Y, et al. Indocyanine green angiography: guided photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007;144:7-14.
43. Akaza E, Yuzawa M, Matsumoto Y, et al. Role of photodynamic therapy in polypoidal choroidal vasculopathy. Jpn
J Ophthalmol. 2007;51:270-7.
77
78

44. Eandi CM, Ober MD, Freund KB, et al. Selective photodynamic therapy for neovascular age-related macular degeneration with polypoidal choroidal neovascularization. Retina. 2007;27:825-31.
45. Lee MW, Yeo I, Wong D, Ang CL. Photodynamic therapy with verteporfin for polypoidal choroidal vasculopathy.
Eye. 2009;23:1417-22.
46. Lee MW, Yeo I, Wong D, Ang CL. Argon laser photocoagulation for the treatment of polypoidal choroidal vasculopathy. Eye. 2009;23:145-8.
47. Kokame GT, Yeung L, Lai JC. Continuous anti-VEGF treatment with ranibizumab for polypoidal choroidal vasculopathy: an Interim 6-month report. Br J Ophthalmol. 2009. Epub ahead of print.
48. Gomi F, Sawa M, Sakaguchi H, Tsujikawa M, Oshima Y, Kamei M, et al. Efficacy of intravitreal bevacizumab for
polypoidal choroidal vasculopathy. Br J Ophthalmol. 2008;92:70-3.
49. Lai TY, Chan WM, Liu DT, Luk FO, Lam DS. Intravitreal bevacizumab (Avastin) with or without photodynamic therapy for the treatment of polypoidal choroidal vasculopathy. Br J Ophthalmol. 2008;92:661-6.
50. Zuo C, Wen F, Li J, Liu Y, Li M. Transitions of multifocal electroretinography following combined intravitreal
bevacizumab and photodynamic therapy for polypoidal choroidal vasculopathy. Doc Ophthalmol. 2009;119:
29-36.
51. Gomi F, Tano Y. Polypoidal choroidal vasculopathy and treatments. Curr Opin Ophthalmol. 2008;19:208-12.
52. Lee WK, Lee PY, Lee SK. Photodynamic therapy for polypoidal choroidal vasculopathy: vaso-occlusive effect on
the branching vascular network and origin of recurrence. Jpn J Ophthalmol. 2008;52:108-15.
53. Yamashiro K, Tsujikawa A, Nishida A, Mandai M, Kurimoto Y. Recurrence of polypoidal choroidal vasculopathy
after photodynamic therapy. Jpn J Ophthalmol. 2008;52:457-62.
54. Tsujikawa A, Hirami Y, Nakanishi H, Ojima Y, Aikawa H, Tamura H, et al. Retinal pigment epithelial tear in polypoidal choroidal vasculopathy. Retina. 2007;27:832-8.
55. Matsushita S, Naito T, Takebayashi M, Sato H, Shiota H. The prognosis of cases with massive subretinal hemorrhage after photodynamic therapy. J Med Invest. 2008;55:231-5.
56. Tong JP, Chan WM, Liu DT, et al. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization. Am J Ophthalmol.
2006;141:456-62.
57. Matsuoka M, Ogata N, Otsuji T, et al. Expression of pigment epithelium derived factor and vascular endothelial
growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy. Br J Ophthalmol.
2004;88:809-15.
58. Lee SY, Kim JG, Joe SG, Chung H, Yoon YH. The therapeutic effects of bevacizumab in patients with polypoidal
choroidal vasculopathy. Korean J Ophthalmol. 2008;22:92-9.
59. Ghazi NG, Knape RM, Kirk TQ, Tiedeman JS, Conway BP. Intravitreal bevacizumab (avastin) treatment of retinal
angiomatous proliferation. Retina. 2008;28:689-95.
60. Gmez-Ulla F, Abraldes MJ, Fernndez M, Olmedo M. Successful treatment of retinal angiomatous proliferation
by photodynamic therapy. Optom Vis Sci. 2006;83:546-9.
61. Bottoni F, Massacesi A, Cigada M, Viola F, Musicco I, Staurenghi G. Treatment of retinal angiomatous proliferation
in age-related macular degeneration: a series of 104 cases of retinal angiomatous proliferation. Arch Ophthalmol. 2005;123:1644-50.
62. Johnson TM, Glaser BM. Focal laser ablation of retinal angiomatous proliferation. Retina. 2006;26:765-72.
63. Gharbiya M, Allievi F, Recupero V, Martini D, Mazzeo L, Gabrieli CB. Intravitreal bevacizumab as primary treatment
for retinal angiomatous proliferation: twelve-month results. Retina. 2009;29:740-9.
64. Krebs I, Krepler K, Stolba U, Goll A, Binder S. Retinal angiomatous proliferation: combined therapy of intravitreal
triamcinolone acetonide and PDT versus PDT alone. Graefes Arch Clin Exp Ophthalmol. 2008;246:237-43.
65. Costagliola C, Romano MR, DellOmo R, Cipollone U, Polisena P. Intravitreal bevacizumab for the treatment of
retinal angiomatous proliferation. Am J Ophthalmol. 2007;144:449-51.
66. Joeres S, Heussen FM, Treziak T, Bopp S, Joussen AM. Bevacizumab (Avastin) treatment in patients with retinal
angiomatous proliferation. Graefes Arch Clin Exp Ophthalmol. 2007;245:1597-602.
67. Meyerle CB, Freund KB, Iturralde D, et al. Intravitreal bevacizumab (Avastin) for retinal angiomatous proliferation.
Retina. 2007;27:451-7.
68. Kang JH, Park KA, Chung SE, Kang SW. Retinal angiomatous proliferation and intravitreal bevacizumab injection.
Korean J Ophthalmol. 2007;21:213-5.
69. Montero JA, Fernndez MI, Gmez-Ulla F, Ruiz-Moreno JM. Efficacy of intravitreal bevacizumab to treat retinal
angiomatous proliferation stage II and III. Eur J Ophthalmol. 2009;19:448-51.
70. Lai TY, Chan WM, Liu DT, Lam DS. Ranibizumab for retinal angiomatous proliferation in neovascular age-related
macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2007;245:1877-80.
71. Konstantinidis L, Mameletzi E, Mantel I, Pournaras JA, Zografos L, Ambresin A. Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP). Graefes Arch Clin Exp Ophthalmol. 2009;247:
1165-71.
72. Rouvas AA, Papakostas TD, Vavvas D, Vergados I, Moschos MM, Kotsolis A, et al. Intravitreal ranibizumab, intravitreal ranibizumab with PDT, and intravitreal triamcinolone with PDT for the treatment of retinal angiomatous
proliferation: a prospective study. Retina. 2009;29:536-44.
73. Song JH, Byeon SH, Lee SC, Koh HJ, Kwon OW. Short-term safety and efficacy of a single intravitreal bevacizumab
injection for the management of polypoidal choroidal vasculopathy. Ophthalmologica. 2009;223:85-92.
74. Reche-Frutos J, Calvo-Gonzlez C, Donate-Lpez J, Garca-Feijoo J, Leila M, Garca-Snchez J. Short-term anatomic effect of ranibizumab for polypoidal choroidal vasculopathy. Eur J Ophthalmol. 2008;18:645-8.
79
Captulo 12
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83
Figura 12-1. Paciente de 78 aos con disminucin de visin y metamorfopsias de 3 das

