This study aimed to investigate the effects of preservative-free latanoprost on meibomian gland function in mice and its possible mechanism. Disproportionality analysis was conducted using the FAERS database to evaluate adverse reaction reports and epidemiological characteristics associated with preservative-free latanoprost. In mouse models, 0.005

Purpose:This study aimed to identify potential drugs associated with drug-related retinal fibrosis (RF) and to analyze their risk characteristics systematically. Methods:This study used a retrospective disproportionality analysis to identify significant drug signals associated with RF from over 17 million reports in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The identified drugs were categorized by therapeutic class, risk level, latency period, and key subgroups (e.g., age, gender, off-label use). Results:Sixteen drugs showed a significant association with RF, including anti-neovascularization agents, corticosteroids, and immunosuppressants. Risk severity varied: Verteporfin, ranibizumab, and brolucizumab had the highest risk, and vigabatrin and sildenafil had a relatively lower risk. The latency periods differed significantly, ranging from a median of 950 days for fluocinolone acetonide to 13 days for triamcinolone. Subgroup analysis revealed that off-label use increased the risk of RF and uncovered distinct susceptibility patterns: Adolescents (0-17 years) faced a higher risk when using specific drug classes such as corticosteroids, whereas elderly patients (≥65 years) were more susceptible to RF when using anti-neovascularization agents. Females showed a higher risk associated with immunosuppressants. Conclusions:This study presents a list of drugs associated with RF, providing a valuable reference to guide rational drug use, preserve visual acuity, and prevent irreversible structural damage. Translational Relevance:Identifying specific drugs associated with RF is crucial for preventing drug-related RF and developing personalized monitoring strategies.

Retinal pigment epithelial (RPE) cells are vulnerable to hypoxia-related and oxidative stress. Cobalt chloride (CoCl₂) is widely used as a chemical hypoxia mimetic; however, an appropriate concentration window for producing measurable RPE injury without the more extensive damage associated with higher concentrations remains incompletely defined. Aldehyde dehydrogenase 2 (ALDH2) contributes to reactive-aldehyde detoxification and cellular stress defense. ARPE-19 cells were exposed to 0, 10, 100, 500, 1000, or 2000 µM CoCl₂. Scratch-wound recovery and representative morphology were evaluated for up to 72 h, and relative CCK-8 metabolic activity was quantified at 24, 48, and 72 h. The 500 µM condition was selected for molecular and pharmacological experiments based on the integrated dose-response profile. Culture-supernatant 4-HNE and VEGF-A were measured by ELISA, whereas HIF-1α, ALDH2, and BAX were assessed by Western blotting. Alda-1 and Daidzin were used as an ALDH2 activator/chemical chaperone and an enzymatic inhibitory comparator, respectively. CoCl₂ caused concentration- and time-associated impairment of scratch-wound recovery. Wound closure was largely preserved at 0–100 µM, whereas 500–2000 µM produced wound-closure failure. The CCK-8 profile showed that 500 µM retained a nonmaximal metabolic signal compared with the substantially greater late reductions observed at 1000 and 2000 µM. Thus, 500 µM represented the lowest tested concentration producing significant functional injury while avoiding the more extensive injury phenotype observed at higher concentrations. Under 500 µM CoCl₂, HIF-1α increased early, ALDH2 protein abundance decreased, and culture-supernatant 4-HNE and VEGF-A increased at the later time point. Alda-1 improved wound recovery and restored ALDH2 protein abundance, whereas Daidzin aggravated the functional injury phenotype and shifted extracellular stress-marker readouts in an unfavorable direction. CoCl₂ produced a concentration-resolved, hypoxia-related and aldehyde-associated RPE injury phenotype. Alda-1 improved wound recovery and increased ALDH2 protein abundance, whereas Daidzin aggravated the functional injury phenotype. These findings support ALDH2-associated aldehyde-detoxifying defense as a modulatory component of CoCl₂-induced RPE stress.

