Search Results (1,185)

Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment, yet identifying effector proteins and tissue-specific mechanisms underlying genome-wide association study (GWAS) loci remains challenging. This study aimed to systematically prioritize candidate causal circulating proteins and delineate their cellular and transcriptional dynamics in AMD. We integrated plasma protein quantitative trait loci (pQTL) summary statistics from the UK Biobank Pharma Proteomics Project (UKB-PPP; $N=\mathrm{53,022}$) with FinnGen AMD GWAS data using proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) with the HEIDI test, and Bayesian colocalization analysis. Prioritized candidates were mapped across human and murine retinal single-cell/single-nucleus RNA sequencing atlases. Transcriptional responsiveness was validated in an independent clinical microarray dataset (GSE103060) and in human retinal pigment epithelial cells (ARPE-19) via in vitro inflammatory stimulation and RT-qPCR. Target tractability was assessed using pharmacological databases. Multi-stage genetic screening prioritized five candidate proteins stratified into two confidence tiers: three Tier 1 causal drivers supported by colocalization (PP4 > 0.80)—including risk factors CSF2, IL20RB, and WARS1 (also known as WARS)—alongside two Tier 2 candidates supported by SMR and HEIDI, comprising risk factor PILRA and inversely associated metabolic factor ACADSB. Retinal transcriptomic mapping localized PILRA specifically to microglia, ACADSB to inner retinal neurons, and WARS1 to photoreceptors, RPE, and vascular compartments, while IL20RB and CSF2 exhibited low baseline expression. In independent validation cohorts, IL20RB and WARS1 were significantly up-regulated in choroidal neovascularization (CNV) membrane-derived RPE from patients with AMD ($p<0.01$). Exposure of ARPE-19 cells to TNF-$\alpha$ markedly induced mRNA levels of IL20RB ($P=0.0025$) and WARS1 ($p<0.0001$). Dual normalization against ACTB as a secondary internal reference yielded consistent significant induction. Pathway enrichment highlighted cytokine-driven receptor cascades (JAK-STAT signaling) and mitochondrial substrate catabolism (branched-chain amino acid and fatty acid metabolism). Drug–target profiling identified small molecules and nutraceuticals interacting with ACADSB, CSF2, and WARS1. By combining large-scale plasma proteomic genetics with single-cell mapping and experimental validation, this study identifies a prioritized set of candidate causal proteins linking neuroimmune activation, vascular remodeling, and mitochondrial bioenergetics in AMD, providing candidate entry points for mechanistic and therapeutic exploration. Full article

Background/Objectives: The purpose of this study was to evaluate associations between quantitative ellipsoid zone (EZ) integrity metrics derived from spectral-domain OCT (SD-OCT) and visual outcomes, including clinically meaningful visual acuity (VA) loss, in dry age-related macular degeneration (AMD). Methods: This single-center retrospective image-analysis cohort included 351 eyes from 351 patients with intermediate AMD or atrophic changes. Macular SD-OCT scans were analyzed using a certified-reader-validated machine learning-based segmentation platform to delineate the EZ, retinal pigment epithelium (RPE), and Bruch’s membrane (BM). EZ metrics included EZ-RPE thickness (i.e., outer segment thickness) and EZ attenuation, defined as partial attenuation (EZ-RPE thickness of ≤20 µm, abnormal outer segment thinning)) or total attenuation/loss (0 µm). Drusen volume was quantified from the RPE-BM compartment. VA was converted to ETDRS letters. Associations between baseline OCT metrics and baseline VA, Year 2 VA, and ≥15-letter VA loss were assessed using nonparametric testing, linear regression, and ANCOVA. Results: Greater EZ-RPE thickness and lower EZ attenuation were associated with better baseline VA (all p < 0.001), and EZ metrics remained significant in cross-sectional regression models. Among 188 eyes with Year 2 follow-up, 38 (20%) experienced ≥15-letter VA loss. These eyes had significantly lower baseline EZ-RPE thickness (i.e., abnormal outer segment thinning) and greater EZ attenuation than eyes without such loss (all p < 0.001). In ANCOVA models, EZ metrics remained associated with Year 2 VA (all p < 0.001), whereas drusen volume was not. Conclusions: Quantitative EZ integrity metrics were associated with cross-sectional and longitudinal visual outcomes in dry AMD. EZ-RPE thickness and EZ attenuation may serve as clinically relevant OCT biomarkers reflecting photoreceptor integrity and risk of meaningful VA loss. Full article

