Resultados a largo plazo del tratamiento de la degeneración macular asociada a la edad neovascular mediante fármacos antiangiogénicos: revisión de la bibliografía / Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature

La degeneración macular asociada a la edad (DMAE) constituye una de las principales causas de la pérdida de agudeza visual (AV) en los mayores de 50 años en el mundo, siendo la DMAE neovascular (DMAEn) la causante del 80% de los casos de pérdida de visión severa debido a esta enfermedad. Hace ya más de una década que se emplean los fármacos antifactor de crecimiento del endotelio vascular (anti-VEGF) para el tratamiento de esta enfermedad, cambiando drásticamente el pronóstico visual de estos pacientes. Sin embargo, los primeros estudios de los que se disponían datos de los resultados eran a corto plazo. En la actualidad existen ya diferentes series publicadas de los resultados de la DMAE a largo plazo tras el tratamiento con anti-VEGF, siendo el objetivo de la presente revisión sintetizar dichos resultados. El seguimiento medio de los estudios incluidos fue de 8,2 años (rango: 5-12 años). La AV inicial media fue 55,3 letras del Early Treatment Diabetic Retinopathy Study (ETDRS) (rango: 45,6-65) siendo la AV final media 50,1 letras (rango: 33,0-64,3), existiendo una pérdida media de 5,2 letras. Al final del seguimiento un 29,4% de los pacientes mantuvieron una AV>70 letras. El 67,9% de los pacientes se mantuvo estable al final del seguimiento (<15 letras de pérdida), existiendo una pérdida severa (≥15 letras) del 30,1%. La fibrosis y la atrofia fueron las principales causas de pérdida de AV a largo plazo, presentándose al final del seguimiento en un 52,5% y un 60,5%, respectivamente.(AU)

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA>70 letters. The 67.9% of patients remained stable at the end of follow-up (<15 letter loss), with a severe loss (≥15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.(AU)

Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature.

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA > 70 letters. The 67.9% of patients remained stable at the end of follow-up (< 15 letter loss), with a severe loss (≥ 15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.

Brolucizumab tras fracaso de aflibercept con terapia fotodinámica en vasculopatía coroidea polipoidea: reporte de un caso / Brolucizumab after failure of aflibercept with photodynamic therapy in polypoidal choroidal vasculopathy: A case report

Describimos un caso de vasculopatía coroidea polipoidea con líquido subretiniano persistente a pesar de múltiples tratamientos intravítreos con bevacizumab, ranibizumab y aflibercept, así como aflibercept asociado a terapia fotodinámica. El paciente alcanzó la resolución completa después de la inyección intravítrea de brolucizumab, pero experimentó una recurrencia del líquido subretiniano 12 semanas después de la suspensión. Brolucizumab podría ser una opción para tratar el líquido subretiniano después del fracaso de otros agentes anti-VEGF asociados con la terapia fotodinámica. (AU)

We describe one case of polypoidal choroidal vasculopathy with persistent subretinal fluid despite multiple treatment with intravitreal bevacizumab, ranibizumab and aflibercept, as well as aflibercept associated with photodynamic therapy. The patient reached complete resolution after intravitreal brolucizumab injection, but experienced recurrence of subretinal fluid 12 weeks after discontinuation. Brolucizumab might be an option in treating subretinal fluid after failure of other anti-VEGF agents associated with photodynamic therapy. (AU)

Brolucizumab after failure of aflibercept with photodynamic therapy in polypoidal choroidal vasculopathy: A case report.

We describe one case of polypoidal choroidal vasculopathy with persistent subretinal fluid despite multiple treatment with intravitreal Bevacizumab, Ranibizumab and Aflibercept, as well as Aflibercept associated with photodynamic therapy. The patient reached complete resolution after intravitreal Brolucizumab injection, but experienced recurrence of subretinal fluid 12 weeks after discontinuation. Brolucizumab might be an option in treating subretinal fluid after failure of other anti-VEGF agents associated with photodynamic therapy.