This study investigated the protective effects of aldehyde dehydrogenase 2 (ALDH2) activation (via Alda-1), ALDH2 inhibition (via Daidzin), and the modulation of sirtuin 1 (SIRT1) and endoplasmic reticulum stress (ERS) on methyl-nitrosourea (MNU)-induced retinal damage in C57BL/6 mice. Seventy-two mice were randomly assigned to eight groups, including a control group, a MNU-alone group, and various treatment combination groups. Mice were administered with intraperitoneal injections of agonists and inhibitors targeting the ALDH2-SIRT1-ERS axis, respectively. Body weight, retinal layer thickness, and aldehyde metabolism biomarkers were assessed on the second and fourth day post-treatment. MNU administration induced retinal degeneration, resulting in significant body weight loss in all groups except the control. Treatment with Alda-1 attenuated retinal damage, while Daidzin exacerbated it. Pharmacological inhibition of SIRT1 (via EX-527) diminished the protective effects of Alda-1, and ERS induction (via TUN) nearly abolished its benefits. Conversely, SIRT1 activation (via SRT1720) mitigated the adverse effects of Daidzin, while ERS inhibition (via 4-PBA) partially alleviated Daidzin's impact. Furthermore, MNU increased levels of aldehyde metabolism markers (malondialdehyde [MDA] and 4-hydroxy-2-nonenal [4-HNE]), with Alda-1 reducing and Daidzin elevating these levels. Besides, pharmacological modulation of the SIRT1/ERS pathways intervened in the regulatory effects of Alda-1 and Daidzin on the aldehyde metabolism. Overall, ALDH2 activation protected retinal structure and regulated aldehyde metabolism, highlighting the critical role of the ALDH2-SIRT1/ERS signaling axis in mitigating retinal degeneration.

This study aimed to find shared gene signatures, molecular processes, and potential pharmacological targets in retinitis pigmentosa (RP) and diabetic retinopathy (DR) through integrated bioinformatics analysis. Two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified using the R software, and co-expression gene weighted expression method (WGCNA) was conducted to find the co-expression networks. Common genes were screened with a Venn tool. Functional and pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Common miRNAs were identified and functionally analyzed. Seven overlapping differentially expressed genes and 2 shared genes from WGCNA core modules were identified. Gene Ontology (GO) analysis highlighted regulation of lipoxin metabolism and membrane-associated oxidoreductase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment focused on linoleic and arachidonic acid metabolism, with ALOX15 as the key oxidase. PPI network analysis also emphasized ALOX15. The overlapping miRNA hsa-mir-133b was associated with organelle-related functions. Integrated bioinformatics revealed that the lipoxygenase pathway and membrane oxidoreductase activity likely contribute to RP and DR pathogenesis, with ALOX15 as a promising therapeutic target. ALOX15's role in lipoxin metabolism and oxidative stressed positions it as a novel pharmacological target for preserving retinal function in RP and DR. These findings paved the way for developing targeted therapies to improve visual outcomes in these diseases.

This study aimed to utilize Mendelian randomization (MR) analysis to investigate potential genetic targets related to aldehyde metabolism in the context of retinitis pigmentosa (RP) and to identify possible therapeutic options. Genome-wide association study data for RP were obtained for MR analysis. We employed various statistical methods, including inverse-variance weighted analysis, to evaluate potential causal associations with RP risk, followed by rigorous sensitivity analysis. Two-sample MR analysis identified a significant causal relationship between aflatoxin B1 (AFB1) aldehyde reductase and the risk of RP, with genetically predicted AFB1 aldehyde reductase contributing to a decreased risk of RP (odds ratio: 0.875; P = .008) based on inverse-variance weighted analysis. Sensitivity analysis suggested no evidence of heterogeneity or horizontal pleiotropy in the observed associations (P > .05). Additionally, the leave-one-out validation confirmed the robustness of these findings without significant alterations. The results from the reverse analysis for the causal relationship between the accidence of RP and AFB1 aldehyde reductase showed no significant statistical differences. Our findings highlighted the role of AFB1 aldehyde reductase in the pathogenesis of RP, proposing it as a promising protective measure for future treatment strategies.

