Search Results (332)

Ocular diseases, such as neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR), have a fibrotic component that negatively impacts vision. Unfortunately, few treatments are available to mitigate fibrosis in the eye. The clearance of inflammatory cells proceeds, at least in part, through the intrinsic cell death pathway in which Bcl-2 family members play integral roles. Here, we assessed the influence of Bcl-2 expression in mononuclear phagocytes (MP) on the engagement and clearance of inflammatory cells, choroidal neovascularization (CNV), and subsequent subretinal fibrosis in a mouse laser-induced CNV model. Lack of Bcl-2 expression in MP (Bcl-2^MP mice) decreased neutrophil (Gr1⁺) and microglia (Iba1⁺) presence without impacting M1 (CD80⁺) and M2 (CD206⁺) macrophage presence, CNV, or fibrosis during the first 2 weeks following laser photocoagulation. Later, after inflammation dampens, decreased later-stage fibrosis and CNV were noted in Bcl-2^MP mice, which were accompanied by increased presence of M2 macrophages (CD206⁺). However, how these increased levels of CD206⁺ M2 macrophages in the absence of Bcl-2 contribute to decreased CNV and fibrosis remains unknown. To address whether Bcl-2 expression affects other forms of ocular fibrosis, we utilized the dispase PVR model. Bcl-2^MP mice, or treatment of wild-type mice with Bcl-2 inhibitors, significantly decreased fibrosis in the PVR model. Furthermore, Bcl-2 inhibitors mitigated CNV and fibrosis (collagen I-defined) in wild-type mice during laser photocoagulation. Thus, inhibition of Bcl-2 activity prevents the late-stage clearance of CD206⁺ M2 macrophages during nAMD and PVR, mitigating ocular neovascularization and fibrosis. Full article

Background: Optical coherence tomography (OCT) and OCT angiography (OCTA) retinal imaging in inherited retinal dystrophies (IRD) has been limited to the posterior pole and central midperiphery (up to about 16.5 × 16.5 mm). Two novel commercially available swept-source (SS) OCT/-OCTA devices provide the possibility of wide-field (WF) evaluation of retinal and choroidal structures, including the vasculature, in a single examination. Methods: A limited consecutive series of 16 IRD patients were examined with a BMizar (400 kHz, 24 × 20 mm scan width) and a Dream OCT (200 kHz, 26 × 21 mm scan width) in addition to the normal clinical examination protocol. This series included patients with retinitis pigmentosa, cone-rod dystrophy, macular dystrophy and autosomal recessive bestrophinopathy. In addition, 12 healthy probands were examined. Results: WF-SS-OCT/-OCTA enabled the detection of retinal, choroidal and choriocapillaris alterations in the macular and midperiphery in a short, single examination session of up to 15 s. Even small foveal lesions and a small silent macular neovascularization were detected on WF screening. Regional alterations of choroidal and choriocapillaris flow patterns were identified. These were mostly in correspondence with areas that appeared clinically affected, but unexpected lesions were identified as well. Occlusion of peripheral retinal vessels was seen in retinitis pigmentosa, though flow was detected in retinal vessels, which were difficult to distinguish on fundus images. In one patient with nystagmus, WF-SS-OCT/-OCTA was performed, whereas standard OCT volume scan could not be obtained. The most frequent artifact were horizontal lines of misalignment, which did not interfere with the detection of pathologies. Conclusions: Both WF-SS-OCT/-OCTA devices provide detailed insights in structural and vascular retinal and choroidal alterations in a single, short examination. Larger series of IRD patients examined with WF-SS-OCT/-OCTA promise to provide novel insights into the pathology of IRDs. Full article

