OBJECTIVE:To establish evidence-based guidance to standardize the clinical application of artificial iris implantation in patients with iris defects. METHODS:A systematic literature search was performed following evidence-based consensus development standards. Eighteen international experts participated in a Delphi process to define six core clinical issues. Evidence was screened, extracted, evaluated and integrated. Recommendations were formulated through iterative expert review. RESULTS:We established six key clinical issues related to artificial iris implantation and evidence-based recommendations to address critical gaps in clinical practice. Key outcomes included standardized criteria for indications, contraindications, and type of artificial iris selection, key aspects of surgeon-patient communication, surgical management principles and critical techniques, comprehensive perioperative care protocols, and strategies for managing long-term postoperative complications associated with artificial iris implantation. CONCLUSIONS:This consensus standardizes artificial iris implantation through six evidence-based recommendations. It provides a standardized protocol for safe clinical implementation to restore visual function and cosmetic integrity in patients with iris defect.

Retinal aging plays a critical role in the pathogenesis of age-related ocular diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy. The epigenetic clock, an aging biomarker derived from DNA methylation patterns, has emerged as a powerful tool for investigating the mechanisms of aging. This review summarizes the applications of epigenetic clocks in assessing retinal aging, emphasizing their potential to advance the understanding of disease pathophysiology, predict disease progression, and inform therapeutic strategies. We discuss the molecular basis of epigenetic age, its relevance to retinal health, and current applications of epigenetic clocks in ophthalmic research. Furthermore, we present both epigenetic and non-epigenetic methods for biological age estimation, along with key markers of cellular senescence relevant to retinal aging studies. Finally, we highlight future research directions, including the development of retina-specific epigenetic clocks and their integration into precision medicine approaches for the treatment of retinal disorders.

PurposeMechanical ocular injury involving the uvea poses significant surgical challenges and risks of irreversible visual impairment. Currently, there is no standardized classification to guide the management and prognosis of uveal injuries. This study aims to establish such a classification system.MethodsA methodological proposal for a novel classification was developed based on the most posterior location of uveal laceration/rupture and the extent of quadrant involvement. The classification was informed by clinical data with uveal injury. The system is designed to be determinable during clinical examination, emergency repair, or vitrectomy.ResultsThis study proposes a novel, standardized classification system for uveal injury based on the most posterior location of uveal laceration or rupture: Zone I (iris), Zone II (ciliary body), Zone III (choroid anterior to the equator), and Zone IV (choroid posterior to the equator), each subdivided (a-d) by extent of quadrant involvement. The system defines reproducible surgical approaches per zone.ConclusionThis novel classification is presented as a proposal to standardize the assessment of uveal injury, addressing a critical gap in existing ocular trauma systems. It provides a structured framework to guide surgical decision-making and anatomical restoration and to facilitate future research in the management of severe ocular trauma.

Wet age-related macular degeneration (wAMD), characterized by pathological choroidal neovascularization (CNV), is a leading cause of irreversible vision loss in the elderly. The current standard treatment-anti-vascular endothelial growth factor (VEGF) therapy-effectively manages neovascularization in many patients. However, some experience suboptimal responses, and frequent intravitreal injections raise safety concerns. Photodynamic therapy is another effective option for treating wAMD, but it can lead to an increase in reactive VEGF after the procedure, resulting in CNV recurrence. In response to these challenges, we propose an integrated approach that combines a DNA nanoflower VEGF degrader with photodynamic therapy. The DNA nanoflower consists of numerous aptamer-based lysosome-targeted chimaera (LYTAC) units, which drive extracellular VEGF in the lesion area to the lysosome for degradation. Simultaneously, the DNA nanoflower acts as a carrier for verteporfin (VER), a clinically used photosensitizer. The resulting nanoflower, named NF@VER, generates reactive oxygen species under near-infrared light to induce endothelial cell death. These combined effects on endothelial cells effectively block VEGF-induced CNV in vivo, without causing noticeable side effects. Overall, this innovative approach presents a precise and effective strategy for treating wAMD, reducing the risk of VEGF reactivation-induced CNV recurrence, and minimizing the systemic side effects associated with photodynamic therapy.