de evolucin, agudeza visual (AV) basal de 0,4; despus de 3 inyecciones de
ranibizumab la AV es de 0,1. A, retinografa que muestra lesin subfoveal
y desprendimiento neurosensorial (DNS), exudacin dura y alteraciones
pigmentarias. B, angiografa fluorescenica. Membrana clsica subfoveal
de pequeo tamao. C, tomografa de coherencia ptica (OCT) basal donde
se aprecia la membrana y el DNS. Obsrvese la hialoides adherida. D, OCT
4 meses despus de iniciado el tratamiento, la lesin es similar con persistencia
de edema macular y DNS.
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Figura 12-2. Paciente que refiere disminucin de agudeza visual (AV) en el ojo izquierdo,
que ha pasado de 0,8 a 0,3; la exploracin revela una lesin compatible con
proliferacin angiomatosa de la retina (RAP). Se trata con ranibizumab,
pasando a una AV de 0,05 al mes, sin recuperacin a pesar de los sucesivos
tratamientos con ranibizumab. A, tomografa de coherencia ptica (OCT) basal
se observa; RAP, edema macular qustico (EMQ) y desprendimiento
neurosensorial; el espesor central es de 399 m.
(Contina)
85
Figura 12-2. (Cont.) B, OCT al mes de la primera inyeccin de ranibizumab. Intenso EMQ,
espesor central de 709 m.
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Figura 12-2. (Cont.) C, OCT al mes de la segunda inyeccin. Perfil foveal casi normal, espesor
central de 217 m.
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Figura 12-2. (Cont.) D, OCT al mes de la tercera inyeccin. Recidiva del EMQ y
desprendimiento neurosensorial (DNS), espesor central de 415 m.
de la retina
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Figura 12-3. Paciente de 82 aos con proliferacin angiomatosa de la retina (RAP) en el ojo
izquierdo. Agudeza visual (AV) basal de 0,2. Se trat con cuatro inyecciones
consecutivas de ranibizumab con respuesta parcial, AV de 0,3 con persistencia
de edema. A, retinografa, microhemorragia, edema macular y traccin
vascular por membrana epirretiniana (MER). B, angiografa fluorescenica: RAP
y traccin vascular. C, tomografa de coherencia ptica (OCT) basal. Se observa
RAP, edema macular qustico (EMQ) y desprendimiento neurosensorial,
engrosamiento de la hialoides y MER. Espesor central de 636 m. D y E, OCT a
los 5 meses. Disminucin del edema; se aprecia mejor la traccin epirretiniana.
Espesor central de 521 m.
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Figura 12-4. Paciente de 79 aos con desprendimiento de epitelio pigmentario (DEP) y

membrana oculta, tratada con dos inyecciones de ranibizumab. Agudeza visual
(AV) basal de 0,25. En la revisin del tercer mes se aprecia desgarro de epitelio
pigmentario, con bajada de AV a 0,05. A, retinografa basal. B, angiografa
fluorescenica. C, retinografa a los 3 meses. Se observa el DEP con afectacin
foveal. D, tomografa de coherencia ptica. Interrupcin de la banda de
epitelio pigmentario, mnimo fluido intrarretiniano, hiperreflectividad
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Tabla 12-1. Actitud teraputica en no respondedores
Cuadro clnico
Tratamiento alternativo
AV estable o disminuida
OCT sin lquido
Observacin
AV estable
OCT con lquido
Cambio de anti-VEGF
Terapia fotodinmica: membranas clsicas
Observacin: membranas ocultas poco activas
AV disminuida
OCT con lquido
Cambio de anti-VEGF
Terapia fotodinmica: membranas clsicas
Tratamiento combinado: terapia fotodinmica
y anti-VEGF
AV, Agudeza visual; OCT, tomografa de coherencia ptica; VEGF, factor de crecimiento
vascular endotelial.
Tabla 12-2. Actitud teraputica en cuadros clnicos especiales
Cuadro clnico
Hemorragia subretiniana
Tratamiento combinado:
Factor activador del plasmingeno, hexafluoruro
de azufre y anti-VEGF
Terapia fotodinmica y triamcinolona intravtrea
Desprendimiento de epitelio
pigmentario

