An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

[Challenges and strategies in the treatment of neovascular age-related macular degeneration].

Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the elderly, and anti-vascular endothelial growth factor (VEGF) therapy is currently the primary treatment approach. However, the real-world effectiveness of nAMD treatment is not always satisfactory and faces various challenges. Frequent administration and follow-up burdens can lead to decreased patient compliance during long-term treatment, resulting in suboptimal outcomes. Some lesions exhibit poor or no response to anti-VEGF treatment, leading to difficulties in maintaining or even declining visual acuity. Factors such as lesion fibrosis and tissue atrophy can contribute to visual deterioration. Therefore, standardizing and individualizing treatment plans, along with enhancing comprehensive monitoring and management throughout the disease course, are crucial improvement measures. The evidence-based guidelines for diagnosis and treatment of age-related macular degeneration in China, released in 2023, provide guidance for standardized clinical diagnosis and treatment. Meanwhile, research and development of new drugs and administration methods are anticipated for the future.

Descriptive study of the challenges when implementing an app for patients with neovascular age-related macular degeneration to monitor their vision at home.

OBJECTIVES: Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack). DESIGN: Diagnostic Test Accuracy study. SETTING: Six UK hospitals. METHODS: The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges. RESULTS: Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers. CONCLUSIONS: Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose. TRIAL REGISTRATION NUMBER: ISRCTN79058224.

Cell therapy for retinal degenerative disorders: a systematic review and three-level meta-analysis.

BACKGROUND: Retinal degenerative disorders (RDDs) cause vision loss by damaging retinal neurons and photoreceptors, affecting individuals of all ages. Cell-based therapy has emerged as an effective approach for the treatment of RDDs with promising results. This meta-analysis aims to comprehensively evaluate the efficacy of cell therapy in treating age-related macular degeneration (AMD), retinitis pigmentosa (RP), and Stargardt macular degeneration (SMD) as the most prevalent RDDs. METHODS: PubMed, Scopus, Web of Science, and Embase were searched using keywords related to various retinal diseases and cell therapy treatments until November 25th, 2023. The studies' quality was evaluated using the Joanna Briggs Institute's (JBI) checklist for quasi-experimental studies. Visual acuity measured as LogMAR score was used as our main outcome. A three-level random-effect meta-analysis was used to explore the visual acuity in patients who received cell-based therapy. Heterogeneity among the included studies was evaluated using subgroup and sensitivity analyses. Moreover, meta-regression for the type of cells, year of publication, and mean age of participants were performed. RESULTS: Overall, 8345 studies were retrieved by the search, and 39 met the eligibility criteria, out of which 18 studies with a total of 224 eyes were included in the meta-analysis. There were 12 studies conducted on AMD, 7 on SMD, and 2 on RP. Cell therapy for AMD showed significant improvement in LogMAR (p < 0.05). Also, cell therapy decreased the LogMAR score in SMD and RP (p < 0.01 and p < 0.0001, respectively). Across all conditions, no substantial publication bias was detected (p < 0.05). CONCLUSION: The findings of the study highlight that the application of cell therapy can enhance the visual acuity in AMD, SMD, and RP.

From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration.

BACKGROUND AIMS: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis. METHODS: This study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365. RESULTS: In total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology & Visual Science published the majority of relevant papers (n = 27). Key words like "clinical trial," "stem cell therapy," "retinal organoid," and "retinal progenitor cells" were predominant. CONCLUSIONS: Research on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between "ipsc," "induced pluripotent stem cell," "cell culture," and "human embryonic stem cell." As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.

Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration.

