This study reveals the pivotal role of the Sterol Regulatory Element-Binding Protein 1 (SREBP1)/Stearoyl-CoA Desaturase 1 (SCD1) lipid metabolic axis in protecting retinal pigment epithelium (RPE) against oxidative damage. We demonstrate SCD1 downregulation in age-related macular degeneration (AMD) patient tissues and sodium iodate (SI)-induced models, while its overexpression enhances cell viability and ameliorates oxidative injury. Mechanistically, we uncover a novel pathway where SCD1-derived oleic acid activates the nuclear factor erythroid 2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) signaling cascade, scavenging reactive oxygen species (ROS) and suppressing lipid peroxidation. Notably, oleic acid also mitigated oxidative stress via this pathway without directly promoting cell survival. These results not only elucidate SCD1's crucial protective mechanism in AMD pathogenesis but also establish the SREBP1/SCD1 axis as a promising therapeutic target for developing innovative interventions against retinal degeneration.

Previous studies used the Normalized Difference Vegetation Index (NDVI) to assess green space and showed its potential protective effect on myopia. However, this top-down measurement of green space cannot fully reflect the eye-level greenness perception. This study used the Vision Greenness Index (VGI) to assess visual greenness from street-view images and compare its effect on myopia with NDVI. This multicenter, cross-sectional study investigated 69,051 children from 146 schools in five cities in Hubei, ranging from kindergarten to high school. Visual greenness was calculated from street-view images with DeepLab v3 and NDVI was calculated from Landsat 8 satellite observations. Regression models were used to analyze the relationship between school myopia and environmental factors. The partial correlation coefficient between VGI within a 5,000-m buffer zone and myopia was − 0.343 (P = 0.038) and − 0.326 (P < 0.001) in Models 1 (all schools) and 2 (schools except high schools), respectively, whereas NDVI showed no significant results. In Model 3 (kindergartens), the partial correlation coefficients between VGI and NDVI within a 5,000-m buffer zone were − 0.675 (P = 0.029) and − 0.380 (P = 0.032), respectively. In Model 4 (elementary schools), the partial correlation coefficients between VGI and NVDI within a 5,000-m buffer zone were − 0.310 (P = 0.027) and − 0.088 (P = 0.043), respectively. Model 5 (high schools) did not demonstrate any correlations between the identified factors and the prevalence of myopia during high school. VGI demonstrated a more significant relation to the myopia than NVDI. Visual greenness was found to be related to myopia in kindergartens and elementary schools rather than in high school, indicating its more significant association with a lower prevalence of myopia in early school ages than in high school.

PURPOSE:To evaluate the clinical efficacy, safety, and immunogenicity of biosimilar SSGJ-601 compared with ranibizumab in patients with macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN:A multicenter, randomized, double-masked, active-controlled phase 3 clinical study. PARTICIPANTS:A total of 351 patients with macular edema secondary to BRVO were enrolled. METHODS:Evaluable patients (N=351) were randomized to receive intravitreal SSGJ-601(1.25mg per eye, Q4W) or intravitreal ranibizumab (0.5mg per eye, Q4W) from day 1 through week 20 (6 injections in total), and treatment transitioned to a pro re nata (PRN) schedule based on investigator-assessed retreatment criteria from week 24 to week 48. All patients completed their end-of-study visit at week 52. MAIN OUTCOME MEASURES:The primary efficacy endpoint was the Least Squares (LS) mean difference in change in best-corrected visual acuity (BCVA), measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, from baseline to week 24. Secondary efficacy endpoints, safety, pharmacokinetics, immunogenicity and change in VEGF concentration of SSGJ-601 were also analyzed. RESULTS:Demographic and baseline characteristics and exposure to treatment were similar between groups. In the study eye, SSGJ-601 was non-inferior to ranibizumab in improving the LS mean in BCVA letter count from baseline to week 24 (17.6 (0.66) vs. 18.2 (0.65) letters, -0.6 with 95%CI: (-2.4,1.3), P for non-inferior<0.0001), thus, the primary clinical efficacy end point was met. At each time point, the proportions of patients achieving BCVA gains of ≥5, ≥10, and ≥15 letters in the SSGJ-601 group were non-inferior to those in the ranibizumab group. Drug-related TEAEs (11.4% vs. 12.5%) and SAEs (6.9% vs. 9.1%) were comparable in the two treatment groups. A low incidence of binding antidrug antibodies was observed in SSGJ-611 group. CONCLUSIONS:This study supports the conclusion of no clinical meaningful differences in efficacy, safety, and immunogenicity between SSGJ-601 and ranibizumab in patients with macular edema secondary to BRVO. Additionally, treatment transitioned to a pro re nata (PRN) schedule based on investigator-assessed retreatment criteria resulted in sustained benefits in visual and anatomical outcomes.

