Search Results (375)

Background: Age-related macular degeneration (AMD) is a common retinal degenerative disease linked to adaptive immune response dysregulation. This study aimed to identify shared immune-related biomarkers and explore their underlying mechanisms. Methods: GSE29801 and GSE135092 served as training and validation sets. Adaptive immune response-related genes (AIR-RGs) from MSigDB were intersected with AMD-related differentially expressed genes (DEGs) to identify candidate genes. Machine learning algorithms were applied to screen biomarkers, validated in datasets and a mouse model of choroidal neovascularization by qPCR. A nomogram was constructed and assessed. GSEA and immune infiltration analyses explored mechanisms and immune microenvironment associations. Results: A total of 148 DEGs were identified, yielding 15 candidate genes after intersection with AIR-RGs. Machine learning identified C3 and HLA-DOA as potential biomarkers, with their differential expression validated across datasets. A nomogram based on these biomarkers demonstrated good predictive performance for AMD pathology (AUC = 0.795). Biomarkers were associated with some immune-inflammatory pathways. Significant differences in immune cell infiltration were observed between AMD and control groups, with biomarkers positively correlated with differentially infiltrated immune cells, such as natural killer cells. Conclusions: The identification of the established biomarker C3 serves as a proof-of-principle for the analytical approach, rather than a novel discovery, thereby validating the model’s capacity to uncover other critical immune targets. Consequently, C3 and HLA-DOA serve as potential biomarkers for AMD, significantly correlated with disease progression via immune pathways and offering insights for immune-based therapeutic strategies. Full article

Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence. Full article

Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal–Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = −0.300, 95% CI [−0.483, −0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = −0.449, 95% CI [−0.879, −0.020], p = 0.041) and HRM width (β = −0.003, 95% CI [−0.005, −0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling. Full article

Background: Neovascular age-related macular degeneration (nAMD) is a progressive chronic disease that represents a major cause of irreversible vision loss worldwide. In this study we aim to assess the short-term functional and anatomical outcomes of brolucizumab therapy in treatment-naïve patients with nAMD presenting with low baseline visual acuity in a single institution setting. Methods: This is a prospective non-randomized study that included 154 treatment-naïve eyes with low baseline visual acuity. We measured visual outcomes (BCVA, logMAR) and structural outcomes (CST, μm). We also stratified the study population into respective age subgroups to evaluate any possible trend between outcome changes and age differences. BCVA and CST were measured at baseline, at each consecutive month (month 1, 2 and 3) of the loading phase, as well as at the final timepoint (6 months). Intraocular pressure (IOP) before and after injection, as well as the incidence of serious adverse events, were monitored throughout the study. Results: Mean BCVA improved by 0.41 logMAR (+20 ETDRS letters) after the first injection, 0.65 logMAR (+32 letters) after the second, and reached a maximum improvement of 0.80 logMAR after the third injection. The most important BCVA improvement was seen in younger patients (<50 years), with mean BCVA decreasing from approximately 1.0 logMAR at baseline to around 0.3–0.4 logMAR at the final measurement. Mean CST declined by 45.5 μm after the first injection, 78.5 μm after the second, 117.8 μm after the third, and 143.6 μm at the final timepoint, indicating a pronounced anatomical response to intravitreal brolucizumab therapy. Conclusions: In conclusion, this study demonstrates that brolucizumab therapy provides significant short-term anatomical and functional improvements in treatment-naïve patients with nAMD and poor baseline visual acuity. Baseline visual acuity, treatment-naïve status, and patient age appear to be key determinants of visual gain. Full article

Background and Objectives: Neovascular age-related macular degeneration (nAMD), including typical nAMD (tAMD) and polypoidal choroidal vasculopathy (PCV), is a leading cause of visual impairment. This study investigated the real-world short-term outcomes of faricimab, a bispecific antibody targeting Ang-2 and VEGF-A, in patients with treatment-naïve or -refractory nAMD. Materials and Methods: This retrospective study analyzed treatment-naïve or -refractory nAMD eyes receiving one, two, or three monthly intravitreal faricimab injections. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) one month after the last injection. Secondary outcomes included the dry macula rate (absence of subretinal and intraretinal fluid) and subgroup comparisons between tAMD and PCV. Results: After a single injection, both treatment-naïve (n = 76) and -refractory (n = 44) eyes showed significant CFT reduction (p < 0.0001) but no significant BCVA improvement (p > 0.05). Dry macula was achieved in 63.2% of treatment-naïve and 71.4% of treatment-refractory eyes. In 38 treatment-naïve eyes receiving three injections, both CFT and BCVA significantly improved from baseline (p < 0.001 and p = 0.02, respectively), with a 94.7% dry macula rate. Subgroup analysis of those receiving three injections revealed that PCV eyes exhibited significant visual improvement, whereas tAMD eyes did not. No serious systemic or ocular adverse events were observed over the short-term follow-up period. Conclusions: Intravitreal faricimab is effective for both treatment-naïve and -refractory nAMD in the short term. While anatomical improvements were comparable between subtypes, the PCV subgroup showed a trend toward greater visual improvement in this small cohort; however, this may be influenced by the significantly younger age of PCV patients. These findings are exploratory and require validation in larger, age-matched prospective studies. Full article