y anti-VEGF

Tabla 12-2. Actitud teraputica en cuadros clnicos especiales. (Cont.)
Cuadro clnico
de la retina

y triamcinolona intravtrea
polipoide idioptica

y anti-VEGF
VEGF, Factor de crecimiento vascular endotelial.
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93
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Figura 13-1. En la columna de la izquierda podemos observar la retinografa en color

y la angiografa fluorescenica (AGF) en tiempos medio y tardo de un paciente
con neovascularizacin coroidea (NVC) asociada a miopa magna. Se aprecia una
hemorragia junto a la NVC, as como una exudacin evidente en tiempos tardos
de la AGF. La agudeza visual es de 65 letras ETDRS. En la columna de la derecha
observamos el resultado tras tres inyecciones consecutivas intravtreas de 1,25 mg
de bevacizumab. La hemorragia ha desaparecido y no hay escape, sino tincin
en la AGF de la lesin fibrtica. La visin ha mejorado a 82 letras ETDRS. En la parte
inferior observamos la tomografa de coherencia ptica inicial (izquierda)
y despus del tratamiento del paciente (derecha), sin que se encuentren cambios
apreciables.
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Arias L, Planas N, Prades S, Caminal JM, Rubio M, Pujol O, et al. Intravitreal bevacizumab (Avastin) for choroidal
neovascularization secondary to pathological myopia: 6-month results. Br J Ophthalmol. 2008;92:1035-9.
Bennett MD, Yee W. Pegaptanib for myopic choroidal neovascularization in a young patient. Graefes Arch Clin Exp
Ophthalmol. 2007;245:903-5.
Chan WM, Lai TY, Chan KP, Li H, Liu DT, Lam DS, et al. Changes in aqueous vascular endothelial growth factor and
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Chan WM, Lai TY, Liu DT, Lam DS. Intravitreal bevacizumab (Avastin) for myopic choroidal neovascularization sixmonth results of a prospective pilot study. Ophthalmology. 2007;114:2190-6.
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Figurska M, Stankiewicz A. Anti-VEGF therapy in the treatment of myopic macular choroidal neovascularization: cases report. Klin Oczna. 2008;110:387-91.
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choroidal neovascularization. Eur J Ophthalmol. 2007;17:620-6.
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Captulo 14
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coroidopata punteada interna (PIC) que muestra una reduccin de la lesin
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Acharya NR, Hong KC, Lee SM. Ranibizumab for refractory uveitis-related macular edema. Am J Ophthalmol.
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113
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visibles sobre todo en rea nasal superior de la proliferacin fibrovascular (flecha).
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una semana despus de la inyeccin. C, retinografa un mes despus de la
inyeccin.
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neovascular. B, 24 h despus de la inyeccin de anti-VEGF intravtreo, los neovasos
de iris han regresado.
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Captulo 17
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Tabla 17-1. Bevacizumab y oclusiones vasculares retinianas
Autor
N.
de ojos
Tipo
de OV
AV
previa
AV
final
OCT
previa
OCT
final
Perodo de
seguimiento
N. de
inyecciones
16
OVC
20/600
20/138
887 m
372 m
12 semanas
2,8 (1,25 mg)
Rabena
27
OVC
20/200
20/100
478 m
332 m
24 semanas
2 (1,25 mg)
Costa
12
5 OVC
2 OVH
20/320
20/100
730 m
260 m
25 semanas
2 (2 mg)
Ferrara
OVC
20/428
20/53
809 m
190 m
48 semanas
5,8 (1,25 mg)
Priglinger
46
OVC
20/250
20/80
535 m
323 m
24 semanas
2,95 (1,25 mg)
Kreutzer
34
OVR
20/123
20/63
474 m
316 m
24 semanas
2,9 (1,25 mg)
Gnduz
12
OVR
20/163
20/76
507 m
322 m
40 semanas
4 (1,25 mg)
Jaissle
23
OVR
20/63
20/32
395 m
255 m
48 semanas
2,4 (1,25 mg)
Rensch
25
OVC
20/200
20/100
530 m
346 m
24 semanas
3 (1,50 mg)
AV, Agudeza visual; OCT, tomografa de coherencia ptica; OV, oclusin venosa; OVC, oclusin vena central; OVR, oclusin vena de rama;
OVH, oclusin de venas hemisfricas.
Anti-VEGF en las oclusiones venosas retinianas
Iturralde
123
124
Figura 17-1. Paciente con edema macular secundario a oclusin de vena central de la retina
tratado con bevacizumab intravtreo. A, en situacin basal, su agudeza visual era de
20/63. B, tras dos inyecciones intravtreas de bevacizumab, la agudeza visual mejora
a 20/20 y se resuelve el edema macular tomogrfico.
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Figura 17-2. Paciente con