Análisis comparativo de la calidad de vida en diferentes patologías de la retina / Comparative analysis of the quality of life among different retinal diseases

Objetivo Evaluar el impacto en la calidad de vida (CdV) entre diferentes enfermedades de la retina como el edema macular diabético (EMD), la oclusión venosa retiniana (OVR), la miopía patológica (MP), la degeneración macular asociada a la edad neovascular (DMAEn) y la coriorretinopatía serosa central (CSC). Métodos Se realizó un estudio transversal en 241 pacientes afectados de EMD (n=44), OVR (n=41), MP (n=34) y DMAEn (n=85) que recibieron inyecciones intravítreas por presencia de edema macular o neovascularización. Los pacientes con CSC incluidos (n=37) eran candidatos a tratamiento con láser. Los pacientes completaron el National Eye Visual Functioning Questioning-25 (NEIVFQ-25). Se registró la mejor agudeza visual corregida (MAVC). Resultados Existieron diferencias significativas entre subgrupos para todos los dominios, excepto para la visión general, en la que todas las puntuaciones entre enfermedades oscilaron entre 40,7 y 45,2 sobre 100 (p=0,436), a pesar de la diferencia en MAVC (CSC: 86,3±11,9; OVR: 78,5±15,5; EMD: 73,3±15,2; DMAEn: 72,9±12,6 y MP: 68,5±18,1 letras, respectivamente (p<0,001). La puntuación total más baja se observó en la MP (52,1±20,9), seguida de DMAEn (55,3±20,8), OVR (65,0±22,3), EMD (68,6±21,0) y CSC (70,9±16,2). El grupo con EMD tuvo la peor puntuación para la salud general (38,9±21,4). La salud mental y las dificultades de rol fueron más bajas en la MP (48,2±28,8 y 48,2±31,9, p<0,007). Conclusiones Este estudio revela las diferencias en la CdV entre EMD, OVR, DMAEn, MP y CSC, describiendo las diferentes repercusiones que pueden sufrir, observándose un mayor impacto en la MP y la DMAEn (AU)

Purpose To assess the impact on the quality of life (QoL) among different retinal diseases such as diabetic macular edema (DME), retinal vein occlusion (RVO), pathologic myopia (PM), neovascular age-related macular degeneration (nAMD) and central serous chorioretinopathy (CSC). Methods A cross-sectional study was carried out in 241 patients, affected by DME (n=44), RVO (n=41), PM (n=34) and nAMD (n=85) receiving intravitreal injections due to the presence of macular edema or choroidal neovascularization. The CSC patients included (n=37) were candidates for laser treatment. The patients included completed the National Eye Visual Functioning Questioning-25 (NEIVFQ-25). Best eye visual acuity (BEVA) was recorded using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Results There were significant differences between subgroups for all the domains, except for the general vision in which all scores among diseases ranged from 40.7 to 45.2 out of 100 (P=.436), despite the difference in BEVA (CSC: 86.3±11.9; RVO: 78.5±15.5, DME: 73.3±15.2, nAMD: 72.9±12.6 and PM: 68.5±18.1 letters, respectively; P<.001). The lowest VFQ-25 total score was observed in the PM patients (52.1±20.9), followed by nAMD (55.3±20.8), RVO (65.0±22.3), DME (68.6±21.0) and CSC (70.9±16.2). The DME group reported the worst score for general health (38.9±21.4). Mental health and role difficulties were lowest for PM (48.2±28.8 and 48.2±31.9, P<.007). Conclusions This study reveals the differences in the QoL among DME, RVO, nAMD, PM and CSC, describing the different repercussions that they can suffer, observing a higher impact in PM and nAMD (AU)

Comparative analysis of the quality of life among different retinal diseases.

PURPOSE: To assess the impact on the quality of life (QoL) among different retinal diseases such as diabetic macular edema (DME), retinal vein occlusion (RVO), pathologic myopia (PM), neovascular age-related macular degeneration (nAMD) and central serous chorioretinopathy (CSC). METHODS: A cross-sectional study was carried out in 241 patients, affected by DME (n=44), RVO (n=41), PM (n=34) and nAMD (n=85) receiving intravitreal injections due to the presence of macular edema or choroidal neovascularization. The CSC patients included (n=37) were candidates for laser treatment. The patients included completed the National Eye Visual Functioning Questioning-25 (NEI VFQ-25). Best eye visual acuity (BEVA) was recorded using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. RESULTS: There were significant differences between subgroups for all the domains, except for the general vision in which all scores among diseases ranged from 40.7 to 45.2 out of 100 (P=.436), despite the difference in BEVA (CSC: 86.3±11.9; RVO: 78.5±15.5, DME: 73.3±15.2, nAMD: 72.9±12.6 and PM: 68.5±18.1 letters respectively; P<.001). The lowest VFQ-25 total score was observed in the PM patients (52.1±20.9), followed by nAMD (55.3±20.8), RVO (65.0±22.3), DME (68.6±21.0) and CSC (70.9±16.2). The DME group reported the worst score for general health (38.9±21.4). Mental health and role difficulties were lowest for PM (48.2±28.8 and 48.2±31.9, P<.007). CONCLUSIONS: This study reveals the differences in the QoL among DME, RVO, nAMD, PM and CSC, describing the different repercussions that they can suffer, observing a higher impact in PM and nAMD.

