Comparison between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration.

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Design: Retrospective study. Participants: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 µm on the en face images generated using a slab extending from 64 to 400 µm beneath Bruch's membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. Main Outcome Measures: The mean sqrt area measurements and the number of hyperTDs were compared. Results: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc = 0.969 and rc = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Conclusions: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Safety and Tolerability of Suprachoroidal Axitinib Injectable Suspension, for Neovascular Age-related Macular Degeneration; Phase I/IIa Open-Label, Dose-Escalation Trial.

Purpose: To evaluate the safety and tolerability of a single dose of axitinib injectable suspension (CLS-AX), a pan-anti-VEGF tyrosine kinase inhibitor (TKI), administered via suprachoroidal injection in patients with neovascular age-related macular degeneration (nAMD). Design: Phase I/IIa, open-label, sequential dose escalation. Participants: Anti-VEGF treatment-experienced patients with active subfoveal choroidal neovascularization secondary to nAMD. Methods: The study included 4 cohorts (0.03, 0.10, 0.50, and 1.0 mg) of approximately 5 patients each enrolled in a dose-escalating fashion. Enrolled patients received intravitreal aflibercept (2 mg) followed by a single unilateral dose of CLS-AX 1 month later. All patients were followed monthly for 3 months with the option of an additional 3 months of extended follow-up for cohorts 2 to 4. End points included systemic and ocular safety and tolerability, visual acuity, retinal thickness, and need for aflibercept therapy. Main Outcome Measures: The number of patients reporting treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), changes in ophthalmic examinations, and the number of patients qualifying for additional therapy for nAMD based on protocol-defined criteria. Results: OASIS enrolled 27 patients with nAMD with mean age of 81 years, mean duration of nAMD diagnosis of 54 months, and between 5 and 90 prior anti-VEGF treatments. Twenty-six patients completed through 3 months, with 14 entering and completing the 3-month extension. No SAEs, drug-related TEAEs, or TEAEs leading to discontinuation were observed after CLS-AX administration; there were no adverse events related to ocular inflammation, vasculitis, intraocular pressure, or dispersion of drug into the vitreous or anterior chamber. Through 6 months, stable mean best-corrected visual acuity and stable mean central subfield thickness (CST) were observed, suggestive of TKI biologic effect. No aflibercept therapy was administered up to 3 months in 58% (15/26) of patients who completed 3 months of follow-up in OASIS. In the Extension, 57% (8/14) of patients went up to 6 months without receiving aflibercept therapy. Conclusions: Up to 1.0 mg CLS-AX, a highly potent TKI targeted to the suprachoroidal space (SCS) via the SCS Microinjector, was well tolerated, with stable mean visual acuity and mean CST. A majority of patients followed for 6 months did not require aflibercept therapy. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration: An observational study.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is critical for managing neovascular age-related macular degeneration (nAMD), but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes. AIM: To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response. METHODS: In this study, 65 eyes of exudative AMD patients after anti-VEGF treatment for ≥ 1 mo were observed using optical coherence tomography angiography. Patients were classified into non-responders (n = 22) and responders (n = 43). Logistic regression was used to determine independent risk factors for treatment response. A predictive model was created using the Akaike Information Criterion, and its performance was assessed with the area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA) with 500 bootstrap re-samples. RESULTS: Multivariable logistic regression analysis identified the number of junction voxels [odds ratio = 0.997, 95% confidence interval (CI): 0.993-0.999, P = 0.010] as an independent predictor of positive anti-VEGF treatment outcomes. The predictive model incorporating the fractal dimension, number of junction voxels, and longest shortest path, achieved an area under the curve of 0.753 (95%CI: 0.622-0.873). Calibration curves confirmed a high agreement between predicted and actual outcomes, and DCA validated the model's clinical utility. CONCLUSION: The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy, enhancing personalized treatment planning.

Untargeted Metabolomic Study of Patients with Wet Age-Related Macular Degeneration in Aqueous Humor.