Importance:Ocular surface malignancies pose risks to vision and survival yet are frequently misdiagnosed as benign lesions because of their subtle presentation and the lack of widely accessible screening tools, potentially resulting in treatment delays and the need for extensive surgical intervention. Objective:To develop and validate a smartphone-based, media-facilitated artificial intelligence (AI) system for proactive self-screening of ocular surface malignancies in the general population. Design, Setting, and Participants:A nonrandomized clinical trial was conducted across China from December 2022 to June 2023. A deep learning model was initially trained and validated using 12 years of multicenter slitlamp images. The system was then optimized for smartphone-based photography and deployed through a widely disseminated mobile application. Data analysis was performed from July 2023 to June 2024. Intervention:Participants used the CaptureTumor standardized smartphone application, incorporating real-time AI-guided photography instructions, to capture images of suspected lesions. The application provided immediate binary (benign vs malignant) and multiclass risk stratification and triaged high-risk cases for expedited clinical referral. Main Outcomes and Measures:The primary outcome was area under the receiver operating characteristic curve (AUC) for differentiating malignant from benign lesions. Secondary outcomes included sensitivity, specificity, and the number of histopathologically confirmed malignancies detected. Results:Multimedia outreach via television, social media, and internet hospitals reached 256 053 individuals, with 614 completing at-home self-screening through the app. Of these participants, the median (IQR) age was 46 (11) years (range, 4-87 years); 301 (49%) were female and 313 (51%) male. After optimizing the image quality, the smartphone-based CaptureTumor achieved an AUC of 0.905 (95% CI, 0.837-0.973), comparable with the performance of the slitlamp-based model (AUC = 0.945; 95% CI, 0.918-0.972). During real-world screening, 20 malignancies were pathologically confirmed among the 614 participants, with 19 of 20 participants (95%) newly diagnosed, and no cases requiring enucleation. At the population level, CaptureTumor demonstrated an AUC of 0.977 (95% CI, 0.964-0.990), a sensitivity of 89.3% (95% CI, 86.7%-91.9%), and a specificity of 95.9% (95% CI, 94.2%-97.6%). Conclusions and Relevance:This trial found that the integration of smartphone-enabled imaging, AI-driven diagnostics, and targeted media outreach established a scalable, accessible, and potentially clinically effective strategy for population-level screening of rare ocular malignancies. This closed-loop mobile health model potentially addresses gaps in early detection and equitable care delivery for vision- and life-threatening rare diseases. Trial Registration:ClinicalTrials.gov Identifier: NCT05645341.

Retinal and choroidal vascular diseases including age-related macular degeneration (AMD), branch and central retinal vein occlusion (BRVO, CRVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) are important causes of blindness. Their treatments by anti-VEGF agents imply heavy economic impact. The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies and medical costs of 15,266 patients in Tianjin (2021–2024), utility values, and transition probabilities derived from clinical trials. Costs and outcomes were calculated separately under societal and medical insurance perspectives. Incremental cost-effectiveness ratios (ICERs) were computed, and sensitivity analyses (one-way, two-way and probabilistic) were conducted to assess result robustness. From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with ICERs as -442,423.176, -2,429,628.701, -69,339.384, -410,661.276 as Chinese Yuan/quality-adjusted life year (RMB/QALY) under the societal perspective, and -370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept’s ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. Sensitivity analyses confirmed the robustness of these findings. Conbercept is a cost-effective alternative to ranibizumab in RVO, DME, and PM from societal and medical insurance perspectives. In AMD, ranibizumab remains more clinically effective option. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China.