Mechanical stress has been implicated in retinal pigment epithelium (RPE) dysfunction and angiogenic signaling in retinal disorders; however, its direct in vivo effects on the RPE–choroid complex remain incompletely understood. Here, we established a mouse model of localized mechanical stress by subconjunctival implantation of glass beads (0.8–1.2 mm in diameter) in eight-week-old C57BL/6J mice to induce transscleral stretching of the RPE. Ocular tissues were analyzed two days after implantation using histological, immunohistochemical, and molecular approaches, and inflammatory mediators were quantified by multiplex cytokine assays. Mechanical stress induced focal serous retinal detachment, elongation of photoreceptor outer segments, and disruption of the RPE tight junction protein ZO-1. VEGF expression in the RPE–choroid complex was significantly upregulated and accompanied by increased levels of inflammatory mediators, including MCP-1. Intravitreal administration of anti-VEGF agents effectively suppressed stress-induced VEGF expression. These findings indicate that mechanical stress is sufficient to induce structural disruption and angiogenic signaling in the RPE in vivo, providing a useful experimental platform for investigating stress-related retinal responses and therapeutic modulation of VEGF signaling. Full article

Vascular endothelial growth factor (VEGF)-driven pathological angiogenesis constitutes a primary driver of neovascular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Although anti-VEGF agents demonstrate clinical efficacy, their limited intraocular half-life mandates repeated intravitreal injections, thereby highlighting the imperative for long-term therapeutic strategies. In the present study, we assessed the anti-angiogenic potential of retinal organoid-derived microRNAs (miRNA) delivered via an engineered adeno-associated virus vector. Human umbilical vein endothelial cells (HUVEC) were transduced with AAV2.7m8 vectors to overexpress three candidate miRNA (miR-26a, miR-122, and let-7a), followed by VEGF stimulation to evaluate downstream signaling pathways and angiogenic responses. AAV2.7m8-mediated transduction of HUVEC demonstrated high efficiency without inducing detectable cytotoxicity. Overexpression of these miRNA markedly attenuated VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Functional assays demonstrated suppression of endothelial cell proliferation and cell cycle progression, with miR-122-5p additionally inhibiting migration. All three miRNA substantially inhibited capillary-like tube formation. In aggregate, these results affirm that AAV2.7m8-mediated delivery of retinal organoid-derived miRNA —namely miR-26a-5p, miR-122-5p, and let-7a-5p—markedly suppresses VEGF-induced angiogenic signaling cascades and endothelial cell activation in vitro, thereby establishing their viability as a sustained therapeutic approach for pathological retinal neovascularization. Full article

Neovascular age-related macular degeneration (nAMD) remains a major cause of visual morbidity worldwide, although its contribution to blindness in developed healthcare systems has declined in the era of anti-VEGF therapy. Although randomized clinical trials have consistently demonstrated meaningful visual gains under structured retreatment protocols, real-world outcomes frequently decline over time due to undertreatment, limited durability, and persistent disease activity. Recent therapeutic advances have shifted the focus from maximizing short-term efficacy to engineering sustained disease control. Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2, introduces dual-pathway vascular modulation, while high-dose aflibercept (8 mg) enhances VEGF suppression through pharmacokinetic intensification. This perspective critically examines the biological rationale, clinical evidence, real-world implications, and strategic positioning of these agents, proposing a durability-centered framework for next-generation management of nAMD. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions—particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients—have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut–eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD. Full article

