Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

INTRODUCTION: Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. OBJECTIVE: To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). METHOD: A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36 months after patients received SRT and compared to the same time interval prior to SRT. RESULTS: Follow-up data at 12, 24, and 36 months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). CONCLUSION: A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36 months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.

A New Generation of Gene Therapies as the Future of Wet AMD Treatment.

Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms, dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the concept of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the progress to the clinic of "one and done" therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study.

INTRODUCTION: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. METHODS: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. RESULTS: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 µm vs. 780.2 µm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 µm vs. 326.5 µm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. CONCLUSION: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

Advancements in the treatment of age-related macular degeneration: a comprehensive review.

Age-related macular degeneration (AMD) stands as a leading cause of irreversible blindness, particularly affecting central vision and impeding daily tasks. This paper provides a thorough exploration of AMD, distinguishing between its two main subtypes-Wet and Dry AMD-while shedding light on the prevalence and risk factors, including age, genetics, and smoking. The focus shifts to the current and future treatment landscape, examining both Dry and Wet AMD. Regarding Dry AMD, interventions such as antioxidant supplementation and ongoing clinical trials offer hope. Notable among these is Pegcetacoplan which is the only Food and Drug Administration (FDA)-approved medication, displaying promising results in reducing geographic atrophy lesions. For Wet AMD, anti-Vascular Endothelial Growth Factor therapies like Ranibizumab (Lucentis®) have been instrumental, and newer drugs like Faricimab and OPT-302 show comparable efficacy with extended dosing intervals. Additionally, gene therapies such as RGX-314 present a potential paradigm shift, reducing or eliminating the need for frequent injections. Biosimilars offer cost-effective alternatives. The paper also delves into the integration of technology and artificial intelligence in AMD management, highlighting the role of smartphone apps for patient monitoring and artificial intelligence algorithms for diagnosis and surveillance. Furthermore, patient perspectives on artificial intelligence demonstrate a positive correlation between understanding and trust. The narrative concludes with a glimpse into ground-breaking technologies, including retinal implants and bionic chips, offering hope for vision restoration. Overall, this paper underscores the multifaceted approach in addressing AMD, combining traditional and innovative strategies, paving the way for a more promising future in AMD treatment.

Análisis de minimización de costos de brolucizumab para la DMAEh en Colombia / Cost minimization analysis of brolucizumab for wAMD in Colombia

Introducción: La degeneración macular asociada a la edad húmeda (DMAEh) tiene un impacto negativo en la calidad de vida. Brolucizumab es una alternativa efectiva y segura. Objetivo: Evaluar la diferencia en costos anuales de tratamiento entre brolucizumab 6 mg (esquema 6 LP → q12/q8), ranibizumab 0.5 mg (esquema Treat and Extend [TREX]) y aflibercept 2 mg (esquema TREX) para pacientes con DMAEh en Colombia. Materiales y métodos: Se realizó un análisis de minimización de costos con un horizonte temporal de cinco años y una tasa de descuento del 5%. Se consideraron costos médicos directos mediante fuentes locales. Se realizó un análisis de sensibilidad univariante. Resultados: El uso de brolucizumab implica un ahorro anual del 7.63% vs. aflibercept y del 12.8% vs. ranibizumab. Estos resultados fueron consistentes con los análisis de sensibilidad. Conclusiones: En un horizonte temporal de cinco años, brolucizumab es una tecnología costo-ahorradora para el tratamiento de la DMAEh en Colombia.

Background: Wet age-related macular degeneration (wAMD) has a negative impact on quality of life. Brolucizumab is an effective and safe alternative. Objective: To assess the difference in annual treatment costs between brolucizumab 6 mg (6 LP → q12/q8 schedule), ranibizumab 0.5 mg (Treat and Extend [TREX schedule]), and aflibercept 2 mg (TREX schedule), for patients with AMD in Colombia. Materials and methods: A cost minimization analysis was performed with a time horizon of five years and a discount rate of 5%. Direct medical costs were considered through local sources. A univariate sensitivity analysis was performed. Results: The use of brolucizumab implies an annual saving of 7.63% vs. aflibercept and 12.8% vs. ranibizumab. These results were consistent with the sensitivity analyses. Conclusions: In a time horizon of 5 years, brolucizumab is a cost-saving technology for the treatment of AMD in Colombia

Guía de práctica clínica para el diagnóstico y tratamiento de la degeneración macular relacionada a la edad: guía en versión extensa / Clinical practice guideline for the diagnosis and treatment of age-related macular degeneration: long version guide

Brindar recomendaciones y puntos de buenas prácticas clínicas basadas en evidencia para el adecuado diagnóstico y tratamiento de los pacientes con degenaración macular relacionada con la edad (DMRE), contestando a las siguientes preguntas: a) En personas mayores de 50 años, ¿cómo se debería diagnosticar y clasificar la DMRE? b) En personas con DMRE, ¿qué intervenciones deben usarse para prevenir la progresión de la enfermedad? c) En personas con DMRE exudativa, ¿se debería utilizar antiangiogénicos para el tratamiento de la enfermedad? d) En personas con DMRE exudativa, ¿se debería utilizar la terapia fotodinámica como tratamiento adyuvante? e) En personas con DMRE exudativa, ¿se debería utilizar corticoides intravítreos como tratamiento adyuvante? f) En personas con DMRE, ¿cuál es la mejor estrategia de seguimiento de la enfermedad?