Purpose: The objective of this study was to ascertain metabolic biomarkers and investigate the metabolic alterations associated with aqueous humor (AH) in wet age-related macular degeneration (AMD). Methods: AH samples were collected from a total of 20 participants, including 10 individuals diagnosed with wet AMD and 10 individuals undergoing cataract surgery, serving as the control group. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and quantify metabolites. Results: A total of 155 metabolites were identified in the AH samples. Among them, 10 metabolites emerged as potential biomarkers capable of differentiating patients with wet AMD from the control group. In the AH of wet AMD patients, there was increased expression of Cardiolipin (CL) (72:5), Diglyceride (DG) (18:3_18:2), DG (36:5e) and Triglyceride (TG) (24:7), while the expression of Ceramides (Cer) (d32:0), Cer (d34:0), Cer (d36:0), Monogalactosyldiacylglycerol (MGDG) (16:1_18:3), Sphingosine (SPH) (d18:0) and TG (16:0_10:4_16:0) was down regulated. Conclusion: Through metabolomics analysis of AH, this study successfully uncovered valuable metabolic biomarkers linked to wet AMD. These findings contribute to a more comprehensive understanding of the pathogenesis of wet AMD and offer potential avenues for the development of innovative treatment strategies for this condition.

Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.

EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.

Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) are eye problems that can make you lose your sight. These eye problems happen when blood vessels in the eye do not work right. Right now, people need lots of shots in their eyes to treat it. EYP-1901 (Duravyu) is a new medicine that helps people with fewer shots in their eyes. It has two parts: one that helps the medicine last longer, and another that helps stop the problem in the eye. Early tests show it works well and helps people keep their sight with fewer treatments.

Intravitreal faricimab for treatment naïve patients with neovascular age-related macular degeneration: a real-world prospective study.

BACKGROUND: Intravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD. METHODS: Single-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up. RESULTS: The study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p < 0.01). The intended interval between injections was ≥ 12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears. CONCLUSIONS: Intravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-naïve nAMD patients.

Reactivation of stable neovascular age-related macular degeneration following treat-and-extend regimen discontinuation.

BACKGROUND: To describe the incidence and pattern of reactivation of neovascular age-related macular degeneration (nAMD) following successful treatment with treat-and-extend intravitreal anti-vascular endothelial growth factor therapy. METHODS: Consecutive patients with treated nAMD who did not require further treatment over a 6-month period and who attended their 3-monthly optical coherence tomography monitoring clinic in Moorfields Eye Hospital from 1 November 2019 to 31 January 2020 were included. Patients with diagnoses of macular neovascularization other than AMD, and patients with incomplete data were excluded. Baseline demographics recorded were age, sex, race, laterality, cause of macular neovascularization, drug, number of injections, and duration of treatment. Date, setting, symptoms, and time to retreatment were collected among patients with disease reactivation. RESULTS: The medical records of 286 patients were included. Most patients were female (64.3%), white (68.18%), and were receiving aflibercept monotherapy (55.2%). Mean number of injections at baseline was 17.79 ± 11.74 (range 3-62) with a mean treatment duration of 39.47 ± 30.68 months (range 2-139). Reactivation of AMD was identified in 32.2% of cases with 87% of recurrences identified via scheduled visit. The most common symptom was blurring of vision in 44.6%, while 39.1% were asymptomatic. Mean time from baseline to retreatment was 29.37 ± 22.40 months (range 5-104), with 20.7%, 73.9% and 88.04% of these patients requiring retreatment within 1, 3, and 5 years, respectively. CONCLUSIONS: Despite prior treatment with no reactivation in 6 months, 32.2% reactivate, 73.9% of which within 3 years. A significant proportion, 39.1%, reactivated without symptoms necessitating regular monitoring in the first 5 years.

Quantifying Changes on OCT in Eyes Receiving Treatment for Neovascular Age-Related Macular Degeneration.