Choroidal neovascularization (CNV) is a common and serious complication in various retinal diseases that involves the growth of new blood vessels from the choroid into the subretinal space, leading to a visual threat. Its underlying mechanism has not been fully uncovered. Discovering new genes related to CNV is an important way to reveal its molecular mechanisms. In this study, we used DisGeNET as the initial data source to identify genes related to CNV. The gene cluster method and additional screening tests were designed to explore the genetic landscape related to CNV. Our comprehensive analysis revealed many genes with high confidence, specifically identifying novel candidates that traditional topological methods missed. Notably, we identified SERPINE1, COL1A1, and ANGPT1 as unique gene signatures using our network embedding approach. Functionally, SERPINE1 regulates the plasminogen activation system to control proteolytic balance, COL1A1 maintains the structural integrity of the extracellular matrix during invasion, and ANGPT1 is critical for the maturation and stabilization of nascent vessels. Meanwhile, some genes were also identified by other methods, such as MMP2, a regulator of extracellular matrix degradation. The newly found genes are essential for understanding the process that initiates CNV. Full article

Background/Objectives: Punctate hyperfluorescence (PH) on indocyanine green angiography (ICGA) is frequently observed in pachychoroid disease. However, the spatial relationship between PH lesions and vortex vein abnormalities remains unclear. This study quantified PH distribution in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) and examined its association with vortex vein asymmetry and watershed-zone status. Methods: This retrospective observational study included 58 fellow eyes with PH from patients with unilateral nAMD. PH lesions were quantified on late-phase ICGA images using ImageJ software. Vortex vein distribution was classified as symmetric, superior-dominant, or inferior-dominant. Eyes were also classified by the presence of a horizontal watershed zone. PH distribution was compared by vortex vein morphology. Results: A watershed zone was absent in 14 eyes (24.1%). Vortex vein distribution was asymmetric in 27 eyes (46.6%), including 17 (29.3%) superior-dominant and 10 (17.2%) inferior-dominant. Overall, 3401 PH lesions were detected. Eyes without a watershed zone had significantly more PH lesions than those with a watershed zone (p = 0.002). The proportion of superior-region PH lesions differed significantly by vertical vortex vein predominance, with preferential distribution on the dominant side (p < 0.001). Although PH distribution did not differ significantly among the four quadrants overall, 30 eyes (51.7%) had >50% of PH lesions clustered in a single quadrant. Conclusions: PH lesions were preferentially distributed on the dominant side of vortex vein asymmetry, and eyes without a watershed zone had more PH lesions. These findings indicate that PH distribution and lesion burden are associated with vortex vein morphology and watershed-zone status and may reflect underlying alterations in choroidal venous drainage. Full article

Background/Objectives: We identified baseline factors associated with early anatomical response to faricimab. Methods: This single-center retrospective study included 78 treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) receiving three monthly faricimab injections. Eyes with complete resolution of intraretinal and subretinal fluid on optical coherence tomography (OCT) at 16 weeks constituted the fluid-free group, and the remaining eyes were assigned to the persistent-fluid group. Baseline OCT features (including subretinal hyperreflective material [SHRM], pigment epithelial detachment [PED] subtypes, and central retinal and choroidal thickness) and clinical characteristics were compared, and ARMS2 (rs10490924) and CFH (rs800292) were genotyped as an exploratory analysis. Multivariable logistic regression identified associated factors. Results: Fifty-five eyes (70.5%) achieved complete fluid resolution. In multivariable analysis, SHRM was independently associated with a favorable early anatomical response, and fibrovascular PED with incomplete early fluid resolution (p = 0.019 and p = 0.026); in an exploratory model, the ARMS2 risk allele was associated with incomplete fluid resolution (p = 0.008), whereas CFH was not. Conclusions: In treatment-naïve nAMD, baseline SHRM was associated with a favorable early anatomical response to faricimab, whereas fibrovascular PED and a higher ARMS2 T-allele count were associated with incomplete early fluid resolution. These characteristic OCT and genetic features may help identify eyes at risk of an incomplete early response. Full article

Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose–safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management. Full article