edema macular
secundario a
oclusin de
vena central de
la retina en
situacin basal
(A), tras recibir
tratamiento
con una
inyeccin
intravtrea de
triamcinolona
y tres de
bevacizumab
(B), y tras
recidiva de
edema macular
a las 3 semanas
de la ltima
inyeccin de
bevacizumab
(C).
FLyQVLPXODGD(OSURWRFRORGHOHVWXGLRHVWDED
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ORVSULPHURVPHVHV\GHVSXpVDGHPDQGD$
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PHGLRGHDJXGH]DYLVXDOIXHGHOHWUDVUD
QLEL]XPDE PJ OHWUDV UDQLEL]XPDE
PJ\OHWUDVLQ\HFFLyQVLPXODGD
125
126
Autor
N.
Tipo
de ojos de OV
AV
previa
AV
final
OCT
previa
OCT
final
Perodo de
N. de
seguimiento inyecciones
Spaide et al
20
OVC
45,8 letras
ETDRS
64,3 letras
ETDRS
574,6 m
186 m
12 meses
8,5
Pieramici et al
10
OVC
56,6 letras
ETDRS
58,8 letras
ETDR
616,2 m
497 m
9 meses
4,5
Rouvas et al
12
OVC
8 pacientes > 15 letras ETDRS 480

3 pacientes AV estable
166 m
1 paciente perdi AV
230
33 m
12 meses
7,4
Campochiaro
et al
40
20 OVC 16,07 letras

24,33 letras
ETDRS 20,25 ETDRS
35,50
20 OVR letras ETDRS
Alfaro et al
11
OVR
letras ETDRS
Ganancia media 16,2 11,4

letras ETDRS
526,71 m
327,67 m 3 meses
513,67 m
198,50 m
letras
ETDRS
Reduccin media de
167,9 244,7 m
12
AV, Agudeza visual; OCT, tomografa de coherencia ptica; OV, oclusin venosa; OVC, oclusin vena central; OVR, oclusin vena de rama;
OVH, oclusin de venas hemisfricas.
Tabla 17-2. Ranibizumab y oclusiones vasculares retinianas
Figura 17-3. Aumento de la isquemia macular tras tratamiento con bevacizumab intravtreo.
A y B, pretratamiento. C y D, postratamiento.
Figura 17-4. Oclusin

venosa
retiniana de
rama en
situacin basal
(A) y a los
2 meses de
recibir una
nica inyeccin
intravtrea de
ranibizumab
(B).
127
128
Pegaptanib (Macugen)
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Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of
patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994; 331:1480-7.
Alfaro VD, Jablon EP, Kerrison JB, Rodriguez-Fontal M, Gmez-Ulla F, Bueno R. Ranibizumab for the treatment of
branch retinal vein occlusion-associated cystoid macular edema. Poster 2699/A480 ARVO apr 2008.
Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, et al. Correlation of increased vascular endothelial
growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol.
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Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, et al. Ranibizumab for macular edema due to retinal
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Iturralde D, Spaide RF, Meyerle CB, Klancnik JM, Yannuzzi LA, Fisher YL, et al. Intravitreal bevacizumab (Avastin)
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Study. Arch Ophthalmol. 2008;126:513-8.
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Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, et al. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion. Graefes
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treatment of central retinal vein occlusion: six-month results of a prospective trial. Retina. 2007;27:1004-12.
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Pieramici DJ, Rabena M, Castellarin AA, Nasir M, See R, Norton T, et al. Ranibizumab for the treatment of macular
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ahead of print.
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2009;147:298-306.
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129
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Figura 18-2. A, hemorragia submacular asociada a pliegues retinianos en el contexto de una

enfermedad de Best. B y C, angiografa fluorescenica que pone de manifiesto la
presencia de una membrana neovascular coroidea subfoveal.
Figura 18-3. A, retinografa de control al mes y medio con restos de hemorragia en reabsorcin.
B y C, tincin de la membrana neovascular tras una inyeccin intravtrea de
ranibizumab.
133
134
Benhamou N, Messas-Kaplan A, Cohen Y, Gaudric A, Souied EH, Soubrane G, et al. Adult-onset foveomacular vitelliform dystrophy with OCT 3. Am J Ophthalmol. 2004;138:294-6.
Da Pozzo S, Parodi MB, Toto L, Ravalico G. Occult choroidal neovascularization in adult-onset foveomacular vitelliform
dystrophy. Ophthalmologica. 2001;215:412-4.
Lee JY, Lim J, Chung H, Kim JG, Yoon YH. Spectral domain optical coherence tomography in a patient with adult-onset
vitelliform dystrophy treated with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging. 2009;40:319-21.
Leu J, Schrage NF, Degenring RF. Choroidal neovascularization secondary to Bests disease in a 13-year-old boy treated by intravitreal bevacizumab. Graefes Arch Clin Exp Ophthalmol. 2007;245:1723-5.
Montero JA, Ruiz-Moreno JM, De La Vega C. Intravitreal bevacizumab for adult-onset vitelliform dystrophy: a case
report. Eur J Ophthalmol. 2007;17:983-6.
Parodi MB, Iacono P, Pedio M, Pece A, Isola V, Fachin A, et al. Autofluorescence in adult-onset foveomacular vitelliform
dystrophy. Retina. 2008;28:801-7.
Querques G, Bocco MC, Soubrane G, Souied EH. Intravitreal ranibizumab (Lucentis) for choroidal neovascularization
associated with vitelliform macular dystrophy. Acta Ophthalmol. 2008;86:694-5.
Spaide RF. Deposition of yellow submacular material in central serous chorioretinopathy resembling adult-onset foveomacular vitelliform dystrophy. Retina. 2004;24:301-4.
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Antiangiognicos en las enfermedades tumorales