Posterior capsule opacification is a common long-term complication of cataract surgery that can cause persistent visual impairment in some patients despite advances in surgical techniques and IOL design. Most current studies focus on single signaling pathways or isolated time windows, showing benefits in some models but with limited overall translation. This review organizes existing evidence into a pathological network in which TGF-β signaling initiation and amplification, mitochondrial dysfunction, and microenvironmental cues related to surgical trauma and aging collectively shape the susceptibility, progression, and persistence of posterior capsule opacification and outlines potential opportunities for combination therapy, time-sensitive intervention windows, and local delivery.

This study investigated the associations between outdoor artificial light at night (ALAN) and type 2 diabetes (T2DM) and metabolic syndrome (MetS) and aimed to characterize the dose-response relationships and potential exposure thresholds. This cross-sectional study included 57,898 Chinese adults who underwent health examinations in Hubei, China, from January 2013 to June 2025 in T2DM analysis. A subset of 25,735 participants with complete data was analyzed for MetS. ALAN exposure was estimated using satellite-derived nighttime light intensity (NPP‑VIIRS‑like data) within a 500 m radius of each residence. Multivariable logistic regression models estimated odds ratios (ORs) and 95

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are emerging optical coherence tomography (OCT) markers for axoplasmic stasis. Accurate volumetric quantification is critical for monitoring their progression but remains challenging due to the complex 3D geometry of these structures. We developed a dual-branch deep convolutional neural network to automatically segment and quantify PHOMS volumes using swept-source OCT data from 70 adolescent eyes. The architecture integrates a segmentation branch and a classification branch to resolve boundary ambiguities. Performance was validated against manual ground truth from expert graders. Our automated segmentation achieved a human-equivalent accuracy level in identifying PHOMS, achieving a mean Dice coefficient of 0.810 and an intraclass correlation coefficient of 0.990 in comparison with expert graders’ assessments. Volumetric measurements demonstrated a robust correlation (r = 0.992) between the automated and manual methods. The proposed deep learning framework enables rapid, reliable, and automated 3D quantification of PHOMS in adolescents. This tool holds significant potential for large-scale clinical screening and the longitudinal monitoring of PHOMS.

While evidence links light at night (LAN) to metabolic disturbances, large-scale, population-based studies of objectively-measured LAN exposure remain limited. This study investigates the association between LAN and the risk of diabetes mellitus (DM) among US adults using data from the National Health and Nutrition Examination Survey. Cross-sectional data from the 2011 to 2014 National Health and Nutrition Examination Survey cycles were analyzed, focusing on participants with complete data on both LAN and DM. Participants were stratified by LAN level. Multivariable logistic regression analyses were employed to examine the association between LAN and DM. Multivariable linear regression analyses assessed relationships between LAN and diabetes risk markers, including hemoglobin A1c (HbA1c), fasting blood glucose, fasting serum insulin, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Subgroup and sensitivity analyses with multiple imputation tested robustness. A total of 4498 participants were enrolled. The prevalence of diabetes was higher in the high-LAN exposure group compared to the no-LAN group (21.01% vs 14.48%). Consistent with this, in the fully adjusted model, high-LAN exposure was independently associated with a significantly increased risk of DM (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.00-1.92). High-LAN exposure was linked to elevated HbA1c and fasting blood glucose in initial models. However, these associations weakened and became nonsignificant after full adjustment for covariates. No significant associations were observed for fasting serum insulin or HOMA-IR. Subgroup analyses showed the association between LAN and DM was more pronounced in middle-aged adults (40-64 years), individuals with obesity, and those with dyslipidemia or hypertension. However, no significant effect modification was found across subgroups (all P for interaction > .05). Sensitivity analyses confirmed the robustness of these findings. This study uses objective actigraphy-based LAN measurement and shows its independent association with DM, especially in metabolically susceptible subgroups. These findings identify LAN as a modifiable environmental risk factor and support its relevance to DM prevention and public health strategy.