Diagnóstico diferencial de las reacciones inflamatorias tras uso de medicación intravítrea en degeneración macular asociada a la edad: estéril vs. infeccioso / Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: Sterile vs. infectious

El interés por las complicaciones inflamatorias tras la inyección intravítrea de fármacos antiangiogénicos ha aumentado tras la comercialización de brolucizumab y el desarrollo de nuevas moléculas como el abicipar pegol. Dichos fármacos se asocian a una tasa de complicaciones inflamatorias mayor a los antiangiogénicos clásicos. En este contexto resulta clave el diferenciar procesos infecciosos y estériles para realizar un tratamiento efectivo y precoz. El solapamiento del cuadro clínico entre procesos infecciosos y estériles, la baja tasa de positividad en los cultivos y la heterogeneidad en la terminología son barreras para el correcto diagnóstico y reporte de las complicaciones inflamatorias tras la inyección de medicación antiangiogénica intravítrea. Los cuadros estériles comienzan de forma precoz tras la inyección, dentro de las primeras 48 h, o alrededor de 20 días después en los casos de vasculitis asociada a brolucizumab. Los procesos infecciosos comienzan como promedio en el tercer día tras la inyección, y hasta una semana después de la misma. La disminución grave de la agudeza visual, el dolor severo, la hiperemia severa, el hipopion y un mayor grado de inflamación intraocular deben orientar hacia procesos infecciosos. En los casos en que exista duda sobre la etiología de la inflamación, debe procederse a un control muy estrecho del paciente o al tratamiento antimicrobiano empírico junto con la toma de muestra para evitar complicaciones derivadas de una endoftalmitis infecciosa. Por el contrario, los fenómenos estériles deben ser tratados con observación en los casos más leves o corticoterapia adaptada a la gravedad de inflamación en los casos más graves (AU)

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or “tap and inject” antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation (AU)

Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: sterile vs. infectious.

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48 h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or "tap and inject" antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation.

[Management optimization of neovascular age-related macular degeneration in Spain: Evolution towards proactive treatment models]. / Optimización del manejo de la degeneración macular asociada a la edad neovascular en España: evolución hacia modelos proactivos de tratamiento.

INTRODUCTION AND OBJECTIVE: Healthcare resources optimization is crucial to assume the growing demand of neovascular age-related macular degeneration (nAMD). This work provides guidelines and support so that each hospital can lead its change management. METHODS: The OPTIMUS project (n=10 hospitals) was based on face-to-face interviews with the key staff of the ophthalmology services, and alignment with the main responsible for each centre (nominal group) to identify potential needs for improving nAMD. The OPTIMUS nominal group was expanded to 12 centres (eVOLUTION). Through different remote work sessions, different guides and tools were defined and developed to implement proactive treatment strategies, one-step treatment administration and potential for remote visits (eConsult) in nAMD. RESULTS: The information collected from the OPTIMUS interviews and working groups (n=10 centres) defined roadmaps to promote the development of protocols and proactive treatment strategies, including healthcare workload optimization and one-stop treatment administration in nAMD. With eVOLUTION, processes and tools were developed to promote eConsult: (i) healthcare burden calculator; (ii) definition of potential patients for telematic management; (iii) definition of nAMD management archetypes; (iv) definition of processes for implementation of eConsult by archetype; and (v) key performance indicators for changing evaluation. CONCLUSIONS: Managing change is an internal task that requires an adequate diagnosis of processes and feasible implementation roadmaps. OPTIMUS and eVOLUTION provide the basic tools for an autonomous advance of hospitals in the optimization of AMD management, with the available resources.

Evaluación de signos tomográficos no exudativos en casos de degeneración macular asociada a la edad de tipo exudativo / Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration

Objetivo Analizar la prevalencia de signos tomográficos no exudativos (signo de cebolla, seudoedema, tubulación de la retina externa, seudoquistes, hendiduras subretinianas y atrofia macular) en pacientes con degeneración macular asociada a la edad neovascular. Material y métodos Un total de 174 ojos de pacientes con degeneración macular asociada a la edad neovascular que no habían recibido tratamiento previo fueron incluidos en el estudio. Se valoró la agudeza visual, la actividad de la neovascularización y la aparición o no de los distintos signos objeto de estudio en los tiempos 0 (visita inicial), 4 meses, un año, año y medio y a los 2 y 3 años de seguimiento. Se evaluaron también: la edad, el sexo, el ojo afecto y el tipo de neovascularización (1, 2, 3, polipoidea o mixta). Los análisis se han realizado mediante el software estadístico R (versión 3.3.2) y el paquete glmmADMB (versión 0.8.3.3). Resultados La presencia de seudoquistes y tubulación de la retina externa va en aumento a lo largo del seguimiento. El signo de cebolla comienza con una frecuencia ascendente hasta los 12 meses, posteriormente desciende a los 18 meses y vuelve a incrementarse a los 24 meses. En cuanto al seudoedema, mantiene un incremento hasta los 18 meses para finalmente descender. Las hendiduras subretinianas son el signo más raro, presentándose en el 1,1% en la primera visita. Finalmente, la atrofia macular, presente en el 12,6% de los ojos inicialmente, se encuentra en el 25% a los 2 años. Conclusión Los seudoquistes, la tubulación de la retina externa y la atrofia macular fueron los signos más prevalentes, mientras que las hendiduras subretinianas fueron los más infrecuentes (AU)

Objective To analyze the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration. Material and methods A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3). Results The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years. Conclusion Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent (AU)

Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration.

OBJECTIVE: To analyse the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3). RESULTS: The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years. CONCLUSION: Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent.

Análisis de minimización de costes de brolucizumab en el tratamiento de la degeneración macular asociada a la edad neovascular / Cost minimization analysis of brolucizumab in the treatment of neovascular age-related macular degeneration

Introducción Brolucizumab es un nuevo fármaco antifactor de crecimiento endotelial vascular (anti-VEGF) administrado con una pauta fija de ocho o 12 semanas que en los estudios HAWK y HARRIER demostró ser no inferior a aflibercept con respecto a la mejor agudeza visual corregida, bajo una menor carga de administración. El objetivo del análisis fue comparar los costes directos sanitarios de ambos anti-VEGF como tratamiento en pacientes con degeneración macular asociada a la edad neovascular. Material y métodos Se realizó un análisis de minimización de costes bajo un horizonte temporal de 25 años y considerando el coste farmacológico, de administración, de pruebas de seguimiento y del manejo de eventos adversos. El uso de recursos fue obtenido de literatura relacionada y validada por expertos clínicos. Se llevaron a cabo diversos análisis de escenarios para comprobar la robustez de los resultados. Resultados Brolucizumab resultó con un menor coste por paciente en comparación con aflibercept, considerando el número de inyecciones derivadas de los estudios HAWK y HARRIER. Este resultado se mantuvo en los diferentes escenarios analizados, excepto frente al número de inyecciones de la pauta flexible de aflibercept del estudio ARIES, ya que la menor discontinuación de tratamiento con brolucizumab conlleva mantener el tratamiento de más pacientes. Al considerar la misma discontinuación, brolucizumab mantuvo los resultados observados en el caso base del análisis. Conclusiones El presente estudio muestra como la pauta de administración fija de brolucizumab puede ayudar a disminuir la carga asistencial para los centros sanitarios y los pacientes (AU)

Introduction Brolucizumab is a novel anti-vascular endothelial growth factor (anti-VEGF) drug administered in a fixed regimen of 8 or 12 weeks which, in the HAWK and HARRIER studies, was shown not to be inferior to aflibercept with respect to the best corrected visual acuity, with a less burdensome treatment regimen. The aim of the analysis was to compare the direct healthcare costs of both anti-VEGF as a treatment in patients with neovascular age-related macular degeneration.Material and methods A cost minimization analysis was performed under a 25-year time horizon and considering the drug costs, administration, follow-up tests, and management of adverse events. Resource use was obtained from the related literature and validated by clinical experts. Various scenario analysis were carried out to check the robustness of the results. Results Brolucizumab resulted in a lower cost per patient compared with aflibercept, considering the number of injections derived from the HAWK and HARRIER studies. This result was maintained in the different scenarios analysed, except for the number of injections of the flexible aflibercept regimen of the ARIES study, since the lower discontinuation of treatment with brolucizumab implies maintaining the treatment of more patients. Considering the same discontinuation, brolucizumab maintained the results observed in the base case of the analysis. Conclusions This study shows how the fixed administration regimen of brolucizumab can help reduce both healthcare and patients’ burden (AU)

Cost minimization analysis of brolucizumab in the treatment of neovascular age-related macular degeneration.