Increasing epidemiological and experimental evidence suggests that age-related macular degeneration (AMD) and cardiovascular disease (CVD) share multiple pathogenic mechanisms. Among these, oxidative stress has emerged as one of the most plausible links connecting retinal degeneration and cardiovascular pathology. Excessive production of reactive oxygen and nitrogen species, combined with declining antioxidant defenses, contributes to lipid peroxidation, mitochondrial dysfunction, chronic inflammation, complement activation, cellular senescence, and impaired cellular stress responses in both the retina and the vascular system. Notably, drusen (AMD) and atherosclerotic plaques (CVD) share several molecular constituents. Therefore, AMD and CVD may represent tissue-specific manifestations of broader age-related disturbances in redox homeostasis and inflammatory regulation. Nevertheless, the coexistence of AMD and CVD is incomplete, suggesting that genetic susceptibility, tissue-specific responses to oxidative stress, biological aging, and mechanisms of cellular resilience influence disease expression. In this review, we summarize current evidence linking AMD and CVD, examine oxidative stress-driven molecular pathways common to both disorders, discuss emerging biomarkers and therapeutic targets, and highlight important unresolved questions regarding disease heterogeneity and causal relationships. A better understanding of the shared mechanisms underlying AMD and CVD may facilitate the development of integrated preventive strategies, improved risk stratification, and more personalized therapeutic approaches for age-related diseases. Full article

Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are leading causes of visual impairment and require long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy. However, treatment burden and suboptimal real-world outcomes remain major challenges. Faricimab is a bispecific monoclonal antibody that simultaneously inhibits VEGF-A and angiopoietin-2 (Ang-2), a key mediator of vascular destabilization, leakage and inflammation, offering a novel dual-pathway approach aimed at improving efficacy and durability. This narrative review summarizes evidence from pivotal clinical trials and recent real-world studies evaluating the efficacy, durability, and safety of faricimab in patients with nAMD and DME. Real-world evidence from international cohorts and emerging data from Spanish routine clinical practice largely corroborate previous findings, showing anatomical improvements, stable or improved visual outcomes, and reduced treatment burden in treatment-naïve and previously treated eyes. Overall, the evidence reviewed indicates that faricimab is an effective and well-tolerated therapeutic option that may help address unmet needs in the long-term management of nAMD and DME. Importantly, data from real-world clinical practice are consistent with findings from pivotal trials, supporting the translation of faricimab’s outcomes into routine care. Full article

Background/Objectives: The timing of exudative recurrence after complete fluid resolution following anti-vascular endothelial growth factor (anti-VEGF) loading in neovascular age-related macular degeneration (nAMD) is unpredictable. We prespecified two questions: whether the speed of fluid resolution during loading, or the baseline pigment epithelial detachment (PED) type, predict recurrence timing. Methods: We retrospectively analyzed 72 treatment-naïve nAMD eyes that achieved complete resolution of subretinal fluid (SRF) and intraretinal fluid (IRF) after three monthly loading injections, then observed them under a pro re nata strategy. Time from the post-loading dry-confirmation visit to first detected recurrence was analyzed with Kaplan–Meier and Cox models; baseline variables with univariable p < 0.10 were entered into a multivariable model. Results: Recurrence was detected in 58 eyes (80.6%); median recurrence-free survival was 139 days (95% CI, 118–158). Resolution of SRF or IRF by one month was not significantly associated with recurrence timing (p = 0.586 and 0.054). Fibrovascular PED was associated with earlier detected recurrence compared with non-fibrovascular PED (adjusted hazard ratio 2.40, 95% CI, 1.17–4.92; p = 0.017; median 130 vs. 602 days). Eyes with fibrovascular PED were monitored more frequently, but the association persisted in an interval-censored sensitivity analysis (adjusted HR 2.71, 95% CI, 1.32–5.60). Conclusions: The speed of fluid resolution was not significantly associated with recurrence timing, whereas fibrovascular PED was associated with earlier detected recurrence and may represent a candidate prognostic marker requiring prospective validation. Full article