Background: To investigate the structural changes and visual outcomes in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor (anti-VEGF) compared with fellow eyes over a long-term follow-up period. Methods: A retrospective paired-eye cohort study was conducted, and 51 patients (80.4% female, mean age 51.8 years) with an average follow-up duration of 32.8 months were enrolled. The study included patients with active, treatment-naïve mCNV in one eye and a fellow eye without mCNV. Final visual outcomes and macular retinoschisis (MRS) progression were compared between mCNV eyes treated with intravitreal anti-VEGF injections and fellow eyes. Baseline parameters potentially associated with MRS progression in mCNV eyes were analysed. Results: The final VA increased in mCNV eyes but remained worse than that in fellow eyes (logMAR 0.3 vs. 0.16, p = 0.037). The percentages of treated mCNV eyes and fellow eyes showing MRS progression were similar (18.6% vs. 16.3%, p = 0.782). When mCNV eyes with and without MRS progression were compared (n = 10 and 41, respectively), MRS at baseline was the only significant predictor of MRS progression (70% vs. 17.1%, p = 0.002). A greater percentage of eyes with MRS progression exhibited higher vitreomacular interface (VMI) grading at baseline, although the difference was not statistically significant (40% vs. 14.7%; p = 0.083). Conclusions: Anti-VEGF treatment in mCNV eyes did not increase the incidence of MRS compared with fellow eyes or aggravate MRS. However, the presence of MRS at baseline may increase the risk of MRS progression after treatment, and close monitoring of this subgroup is warranted. Full article

Background/Objectives: The utility of optical coherence tomography angiography (OCTA) for neovascular age-related macular degeneration (nAMD) remains unclear. The current study investigated the choroidal neovascularization (CNV) detection rate by OCTA in comparison with standard fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Methods: Subjects underwent multimodal imaging, including FA, SD-OCT, and OCTA imaging, which were compared. In patients with unilateral nAMD, the contralateral eye with dry AMD (n = 39) was included to determine imaging modality sensitivity and specificity. Eyes with inaccurate automated segmentation from retinal distortion were manually resegmented. Results: The diagnostic performance for nAMD was 86% sensitivity and 100% specificity by OCT (AUC: 0.93; 95% CI 0.87–0.99; p < 0.001); 82% sensitivity and 100% specificity by FA (AUC: 0.91; 95% CI 0.84–0.98; p < 0.001); and 68% sensitivity and 100% specificity by automatically segmented OCTA (AUC: 0.84; 95% CI 0.76–0.93; p < 0.001). OCTA diagnostic accuracy improved following manual resegmentation to 88% sensitivity and 100% specificity (AUC: 0.94; 95% CI 0.89–1.0; p < 0.001). Diagnostic accuracy of OCT combined with manually resegmented OCTA (AUC: 1.0; 95% CI 1.0–1.0; p < 0.001) was greater than that of OCT or FA combined (AUC: 0.96; 95% CI 0.92–1.0; p < 0.001) but both were very accurate. Conclusions: Manual segmentation of the OCTA images can help identify CNV in eyes otherwise undetected by automated segmentation algorithms due to errors in segmentation of retinal layers. Eyes with substantial elevation in one or more layers of the retina were most likely to benefit from resegmentation. Full article

Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of −23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway. Full article

Current treatments for choroidal neovascularization (CNV) and its associated subretinal fibrosis (SRF), major causes of vision loss, are limited by the need for frequent intravitreal injections and the emergence of drug resistance. This study evaluated the safety and efficacy of the intravitreal administration of engineered humanized anti-vascular endothelial growth factor Nanobodies, including a wild-type Nanobody (WHNb) and two mutated variants (MHNb136 and MHNb256), in a rat model of laser-induced CNV and associated SRF. Safety was assessed through in vivo electrophysiological and histopathological analyses following intravitreal injection of Nanobodies at doses of 12.5, 25, 50, and 100 µg. Efficacy was evaluated in rat models of laser-induced CNV and SRF using double immunohistochemistry for isolectin B4 and anti-collagen type I on sclerochoroidal flat mounts. Mean CNV and SRF areas in Nanobody-treated groups were compared with those in bevacizumab-treated and sham control groups. None of the Nanobodies showed retinal toxicity in safety assessments. Compared with bevacizumab, MHNb136 and MHNb256 reduced the CNV area by 1.72-fold and 1.8-fold, respectively (both p < 0.0001), whereas WHNb showed an effect nearly identical to that of bevacizumab. In addition, 12.5 µg MHNb136 and 100 µg MHNb256 reduced the SRF area by 1.3-fold (p = 0.047) and 1.6-fold (p = 0.0007), respectively, relative to bevacizumab. For CNV reduction, 12.5 µg MHNb136 was comparable to 25 µg MHNb256; both outperformed bevacizumab. For SRF reduction, 12.5 µg MHNb136 was more effective than bevacizumab and comparable to 100 µg MHNb256. These findings suggest that 12.5 µg MHNb136 may represent a cost-effective bioengineered Nanobody candidate for future clinical studies. Full article