This nonrandomized clinical trial reports data from developing and validating a smartphone-based, media-facilitated artificial intelligence system for self-screening for ocular surface malignancies in the general population. QuestionCan a smartphone-based artificial intelligence system integrated with mass media outreach enable large-scale screening for rare ocular surface malignancies in the general population?FindingsIn this nonrandomized clinical trial, the smartphone-optimized CaptureTumor application achieved diagnostic accuracy comparable with that of specialist-graded slitlamp evaluation. This application demonstrated accuracy for malignancy detection and identified cases with 5-fold greater efficiency than conventional hospital-based referral pathways.MeaningThese findings suggest that combining smartphone photography, artificial intelligence, and media-facilitated public engagement can establish a scalable and accessible model for population screening of rare sight and life-threatening ocular tumors, advancing early detection and health equity for underrecognized conditions. ImportanceOcular surface malignancies pose risks to vision and survival yet are frequently misdiagnosed as benign lesions because of their subtle presentation and the lack of widely accessible screening tools, potentially resulting in treatment delays and the need for extensive surgical intervention.ObjectiveTo develop and validate a smartphone-based, media-facilitated artificial intelligence (AI) system for proactive self-screening of ocular surface malignancies in the general population.Design, Setting, and ParticipantsA nonrandomized clinical trial was conducted across China from December 2022 to June 2023. A deep learning model was initially trained and validated using 12 years of multicenter slitlamp images. The system was then optimized for smartphone-based photography and deployed through a widely disseminated mobile application. Data analysis was performed from July 2023 to June 2024.InterventionParticipants used the CaptureTumor standardized smartphone application, incorporating real-time AI-guided photography instructions, to capture images of suspected lesions. The application provided immediate binary (benign vs malignant) and multiclass risk stratification and triaged high-risk cases for expedited clinical referral.Main Outcomes and MeasuresThe primary outcome was area under the receiver operating characteristic curve (AUC) for differentiating malignant from benign lesions. Secondary outcomes included sensitivity, specificity, and the number of histopathologically confirmed malignancies detected.ResultsMultimedia outreach via television, social media, and internet hospitals reached 256 053 individuals, with 614 completing at-home self-screening through the app. Of these participants, the median (IQR) age was 46 (11) years (range, 4-87 years); 301 (49%) were female and 313 (51%) male. After optimizing the image quality, the smartphone-based CaptureTumor achieved an AUC of 0.905 (95% CI, 0.837-0.973), comparable with the performance of the slitlamp-based model (AUC = 0.945; 95% CI, 0.918-0.972). During real-world screening, 20 malignancies were pathologically confirmed among the 614 participants, with 19 of 20 participants (95%) newly diagnosed, and no cases requiring enucleation. At the population level, CaptureTumor demonstrated an AUC of 0.977 (95% CI, 0.964-0.990), a sensitivity of 89.3% (95% CI, 86.7%-91.9%), and a specificity of 95.9% (95% CI, 94.2%-97.6%).Conclusions and RelevanceThis trial found that the integration of smartphone-enabled imaging, AI-driven diagnostics, and targeted media outreach established a scalable, accessible, and potentially clinically effective strategy for population-level screening of rare ocular malignancies. This closed-loop mobile health model potentially addresses gaps in early detection and equitable care delivery for vision- and life-threatening rare diseases.Trial RegistrationClinicalTrials.gov Identifier: NCT05645341

Background:The myopia rate has increased rapidly worldwide, yet evidence regarding the association between dietary factors and myopia remains limited. This study assessed the association between dietary patterns and myopia among children and adolescents. Methods:This study used the Child and Adolescent Research of Eye data between August and October 2022. Myopia was defined based on uncorrected visual acuity and noncycloplegic refraction. Dietary assessment was parent-reported via a food frequency questionnaire (FFQ). Principal component analysis was used to extract dietary patterns. Binary logistic regression was used to evaluate the association between dietary patterns and myopia. Results:A total of 24,797 participants were included in the analysis. Controlling for confounders, the highest adherence to nuts-tubers vegetables pattern (characterized by high intake of nuts, tubers vegetables, legumes, whole grains, and aquatic products) was associated with a decreased risk of myopia compared with the lowest adherence (odds ratio [OR] = 0.933, 95% confidence interval [CI]: 0.872 to 0.999, p = 0.046). Conversely, the highest adherence to snacks pattern (characterized by high intake of fried and barbecued, fast foods and savoury snacks, sugar-sweetened beverages, desserts, and processed meats) was associated with an increased risk of myopia (OR = 1.083, 95% CI: 1.012 to 1.158, p = 0.021). Conclusions:These findings indicate a link between dietary patterns and myopia in children and adolescents. Dietary modification could be a potential public health measure for the primary prevention of childhood myopia.