Purpose: Application of artificial intelligence (AI) to macular OCT scans to segment and quantify volumetric change in anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD). Design: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. Participants: A total of 2115 eyes from 1801 patients starting anti-VEGF treatment between June 1, 2012, and June 30, 2017. Methods: The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes receiving anti-VEGF treatment and had an OCT scan at baseline and 12 months. Follow-up scans were input into the AI system and volumes of OCT variables were studied at different time points and compared with baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test. Main Outcome Measures: Volume outputs of the following variables were studied: intraretinal fluid, subretinal fluid, pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci, neurosensory retina, and retinal pigment epithelium. Results: Mean volumes of analyzed features decreased significantly from baseline to both 4 and 12 months, in both first-treated and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (intraretinal fluid and subretinal fluid) and those with fluid and fibrovascular tissue (PED and SHRM), displayed similar responses to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first 2 months, reaching a plateau postloading phase, and minimal change to 12 months. Both neurosensory retina and retinal pigment epithelium volumes showed gradual reductions over time, and were not as substantial as exudative features. Conclusions: We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pretreatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid the personalization of care. Data will be made public for future studies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Novel Application of EUK-134 in Retinal Degeneration: Preventing Mitochondrial Oxidative Stress-Triggered Retinal Pigment Epithelial Cell Apoptosis by Suppressing MAPK/p53 Signaling Pathway.

Age-related macular degeneration (AMD), a leading cause of blindness, is characterized by mitochondrial dysfunction of retinal pigment epithelium (RPE) cells. EUK-134 is a mimetic of SOD2 and catalase, widely used for its antioxidant properties in models of light-induced damage or oxidative stress. However, its effects on the retina are not yet clear. Here, we investigated the capability of EUK-134 in averting AMD using sodium iodate (NaIO3)-induced Balb/c mouse and ARPE-19 cells (adult RPE cell line). In vivo, EUK-134 effectively antagonized NaIO3-induced retinal deformation and prevented outer and inner nuclear layer thinning. In addition, it was found that the EUK-134-treated group significantly down-regulated the expression of cleaved caspase-3 compared with the group treated with NaIO3 alone. Our results found that EUK-134 notably improved cell viability by preventing mitochondrial ROS accumulation-induced membrane potential depolarization-mediated apoptosis in NaIO3-inducted ARPE-19 cells. Furthermore, we found that EUK-134 could inhibit p-ERK, p-p38, p-JNK, p-p53, Bax, cleaved caspase-9, cleaved caspase-3, and cleaved PARP by increasing Bcl-2 protein expression. Additionally, we employed MAPK pathway inhibitors by SB203580 (a p38 inhibitor), U0126 (an ERK inhibitor), and SP600125 (a JNK inhibitor) to corroborate the aforementioned observation. The results support that EUK-134 may effectively prevent mitochondrial oxidative stress-mediated retinal apoptosis in NaIO3-induced retinopathy.

Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration.

INTRODUCTION: Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT®PBM treatment device in patients with dAMD. METHODS: The EYE-LIGHT® device employs two wavelengths, 590 nm (yellow) and 630 nm (red), in both continuous and pulsed modes. Patients over 50 years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4 weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month. RESULTS: This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013). CONCLUSION: These preliminary results indicate that PBM treatment using the EYE-LIGHT® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment's short-term efficacy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06046118.

Atrophic Macular Degeneration and Stem Cell Therapy: A Clinical Review.

Age-related macular degeneration (AMD) is one of the leading causes of visual loss in older patients. No effective drug is available for this pathology, but studies about therapy with stem cells replacing the damaged retinal cells with retinal pigment epithelium (RPE) were described. The documentation of AMD progression and the response to stem cell therapy have been performed by optical coherence tomography, microperimetry, and other diagnostic technologies.This chapter reports a clinical review of the most important clinical trials and protocols regarding the use of stem cells in AMD.

Association of rheumatoid arthritis with age-related macular degeneration in nationwide longitudinal cohort study.

Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02-1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03-1.21) and those with VD (aHR 0.90; 95% CI 0.64-1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.

Protective effect of ghrelin in oxidative stress-induced age-related macular degeneration in vitro and in vivo.

Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors.