PurposeAge-related macular degeneration (AMD) involves dysfunction of the retinal pigment epithelium (RPE), where cellular senescence and epithelial-mesenchymal transition (EMT) are key pathological features. The upstream mechanisms linking these processes are not fully understood. This study investigates the potential role of ferroptosis in contributing to senescence-associated EMT in RPE cells.MethodsWe utilized an aging mouse model and two cellular models in ARPE-19 cells, induced by D-galactose (D-gal) and low-dose sodium iodate (SI), respectively. Ferroptosis, EMT, and oxidative stress markers were evaluated via immunofluorescence, flow cytometry, and Western blotting. The specific ferroptosis inhibitor Ferrostatin-1 was used to assess the involvement of ferroptosis.ResultsAged mouse RPE/choroid complexes and stressed ARPE-19 cells exhibited features of EMT along with increased ferroptosis hallmarks, including lipid peroxidation and iron accumulation. A downregulation of the xCT/GPX4 anti-ferroptotic axis was observed. Pretreatment with Fer-1 alleviated ferroptosis by reducing iron levels and lipid peroxidation, and restored xCT/GPX4 expression. Furthermore, Fer-1 attenuated the EMT phenotype, as evidenced by the restoration of epithelial markers and reduction of mesenchymal markers (Vimentin, α-SMA) in both D-gal and SI models.ConclusionOur findings suggest that ferroptosis may contribute to linking RPE senescence with EMT, potentially via oxidative stress pathways. The combined targeting of both senescence and ferroptosis could therefore represent a potential therapeutic strategy for addressing RPE dysfunction and AMD progression.

Myopia is a major global public health concern, and near work has been identified as a key risk factor for its onset and progression. This study aimed to evaluate short-term retinal and choroidal vascular and structural responses to near work and subsequent eye-closure rest in young adults. Thirty medical students (aged 18–24 years) underwent wide-field swept-source OCTA at baseline, after 20, 40, and 60 min of near work, and after 10, 20, and 30 min of eye-closure rest. Vascular parameters of the nerve fiber layer vascular plexus (NFLVP), superficial vascular complex (SVC), deep vascular complex (DVC), choriocapillaris, and choroid were analyzed. During near work, NFLVP vessel density (VD) and vessel diameter index increased in the temporal 1–3 mm and 6–9 mm sectors; the 6–9 mm temporal sector remained elevated above baseline throughout rest (all p < 0.05). SVC VD, small vessel density, and vessel length density in the superior 3–6 mm sector fell below baseline during rest (all p < 0.05). Choroidal perfusion area, thickness, and stromal volume declined significantly relative to pre-rest values at 20 min of rest (all p < 0.05). NFLVP perfusion in the temporal 6–9 mm sector increased during near work and remained elevated above baseline throughout the rest period; SVC perfusion in the same sector likewise remained above baseline during rest, while SVC perfusion in the superior 3–6 mm sector fell below baseline. These alterations may provide important insights into the vascular regulatory mechanisms underlying myopia development.

Diabetic retinopathy (DR) is the main cause of vision loss, with retinal pigment epithelial (RPE) cell dysfunction as a key contributor. Ferroptosis is implicated in RPE injury under hyperglycemia; however, its upstream regulatory mechanisms remain unclear. High glucose (HG)-induced human RPE ARPE-19 cells and a diabetic mouse model were used. Ferroptosis was assessed through biochemical assays, Western blot, fluorescence probes, and histological staining. Protein interactions and transcriptional regulation were examined using Co-IP, glutathione S-transferase pull-down, ChIP, and luciferase reporter assays. Immunofluorescence staining was used as key indicator expression in retinal tissues. Nuclear receptor 4A1 (NR4A1) expression was upregulated under HG-induced ARPE-19 cells. NR4A1 knockdown alleviated HG-induced iron accumulation, lipid peroxidation, and ferroptosis marker changes. Mechanistically, SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) interacted with NR4A1 and promoted its ubiquitination and degradation. Forkhead box O6 (FOXO6) was upregulated by HG and repressed SMURF2 transcription. SMURF2 overexpression mitigated HG-induced ARPE-19 ferroptosis and retinal injury in DR mice, an effect reversed by NR4A1 co-overexpression. SMURF2 knockdown reversed the effect of FOXO6 knockdown on HG-induced ferroptosis in ARPE-19 cells and retinal injury in DR mice. The FOXO6-SMURF2-NR4A1 axis critically regulates ferroptosis in RPE cells during DR.