INTRODUCTION: Brolucizumab is a novel anti-vascular endothelial growth factor (anti-VEGF) drug administered in a fixed regimen of 8 or 12 weeks which, in the HAWK and HARRIER studies, was shown not to be inferior to aflibercept with respect to the best corrected visual acuity, with a less burdensome treatment regimen. The aim of the analysis was to compare the direct healthcare costs of both anti-VEGF as a treatment in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A cost minimization analysis was performed under a 25-year time horizon and considering the drug costs, administration, follow-up tests, and management of adverse events. Resource use was obtained from the related literature and validated by clinical experts. Various scenario analysis were carried out to check the robustness of the results. RESULTS: Brolucizumab resulted in a lower cost per patient compared with aflibercept, considering the number of injections derived from the HAWK and HARRIER studies. This result was maintained in the different scenarios analysed, except for the number of injections of the flexible aflibercept regimen of the ARIES study, since the lower discontinuation of treatment with brolucizumab implies maintaining the treatment of more patients. Considering the same discontinuation, brolucizumab maintained the results observed in the base case of the analysis. CONCLUSIONS: This study shows how the fixed administration regimen of brolucizumab can help reduce both healthcare and patients' burden.

Implante de dexametasona antes de tratamiento anti-VEGF en desprendimientos del epitelio pigmentario secundarios a degeneración macular asociada a la edad con características de alto riesgo de rotura / Dexamethasone implant prior to anti-VEGF therapy in pigment epithelium detachments with high-risk rupture characteristics secondary to neovascular age-related macular degeneration

Objetivo Evaluar la incidencia de desgarro del epitelio pigmentario cuando se administra un implante intravítreo de dexametasona de liberación retardada (uso off-label) previo al tratamiento antiangiogénico en desprendimientos del epitelio pigmentario (DEP) secundarios a degeneración macular neovascular asociada a la edad (DMAEn) con características de alto riesgo de rotura e investigar si provoca una disminución del tamaño del DEP. Métodos Se incluyeron pacientes con DMAEn, altura del DEP >500micras e implante de Ozurdex previo a la terapia antiangiogénica. Se registró la presencia de rotura del epitelio pigmentario en tomografías de coherencia óptica, agudeza visual mejor corregida (AVMC) y medidas del DEP (altura y diámetro máximos). Resultados El estudio incluyó a 14 ojos de 14 pacientes: edad media 77±7 años, 11 (79%) mujeres. 25±13 días después del Ozurdex los pacientes comenzaron con al menos 3 inyecciones mensuales de anti-VEGF. La AVMC mejoró de 64±14 a 69±11 letras después de la terapia anti-VEGF (p>0,05). La altura media inicial del DEP fue de 817±269μm, siendo 639±268μm después de Ozurdex y 370±260μm después de las inyecciones de anti-VEGF (p=0,035 y p=0,009). Se produjo un desgarro del epitelio pigmentario de la retina (7%). No se hallaron otros efectos adversos. Conclusione El implante de dexametasona antes de la terapia anti-VEGF puede representar una modalidad terapéutica prometedora para los DEP grandes en la DMAEn, reduciendo las dimensiones del DEP y el riesgo de desgarros del epitelio pigmentario antes de la terapia anti-VEGF (AU)

Objective Evaluate the incidence of pigment epithelial tear when intravitreal delayed-release dexamethasone implant is administered (off-label use) prior to antiangiogenic treatment in pigment epithelium detachments (PED) secondary to neovascular age-related macular degeneration (nAMD) with high-risk rupture characteristics and investigate if it causes a decrease in the PED size. Methods Patients with nAMD, PED height >500microns and Ozurdex implant prior to the antiangiogenic therapy were included. The presence of pigment epithelium rupture in optical coherence tomography scans, best-corrected visual acuity (BCVA) and PED measurements (maximum height and diameter) were registered. Results The study included 14 eyes of 14 patients: mean age 77±7 years, 11 (79%) females. 25±13 days after the Ozurdex, patients started with at least 3 anti-VEGF monthly injections. BCVA improved from 64±14 to 69±11 letters after anti-VEGF therapy (P>.05). Mean baseline PED height was 817±269μm, being 639±268μm after Ozurdex and 370±260μm after anti-VEGF injections (P=.035 and P=.009). One retinal pigment epithelium tear occurred (7%). No other adverse effects were reported. Conclusions Dexamethasone implant prior to anti-VEGF therapy may represent a promising therapeutic modality for large PED in nAMD, reducing PED dimensions and the risk of pigment epithelium tears prior to anti VEGF therapy (AU)

Calidad de vida según función visual en degeneración macular húmeda asociada a la edad tratada con Bevacizumab / Quality of Life According to Visual Function in Age-related Wet Macular Degeneration Treated with Bevacizumab