Age-related macular degeneration (AMD) is the most common cause of untreatable blindness in the developed world. Recently, CDHR1 has been identified as the cause of a subset of AMD that has the appearance of the "dry" form, or geographic atrophy. Biallelic variants in CDHR1-a specialized protocadherin highly expressed in cone and rod photoreceptors-result in blindness from shortened photoreceptor outer segments and progressive photoreceptor cell death. Here we demonstrate long-term morphological, ultrastructural, functional, and behavioral rescue following CDHR1 gene therapy in a relevant murine model, sustained to 23-months after injection. This represents the first demonstration of rescue of a monogenic cadherinopathy in vivo. Moreover, the durability of CDHR1 gene therapy seems to be near complete-with morphological findings of the rescued retina not obviously different from wildtype throughout the lifespan of the mouse model. A follow-on clinical trial in patients with CDHR1-associated retinal degeneration is warranted. Hypomorphic CDHR1 variants may mimic advanced dry AMD. Accurate clinical classification is now critical, as their pathogenesis and treatment are distinct.

Factors associated with loss to follow-up in patients with advanced age-related macular degeneration: A telehealth recall initiative.

INTRODUCTION: Patients with advanced age-related macular degeneration (AMD) frequently experience loss to follow-up (LTFU), heightening the risk of vision loss from treatment delays. This study aimed to identify factors contributing to LTFU in patients with advanced AMD and assess the effectiveness of telephone-based outreach in reconnecting them with eye care. METHODS: A custom reporting tool identified patients with advanced AMD who had not returned for eye care between 31 October 2021 and 1 November 2022. Potentially LTFU patients were enrolled in a telephone outreach programme conducted by a telehealth extender to encourage their return for care. Linear regression analysis identified factors associated with being LTFU and likelihood of accepting care post-outreach. RESULTS: Out of 1269 patients with advanced AMD, 105 (8.3%) did not return for recommended eye care. Patients LTFU were generally older (89.2 ± 8.9 years vs. 87.2 ± 8.5 years, p = 0.02) and lived farther from the clinic (25 ± 43 miles vs. 17 ± 30 miles, p = 0.009). They also had a higher rate of advanced dry AMD (26.7% vs. 18.5%, p = 0.04) and experienced worse vision in both their better-seeing (0.683 logMAR vs. 0.566 logMAR, p = 0.03) and worse-seeing (1.388 logMAR vs. 1.235 logMAR, p = 0.04) eyes. Outreach by a telehealth extender reached 62 patients (59%), 43 through family members or healthcare proxies. Half of the cases where a proxy was contacted revealed that the patient in question had died. Among those contacted directly, one third expressed willingness to resume eye care (20 patients), with 11 scheduling appointments (55%). Despite only two patients returning for in-person eye care through the intervention, the LTFU rate halved to 4.4% by accounting for those patients who no longer needed eye care at the practice. CONCLUSIONS: There is a substantial risk that older patients with advanced AMD will become LTFU. Targeted telephone outreach can provide a pathway for vulnerable patients to return to care.

Understanding and Rescuing the Splicing Defect Caused by the Frequent ABCA4 Variant c.4253+43G>A Underlying Stargardt Disease.

Pathogenic variants in ABCA4 are the underlying molecular cause of Stargardt disease (STGD1), an autosomal recessive macular dystrophy characterized by a progressive loss of central vision. Among intronic ABCA4 variants, c.4253+43G>A is frequently detected in STGD1 cases and is classified as a hypomorphic allele, generally associated with late-onset cases. This variant was previously reported to alter splicing regulatory sequences, but the splicing outcome is not fully understood yet. In this study, we attempted to better understand its effect on splicing and to rescue the aberrant splicing via antisense oligonucleotides (AONs). Wild-type and c.4253+43G>A variant-harboring maxigene vectors revealed additional skipping events, which were not previously detected upon transfection in HEK293T cells. To restore exon inclusion, we designed a set of 27 AONs targeting either splicing silencer motifs or the variant region and screened these in maxigene-transfected HEK293T cells. Candidate AONs able to promote exon inclusion were selected for further testing in patient-derived photoreceptor precursor cells. Surprisingly, no robust splicing modulation was observed in this model system. Overall, this research helped to adequately characterize the splicing alteration caused by the c.4253+43G>A variant, although future development of AON-mediated exon inclusion therapy for ABCA4 is needed.

Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells.

BACKGROUND AIMS: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively degenerates, resulting in subsequent loss of photoreceptors and ultimately vision. There is currently no cure for AMD, but therapeutic strategies targeting the complement system are being developed to slow the progression of the disease. METHODS: Replacement therapy with pluripotent stem cell-derived (hPSC) RPEs is an alternative treatment strategy. A cell therapy product must be produced in accordance with Good Manufacturing Practices at a sufficient scale to facilitate extensive pre-clinical and clinical testing. Cryopreservation of the final cell product is therefore highly beneficial, as the manufacturing, pre-clinical and clinical testing can be separated in time and location. RESULTS: We found that mature hPSC-RPE cells do not survive conventional cryopreservation techniques. However, replating the cells 2-5 days before cryopreservation facilitates freezing. The replated and cryopreserved hPSC-RPE cells maintained their identity, purity and functionality as characteristic RPEs, shown by cobblestone morphology, pigmentation, transcriptional profile, RPE markers, transepithelial resistance and pigment epithelium-derived factor secretion. Finally, we showed that the optimal replating time window can be tracked noninvasively by following the change in cobblestone morphology. CONCLUSIONS: The possibility of cryopreserving the hPSC-RPE product has been instrumental in our efforts in manufacturing and performing pre-clinical testing with the aim for clinical translation.

Age-Related Macular Degeneration and Mitochondria-Associated Autoantibodies: A Review of the Specific Pathogenesis and Therapeutic Strategies.

Age-related macular degeneration (AMD) is a severe retinal disease that causes irreversible visual loss and blindness in elderly populations worldwide. The pathological mechanism of AMD is complex, involving the interactions of multiple environmental and genetic factors. A poor understanding of the disease leads to limited treatment options and few effective prevention methods. The discovery of autoantibodies in AMD patients provides an opportunity to explore the pathogenesis and treatment direction of the disease. This review focuses on the mitochondria-associated autoantibodies and summarizes the functional roles of mitochondria under physiological conditions and their alterations during the pathological states. Additionally, it discusses the crosstalk between mitochondria and other organelles, as well as the mitochondria-related therapeutic strategies in AMD.

CRISPR Manipulation of Age-Related Macular Degeneration Haplotypes in the Complement System: Potential Future Therapeutic Applications/Avenues.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3).

Recent Progress in Retinal Pigment Epithelium Cell-Based Therapy for Retinal Disease.

Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of retinal pigment epithelial cells and/or photoreceptors as a treatment for these conditions are underway. In this review, we summarize recent progress in the field of retinal pigment epithelium transplantation, including some pertinent clinical trial results as well as preclinical studies that address issues of transplant immunology, cell delivery, and cell manufacturing.

Recent Progress in Photoreceptor Cell-Based Therapy for Degenerative Retinal Disease.

Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of photoreceptors as treatment for these conditions are underway. In this review, we summarize recent progress in the field of photoreceptor transplantation, including some pertinent results regarding photoreceptor manufacture, photoreceptor transplantation, mechanisms of donor-host cell integration such as material transfer and photoreceptor transplant immunology. We conclude by proposing several approaches that may provide a rational basis for selecting a vision restoration strategy (eg, donor-host synapse formation vs donor-host nanotube formation) and improved transplant efficiency.

DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells.

BACKGROUND: Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. METHODS: We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. RESULTS: Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. CONCLUSIONS: Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.

Cell therapy for retinal disease.