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment, and AREDS2-based nutritional supplementation is recommended for clinically eligible patients to reduce the risk of disease progression. However, successful implementation depends on regular supplement use and sustained adherence. This study investigated demographic, socioeconomic, clinical, and physician-related factors associated with regular AREDS2 supplement use and evaluated medication adherence, physician counseling, and patient-reported barriers among clinically eligible patients with AMD. Methods: In this single-center cross-sectional study, 389 patients with intermediate AMD or advanced AMD in one eye who fulfilled the indications for AREDS2 supplementation were enrolled. Participants reporting occasional supplement use were excluded. A structured interviewer-administered questionnaire was used to collect demographic, socioeconomic, and clinical data, together with information on physician recommendation, medication adherence, patient knowledge, and perceived barriers to supplementation. Factors associated with regular AREDS2 supplement use were evaluated using univariable and multivariable logistic regression analyses, whereas adherence patterns and patient-reported barriers were analyzed descriptively. Results: Of the 389 participants, 273 (70.2%) reported regular AREDS2 supplement use, whereas 116 (29.8%) were non-users. Multivariable analysis showed that younger age, educational attainment, and physician recommendation were independently associated with regular supplement use (adjusted OR for physician recommendation, 5.38; 95% CI, 2.68–10.81; p < 0.001). Among regular users, 53.5% met the study-defined criteria for good medication adherence. The most frequently reported barriers among non-users were financial burden, limited supplement availability, polypharmacy, and insufficient knowledge regarding AREDS2 supplementation. Conclusions: Regular AREDS2 supplement use among clinically eligible patients with AMD was associated with demographic, educational, and physician-related factors, whereas long-term adherence remained suboptimal despite substantial uptake. These findings emphasize the importance of effective physician counseling, structured patient education, and interventions addressing socioeconomic barriers to improve the real-world implementation of evidence-based nutritional supplementation in AMD. Full article

Background: Age-related macular degeneration (AMD) represents a leading cause of irreversible vision loss worldwide, driven by intricate interactions among oxidative stress, low-degree chronic inflammation, and macular pigment depletion in aging retinas. Lutein, a component of the macular pigment, has attracted significant attention in AMD management for its antioxidant and blue-light filtering properties. Its oral supplementation, however, although showing potential in slowing AMD progression, requires daily intake and results in variable macular absorption. Trans-scleral iontophoresis (TSI) is a non-invasive technique using low-intensity electric currents to deliver charged molecules into biological tissues and represents an innovative method to deliver lutein into the retina. Methods: The present narrative review synthesizes and discusses the results of lutein supplementation in AMD patients; the ocular iontophoresis basal principles, efficacy, safety and limitations in treating different ophthalmic pathologies; and the evolving clinical evidence supporting lutein TSI in the AMD management. Results: Ex-vivo studies have shown that lutein TSI may provide efficient, localized, rapid, and sustained retinal supplementation of macular pigment, overcoming oral intake limitations. Recent preliminary clinical studies have demonstrated that this technique is well-tolerated and effective in enhancing macular pigment optical density and improving some visual functions in AMD patients. Conclusions: Ex-vivo and pilot clinical studies highlight the capacity of TSI to deliver lutein inside the retina, overcoming physiological barriers that may limit the efficacy of lutein oral administration. The demonstration of the efficacy of the procedure in preserving/improving visual functions and delaying disease progression in AMD patients requires further long-term randomized controlled clinical studies. Full article