Introducción: La degeneración macular asociada a la edad, es causa frecuente de ceguera o baja visión en el adulto mayor. La valoración de la calidad de vida relativa a la función visual, es fundamental en estos pacientes tratados con Bevacizumab. Objetivo: Evaluar la calidad de vida en relación con la función visual en pacientes con degeneración macular tratada con Bevacizumab asociada a la edad. Métodos: Estudio descriptivo longitudinal prospectivo realizado en el ICO "Ramón Pando Ferrer", desde enero de 2019 hasta mayo de 2021. La muestra fue de 52 pacientes. El cuestionario NEI VFQ-25 fue aplicado antes y después de la administración de las tres dosis del medicamento intravítreo. Resultados: Predominó el sexo femenino, el grupo etario de mayor representación fue el de 60 a 79 años, la enfermedad sistémica más frecuente fue la hipertensión y ocular, la catarata. Casi todos los pacientes ganaron más de dos líneas en la cartilla de Snellen, el 42,3 por ciento presentó una ganancia de 3 líneas o más. El resultado de la mayoría de los elementos que explora el test, así como la función visual total es significativo desde el punto de vista estadístico. Conclusiones: Hubo una mejoría en la calidad de vida relativa a la función visual en los pacientes después de ser tratados con Bevacizumab. No existió una relación directamente proporcional entre la mejor agudeza visual post tratamiento y la mejora de la función visual total(AU)

Introduction: Age-related macular degeneration constitutes a frequent cause of blindness or low vision in the older adult. The assessment of quality of life related to visual function is essential in these patients treated with Bevacizumab. Objective: To assess the quality of life in relation to visual function in patients with age-related macular degeneration treated with Bevacizumab, at the ICO "Ramón Pando Ferrer", from January 2019 to May 2021. Methods: Prospective longitudinal descriptive study. The sample was 52 patients and the NEI VFQ-25 questionnaire was applied before and after three doses of the intravitreal drug. Results: Female gender predominated, the most represented age group was 60 to 79 years, the most frequent systemic disease was hypertension and the most frequent ocular disease was cataract. Almost all patients gained more than two lines in the Snellen chart, 42.3 percent presented a gain of 3 lines or more. The result of most of the items explored by the test, as well as the total visual function is statistically significant. Conclusions: There was an improvement in quality of life relative to visual function in patients after being treated with Bevacizumab. There was no directly proportional relationship between improved post-treatment visual acuity and improvement in total visual function(AU)

Biomarcadores de OCT-angiografía en la neovascularización coroidea tipo1 tras tratamiento con aflibercept durante 1 año / OCT angiography biomarkers in type1 choroidal neovascularisation after one year of aflibercept treatment

Objetivos: Evaluar la actividad de los biomarcadores, mediante OCT-angiografía (OCTA), en la neovascularización coroidea (NVC) secundaria a degeneración macular asociada a la edad (DMAE) tratada con aflibercept. Como objetivos secundarios se estudiaron la agudeza visual (AV) y la relación existente entre biomarcadores y pronóstico visual. Material y métodos: Estudio prospectivo en el que se estudiaron 33 ojos de 40 pacientes naïve diagnosticados de NVC tipo1 secundaria a DMAE y que habían sido tratados con aflibercept, según ficha técnica, durante 1año. Los pacientes fueron evaluados en el momento del diagnóstico, a los 4, a los 8 y a los 12meses. Resultados: La ganancia media de AV a los 12meses fue de 15,2±3,3 letras. El área de lesión disminuyó 1,2±1,0mm2 en el cuarto mes (p<0,0001), permaneciendo estable después. La presencia de capilares finos, anastomosis y halo hipointenso perilesional se redujo en el 85, el 70 y el 25%, respectivamente, a los 12meses de seguimiento. La arcada vascular periférica cambió de morfología, pasando de tener un aspecto frondoso a tener un aspecto afilado en el 90% de los casos. El tamaño de la lesión y la presencia/ausencia de halo hipointenso perilesional se asociaron, de manera independiente, a la AV final, de tal forma que las lesiones de mayor tamaño y la ausencia de halo hipointenso perilesional en la visita basal se asociaron a menor ganancia de AV. Conclusiones: La OCTA se trata de una herramienta útil, no invasiva, que nos aporta información cuantitativa y cualitativa del remodelado de la red vascular de la NVC tras terapia antiangiogénica. (AU)