Purpose: We investigated neurohomeostasis and its possible underlying mechanisms in the choroids of diabetic mice. Methods: Streptozotocin-induced diabetic mice were used in this study. Choroidal nerve fiber alterations were observed via transmission electron microscopy (TEM). The levels of epinephrine and acetylcholine in the choroid were determined via ultra-high-performance liquid chromatography-tandem mass spectrometry. Tyrosine hydroxylase (TH), choline acetyl transferase (ChAT), and neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) levels were evaluated by western blot or quantitative real-time polymerase chain reaction. In addition, immunofluorescence staining were used to analyze the changes in key enzymes (TH, dopamine beta-hydroxylase (D beta H), and CGRP) in the superior cervical sympathetic ganglia (SCG) and trigeminal ganglia (TG). Results: TEM revealed a loose myelin sheath around nerve fibers, axon atrophy, and cytoplasmic vacuoles Schwann cells in diabetic choroids. Lower epinephrine levels were observed in diabetic mice. Although no difference was found in acetylcholine level, the epinephrine-to-acetylcholine ratio was greatly decreased. Decreased TH and increased ChAT, nNOS, VIP, NPY, and CGRP were found in diabetic choroids. Fewer TH-positive and D beta H-positive neuronal cells were found in the SCGs of diabetic mice. More CGRP-positive and fewer TH-positive neuronal cells were observed in the TG of diabetic mice. Conclusions: Altered markers of the sympathetic, parasympathetic and sensory systems were present in diabetic mouse choroids. An imbalanced choroidal nervous system might explain the initiation of choroidal neovascularization in diabetic patients.

Objective To analyse retinal and choroidal microvascular alterations in patients with thyroid-associated ophthalmopathy (TAO) and hyperthyroidism without signs of TAO using swept-source optical coherence tomography angiography (SS-OCTA) and to investigate the potential reasons for ocular microvascular changes in patients with TAO.Methods Thirty patients with active TAO (group A), thirty patients with hyperthyroidism without signs of TAO (group B), and thirty healthy subjects (group C) were recruited. The images of macula and optic nerve head were obtained by SS-OCTA. Vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus, radial peripapillary capillary and choriocapillaris (CC), choroidal vascularity index, foveal avascular zone area, macular thickness, macular ganglion cell complex thickness, choroidal thickness (CT), and retinal nerve fibre layer thickness were measured.Results Group A had significantly higher VD of SCP than group C (all p < 0.05), and group B had significantly lower VD of SCP than group C (all p < 0.05). The VD of CC was significantly lower in group A than in groups B and C (p < 0.05). CT was significantly thicker in groups A and B than in group C (all p < 0.05). Multivariable regression analysis showed that the free triiodothyronine was significantly negatively correlated with the VD of SCP in the parafoveal regions in groups B and C (p < 0.05) and proptosis was significantly positively correlated with the VD of SCP in groups A and B (all p < 0.05).Conclusion We noted a difference in the VD of SCP and CC between patients with TAO and patients with hyperthyroidism without signs of TAO. These relative differences in ocular microvasculature indicated that local (orbital) and systemic (thyroid-related) factors may both play a role in disease presentation and progression, with orbital factors having a greater impact.

PURPOSE. To investigate the prevalence and risk factors of enlarged blind spots in non-pathological highly myopic eyes. METHODS. Visual field conditions of 313 eyes in 172 individuals with high myopia were evaluated. Clinical characteristics of 116 eyes with enlarged blind spots and 116 eyes with normal visual fields were compared. Generalized-estimating equation (GEE) regression model were used to assess the factors associated with enlarged blind spots. RESULTS. The frequency of enlarged blind spots in non-pathological highly myopic eyes was 37.06% in this sample. Eyes with enlarged blind spots had larger gamma zone (P 0.038), larger PHOMS area (P < 0.001), increased peripapillary retinal nerve fiber layer thickness (P = 0.006), and decreased macular ganglion cell-inner plexiform layer thickness (P = 0.016) compared with eyes with normal visual fields. In multivariate regression analysis, an expanded gamma zone (OR = 2.004; P = 0.022) and a larger PHOMS area (OR = 4.414; P = 0.009) were associated with an enlarged blind spot. CONCLUSIONS. An expanded gamma zone and a larger PHOMS area are associated with an enlarged blind spot, indicating that these two parameters may suggest a possibility of functional damage in early nonpathological, highly myopic eyes. This pattern of impairment might provide clues for the differential diagnosis between high myopia and glaucoma.

Tear Film Break-Up Time (TBUT) is a critical clinical parameter in the management of dry eye disease (DED). However, traditional TBUT assessments rely on costly and time-consuming clinical procedures, while existing home-based solutions fail to provide precise TBUT values. In this work, we present Blinic, a contactless system leveraging commercial millimeter-wave (mmWave) radar to predict precise TBUT values and assess DED severity grades at home. Blinic incorporates detailed blink kinematics that are closely linked to TBUT. To address the challenge of predicting TBUT directly from radar data, we propose a teacher-student learning framework. The teacher model, trained on electronic health records (EHRs) including image-based diagnostic tests, transfers medical insights to the student model, which uses radar-captured blink dynamics. This knowledge transfer is further enhanced by a fine-tuned large language model, DryEye-LLM, which is based on clinical diagnostic reports and employs unsupervised domain adaptation to align EHRs with radar data. To ensure accurate blink motion capture, Blinic employs an antenna-coded MIMO mmWave radar design. Additionally, a query-based multitask learning module simultaneously predicts TBUT and DED severity grades, addressing potential conflicts in feature representation. Evaluated on 192 participants in collaboration with an eye clinic, Blinic demonstrates achieving a mean absolute error of 2.73 seconds for TBUT with an average accuracy of 90.54% for DED grading in real-world settings, providing a practical solution for home-based DED management. [GRAPHICS] .