Neurosensory retina detachment combined with retinal pigment epithelium separation from the choroid in the course of dry macular degeneration - A case report.

of advanced diagnostic methods shed the light on the variable course of age-related macular degeneration (AMD). Despite establishing AMD classifications used in clinical practice, there are still forms of AMD that do not fit into these systems. The case report presents a rare evolution of non-neovascular form of AMD presenting at baseline as large soft drusen. Within the 5 years of observation one eye with such form of AMD transformed to retinal pigment epithelial detachment and subsequently simultaneous separation of the neurosensory retina and the choroid from the RPE. As a result, on the spectral domain optical coherence tomography scan, the case presented with lone line of the RPE neighbored by subretinal fluid from the inner side and choroidal excavation from the outside. Macular neovascularization was excluded at each timepoint of the follow-up. During 2.5 years of observation post the onset of RPE separation, the case remained stable with maintained visual acuity at 0.25 Snellen and lack of progression to wet form of AMD. Further observation is needed to fully assess the eye's potential for visual preservation in the long term.

Harnessing the potential of mesenchymal stem cells-derived exosomes in degenerative diseases.

Mesenchymal stem cells (MSCs) have gained attention as a promising therapeutic approach in both preclinical and clinical osteoarthritis (OA) settings. Various joint cell types, such as chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and release extracellular vesicles (EVs), which subsequently influence the biological activities of recipient cells. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown the potential to modulate various physiological and pathological processes through the modulation of cellular differentiation, immune responses, and tissue repair. This review explores the roles and therapeutic potential of MSC-EVs in OA and rheumatoid arthritis, cardiovascular disease, age-related macular degeneration, Alzheimer's disease, and other degenerative diseases. Notably, we provide a comprehensive summary of exosome biogenesis, microRNA composition, mechanisms of intercellular transfer, and their evolving role in the highlight of exosome-based treatments in both preclinical and clinical avenues.

Salidroside alleviates ferroptosis in FAC-induced Age-related macular degeneration models by activating Nrf2/SLC7A11/GPX4 axis.

INTRODUCTION: Age-related macular degeneration (AMD) is a significant contributor to irreversible impairment in visual capability, particularly in its non-neovascular (dry) form. Ferroptosis, an emerging form of programmed necrosis, involves generating lipid peroxidation (LOS) through free iron and reactive oxygen species (ROS). Salidroside, a glycoside from Rhodiola rosea, known for anti-inflammatory and antioxidant properties. The research aim was exploring whether ferroptosis exists in dry AMD pathogenesis and elucidate salidroside's protective mechanisms against ferroptosis in AMD murine models and ARPE-19 cells. METHODS: ARPE-19 cells were treated with varying concentrations of ferrous ammonium citrate (FAC) and salidroside. In an in vivo model, C57BL/6 mice were administered intraperitoneal injections of salidroside for 7 consecutive days, followed by an intravitreal injection (IVT) of FAC. After 7 days, the eyeballs were harvested for subsequent analyses. Ferroptosis markers were assessed using western blotting, immunofluorescence staining, and flow cytometry. To further elucidate the modulatory role of Nrf2 in ferroptosis, ARPE-19 cells were transfected with si-Nrf2. RESULTS: In vitro, FAC-treated ARPE-19 cells exhibited reduced viability, decreased mitochondrial membrane potential (MMP), and accumulation of iron and lipid peroxidation (LOS) products. In vivo, FAC administration by IVT led to outer nuclear layer thinning and compromised tight junctions in RPE cells. The GPX4, Nrf2, and SLC7A11 expressions were downregulated both in vitro and in vivo. Salidroside upregulated Nrf2 and ameliorated these outcomes, but its effects were attenuated in ARPE-19 cells transfected with si-Nrf2. CONCLUSION: Our study establishes that FAC induces RPE cell ferroptosis within dry AMD, and salidroside exerts therapeutic effects by triggering Nrf2/SLC7A11/GPX4 signaling axis.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

A potential biomarker for age-related macular degeneration disease: iris freckles.