Background/Objectives: Double reading with arbitration improves diagnostic reliability in fundus screening but requires repeated human interpretation. Whether artificial intelligence (AI) can serve as a first-pass decision source within this workflow, and whether this applies consistently across retinal diseases with differing inter-reader agreement, remains unclear. Methods: In this retrospective study, 6904 color fundus photographs from 2593 patients at a tertiary screening center were analyzed for age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Three retina specialists independently labeled each image, and an AI system provided binary classifications at a prespecified operating threshold targeting 0.99-sensitivity. In AI–human double reading, the AI and one reader independently interpreted each image, and a second reader arbitrated discordant cases; this was compared with conventional human–human double reading. Three reader combinations were evaluated per disease. Results: AI–human reading required 1.02–1.11 human reads per image versus 2.00–2.10 for human–human reading. For DR and RVO, human–human reading yielded sensitivities of 0.974 and 0.982 and specificities of 0.999 and 1.000, respectively. Across AI–human combinations, sensitivity and specificity did not differ significantly from human–human reading (all p ≥ 0.05; specificity differences ≤0.001). For AMD (human–human sensitivity 0.845, specificity 1.000), AI–human sensitivity varied: two combinations were higher (0.916 and 0.950; both p < 0.001) and one comparable (0.842; p = 0.742). AMD specificity remained ≥0.978. Conclusions: AI–human reading halved human reading volume without significant loss for DR and RVO; AMD varied by configuration. AI use within double-reading workflows should account for disease-specific inter-reader agreement, reader composition, and operating threshold. This was a single-center, retrospective study, prospective external validation in a multicenter setting is warranted before clinical implementation. Full article

Background: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and is strongly driven by oxidative stress and inflammation. This study investigated the protective effects of cynarin against sodium iodate (NaIO₃)-induced retinal pigment epithelium (RPE) injury, focusing on the MAPK and NF-κB signaling pathways. Materials and Methods: Human ARPE-19 cells were exposed to NaIO₃, and cell viability was assessed by the MTT assay. Protein expression of MAPK components (p38, JNK, ERK) and the NF-κB pathway was analyzed by Western blotting, and pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) mRNA expression was measured by RT-qPCR. In vivo, NaIO₃-induced retinal degeneration in C57BL/6 mice was treated with cynarin (3 or 10 mg/kg) for seven days, and retinal changes were evaluated by fundus photography, fluorescein angiography, and OCT. Results: Cynarin preserved ARPE-19 cell viability without cytotoxicity. It significantly attenuated NaIO₃-induced p38 and JNK phosphorylation, IκB degradation, and NF-κB activation while downregulating IL-1β, IL-6, and TNF-α expression. In vivo, cynarin reduced drusen-like lesions, hyperfluorescent abnormalities, and retinal thinning, and dose-dependently suppressed ocular pro-inflammatory cytokines. Conclusions: Cynarin protects against oxidative stress-induced retinal degeneration by suppressing MAPK and NF-κB inflammatory signaling, representing a promising therapeutic candidate for preventing or delaying NaIO₃-induced dry AMD-like retinal injury. Full article

Optical coherence tomography (OCT) is a high-resolution and non-contact optical imaging and sensing modality that provides depth-resolved cross-sectional visualization of retinal microstructures. It plays an important role in the assessment of retinal diseases, including age-related macular degeneration (AMD) and diabetic macular edema (DME). However, automated OCT image classification commonly relies on fully supervised models that require large-scale expert annotations, which are costly and time-consuming because of the complex layered anatomy and subtle pathological patterns present in retinal OCT images. To reduce annotation dependence, this study proposes a self-supervised representation learning framework with local dimensionality regularization for retinal OCT image classification. The proposed method estimates the local intrinsic dimensionality of learned representations and incorporates it into an asymptotic Fisher-Rao regularization objective to mitigate local dimensional degeneration and preserve fine-grained structural information. Logarithmic scaling and geometric averaging are further introduced to reduce sensitivity to outliers and improve optimization stability. Experiments on three independent OCT datasets achieved classification accuracies of 94.35%, 92.48%, and 92.56%, respectively, demonstrating competitive performance compared with mainstream self-supervised methods. These results demonstrate that explicitly modeling local feature geometry can improve the discrimination of sensor-acquired OCT images while reducing reliance on manual annotations, providing an effective approach for intelligent analysis of biomedical optical imaging data. Full article