We employed an integrated bioinformatics screening approach along with Mendelian randomization (MR) analysis to explore potential genetic targets for varicose veins of lower extremities (VVs) and identify potential treatment options for VVs. Differential expression analysis was conducted using R software to identify differentially expressed genes (DEGs) of VVs from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression networks. Functional enrichment analyses were conducted for the identified genes. A protein-protein interaction network was constructed to analyze the interactions among the identified genes. Additionally, genome-wide association studies data for VVs were downloaded for MR analysis. Various methods, including inverse-variance weighted, were employed to assess potential causal associations with VVs risk, followed by sensitivity analysis. The DEGs identified from the VVs Gene Expression Omnibus dataset included 180 upregulated genes and 335 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that the downregulated DEGs were significantly associated with nuclear protein-containing complexes and nucleic acid binding (P < .05). WGCNA highlighted a highly significant "turquoise" module comprising 78 downregulated genes (P = 2e - 04). The protein-protein interaction network analysis of the significant DEGs and the WGCNA "turquoise" module identified 224 nodes and 491 edges, uncovering several hub genes such as BRCA1, NCBP2, GTPBP4, HDAC2, KHDRBS1, and HNRNPR. Detailed functional enrichment analysis indicated involvement in tumor-like cellular proliferation and differentiation processes, including protein acetylation, RNA splicing, and metabolic processes. MR analysis revealed a causal association between the tumor-related gene Ecto-NOX disulfide-thiol exchanger 2 (ENOX2) and the risk of VVs, with a statistical significance (odds ratio: 1.0016; 95% confidence interval: 1.0003-1.0029; P = .015) according to inverse-variance weighted analysis. Sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy in the observed associations (P > .05). "Leave-one-out" validation analysis did not indicate any changes. Our study unveils the involvement of ENOX2 and the related mechanisms in the pathogenesis of VVs, suggesting their potential as genetic targets for treatment.

Purpose:To explore the causal associations among circulating proteins, plasma metabolites, and age-related macular degeneration (AMD). Methods:We employed Mendelian randomization (MR) analysis and colocalization analysis to discern the causal relationship between proteomes and AMD. This investigation utilized data from protein quantitative trait loci (pQTL) studies in deCODE and the UK Biobank. Additionally, plasma metabolite-related genome-wide association studies (GWAS) data and AMD-related GWAS data were incorporated. Results:Our findings confirmed a potential causal relationship between cytoplasmic tryptophanyl-tRNA synthetase 1 (WARS1) and a higher risk of AMD. The observed causal impact of WARS1 on the two subtypes of AMD (dry and wet) align consistently with the aforementioned outcomes. Three plasma metabolites-N-acetyl-kynurenine, N-acetyltyrosine, and caproate (6:0)-were identified as mediators of the causal effect of WARS1 on AMD, and subgroup analysis revealed that N-acetyltyrosine is a specific negative metabolite associated with WARS1 and dry AMD, whereas X-16580 is a specific positive metabolite linked to WARS1 and wet AMD. Conclusions:The outcomes of this study suggest a potential causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD by integrating multiple genetic analyses. Nevertheless, further research is essential to validate and strengthen these conclusions. Translational Relevance:This study establishes the causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD.

Objective:Dimethyl sulfoxide (DMSO) is known to enhance the absorption of chemicals. This study investigated the effects of DMSO in combination with the alkylating agent, N-methyl-N-nitrosourea (MNU), on the activity and mortality of mice, providing foundational data for solvent mixture use and health impact assessment. Methods:Twelve male SPF C57BL/6J mice were divided into three groups (n=4): DMSO group (D), DMSO combined with low-dose (L), and high-dose MNU group (H). Mice in D received intraperitoneal injections of pure DMSO solution at 12 mL/kg. The L or D group was injected with a DMSO solution containing 40 mg/kg or 60 mg/kg MNU at 12 mL/kg, respectively. Mice were monitored for changes in body weight, activity levels (walking, body stretching, fur condition), and mortality at various time points. Results:Pre-injection, all groups showed no statistical differences in weight or DMSO dose, while the MNU injection dose was significantly different (H>L>D). Within 2 hours post-injection, all mice except one in the D group exhibited reduced mobility, hunched posture, and lethargy. Mortality progressed rapidly, with one D and two L mice dying by 12 hours, followed by additional deaths (one D, two L, and two H mice) at 24 hours. By 36 hours, all mice in L and H groups had died, while one D mouse recovered normal activity. At the 48-hour endpoint, only one D mouse survived with normal behavior. No significant differences in weight, activity levels and mortality changes were observed in surviving mice throughout the study period. Conclusion:DMSO has certain toxicity, and when combined with alkylating agents such as MNU, it can lead to reduced activity and an increased mortality rate in mice. It is recommended to closely monitor the mice during the use of such reagents and to establish appropriate research observation protocols.