Objectives: The objective of this study was to investigate choroidal structural alterations and evaluate the outcomes of switching to faricimab in patients with neovascular age-related macular degeneration (nAMD) previously treated with other anti-vascular endothelial growth factor (anti-VEGF) therapies after 12 months of follow-up. Methods: We performed a retrospective study of 30 eyes from 30 patients with nAMD who were switched to faricimab. The choroidal vascularity index (CVI), best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (CST), and the presence of subretinal fluid, intraretinal fluid, and wet macula were assessed at baseline and after 6 and 12 months. Results: CVI remained stable during follow-up (p > 0.05). BCVA improved significantly after 6 months (p = 0.041), but not at 12 months (p = 0.075). A significant reduction in CMT was observed (p < 0.05). Additionally, wet macula improved after 12 months (p < 0.05). Moreover, treatment intervals increased from 7.53 ± 2.39 to 12.47 ± 4.51 weeks. Conclusions: Switching to faricimab in patients with nAMD previously treated with other anti-VEGF therapies was associated with anatomical improvement, extended treatment intervals, and short-term visual gains, while choroidal vascular structure was maintained. Nonetheless, additional studies are warranted to more comprehensively evaluate the effectiveness of switching to faricimab, as well as the associated changes in choroidal vascular structure. Full article

Age-related macular degeneration (AΜD) remains a leading cause of irreversible vision loss. Ιn neovascular AΜD (nAΜD), frequent intravitreal anti-VΕGF injections create substantial treatment burden, while approved therapies for geographic atrophy (GA) provide modest slowing of progression. Ocular gene therapy aims to achieve sustained intraocular expression of therapeutic proteins after a single administration. Τhis review summarises the biological rationale, vector platforms, and delivery routes relevant to AΜD, with emphasis on adeno-associated virus (AAV) systems, capsid engineering, and compartment-specific administration (intravitreal, subretinal, and suprachoroidal). We synthesise the clinical landscape for sustained anti-VΕGF expression approaches in nAΜD and complement-modulating strategies for GA, and highlight how trials increasingly prioritise injection-burden reduction, anatomical endpoints, and biomarkers of target engagement. Κey challenges include intraocular inflammation and neutralising antibodies (particularly with intravitreal dosing), variability and durability of transgene expression, surgical risks associated with subretinal delivery, and practical constraints related to manufacturing scale, cost, and long-term safety surveillance for non-removable therapies. Overall, gene therapy offers a plausible route towards durable, mechanism-targeted AΜD management, but its clinical role will depend on robust controlled trials and multi-year follow-up. Full article

Background: Polypoidal choroidal vasculopathy (PCV) may be underdiagnosed in Europe due to the limited use of indocyanine green angiography (ICGA), in particular, in patients with occult or poorly responsive neovascular age-related macular degeneration (AMD). Based on this, we aimed to assess the prevalence of PCV beyond clinically typical recalcitrant nAMD using OCT criteria, and to report on the anatomical and functional outcomes following a switch to brolucizumab (bro). Methods: This retrospective case series used recently established optical coherence tomography (OCT)-based criteria to differentiate clinically typical nAMD and PCV in eyes with recalcitrant disease requiring treatment every six weeks or less. The aim was to compare the impact of switching to bro on disease activity in patients with recalcitrant nAMD and PCV over 12 months. Descriptive statistics and subgroup comparisons were performed. Data are presented as mean ± standard deviation (SD) as well as median and interquartile ranges (IQR), since data were not normally distributed. Results: Of the 27 eyes examined, 16 (59.3%) presented with typical recalcitrant nAMD and 11 (40.7%) with PCV. Patients with typical nAMD were older (81.4 ± 5.7 vs. 74.7 ± 7.7 years; p = 0.016) and exhibited less fluid (central retinal thickness in typical nAMD: 349.3 ± 95.3 µm; in PCV: 597.1 ± 348.4 µm; p = 0.005). This difference could be attributed to variations in pigment epithelial detachment heights (typical nAMD: 176.5 ± 102.6 µm, PCV: 384.6 ± 284.6 µm; p = 0.023). Twelve months after switching to bro (159 injections), the treatment interval increased from 5.7 ± 1.8 to 12.6 ± 5.1 weeks in nAMD and from 5.5 ± 1.9 to 8.0 ± 1.5 weeks in PCV patients (at switch: p = 0.81; after 12 months: p = 0.040). Visual gains after switching were maintained in two out of three patients with intraocular inflammation (IOI). Conclusions: PCV is remarkably underdiagnosed and overrepresented in the group of eyes with recalcitrant nAMD. Despite the inherent risk of IOI in response to bro, these results support the potential of bro as a third-line option for patients with eyes requiring anti-VEGF treatment every 6 weeks or less, provided that patients are monitored closely. Full article