Purpose: We aimed to describe retinal pigment epithelium (RPE) tears in patients with neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED), focusing on OCT features and AI-assisted image analysis. Methods: This retrospective case series included patients with neovascular AMD and PED who developed RPE tears between 2020 and 2025 after treatment with intravitreal aflibercept (2 mg or 8 mg) or faricimab. Multimodal imaging, including spectral-domain OCT and infrared imaging, was reviewed. PED morphology, fluid characteristics, RPE denudation, timing of RPE tear, and visual outcomes were analyzed using manual grading and AI-assisted software. Results: Among 375 PED-bearing eyes, 11 eyes of 11 patients developed an RPE tear (2.9%), of which 10 (90.9%) were temporally associated with anti-VEGF treatment. Rates were similar across agents—2.7% (aflibercept 2 mg), 3.0% (aflibercept 8 mg) and 2.4% (faricimab)—with no significant difference. Eight eyes (72.7%) were treatment-naïve and one tear (9.1%) occurred spontaneously after hemorrhage without recent injection. Among treatment-associated tears, 30% followed the first and 50% the second injection (mean 2.1 injections), detected a mean of 44 ± 30 days after the last injection. Mean baseline PED height was 594.8 ± 239.2 μm and median AI-derived PED volume was 2922 nL. Mean RPE-denudation area at detection was 5.25 ± 3.87 mm², remaining stable in 7 of 9 evaluable eyes. Visual acuity was stable or improved in seven eyes; four lost ≥15 ETDRS letters. Conclusions: RPE tears were an uncommon, predominantly early complication occurring in eyes with large PEDs, with no excess risk from second-generation agents. AI-assisted OCT may aid anatomical characterisation, and most eyes retained vision with continued therapy. Full article

Background: Faricimab 6 mg and aflibercept 8 mg permit extended treatment intervals in neovascular age-related macular degeneration (nAMD), but their pivotal programmes used different loading and maintenance schedules. This study compared treatment burden under the same loading and treat-and-extend protocol and included an exploratory longitudinal analysis of published aggregate visual and anatomical outcomes. Methods: Treatment-specific Dirichlet distributions represented persistent Q8W, Q12W and Q16W capability. Both treatments received injections at weeks 0, 4, 8 and 16, followed by identical four-week extensions from Q8W to Q16W. The primary analysis comprised 30,000 evidence draws, 100,000 paired virtual eyes, a 1.5-million-pair scenario grid and a nested five-million-pair probabilistic analysis. Exploratory multilevel meta-regressions estimated BCVA and change in retinal thickness through week 52; IRF, SRF and complete retinal dryness were analysed separately. Results: Mean injections with faricimab and aflibercept 8 mg were 7.255 and 7.212 at week 52 and 11.522 and 11.144 at week 104. The nested 104-week difference was −0.393 injection (95% uncertainty interval −0.682 to −0.107), but broad source-weight uncertainty included no difference and credible source analyses changed the direction of the contrast. Exploratory week-52 BCVA gains were 5.65 and 6.29 letters, respectively; the difference was 0.64 letter (95% uncertainty interval −1.41 to 2.70) and should be interpreted in the context of three aflibercept 8 mg study families. The expanded retinal-thickness sensitivity model estimated changes of −171.8 and −147.2 micrometres, while the between-treatment direction varied in the three-dose-only analysis. Complete retinal dryness was projected in 57.0% and 69.0% of eyes, respectively, based on three study families per treatment. Conclusions: Use of the same protocol predicted essentially equal one-year burden and a small two-year fixed-weight difference that varied across source choices. The exploratory longitudinal projections, informed by three independent aflibercept 8 mg study families at one year, provide supportive context for the visual and anatomical findings but should be interpreted as hypothesis-generating rather than confirmatory. Full article