BACKGRAUND: To determine the potential relationship between age-related macular degeneration and iris freckles. METHOD: In this case-control study, iris photographs of 300 eyes of 300 patients diagnosed with age-related macular degeneration and 300 eyes of 300 healthy volunteers were obtained with the help of a high-resolution mobile phone camera. The evaluated iris photographs were classified according to the Descriptive Iris Color Classification Scale. RESULTS: The average age of the AMD group is 73.05 ± 6.93, and the average age of the control group is 73.43 ± 5.72. (p = 0.124) While freckles were present in 200 (66.7%) of the patients in the AMD group, freckles were not observed in 100 patients (33.3%) of AMD group. While freckles were present in 142 (47.3%) of the patients in the control group, freckles were not observed in 158 of control group(52.7%). There was a significant difference in the presence of freckles between the two groups. (p < 0.001) The average number of freckles in the AMD group was 3.97 ± 3.07, and the number of freckles in the control group was 3.06 ± 2.55. (p = 0.001) CONCLUSION: We think that evaluation of iris details, especially the presence of iris freckles, should be used routinely in age-related macular degeneration screening. The risk of age-related macular degeneration can be predicted by evaluating iris details, which is an easy and inexpensive method.

A Comprehensive Evaluation of Serum Iron Status Indicators in Patients with Age-Related Macular Degeneration.

Objectives: Iron is recognized as a significant contributor to oxidative damage, and its levels tend to rise with age, potentially worsening age-related diseases. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of age-related macular degeneration (AMD). Methods: The files of all AMD patients in Kocaeli University School of Medicine between January 2017 and March 2020 were reviewed retrospectively. By examining the files of AMD patients who applied to the eye outpatient clinic on the same dates, those dry AMD (dAMD) and neovascular AMD (nAMD) were recorded. As a control group, the records of patients without any AMD findings were obtained from the files of all patients who visited the clinic during the same time period. All records were recorded for analysis, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination. Results: Of the 164 participants, 50 were dAMD patients, 51 were nAMD patients, and 63 were patients non-AMD (control group). There was a significant difference between the groups' mean corpuscular volume (MCV), serum ferritin, and total iron-binding capacity (TIBC) (p<0.050). It was observed that the ferritin of those with AMD was significantly higher than the control group, whereas MCV and TIBC were found to be significantly lower (p<0.050). There was no significant difference in serum iron marker levels between nAMD and dAMD patients (p>0.05). Conclusion: Assessing serum iron status indicators during the routine monitoring of AMD may provide insights into the associated risk profile of the condition.

Inflammasome activation aggravates choroidal neovascularization.

Inflammasome activation is implicated in diseases of aberrant angiogenesis such as age-related macular degeneration (AMD), though its precise role in choroidal neovascularization (CNV), a characteristic pathology of advanced AMD, is ill-defined. Reports on inhibition of inflammasome constituents on CNV are variable and the precise role of inflammasome in mediating pathological angiogenesis is unclear. Historically, subretinal injection of inflammasome agonists alone has been used to investigate retinal pigmented epithelium (RPE) degeneration, while the laser photocoagulation model has been used to study pathological angiogenesis in a model of CNV. Here, we report that the simultaneous introduction of any of several disease-relevant inflammasome agonists (Alu or B2 RNA, Alu cDNA, or oligomerized amyloid ß (1-40)) exacerbates laser-induced CNV. These activities were diminished or abrogated by genetic or pharmacological targeting of inflammasome signaling constituents including P2rx7, Nlrp3, caspase-1, caspase-11, and Myd88, as well as in myeloid-specific caspase-1 knockout mice. Alu RNA treatment induced inflammasome activation in macrophages within the CNV lesion, and increased accumulation of macrophages in an inflammasome-dependent manner. Finally, IL-1ß neutralization prevented inflammasome agonist-induced chemotaxis, macrophage trafficking, and angiogenesis. Collectively, these observations support a model wherein inflammasome stimulation promotes and exacerbates CNV and may be a therapeutic target for diseases of angiogenesis such as neovascular AMD.