AIMS:To evaluate the efficacy of intravitreal conbercept (IVC) combined with pars-plana vitrectomy (PPV) for severe, non-clearing vitreous haemorrhage (VH) caused by proliferative diabetic retinopathy (PDR) in real-world practice. METHODS:This prospective, observational, multicentre, cohort study enrolled 523 patients with VH due to PDR at 26 hospitals from August 2022 to June 2024. Patients were treated with preoperative IVC (3-7 days prior to PPV), intraoperative IVC (at completion of PPV) and PPV alone as control. The primary outcome was the incidence of early (7-30 days) postoperative VH (POVH). Secondary outcomes included late POVH (30-180 days), postoperative best-corrected visual acuity (BCVA) and distribution of POVH severity. RESULTS:Of 425 participants (425 eyes) finally enrolled, 406 completed 30-day-visit, and 341 completed 180-day-visit. The incidence of early POVH was 24.0% (36 of 150) in preoperative IVC versus 23.2% (33 of 142) intraoperative IVC compared with 37.6% (50 of 133) in control (p=0.0160, 0.0122). The incidence of late POVH was 11.9% (16 of 134) in preoperative IVC versus 17.5% (20 of 114) intraoperative IVC versus 17.8% (19 of 107) in control (p=0.4109, 0.4661). The early POVH was less severe in preoperative and intraoperative IVC cohorts compared with control (p=0.0067, 0.0304), while the severity of late POVH was comparable (p=0.4860, 0.8353). Mean postoperative BCVA was all improved but showed no significant intergroup differences (p>0.05). CONCLUSIONS:This study, with the largest participants to date, demonstrates that IVC administered preoperatively or intraoperatively effectively reduces early POVH incidence, rather than late POVH. Preoperative IVC may be preferable for patients with more severe baseline disease characteristics.

Sports-related ocular trauma is a significant cause of unilateral visual impairment and blindness, yet large-scale epidemiological studies on hospitalized cases are lacking. The aim of this study is to analyze the epidemiological characteristics, injury mechanisms, and visual outcomes of sports-related ocular trauma in China, and provide evidence for developing prevention strategies. A multicenter cross-sectional study was conducted based on data from hospitalized patients with sports-related ocular trauma from 99 medical institutions registered in the “China Ocular Trauma Registry System” (COTS) between 2021 and 2024. Demographic characteristics, sports types, ocular injuries, and visual acuity were analyzed using descriptive statistics. Sports-related injuries constituted 3.60

Background: Platelet factor 4 (PF4/CXCL4) is a chemokine with reported anti-angiogenic and immunomodulatory properties; however, the role of PF4 in neovascular age-related macular degeneration (nAMD) remains unclear. Thus, this study aimed to evaluate the therapeutic potential of PF4 in experimental models of ocular pathological neovascularization and explored the underlying mechanisms. Methods: PF4 expression was assessed in a laser-induced choroidal neovascularization (CNV) mouse model using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Recombinant PF4 was administered intravitreally in laser-induced CNV mice and very low-density lipoprotein receptor knockout (Vldlr⁻/⁻) mice, a model of spontaneous retinal neovascularization with retinal angiomatous proliferation (RAP)-like lesions. Pathological neovascularization and vascular leakage were quantified by fundus fluorescein angiography and choroidal/retinal flat-mount analyses. Immunofluorescence, qRT-PCR, and RNA sequencing were employed to evaluate inflammatory responses. Moreover, the effects of PF4 on vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human retinal microvascular endothelial cells were examined in vitro, and VEGF-mediated signaling was analyzed by Western blotting. Ocular safety was assessed by optical coherence tomography (OCT), electroretinography (ERG), hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results: Intravitreal PF4 significantly reduced pathological neovascularization and vascular leakage in both models and attenuated intraocular inflammation, as indicated by decreased expression of proinflammatory cytokines and reduced microglial/macrophage recruitment. PF4 inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation in vitro. Mechanistically, PF4 downregulated VEGF expression in CNV lesions in vivo and suppressed VEGF-induced activation of vascular endothelial growth factor receptor 2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and signal transducer and activator of transcription 3 (STAT3) signaling in vivo and in vitro. PF4 administration was well tolerated, with no detectable adverse effects on retinal structure or function. Conclusions: PF4 effectively inhibits ocular pathological neovascularization and inflammation by modulating the VEGF/VEGFR2 signaling pathway. These findings support PF4 as a promising therapeutic candidate for nAMD and warrant further investigation.