Objective: To assess the activity of biomarkers, through OCT angiography (OCTA), of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) treated with aflibercept. As secondary endpoints, visual acuity (VA) and the relationship between biomarkers and visual prognosis were also studied. Material and methods: Prospective study that examined 33 eyes of 40 naïve patients with type1 CNV secondary to AMD, who had been treated with aflibercept, according to summary of product characteristics, for one year. The patients were evaluated at the time of diagnosis, and at 4, 8 and 12months. Results: The mean VA gain at 12months was 15.2±3.3 letters. The area of lesion decreased 1.2±1.0mm2 in the 4th month (P<.0001), remaining stable afterwards. The presence of tiny capillaries, anastomosis and perilesional hypointense halo was reduced by 85%, 70% and 25%, respectively, at 12 months of follow-up. The peripheral vascular arcade changed morphology, from having a leafy appearance to having a sharp appearance in 90% of cases. The size of the lesion and the presence/absence of perilesional hypointense halo were independently associated with the final VA, in such a way that larger lesions and the absence of a perilesional hypointense halo at the baseline visit were associated with less VA gain. Conclusions: The OCTA is a useful, non-invasive tool that provides quantitative and qualitative information on the remodelling of the CNV vascular network after antiangiogenic therapy. (AU)

Dexamethasone implant prior to anti-VEGF therapy in pigment epithelium detachments with high-risk rupture characteristics secondary to neovascular age-related macular degeneration.

OBJECTIVE: Evaluate the incidence of pigment epithelial tear when intravitreal delayed-release dexamethasone implant is administered (off-label use) prior to antiangiogenic treatment in pigment epithelium detachments (PED) secondary to neovascular age-related macular degeneration (nAMD) with high-risk rupture characteristics and investigate if it causes a decrease in the PED size. METHODS: Patients with nAMD, PED height >500 microns and Ozurdex implant prior to the antiangiogenic therapy were included. The presence of pigment epithelium rupture in optical coherence tomography scans, best-corrected visual acuity (BCVA) and PED measurements (maximum height and diameter) were registered. RESULTS: The study included 14 eyes of 14 patients: mean age 77 ±â€¯7 years, 11 (79%) females. 25 ±â€¯13 days after the Ozurdex, patients started with at least 3 anti-VEGF monthly injections. BCVA improved from 64 ±â€¯14-69 ±â€¯11 letters after anti-VEGF therapy (p > 0.05). Mean baseline PED height was 817 ±â€¯269 µm, being 639 ±â€¯268 µm after Ozurdex and 370 ±â€¯260 µm after anti-VEGF injections (p = 0.035 and p = 0.009). One retinal pigment epithelium tear occurred (7%). No other adverse effects were reported. CONCLUSIONS: Dexamethasone implant prior to anti-VEGF therapy may represent a promising therapeutic modality for large PED in nAMD, reducing PED dimensions and the risk of pigment epithelium tears prior to anti VEGF therapy.

Vitrectomy with subretinal tissue plasminogen activator (r-TPA) and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) for submacular hemorrhages treatment: Retrospective analysis of 22 cases.

BACKGROUND: Macular hemorrhages are a severe complication of other retinal pathologies, such as age-related macular degeneration (AMD) or macroaneurysms. Their therapeutic approach is not standardized, and can vary from observation to surgical treatment. MATERIAL AND METHODS: Retrospective analysis of 22 cases of macular hemorrhage, treated with vitrectomy associated to subretinal rTPA and intravitreal anti-VEGF over a period of 5 years. RESULTS: 22 eyes of 22 patients were included, of which 12 (52%) were women. The mean age at diagnosis was 84.4 years. 13 patients were pseudophakic (54.1%) and 19 (86.36%) had previous ophthalmological comorbidities. The etiology of the macular hemorrhage was AMD in 19 patients (86.36%). The mean of best VA corrected at diagnosis was 24.55 (Early Treatment Diabetic Retinopathy Study score -ETDRS), with a statistically significant improvement to 36.78 3 months after surgery (p = 0.011). With an average of 23.5 months of follow-up, no differences in prognosis associated with the etiology or size of the hemorrhage were observed. CONCLUSION: The treatment of macular hemorrhages by vitrectomy, subretinal rTPA and antiVEGF improves the visual prognosis of affected patients.

Vitrectomía asociada a activador tisular del plasminógeno (rTPA) subretiniano e inyección intravítrea de anti-VEGF como tratamiento de hemorragias submaculares: análisis retrospectivo de 22 casos / Vitrectomy with subretinal tissue plasminogen activator (r-TPA) and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) for submacular hemorrhages treatment: Retrospective analysis of 22 cases