To address the difficulty in comprehensive screening of fundus diseases, we develop three deep learning algorithms (DLAs) based on different algorithms (Swin Transformer and cross-domain collaborative learning [CdCL]) and imaging modalities (ultra-wide-field [UWF] images and the cropped posterior-pole-region [PPR] images) to identify 25 fundus conditions and provide referral suggestions: WARM (CdCL + UWF images), BASE (Swin Transformer + UWF images), and WARM-PPR (CdCL + PPR images). 59,475 UWF images are included to establish internal and external datasets. WARM shows the best performance on the internal test (area under the receiver operating characteristic curve [AUC] for screening = 0.915; AUC for referral = 0.911) and the external multi-center test (AUC for screening = 0.912; AUC for referral = 0.902). UWF images and the CdCL approach significantly enhance the DLA's ability to detect abnormalities in the peripheral retina. The WARM model shows promise as a reliable and accurate tool for comprehensive fundus screening on a large scale.

To evaluate the changes in vascular density of the retina and choriocapillaris (CC) using swept-source optical coherence tomography angiography (SS-OCTA) after retinal laser photocoagulation in patients with diabetic retinopathy (DR). This prospective observational study included 45 eyes from 45 patients, comprising 20 with severe nonproliferative DR and 25 with proliferative DR. SS-OCTA images of the photocoagulation-treated areas were acquired before laser photocoagulation and at 1 h, 1 week, and 1 month follow-ups. Vessel densities of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and CC were analysed in the laser spot area (LSA), total area (TA), and non-laser spot area (NLSA). At baseline, the vascular density of the CC within the LSA was 65.4 ± 5.0

PURPOSE:To investigate the distribution of macrophage-like cells (MLCs) across different stages of posterior vitreous detachment (PVD). METHODS:A total of 168 eyes from 168 subjects were included. MLCs were imaged by acquiring en face OCT images at depths of 5 µ m to 10 µ m on the inner limiting membrane, and using B-scan OCT. Participants were categorized into three groups according to the degree of PVD: Group A for Stage 1a PVD, Group B for Stages 1b and 2 PVD, and Group C for Stages 3 and 4 PVD. Localized vitreoretinal relationships were categorized into vitreoretinal adhesions, Type 1a PVD, where the vitreous and retina are not clearly separated, and Type 1b PVD, where there is clear separation. RESULTS:MLC density was sequentially lower in Groups A, B, and C. Multiple linear regression analysis revealed that MLC density was correlated with both the PVD group and age (both P < 0.001). In Group A, MLC density was significantly higher in Type 1a PVD than in the vitreoretinal adhesion area. In Group B, the distribution of MLCs in the vitreoretinal adhesion region was significantly less than in Type 1a PVD and Type 1b PVD. MLCs were more sparsely distributed in Group C. CONCLUSION:MLCs exhibit distinct distribution patterns in various stages of PVD.

Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types. Glial cells, the most abundant cells in the nervous system, play a vital role in intercellular signaling and can show abnormal activation under pathological conditions. Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades, highlighting their important role in cellular communication. This review focuses on the formation of tunneling nanotubes in various types of glial cells, including astrocytes, microglia, glioma cells, and Schwann cells, as well as their roles in cellular communication and cargo transport. We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes. Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances. However, they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients. Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.

The global prevalence of high myopia is rising, posing a significant public health concern. Limited research exists on risk factors for prelaminar schisis (PLS) and its impact on visual field changes in highly myopic eyes. Herein, we investigated clinical features of prelaminar schisis (PLS) in highly myopic eyes. This cross-sectional study included 245 eyes with high myopia and 64 eyes with emmetropia and low myopia. PLS was classified on a 3-point scale (0–2), and clinical characteristics were compared between two groups and three sub-groups. Factors associated with PLS presence and severity were evaluated in highly myopic eyes. Highly myopic eyes had a higher frequency (P = 0.008) and severity (P = 0.001) of PLS than controls. Among them, 33.47