Despite the paradigm shift brought about by anti-VEGF therapy against neovascular age-related macular degeneration, significant challenges persist, including the risk of intraocular infection and retinal structural damage caused by frequent intravitreal injections, suboptimal long-term outcomes in some patients, as well as economic and psychological burdens. Attempts to identify novel therapeutic targets with more compliant drug delivery strategies are warranted. In this study, we identify that nucleolin (NCL) is upregulated in choroidal neovascularization lesions and mobilized to the endothelial cell surface upon VEGF stimulation. Inspired by this localization change and the critical role of NCL in angiogenesis, we developed an integrated delivery and degradation platform, named dNCL@tFNAs, which leverages tetrahedral framework nucleic acids (tFNAs) to decorate an aptamer-based proteolysis-targeting chimera for NCL through a simple Watson-Crick pairing. dNCL@tFNAs exhibits notable stability, improved ocular penetration and degradation efficiency. Mechanistic study reveals that membrane-associated NCL promotes the uptake of dNCL@tFNAs into the endothelial cells, followed by engaging the cytosolic PROTAC machinery to degrade intracellular NCL via the ubiquitin-proteasome pathway. In vivo study demonstrates that dNCL@tFNAs enables administration via a minimally invasive subconjunctival injection to suppress choroidal neovascularization with a favorable safety profile. Collectively, our work establishes a programmable delivery and degradation modality for the treatment of choroidal neovascularization and other ocular neovascular diseases.

This study developed deep learning (DL) models to predict axial length (AL) in 6-10-year-old schoolchildren using minimally abnormal color fundus photographs (CFPs), while evaluating the impact of integrating age, Diopter Sphere (DS), and sex. Following quality assessment of 5460 initial CFPs from 3840 children, 3840 images from 2779 children were utilized and partitioned into training (70 %), validation (20 %), and test (10 %) sets. ResNet101 served as the core architecture, with supplemental clinical parameters integrated into the fully connected layer for continuous AL prediction. Model interpretation employed Grad-CAM-generated heatmaps. Comparative analysis demonstrated that DS and age achieved moderate predictive accuracy (R2 = 0.37), a CFP-only model showed significantly stronger performance (R2 = 0.70), and combining CFPs with DS and age further improved accuracy (R2 = 0.75). However, incorporating sex alongside CFPs, DS, and age substantially reduced efficacy (R2 = 0.41). Heatmaps revealed that regions critical for AL predictions anatomically corresponded to retinal vasculature and immediate perivascular tissues. These findings collectively indicate that DL may leverage near-normal CFPs for pediatric AL prediction, with selective enhancement by age and DS, but degradation when categorical variables (such as sex) are included. Subtle changes in the fundus vasculature may help DL to identify the cause of CFP changes with AL.

The discovery of glycosylated RNAs (glycoRNAs) on the surface of living cells has introduced a novel paradigm in RNA biology, redefining long-held assumptions about the localization and function of extracellular RNA. These structurally unique molecules, identified through advanced technologies and imaging, are increasingly recognized as mediators of cell-cell communication, immune recognition, and cellular homeostasis. In this review, we summarize the current understanding of glycoRNAs, with particular emphasis on their potential relevance to ocular homeostasis and the possible involvement of glycoRNAs in a range of ocular diseases, including inflammatory and autoimmune disorders, degenerative retinal diseases, proliferative vitreoretinopathy, and neoplasms. We further discuss the prospects of glycoRNA-based biomarkers and therapeutic strategies, while highlighting critical challenges in detection, functional validation, and mechanistic elucidation. A deeper understanding of glycoRNA biology in the ocular system may not only uncover new layers of regulatory complexity but also open translational avenues for the diagnosis and treatment of complex eye diseases.