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

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

Background and Objectives: Myopic choroidal neovascularization (mCNV) is a vision-threatening complication of pathologic myopia. While anti-VEGF monotherapy is the current standard of care, recurrence and suboptimal responses remain challenges. Faricimab is a novel bispecific antibody that targets both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) to improve vascular stability. This study aims to evaluate the short-term efficacy and safety of a single intravitreal faricimab injection in eyes with active mCNV. Materials and Methods: This retrospective, single-center study included 27 eyes from 24 patients with active mCNV, including both treatment-naïve and previously treated cases. All eyes received a single intravitreal injection of faricimab (6.0 mg/0.05 mL). Best-corrected visual acuity (BCVA) in logMAR and central retinal thickness (CRT) via spectral-domain optical coherence tomography were assessed at baseline and one month post injection. Statistical significance was determined using paired and independent t-tests (p < 0.05). Results: The study population (mean age 55.5 ± 13.9 years; mean axial length 29.3 ± 1.6 mm) showed significant improvements at one month. Mean BCVA improved from 0.77 ± 0.71 logMAR to 0.51 ± 0.52 logMAR (p < 0.005). Mean CRT decreased from 290.2 ± 66.0 μm to 242.5 ± 45.7 μm (p < 0.005). No ocular adverse events, such as intraocular inflammation, retinal detachment, or endophthalmitis, were observed. Conclusions: A single intravitreal injection of faricimab provides significant short-term functional and anatomical improvement in this small retrospective series. Dual inhibition of VEGF-A and Ang-2 appears to be a safe and effective approach for stabilizing retinal vasculature in patients with high myopia. Larger, long-term prospective studies are needed to determine optimal treatment intervals for mCNV. Full article

Age-related macular degeneration (AMD) remains the leading cause of irreversible central vision loss in the elderly. Increasing attention has been directed toward lipid metabolism as a potential contributor to disease onset and progression. The overlap between AMD and atherosclerosis—particularly regarding lipid accumulation, endothelial dysfunction, and chronic inflammation—has prompted interest in lipid-lowering therapies. This narrative review synthesizes the clinical evidence published between 2020 and 2025 on the potential role of statins and fenofibrate in AMD risk modification and disease progression. A structured literature search was conducted in PubMed, Scopus, and Web of Science using combined MeSH and free-text terms related to lipid-lowering agents and AMD. Human studies evaluating clinical incidence or progression outcomes were considered alongside contextual evidence from prior evidence syntheses. Overall, findings remain heterogeneous. Most studies did not demonstrate a consistent association between statin therapy and AMD incidence or progression in unselected populations. However, selected reports suggested a potential delay in dry AMD onset or slower disease progression among patients receiving prolonged or higher-intensity statin treatment. Evidence regarding fenofibrate was more limited and heterogeneous, with only a tentative protective signal observed in adherent users, particularly for non-exudative AMD. The current literature does not support lipid-lowering therapy as a universal preventive strategy for AMD. Nonetheless, subgroup-specific benefits cannot be excluded, especially in early disease stages or metabolically high-risk populations. Further well-designed prospective and randomized studies are needed to clarify therapeutic relevance and identify the patients who are most likely to benefit. Full article