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25. Buelow M, Pape S, Hoerauf H. Systemic bevacizumab treatment of a juxtapapillary retinal haemangioma. Act
Ophthalmol Scand. 2007;85:114-6.
26. Wong WT, Liang KJ, Hammel K, Coleman HR, Chew EY. Intravitreal ranibizumab therapy for retinal capillary hemangioblastoma related to von Hippel-Lindau disease. Ophthalmol. 2008;115:1957-65.
27. Dahr SS, Cusick M, Rodrguez-Oleman H, Srivastava SK, Thompson DJ. Intravitreal anti-vascular endothelial
growth factor therapy with pegaptanib for advanced von Hippel-Lindau disease of the retina. Retina. 2007;
27:150-8.
28. Ziemssen F, Voelker M, Inhoffen W, Bartz-Schmidt KU. Combined treatment of a juxtapapillary retinal capillary
haemangioma with intravitreal bevacizumab and photodynamic therapy. Eye. 2007;21:1125-6.
29. Kenawy N, Groenwald C, Damato B. Treatment of a vasoproliferative tumour with intravitreal bevacizumab
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139
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Chow LC, Wright KW, Sola A; CSMC Oxygen Administration Study Group. Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants? Pediatrics.
2003;111:339-45.
Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of
retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch
Ophtalmol. 2003;121:1684-94.
Sonmez K, Drenser KA, Capone A Jr, Trese MT. Vitreous levels of stromal cell-derived factor 1 and vascular endothelial growth factor in patients with retinopathy of prematurity. Ophthalmology. 2008;115:1065-1070.e1.
Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone I. Retina. 2008;28:831-8.
Chung EJ, Kim JH, Ahn HS, Koh HJ. Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2007;245:1727-30.
Travassos A, Teixeira S, Ferreira P, Regadas I, Travassos AS, Esperancinha FE, et al. Intravitreal bevacizumab in
aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging. 2007;38:233-7.
Kusaka S, Shima C, Wada K, Arahori H, Shimojyo H, Sato T, et al. Efficacy of intravitreal injection of bevacizumab
for severe retinopathy of prematurity: a pilot study. Br J Ophthalmol. 2008;92:1450-5.
Quiroz-Mercado H, Martnez-Castellanos MA, Hernndez-Rojas M, Salazar-Tern N, Chan RVP. Antiangiogenic
therapy with intravitreal bevacizumab for retinopathy of prematurity. Retina. 2008;28:s19-s25.
Lalwani GA, Berrocal AM, Murray TG, Buch M, Cardone S, Hess D, et al. Off-label use of intravitreal bevacizumab
(Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Retina. 2008;28
Suppl:s13-8.
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2008;246:1061-3.
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Pediatr. 2009;21:182-7.
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Tabla 21-1. Efecto de los anti-VEGF sobre los tejidos oculares en modelos animales
Nishijima, 2007
Prdida de clulas ganglionares en inhibicin crnica
Ishida, 2003
VEGF 164: inhibicin neovascularizacin patolgica de forma

predominante
Bakri, 2006
Ausencia de signos ultraestructurales de toxicidad a corto plazo
Iriyama, 2007
Ausencia de toxicidad sobre clulas ganglionares a corto plazo
Luthra, 2006
Ausencia de toxicidad a dosis bajas sobre distintas poblaciones

celulares
Spitzer, 2006
Efecto antiproliferativo endotelial y citotxico sobre epitelio

pigmentario dosis-dependiente
Avci, 2009
Aumento de apoptosis de fotorreceptores dosis-dependiente

con inhibidor no selectivo
Seguridad ocular del tratamiento anti-VEGF

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a la
administracin
de inyecciones
intravtreas.
149
150

Tabla 21-2. Tcnica bsica de la inyeccin intravtrea
Procedimiento para inyeccin intravtrea

Maniobra
Justificacin
Preparacin
ocular
Povidona yodada en piel

y prpados
Colirios estriles:
Dilatacin pupilar
Anestesia suficiente
Povidona al 5% en
conjuntiva
Colocacin de blefarostato
Prevencin de la
contaminacin con la flora
bacteriana
Visualizacin ptima
Bienestar del paciente
Aislamiento de borde
palpebral y pestaas
Procedimiento
Agujas de calibre igual o

inferior a 27 g
Marcado en cuadrante
temporal inferior:
3-3,5 en seudofacos
3,5-4 en fquicos
Inyeccin lenta hacia el centro
del globo
Retirada lenta con presin
simultnea (bastoncillo o
hemosteta)
Prevencin del reflujo

Profilaxis del desprendimiento
de retina
Profilaxis de catarata
yatrognica
Evitar dispersin del frmaco
Evitar reflujo
Control
inmediato
Verificacin de percepcin
de luz
Visualizacin de la perfusin
en el disco ptico
Profilaxis del cierre de la

arteria central de la retina
Maniobras que
se deben evitar
Manipulacin excesiva o masaje palpebral previo o posterior

a la inyeccin
Contacto de la aguja con borde libre palpebral o pestaas
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Figura 21-2. Secuencia de maniobras en la inyeccin intravtrea.
Tabla 21-3. Maniobras debatidas en el procedimiento de inyeccin intravtrea
Maniobra
Discusin
Antibiticos
tpicos previos
Sinergia con la povidona en la reduccin de la flora conjuntival