Aportaciones en el tratamiento de formas atípicas de degeneración macular asociada a la enfermedad / Contributions to the treatment of atypical forms of age-related macular degeneration

Se realiza un estudio de las 2 entidades clínicas que presentan un diagnóstico diferencial con la degeneración macular asociada a la enfermedad (DMAE) húmeda, que son la vasculopatía coroidea polipoidea idiopática y la proliferación angiomatosa retiniana. Analizamos sus entidades clínicas y características funduscópicas, así como sus diferencias con la DMAE. Presentamos 2 casos clínicos representativos de estas 2 entidades. Se estudian las posibilidades terapéuticas y los resultados, y las últimas publicaciones referidas a ellas, comparándolas y haciendo un estudio estadístico de las últimas publicaciones(AU)

We performed a study of the two clinical entities with a differential diagnosis with wet age-related macular degeneration, namely, idiopathic polypoidal choroidal vasculopathy (IPCV) and retinal angiomatous proliferation. We analyze the clinical and funduscopic characteristics of these entities as well as their differences with wet age-related macular degeneration. We present two cases that are representative of these two entities. The therapeutic possibilities, results and the latest publications are analyzed and compared. A statistical analysis of the latest publications is also presented(AU)

Evaluation of photodynamic ther-apy for the treatment of exudative age-related macular degenerati on (ARMD) with subfoveal neovascularization

OBJECTIVES: Over the past few decades, most industrialized countries have experienced an increase in their elderly populations. This inversion of the age pyramid is leading to an increased incidence of many diseases, including age-related macular degeneration (ARMD). ARMD is characterized by degenerative lesions in the macular region of the retina resulting in a gradual decrease in vision that can lead to a loss of central vision. In fact, this disease is the leading cause of blindness in Western countries. Its prevalence is approximately 0.2% in people aged 55 to 64 and climbs to more than 13% in the over-85 population. Based on epidemiological data, the number of affected individuals in Québec can be estimated at approximately 37,200. ARMD has been divided into three histopa-thologic forms: an early form, also known as age-related maculopathy (ARM) or pre-ARMD (it should be noted that the early form is not included in the prevalence and inci-dence data provided in this report), and two advanced or progressive forms, called atro-phic and neovascular (or exudative) forms. At the present time, only the neovascular form is treatable. It accounts for about 47% of the cases of advanced ARMD, which, in Quebec, number close to 16,000. This disease therefore generates significant social costs, hence the need for effective therapeutic modalities to treat it. It was in this context that ophthalmologists representing the New Technologies Axis of the Vision Network, which is sponsored by the Fonds de la recherche en santé du Québec (FRSQ), asked the Agence d'évaluation des technologies et des modes d'intervention en santé (AETMIS) to assess the efficacy of photodynamic therapy (PDT) with verteporfin photosensitizer for the treatment of ARMD. This report also looks at the costs associated with this therapeutic modality and examines, on an exploratory basis, the organization of the care and services involved. METHODOLOGY: A literature search was conducted in the Pub-Med, Current Content Search and Cochrane Library databases by combining the terms macular degeneration, photodynamic therapy and verteporfin (Visudyne®); Amsler grid; an-tioxidant; vitamin; risk factors; side effects and fluorescein angiography for the period from 1975 to June 2004. We also used reports from several health technology assessment agencies that have examined PDT, abstracts of papers presented at international scientific confer-ences, a number of Web sites, and interviews with experts in ophthalmology and visual rehabilitation. The decision tree for the economic analysis was designed for the purpose of predicting the costs and effects of PDT in individuals with ARMD. The population selected for this Markov-type model includes all Quebecers who were over the age of 55 in 2001 (1,730,000). The incidence data for the disease are applied to this cohort. Two options are compared in the model: a treatment option and a no-treatment option. To include all the possible treatment scenarios, the time horizon in this model was set at eight years, and the outcomes used are the loss and non-loss of three lines of vision. It will be noted that visual rehabilitation costs are included in both options on the basis of the patient's visual acuity. The exploratory study of the organization of the care and services provided to ARMD pa-tients was conducted in the summer 2002 using a qualitative approach based on semi-structured telephone interviews with eye specialists at all of the university and com-munity hospitals and at certain private clinics in Québec that offer PDT, and with reception-ists and nurses who work at these facilities. CONCLUSION: From the evidence accumulated on photody-namic therapy with verteporfin photosensi-tizer we can conclude that this technology is effective in slowing the progression of subfo-veal neovascular ARMD with predominantly classic neovascularization or pure occult neo-vascularization. Further-more, the estimated budget impact for a Québec cohort is accept-able if the improvement in quality of life is taken into account. However, a major reor-ganization of services and ocular health care should be considered in the near future to permit the optimal implementation of this technology, to reduce waiting times for this treatment and to deal with the demand that will be increasing in the coming years. Furthermore, measures aimed at promoting the early detection of ARMD in the popula-tion, both at the individual and primary -care levels, could reduce the risk of severe, irre-versible vision loss and thus reduce the social costs of this disease.