Introducción: Las hemorragias maculares suponen una complicación severa de otras patologías retinianas, como la degeneración macular asociada a la edad (DMAE) o los macroaneurismas. El abordaje terapéutico de las mismas no se encuentra estandarizado, pudiendo variar desde la observación hasta el tratamiento quirúrgico.Material y métodosAnálisis retrospectivo de 22 casos de hemorragia macular, tratados mediante vitrectomías asociada a rTPA subretiniano y antiVEGF intravítreo durante un período de cinco años.ResultadosSe incluyeron 22 ojos de 22 pacientes, de los que 12 (52%) eran mujeres. La edad media al diagnóstico fue de 84,4 años. Del total de pacientes, 13 eran pseudofáquicos (54,1%) y 19 (86,36%) presentaban comorbilidades oftalmológicas previas. La etiología de las hemorragias maculares fue DMAE en 19 pacientes (86,36%). La media de mejor agudeza visual (AV) corregida al diagnóstico fue de 24,55 (puntuación Early Treatment Diabetic Retinopathy Study - ETDRS), con una mejoría estadísticamente significativa a 36,78 a los tres meses de la cirugía (p=0,011). Con un promedio de 23,5 meses de seguimiento, no se observaron diferencias en el pronóstico asociadas a etiología o tamaño de la hemorragia.ConclusiónEl tratamiento de las hemorragias maculares mediante vitrectomía, rTPA subretiniano y antiVEGF mejora el pronóstico visual de los pacientes afectos. (AU)

Background: Macular hemorrhages are a severe complication of other retinal pathologies, such as age-related macular degeneration (AMD) or macroaneurysms. Their therapeutic approach is not standardized, and can vary from observation to surgical treatment.Material and methodsRetrospective analysis of 22 cases of macular hemorrhage, treated with vitrectomy associated to subretinal rTPA and intravitreal anti-VEGF over a period of 5 years.Results22 eyes of 22 patients were included, of which 12 (52%) were women. The mean age at diagnosis was 84.4 years. 13 patients were pseudophakic (54.1%) and 19 (86.36%) had previous ophthalmological comorbidities. The etiology of the macular hemorrhage was AMD in 19 patients (86.36%). The mean of best VA corrected at diagnosis was 24.55 (Early Treatment Diabetic Retinopathy Study score -ETDRS), with a statistically significant improvement to 36.78 3 months after surgery (p = 0.011). With an average of 23.5 months of follow-up, no differences in prognosis associated with the etiology or size of the hemorrhage were observed.ConclusionThe treatment of macular hemorrhages by vitrectomy, subretinal rTPA and antiVEGF improves the visual prognosis of affected patients. (AU)

Pseudodrusen reticulares y degeneración macular asociada a la edad / Pseudodrusen reticularis and age-related macular degeneration

Objetivo: Identificar la relación de los pseudodrusen reticulares con la degeneración macular asociada a la edad mediante imágenes tomográficas. Método: Estudio observacional, descriptivo y transversal en pacientes con pseudodrusen reticulares atendidos en consulta de retina a los que se les realizó tomografía de coherencia óptica espectral desde enero de 2009 hasta diciembre de 2014 en el Instituto Cubano de Oftalmología "Ramón Pando Ferrer". La población estuvo constituida por 69 pacientes de 55 años y más con pseudodrusen reticulares en dichas imágenes. Resultados: Los pseudodrusen predominaron en pacientes con edades comprendidas entre los 70 y 79 años para un 49,3 por ciento. El sexo femenino fue el más numeroso con un 76,8 por ciento. De los 122 ojos con pseudodrusen, 86 presentaron algún signo de degeneración macular asociada a la edad representado por el 70,5 por ciento. El 58,1 por ciento de estos últimos tuvo la forma avanzada. La membrana neovascular tipo II fue la más frecuente con un 58,0 por ciento. El grosor coroideo se estimó disminuido en el 77,9 por ciento de los casos. Conclusiones: Los pseudodrusen reticulares mantienen una relación directa con la degeneración macular asociada a la edad e influyen en la progresión de esta(AU)

Objective: To identify the relationship of reticular pseudodrusen with age-related macular degeneration using tomographic imaging. Methods: An observational, descriptive and cross-sectional study was conducted in patients with reticular pseudodrusen seen in retina consultation who underwent spectral optical coherence tomography from January 2009 to December 2014 at the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". The population consisted of 69 patients aged 55 years and older with reticular pseudodrusen in these images. Results: Pseudodrusen predominated in patients between 70 and 79 years of age (49.3 percent). The female gender was the most numerous with 76.8 percent. Out of the 122 eyes with pseudodrusen, 86 showed some sign of age-related macular degeneration (70.5 percent). Out of the latter, 58.1 percent had the advanced form. Type II neovascular membrane was the most frequent with 58.0 percent. Choroidal thickness was estimated decreased in 77.9 percent of cases. Conclusions: Reticular pseudodrusen maintain a direct relationship with age-related macular degeneration and influence its progression(AU)