No demostrado su impacto en la reduccin de la endoftalmitis
(Scott, 2008)
Creacin de resistencias (Flynn, 2005)
Dilatacin pupilar
Innecesaria, fuente adicional de contaminacin (Weber et al,

2008)
Anestesia
subconjuntival
Mayor frecuencia de hemorragia subconjuntival (Kozak et al,

2005)
Anestesia en gel
Barrera fsica a la accin de la povidona (SERV, 2009)
Pao quirrgico
estril
Preceptivo (AFSSAPS, 2006), (DOG, 2007)

(Contina)
151
152

Tabla 21-3. Maniobras debatidas en el procedimiento de inyeccin intravtrea (Cont.)
Maniobra
Discusin
Povidona yodada
en irrigacin
conjuntival
Mayor reduccin de la colonizacin conjuntival (Safar et al,

2007)
Desplazamiento
conjuntival
Impedir acceso directo de grmenes a la cavidad vtrea

(RANZCO, 2006)
Inyeccin oblicua
Creacin de una va valvulada y reduccin del reflujo (LpezGuajardo et al, 2008)
Paracentesis
Inmediata si no se observa perfusin (AAO, 2008)
Antibiticos
tpicos
posteriores
Evidencia documentada de bridas vtreas (Beer et al, 2007)
Inyeccin bilateral
simultnea
Comodidad del paciente, reduccin del nmero de visitas

(Bakri et al, 2009)
AAO, American Academy of Ophthalmology; AFSSAPS, Agence Franaise de Scurit

Sanitaire et des Produits de Sant; RANZCO, Royal Australian and New Zealand College
of Ophthalmologists; SERV, Sociedad Espaola de Retina y Vtreo.
Aiello LP, Brucker AJ, Chang S, Cunningham ET Jr, DAmico DJ, Flynn HW Jr, et al. Evolving guidelines for intravitreous
injections. Retina. 2004;24 Suppl:S3-19.
Agence Franaise de Scurit Sanitaire et des Produits de Sant [accedido. 4 de julio de 2009]. Disponible en: http://
www.afssaps.fr/var/afssapssite/storage/original/application/2fa13fc93be90ca605d05d2621849d19.pdf.
American Academy of Ophthalmology. Policy statement intravitreal injections [accedido 4 de julio de 2009]. Disponible en: http://www.aao.org/about/policy/upload/Intravitreal-Injections-2008.pdf.
Angulo Bocco MC, Glacet-Bernard A, Zourdani A, Coscas G, Soubrane G. Intravitreous injection: retrospective study
on 2028 injections and their side effects. J Fr Ophtalmol. 2008;31:693-8.
Arvalo JF, Maia M, Flynn HW Jr, Saravia M, Avery RL, Wu L, et al. Tractional retinal detachment following intravitreal
bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol. 2008;92:
213-6.
Avci B, Avci R, Inan UU, Kaderli B. Comparative evaluation of apoptotic activity in photoreceptor cells after intravitreal
injection of bevacizumab and pegaptanib sodium in rabbits. Invest Ophthalmol Vis Sci. 2009;50:3438-46.
Bakri SJ, Cameron JD, McCannel CA, Pulido JS, Marler RJ. Absence of histologic retinal toxicity of intravitreal bevacizumab in a rabbit model. Am J Ophthalmol. 2006;142:162-4.
Bakri SJ, Risco M, Edwards AO, Pulido JS. Bilateral simultaneous intravitreal injections in the office setting. Am
J Ophthalmol. 2009;148:66-9.
Beer PM, Beer EA, Stepien KE, Stanciu N, Falk NS. Photographic evidence of vitreous wicks after intravitreal injections.
Retina Today [edicin electrnica] 2007 (citado 4 de julio de 2009). Disponible en: http://www.bmctoday.net/
retinatoday/2007/03/article.asp?f=0307_07.html

Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-44.
Deutsche Ophthalmologische Gesellschaft. Statement of the German Ophthalmological Society, the Retinological
Society and the Association of Ophthalmologists in Germany on current therapeutic options in neovascular
age-related macular degeneration [accedido 19 de septiembre de 2009]. Disponible en: http://www.dog.org/
engl/publikationen/DOG_Statement_AMDTherapy.pdf.
Diago T, McCannel CA, Bakri SJ, Pulido JS, Edwards AO, Pach JM. Infectious endophthalmitis after intravitreal injections of antiangiogenic agents. Retina. 2009;29:601-5.
Falkenstein IA, Cheng L, Freeman WR. Changes of intraocular pressure after intravitreal injection of bevacizumab
(Avastin). Retina. 2007;27:1044-7.
Famiglietti EV, Stopa EG, McGookin ED, Song P, LeBlanc V, Streeten BW. Immunocytochemical localization of vascular
endothelial growth factor in neurons and glial cells of human retina. Brain Res. 2003;969:195-204.
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Captulo 22
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Tabla 22-1. Efectos adversos potenciales del bloqueo del VEGF
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en pacientes diabticos
Afectacin de la circulacin colateral

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(%)
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2 frente a 3
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Tabla 22-2. Eficacia y efectos adversos sistmicos observados en estudios prospectivos del tratamiento con anti-VEGF