PURPOSE OF REVIEW: This review presents an update on completed stem cell therapy trials aimed at retinal diseases. RECENT FINDINGS: In recent years, several clinical trials have been conducted examining the safety and role of cell therapy in diseases, including age-related macular degeneration, Stargardt's macular dystrophy, and retinitis pigmentosa. Studies have utilized a variety of cell lines, modes of delivery, and immunosuppressive regimens. The prevalence of fraudulent cell therapy clinics poses threats to patients. SUMMARY: Clinical trials have begun to characterize the safety of cell therapy in retinal disease. While studies have described the potential benefits of cell therapy, larger studies powered to evaluate this efficacy are required to continue progressing toward preventing retinal disease. Nonapproved cell therapy clinics require regulation and patient education to avoid patient complications.

Stargardt macular dystrophy and therapeutic approaches.

Stargardt macular dystrophy (Stargardt disease; STGD1; OMIM 248200) is the most prevalent inherited macular dystrophy. STGD1 is an autosomal recessive disorder caused by multiple pathogenic sequence variants in the large ABCA4 gene (OMIM 601691). Major advances in understanding both the clinical and molecular features, as well as the underlying pathophysiology, have culminated in many completed, ongoing and planned human clinical trials of novel therapies.The aims of this concise review are to describe (1) the detailed phenotypic and genotypic characteristics of the disease, multimodal imaging findings, natural history of the disease, and pathogenesis, (2) the multiple avenues of research and therapeutic intervention, including pharmacological, cellular therapies and diverse types of genetic therapies that have either been investigated or are under investigation and (3) the exciting novel therapeutic approaches on the translational horizon that aim to treat STGD1 by replacing the entire 6.8 kb ABCA4 open reading frame.

AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vascular diseases with high prevalence, ranking among the leading causes of blindness and vision loss worldwide. Despite being effective, current treatments for AMD and DR are burdensome for patients and clinicians, resulting in suboptimal compliance and real risk of vision loss. Thus, there is an unmet need for long-lasting alternatives with improved safety and efficacy. Adeno-associated virus (AAV) is the leading vector for ocular gene delivery, given its ability to enable long-term expression while eliciting relatively mild immune responses. Progress has been made in AAV-based gene therapies for not only inherited retinal diseases but also acquired conditions with preclinical and clinical studies of AMD and DR showing promising results. These studies have explored several pathways involved in the disease pathogenesis, as well as different strategies to optimise gene delivery. These include engineered capsids with enhanced tropism to particular cell types, and expression cassettes incorporating elements for a targeted and controlled expression. Multiple-acting constructs have also been investigated, in addition to gene silencing and editing. Here, we provide an overview of strategies employing AAV-mediated gene delivery to treat AMD and DR. We discuss preclinical efficacy studies and present the latest data from clinical trials for both diseases.

Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). MATERIALS AND METHODS: A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies. RESULTS: A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events. CONCLUSIONS: Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.

Relación del tratamiento y coste con la ganancia de agudeza visual en la degeneración macular asociada a la edad / Relationship between treatment and cost with visual acuity improvement in age-related macular degeneration

Fundamento. Relacionar la ganancia de agudeza visual (AV) con el coste asistencial y de tratamiento con terapia anti-factor de cre-cimiento endotelial vascular (antiVEGF) en pacientes diagnostica-dos de degeneración macular asociada a la edad exudativa (DMAE exudativa).Pacientes y métodos. Estudio observacional, longitudinal, retros-pectivo, de pacientes ≥50 años diagnosticados de DMAE exudativa, con AV logMAR entre 0,6 y 0,06, en seguimiento y tratamiento en nuestro hospital de tercer nivel entre el 01/01/2014 y el 31/12/2018.Resultados. Se incluyeron 778 pacientes, 62,2% mujeres y media de edad 79,83±7,94 años, con 957 ojos con DMAE exudativa. La AV final global (0,65±0,45) aumentó un 3,2% respecto de la inicial. El 60,3% de los ojos recibieron antiVEGF con ranibizumab, el 10,2% con aflibercept y el 29,5% con ambos (mixto). El grupo mixto in-crementó significativamente la AV respecto de la inicial, sin dife-rencias entre grupos. Aunque el seguimiento/tratamiento fue más largo para el grupo mixto, este recibió menos inyecciones antiVE-GF y tomografías de coherencia óptica (OCT). El gasto total por año y ojo tratado fue de 1.972,7 €±824,5; los costes fueron mayores para visita, OCT y tratamiento en el grupo de aflibercept, y menores para angiografías con fluoresceína, tratamiento antiVEGF y costes totales en el grupo mixto. La ganancia decimal de AV tuvo un coste de 872 €±1.077,7 sin diferencias significativas entre grupos.Conclusiones. Los tratamientos antiVEGF con ranibizumab, afli-bercept y ambos mantuvieron la AV en pacientes con DMAE exu-dativa. En general, los costes asistenciales y de tratamiento fueron menores en el grupo que recibió ambos fármacos (AU)