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

Photoreceptors work in a biologically demanding compartment of the eye. They consume large amounts of energy, receive continuous light and oxygen, and renew outer-segment membranes enriched in polyunsaturated lipids. These conditions are necessary for vision, but they also make the outer retina poorly tolerant to persistent mitochondrial dysfunction and oxidative stress. Photobiomodulation (PBM), mainly based on red and near-infrared light, has been investigated as a way to support retinal cells that are functionally impaired but not yet irreversibly lost. The field has also acquired new clinical relevance after the 2024 De Novo marketing authorization by the United States Food and Drug Administration (FDA) of the Valeda Light Delivery System for dry age-related macular degeneration (AMD). This narrative review examines the mitochondrial, redox, inflammatory, and neurovascular mechanisms proposed for PBM, and discusses preclinical and clinical evidence across nonexudative AMD, inherited retinal degeneration, diabetic retinal disease, and light-induced damage. Current findings are encouraging, but devices, doses, schedules, endpoints, and sponsorship patterns differ substantially among studies. PBM therefore deserves further investigation, especially in early or intermediate disease, but its clinical use should remain linked to tested protocols, rigorous safety monitoring, and biomarkers of residual retinal functional reserve. Full article

Kaempferol is a natural flavonol compound widely present in various single-herb remedies and compound formulations used for the treatment of ocular diseases. Despite its inherent pharmaceutical limitations, accumulating evidence indicates that kaempferol exerts broad protective effects against diverse ocular disorders through multiple biological pathways, highlighting its potential as a multi-target therapeutic candidate in ophthalmology. However, current evidence regarding kaempferol-based ophthalmic applications remains fragmented across different ocular diseases and mechanistic investigations, and a comprehensive evaluation of its therapeutic potential, translational challenges, and existing limitations is still lacking. This review systematically summarizes the research progress on kaempferol in the treatment of eye diseases, encompassing its source distribution, structural characteristics, ocular delivery strategies, disease spectrum coverage, molecular mechanisms, and safety profile. By critically evaluating currently available evidence, this review further identifies unresolved issues and translational barriers that hinder the clinical application of kaempferol in ophthalmology. Regarding delivery strategies, carriers such as gelatin nanoparticles, porous bovine serum albumin membranes, platelet-derived extracellular vesicles, and polyvinylpyrrolidone-based nanocomposites have preliminarily improved ocular surface retention and corneal permeability of kaempferol in models of corneal neovascularization and alkali burns. In terms of therapeutic indications, kaempferol has demonstrated protective effects in diverse experimental models, including age-related macular degeneration (AMD), diabetic retinopathy, diabetic cataract, dry eye disease, fungal keratitis, corneal transplant rejection, acute glaucoma, and retinoblastoma. At the mechanistic level, kaempferol exerts comprehensive pharmacological actions—anti-inflammatory, antioxidant, metabolic regulation, anti-angiogenic, and immunomodulatory—by modulating multiple signaling pathways, including MAPK, NF-κB, STAT1/IRF7, Nrf2/HO-1, VEGF/PI3K/Src/Akt/ERK, aldose reductase, estrogen-related receptor alpha (ERRα), and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Available safety assessments suggest that kaempferol exhibits a generally favorable safety profile across ocular, cellular, systemic, and genetic evaluations. Despite these advances, the clinical translation of kaempferol in ophthalmology remains limited by insufficient clinical and pharmacokinetic evidence, underdeveloped targeted delivery strategies, and a lack of integrated understanding of its molecular basis in ocular protection. By systematically integrating evidence from ocular disease models, molecular mechanisms, delivery strategies, and safety evaluations, this review bridges fragmented knowledge regarding kaempferol-based ophthalmic applications and provides an integrated framework for understanding its therapeutic potential and translational prospects. Overall, this review highlights kaempferol as a promising multi-target therapeutic candidate for ocular diseases and provides insights into its future translational development. Full article