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161
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Relacin coste-eficacia del tratamiento anti-VEGF
Tabla 23-1. Parmetros considerados en el estudio coste-eficacia comparativo entre terapia

fotodinmica y ranibizumab
Grupo de terapia fotodinmica

Pacientes
Tratamientos
Lneas ganadas en 1 ao
Gastos persona/acto
Gastos fungibles/tratamiento
Gastos frmaco/tratamiento
Consulta sin tratamiento
Gasto/AGF
AGF en TFD (4/ao)
1.650
Grupo de ranibizumab 5,8 meses

Pacientes
570
Tratamientos
Lneas ganadas 5,4 meses
Gasto persona/tratamiento
Gasto persona/cons
Gastos fungibles/tratamiento
Gastos frmaco/tratamiento
Consulta sin tratamiento
Gasto/AGF
AGF en TFD (3/ao)
AGF, Angiografa fluorescenica; TFD, terapia fotodinmica.
Tabla 23-2. Gasto por paciente y ao en el estudio coste-eficacia comparativo entre terapia
Gasto por paciente/Ao
Terapia fotodinmica
5.488.454,12 /1.650
pacientes
3.326,34
Ranibizumab 5,8 meses Ranibizumab 6,2 meses/

(PIER)
ao
2.088.309,16 /1.824
pacientes
3.663,70
3.182.534,34 /570
pacientes
5.583,39
Tabla 23-3. Coste por letra ganada en el estudio coste-eficacia comparativo entre terapia
Gasto por letra ganada (dejamos de perder)

TFD /RBZ
TFD
RBZ
Coste por letra

ganada
Letras perdidas sin tratamiento (TAP/VIP)

Letras perdidas con tratamiento
Ganancia de letras:
-20,80
-12,20
6,80
3.326,34 /6,80
Letras perdidas sin tratamiento (TAP/VIP)

Dejamos de perder con tratamiento
Ganancia de letras:
-20,80
+6,00
26,80
9.247,09 /26,80
RBZ, Ranibizumab; TFD, tratamiento fotodinmica.
386,78
165
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Fletcher EC, Lade RJ, Adewoyin T, Chong NV. Computerized model of cost-utility analysis for treatment of age-related
macular degeneration. Ophthalmology. 2008;115(12):2192-8.
Gower EW, Cassard SD, Bass EB, Schein OD, Bressler NM. A cost-effectiveness analysis of three treatments for age-related macular degeneration. Retina. 2009;23. [Epub ahead of print]
Hernndez-Pastor LJ, Ortega A, Garca-Layana A, Girldez J. Cost-effectiveness of ranibizumab compared with photodynamic treatment of neovascular age-related macular degeneration. Clin Ther. 2008;30(12):2436-51.
Hernndez-Pastor LJ, Ortega A, Garca-Layana A, Girldez J. Cost-effectiveness of ranibizumab compared with
pegaptanib in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2009;11.
[Epub ahead of print].
Hurley SF, Matthews JP, Guymer RH. Cost-effectiveness of ranibizumab for neovascular age-related macular degeneration. Cost Eff Resour Alloc. 2008;24;6:12.
Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J; for the Vision Health Cost-Effectiveness
Study Group. Arch Ophthalmol. 2009;127:553-40.
Smiddy WE. Relative cost of a line of vision in age-related macular degeneration. Ophthalmology. 2007;114(5):847-54.
Stel VS, Pluijm SM, Deeq DJ, et al. A clasification tree for predicting recurrent falling in community-dwelling older persons. J Am Geriatr Soc. 2003;51(10):1356-64.
Vedula SS, Krzystolik MG. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2008;16(2):CD005139. Review.
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Tabla 24-1. Caractersticas de una consulta

de tratamiento antiangiognico
Frecuencia de visitas muy alta mensual
hasta trimestral
Gran dependencia de la relacin
mdico-paciente
Enfermedad crnica: muy difcil hablar
de alta
Abanico de enfermedades cada vez
ms amplio
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Tabla 24-2. Consideraciones que se deben tener siempre presentes

El nmero de pacientes crecer de manera exponencial
Importante ejercer control sobre la entrada
Disponer de personal auxiliar entrenado es fundamental para optimizar cada uno
de los pasos
Las enfermedades neovasculares, en especial, la degeneracin macular exudativa,
son procesos crnicos, no se curan
Los resultados estn ligados a un seguimiento bien protocolarizado
Optimizar cada visita y no realizar pruebas que supongan cambios de actitud
Invertir tiempo en la primera visita
Ofrecer un acceso alternativo a la cita como, por ejemplo, el telfono
Establecer criterios de alta que permitan remitir las revisiones sistemticas
a las aferencias (consulta ambulatoria, oftalmlogo habitual, etc.)
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Pacientes que vuelven tras un alta

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Entrada de pacientes
- Replanteamiento tratamiento
- Atencin primaria
- Atencin especializada
- Urgencia
- Consulta intraservicio
- Derivado de otras unidades
Consulta especializada
Alternativas a cita
- Acceso telefnico
- Acceso a consulta sin cita
Revisiones 8-10 primer ao
Respetar cadencia recomendada
Tratamientos
Sistematizados
Repeticin de rutinas
Personal entrenado
Control sobre listados de pacientes pendientes
de tratamiento
Primera visita
Examen exhaustivo
Tiempo: invertir en explicar la patologa
Visitas sucesivas
Optimizar protocolo
Racionalizar uso de pruebas laboriosas
Enfermera/personal auxiliar
Recogida de informacin
Toma de AV (reproducible)
Toma de PIO (segn protocolo)
Midiriasis
Facultativo especialista
BMC (cuando posible y/o protocolo
Pruebas diagnsticas
OCT (imprescindible)
AGF (segn protocolo)
Toma de decisiones
Guiar al paciente
Programacin de tratamiento
Salida de pacientes
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- Mala respuesta a tratamiento
- Rechazo a ms tratamiento
- Cambio de centro especializado
Figura 24-1. Organizacin de una unidad especializada de terapia anti-VEGF.