Retinal angiogenesis requires precise transcriptional regulation. Krüppel-like factor 9 (Klf9) has been implicated in various biological processes; however, its specific role in retinal vascular development and ocular neovascular disease remains unclear. In this study, we identified Klf9 as a critical transcriptional regulator of retinal vascular homeostasis. Spatiotemporal transcriptomic and single-cell RNA sequencing analyses revealed that Klf9 was highly enriched in retinal endothelial cells and upregulated during vascular maturation. Using genetic mouse models, we demonstrated that endothelial-specific Klf9 deletion accelerated neonatal retinal vascular expansion and tip cell formation, whereas its overexpression delayed angiogenesis and disrupted barrier function. In oxygen-induced retinopathy, Klf9 loss exacerbated pathological neovascularization and leakage, while its overexpression conferred protection. Integrated RNA-seq and ATAC-seq profiling of human retinal microvascular endothelial cells revealed that Klf9 represses a network of genes involved in the PI3K-Akt pathway and focal adhesions. Key effectors, including AKT1, PTK2, and RAC1, were suppressed by reduced chromatin accessibility at their promoters. Both in vitro and in vivo rescue experiments confirmed that Akt activation reverses vascular hypoplasia caused by Klf9 overexpression, whereas Akt inhibition normalizes the hyper-angiogenic phenotype of the Klf9-deficient endothelium. Collectively, these findings establish Klf9 as a transcriptional brake on retinal angiogenesis, acting through chromatin-mediated suppression of the PI3K-Akt pathway, and provide new mechanistic insights and potential therapeutic targets for pathological retinal angiogenesis.

PURPOSE:To explore the efficacy of vitrectomy combined with intravitreal injection of Triamcinolone acetonide (TA) in the treatment of proliferative diabetic retinopathy (PDR). METHODS:This was a retrospective cohort study of patients who received intraocular surgery at Wuhan Tongji Hospital between January and December 2024. One hundred and thirty-three cases (138 eyes) with PDR were randomly divided into two groups: 72 cases (75 eyes) in the combined TA group and 61 cases (63 eyes) in the simple vitrectomy group (control group). Both groups underwent vitrectomy. Before closing the incision, the combination group was intravitreal injected with 4 mg TA. The patients were followed up for 3 months. The recovery of visual function and the control of PDR were analyzed. RESULTS:The postoperative outcomes revealed that in the combined treatment group, 86.67% of patients experienced improved visual acuity, with 13.33% showing no change and no cases of decreased vision, leading to a significant improvement compared to the control group where visual acuity increased in 71.43% of patients, remained unchanged in 12.70%, and decreased in 15.87% (p < 0.05). Additionally, the combined group had a lower incidence of postoperative bleeding at 12.00 versus 23.81% in the control group (p < 0.05). Notably, the incidence of tractional retinal detachment was similar in both groups (p > 0.05), but macular epiretinal membrane was observed in 24.00% of the combined group's eyes compared to 41.27% in the control group, which was a significant difference (p < 0.05). CONCLUSIONS:Vitrectomy combined with intravitreal injection of TA in the treatment of PDR can better improve the postoperative visual outcome and may help reduce the occurrence of postoperative proliferation, postoperative bleeding and other complications.

Ocular neovascular disease, characterized by aberrant angiogenesis in the eye, is a primary cause of global vision impairment and blindness. As the primary barrier exposed to hypoxia-related blood metabolites, endothelial cells (ECs) undergo metabolic reprogramming that drives pathological angiogenesis. However, the epigenetic mechanisms that link EC metabolic dysfunction to retinal vasculopathy remain elusive. Methods:Using western blotting and immunofluorescence analysis of retinal sections/whole-mounts, we confirmed increased histone 3 lactylation at lysine 18 (H3K18la). We subsequently identified downstream target genes through integrated CUT&Tag and RNA sequencing (RNA-seq), assessed their angiogenic regulatory functions using siRNA, and validated the mechanisms in vivo employing adeno-associated virus (AAV)-based gene transfer. Results:Our data indicated that histone lactylation levels were elevated in retinal vascular ECs under hypoxic conditions both in vivo and in vitro. In oxygen-induced retinopathy (OIR) retinal vascular ECs, H3K18la was the most prominent modification. Pharmacological inhibition of glycolysis suppressed H3K18la levels, concurrently abrogating EC activation and neovascularization. Combined CUT&Tag and RNA-seq analyses revealed that ETS1 was a direct transcriptional target governed by H3K18la in retinal ECs. Silencing ETS1 substantially inhibited hypoxia-induced proliferation, migration, sprouting, and tube formation in human retinal microvascular endothelial cells (HRMECs). Crucially, in vivo rescue experiments confirmed that ETS1 overexpression reversed the suppression of pathological neovascularization in OIR mice treated with AAV-Pfkfb3-RNAi. Conclusions:Collectively, this study revealed a lactate-driven epigenetic cascade wherein H3K18la licenses ETS1-dependent pathological angiogenesis, providing a promising therapeutic avenue for ischemic retinal diseases.