Age-related macular degeneration (AMD) is the leading cause of central vision loss in aging populations. Geographic atrophy (GA) is the advanced, non-neovascular form of AMD. Predicting the longitudinal progression of GA remains a critical challenge in ophthalmic clinical practice and clinical trial design. Forecasting the trajectory of GA is complicated by highly variable growth rates and the inherent scarcity of long-term, high-quality imaging data. To address these challenges, we introduce the Sliding Window Attention U-Net (SWAU-Net), a hybrid architecture that integrates Transformer-based temporal modeling of GA growth with precise spatial modeling of GA location with a U-Net convolutional neural network (CNN). To ensure generalization in the low-data regime, SWAU-Net embeds explicit temporal and geometric consistency priors via a weight-shared Sliding Window Attention core and feature-level regularization that preserves sparse, high-frequency lesion boundaries across frames. Experimental results demonstrate that these structural constraints prevent the model from overfitting to imaging noise, achieving a Growth Mask Dice Similarity Coefficient (DSC) of 0.66 (representing the spatial overlap between the predicted and ground truth lesion expansion regions), a significant improvement over unregularized Transformer and standard recurrent baseline models. Our framework provides a robust tool for predicting GA lesion trajectories, potentially supporting more efficient clinical trial designs and personalized patient monitoring. Full article

Background/Objectives: To investigate the rate of exudative progression over time in patients with non-exudative macular neovascularization (NE-MNV) associated with various acquired macular degenerations presenting with a double-layer sign (DLS) or triple-layer sign (TLS) on optical coherence tomography (OCT), and to identify potential predictors of this progression. Methods: Fifty-one eyes of fourty-nine patients with a DLS or TLS on OCT images were identified. OCT angiography (OCTA) was performed to detect NE-MNV, and only eyes with confirmed NE-MNV were included in the final analysis. Central macular thickness (CMT), choroidal thickness (CT), morphology of the abnormal vessels, the duration of follow-up, progression to active exudative MNV, and the status of the contralateral eye were assessed. Results: The final analysis included 32 eyes of 30 participants with NE-MNV. The median observation period was 46 months. The causes of NE-MNV were age- related macular degeneration (AMD) in 59.38% of eyes, pachychoroid epitheliopathy (PPE) in 37.50%, and other causes in 3.12%. Exudation developed in 15.62% of eyes (median time to onset: 24 months), predominantly in the AMD subgroup. Abnormalities in the fellow eye were present in 59.38% of cases. Neither age nor other factors, including sex, cause of MNV, CMT, CT, MNV morphology, or fellow eye status, were statistically significant predictors of progression to active MNV (p = 0.67, p > 0.99, p = 0.62, p = 0.09, p = 0.09, p = 0.2, p = 0.62, resp.). Conclusions: NE-MNV is an asymptomatic condition that may occur in the course of various retinal diseases. While DLS and TLS demonstrate high sensitivity and specificity for the diagnosis of NE-MNV, their presence does not always indicate concurrent MNV. Multimodal imaging is essential for accurate monitoring of these patients and detection of potential disease progression. Full article

Ophthalmic diseases, including inherited retinal dystrophies, age-related macular degeneration (AMD), and glaucomatous neuropathies, are often driven by the expression of pathogenic proteins or dysfunctional non-coding RNAs that are currently considered ‘undruggable’ with conventional small-molecule therapeutics. The emerging strategy of Ribonuclease-Targeting Chimeras (RIBOTACs) offers a revolutionary approach to address this therapeutic gap. RIBOTACs are heterobifunctional small molecules designed to bind a specific target RNA with one moiety and recruit a latent endogenous ribonuclease, such as RNase L, with the other, thereby catalyzing the RNA’s degradation. This targeted degradation can potentially halt the production of mutant proteins, eliminate toxic gain-of-function RNAs, or modulate key regulatory pathways involved in angiogenesis, inflammation, and apoptosis—core processes in many blinding diseases. This review explores the immense potential of applying RIBOTAC technology to ophthalmology, discussing prospective targets such as mutant alleles in retinitis pigmentosa, VEGF transcripts in neovascular AMD, and inflammatory mediators in uveitis. We will also address the unique challenges and opportunities for RIBOTAC development in the eye, including delivery strategies to overcome ocular barriers, the need for high specificity to avoid off-target RNA degradation, and the optimization of pharmacokinetic properties for intraocular administration. With continued innovation, RIBOTACs are poised to evolve into a robust therapeutic platform, expanding the druggable genome and enabling precise, durable treatments for a range of currently intractable ophthalmic conditions. Full article