AGF, Angiografa fluorescenica; AV, agudeza visual; BMC, biomicroscopia; PIO, prueba de
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rea de Investigacin y Estudios Sanitarios. Eficacia, efectividad y seguridad de la terapia fotodinmica. Impacto econmico en la Comunidad de Madrid. Agencia Lan Entralgo; nov. 2004.
Schmier JK, Jones ML, Halpern MT. The burden of age-related macular degeneration. Pharmacoeconomics. 2006;
24(4):319-34.
Brown GC, Brown MM, Brown HC, Kindermann S, Sharma S. A value-based medicine comparison of interventions for
subfoveal neovascular macular degeneration. Ophthalmology. 2007;114(6):1170-8.
171
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Actualizacion de Terapia Anti-VEGF en Enfermedades de La Retina y Coroides

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ActualizaciN

Profesor asociado de Oftalmologa,

2010 Elsevier Espaa, S.A.

Fotocopiar es un delito. (Art. 270 C. P.)

Frmacos anti-VEGF (vascular endothelial growth factor)...........

Captulo 2 Principales ensayos clnicos con frmacos anti-VEGF

Captulo 3 Pautas de seguimiento y retratamiento en pacientes

Captulo 4 Gentica del VEGF en la degeneracin macular asociada

Papel de la angiografa en la era anti-VEGF...........................

Captulo 6 Tomografa de coherencia ptica en el seguimiento

Captulo 7 Tratamientos combinados: terapia fotodinmica

Captulo 8 Tratamiento combinado: anti-VEGF y corticoides.................

Captulo 9 Anti-VEGF en combinacin con fotocoagulacin lser..........

Captulo 11 Anti-VEGF en las lesiones polipoideas y la proliferacin

Pacientes no respondedores a anti-VEGF...............................

Captulo 13 Tratamiento de la neovascularizacin coroidea

Captulo 14 Anti-VEGF en las enfermedades inflamatorias....................... 101

Frmacos anti-VEGF en el edema macular diabtico............. 107

Captulo 16 Anti-VEGF en retinopata diabtica proliferativa................... 115

Retinopata de la prematuridad y antiangiognicos................. 141

Seguridad ocular del tratamiento anti-VEGF......................... 145

Seguridad sistmica del tratamiento anti-VEGF..................... 155

Relacin coste-eficacia del tratamiento anti-VEGF................. 163

Organizacin de una unidad de tratamiento anti-VEGF......... 167

Captulo 25 Tratamiento combinado farmacolgico

Santiago Abengoechea Hernndez

Flix Armad Maresca

lvaro Fernndez-Vega Sanz

Jos Luis Olea Vallejo

Jorge Mataix Boronat

Jess Peralta Calvo

Jordi Mons Carilla

Antonio Piero Bustamante

Javier A. Montero Moreno

Daniel Vilaplana i Blanch

Jos Mara Ruiz-Moreno

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y de la tomografa de coherencia ptica como

sustancias bloqueadoras y no inhibidoras del

que leers con gran inters y que te ayudar a

Este libro pretende ser una puesta al da del

2010. ELSEVIER Espaa, S.L. Reservados todos los derechos.

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Actualizacin de terapia anti-VEGF en enfermedades de la retina y coroides

Figura 1-1. Estructura

Figura 1-2. Estructura molecular

ELSEVIER. Fotocopiar sin autorizacin es un delito.

Frmacos anti-VEGF (vascular endothelial growth factor)

Figura 1-3. Estructura molecular y preparacin comercial de bevacizumab.

Actualizacin de terapia anti-VEGF en enfermedades de la retina y coroides

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Figura 1-4. Diferencias

Frmacos anti-VEGF (vascular endothelial growth factor)

ELSEVIER. Fotocopiar sin autorizacin es un delito.

ENSAYOS CLNICOS CON ANTIVEGF PARA EL TRATAMIENTO

Actualizacin de terapia anti-VEGF en enfermedades de la retina y coroides

Estudios con ranibizumab

Ensayos clnicos principales

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Principales ensayos clnicos con frmacos anti-VEGF en la DMAE exudativa

Inyecciones mensuales 0,5 mg ranibizumab

Inyecciones mensuales 0,3 mg ranibizumab

2010 Elsevier Espaa, S.A.

Captulo 2 Principales ensayos clnicos con frmacos anti-VEGF

Captulo 3 Pautas de seguimiento y retratamiento en pacientes

Captulo 4 Gentica del VEGF en la degeneracin macular asociada

Captulo 6 Tomografa de coherencia ptica en el seguimiento

Captulo 7 Tratamientos combinados: terapia fotodinmica

Captulo 8 Tratamiento combinado: anti-VEGF y corticoides.................

Captulo 11 Anti-VEGF en las lesiones polipoideas y la proliferacin

Captulo 13 Tratamiento de la neovascularizacin coroidea

Captulo 25 Tratamiento combinado farmacolgico

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