Background. We examined the relationship between visual acuity changes (VA) and the cost of care and treatment with anti-vascular endothelial growth factors (antiVEGF) in patients diagnosed with age-related exudative macular degeneration(exudative AMD).Methods. Observational, longitudinal, retrospective study of pa-tients ≥50 years of age diagnosed with exudative AMD, with a log-MAR VA between 0.6 and 0.06. and 0.06. Follow-up and treatment were done in our tertiary hospital between January 1, 2014 and December 31, 2018.Results. The study included 778 patients; 62.2% female and mean age 79.83±7.94 years; 957 eyes had exudative AMD. Mean of final VA (0.65±0.45) increasing 3.2% compared to initial values. Ranibi-zumab was administered to 60.3% of the eyes, aflibercept to 10.2% and ranibizumab + aflibercept (mixed group) to 29.5%. Significant increase in VA was seen in the group with the mixed treatment, with no inter-group differences. Although follow-up/treatment was longer for the mixed group, they received fewer anti-VEGF injections and optical coherence tomography (OCT). The total expenditure per year and treated eye was €1,972.7±824.5; costs were higher for visit, OCT, and treatment in the aflibercept group, and lower for fluorescein angiography, antiVEGF treatment, and total costs in the mixed group. Decimal VA gain had a cost of €872±1,077.7 with no significant inter-group differences.Conclusion. AntiVEGF treatments (ranibizumab, aflibercept, or both) maintained VA in patients with exudative AMD. Overall, care and treatment costs were lower in the group that received both drugs (AU)

Current Management of Subretinal Hemorrhage in Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among individuals aged 65 years and older in the USA. For individuals diagnosed with AMD, approximately 12% experience varying levels of subretinal hemorrhage (SRH), which can be further classified by size into small, medium, and massive measured in disc diameters. SRH is an acute and rare sight-threatening complication characterized by an accumulation of blood under the retina arising from the choroidal or retinal circulation. Released iron toxins, reduced nutrient supply, fibrin meshwork contraction, and outer retinal shear forces created by SRH contribute to visual loss, macular scarring, and photoreceptor damage. SRH treatment strategies aim to displace hemorrhage from the foveal region and prevent further bleeding. Although there are no standardized treatment protocols for SRH, several surgical and nonsurgical therapeutical approaches may be employed. The most common surgical approaches that have been utilized are pars plana vitrectomy (PPV) combined with multiple maneuvers such as the removal of choroidal neovascularization lesions, macular translocation, retinal pigment epithelium patch repair, SRH drainage, intravitreal injection of recombinant-tissue plasminogen activator (tPA), expansile gas and air displacement, and anti-vascular endothelial growth factor (anti-VEGF) injections. Nonsurgical therapeutical approaches include intravitreal anti-VEGF monotherapy, intravitreal tPA administration without PPV, and photodynamic therapy. This review article aims to explore the current treatment strategies and supporting literature regarding both surgical and nonsurgical, of SRH in patients with AMD. Moreover, this article also aims to highlight the distinct treatment modalities corresponding to different sizes of SRH.