To elucidate the contributions of M-cone to the negative off-response of rat Electroretinogram (ERG) using specific drugs and spontaneous mutation rat models. The ON/OFF responses of ERG were evoked by long duration flash (200 ms) pre or post the application of 2-amino-4-phosphonobutyric acid (APB), cis-piperidine-2,3-dicarboxylic acid (PDA) or BaCl2 to the Sprague-Dawley (SD) rats. Furthermore, the ON/OFF responses of other two types of mutation rats, the middle-wavelength opsin cone dysfunction (MCD) rats and congenital stationary night blindness (CSNB) rats, were recorded. Typical scotopic and photopic ON/OFF responses were recorded in SD rats. At light offset, the OFF response showed a rapid negative deflection, then the retinal potential slowly returned to baseline from the trough of the negative off-response. The negative off-response was completely eliminated by the intravitreal injection of 400 µM APB. The amplitude of the negative off-response was reduced by the application of 5 mM PDA. However, the off component was not blocked by the application of 50 µM BaCl2. In addition, distinct differences of OFF response were found among MCD, CSNB and SD rats. The scotopic ON/OFF ERG of the MCD and CSNB rats showed no obvious negative off component at light offset, while the negative off component of photopic ON/OFF ERG was found in the CSNB rats, though with lower amplitude. The negative off-response of rat ERGs is not the off component of M-wave: a negative potential change at stimulus onset or offset. M-cone and the depolarizing bipolar cell play a central role in the signal transmission of this negative off-response.

This study aimed to explore the relationship between biochemical profiles and the risk of age-related macular degeneration (AMD) through a cross-sectional observational analysis. We examined data of U. S. population from the 2005-2008 National Health and Nutrition Examination Survey (NHANES) database. Student's t-test, multivariable logistic regression, Pearson's correlation, restricted cubic spline (RCS) model, and linear regression were applied to analyze the underlying relationship between biochemical profiles and the AMD risk, through comparing data between the non-AMD and AMD subgroups. Multivariable logistic regression, adjusted for age and demographic factors, showed no significant associations between the AMD risk and the levets of specific biochemical parameters (P > 0.05). Pearson's correlation revealed a positive linear relationship between age and total bilirubin, uric acid in the non-AMD subgroup (P < 0.05), but no such liner association was found in the AMD subgroup (P > 0.05). The RCS model confirmed no non-linear relationships presented between these variables in the AMD subgroup. In addition, without age adjustment, significant associations were found between total bilirubin, uric acid, and the AMD presence (P < 0.05). Biochemical profiles, after adjusting for age, did not significantly influence the AMD risk. However, total bilirubin and uric acid might potentially be related to the AMD presence. Our findings suggest a need for further research to clarify the role of these biomarkers in AMD development.

BACKGROUND:Metabolic dysregulation involving nicotinamide adenine dinucleotide (NAD) has been implicated in the pathogenesis of various diseases; however, its role in diabetic retinopathy (DR) remains poorly understood. This study aimed to identify NAD-associated biomarkers and elucidate their molecular mechanisms in DR. METHODS:DR-related data were retrieved from public databases. NAD-associated biomarkers were identified through differential expression analysis, NAD-related gene (NAD-RG) score comparison, Mendelian randomization (MR) analysis, and experimental validation. Functional enrichment and immune microenvironment analyses were conducted to explore the mechanisms underlying biomarker involvement in DR. Single-cell RNA sequencing (scRNA-seq) was employed to identify key cell types, and pseudo-temporal trajectory analysis was performed to assess dynamic biomarker expression during cellular differentiation. Reverse transcription quantitative PCR (RT-qPCR) was used to validate biomarker expression levels. RESULTS:CCDC88A and GPD2 were identified as DR potential biomarkers and risk factors for disease progression. These genes were co-enriched in key pathways, including oxidative phosphorylation. CCDC88A exhibited the strongest positive correlation with monocytes (cor = 0.35, p < 0.05). scRNA-seq analysis highlighted microglia as key cells in DR. During microglia differentiation, CCDC88A expression initially decreased before rising, while GPD2 expression increased initially, declined, and then slowly increased in later stages. RT-qPCR confirmed significantly elevated expression of CCDC88A and GPD2 in the DR group (P < 0.05). CONCLUSION:This study integrates bulk and single-cell transcriptomic analyses to identify CCDC88A and GPD2 as DR potential biomarkers and microglia as key cellular players, providing new insights into DR pathogenesis and potential diagnostic strategies.

PurposeThis study aims to investigate the effects and mechanism of action of metformin on retinal neovascularization and fibrosis in a mouse model of neovascular age-related macular degeneration (nAMD).MethodsVery low-density lipoprotein receptor knockout (Vldlr−/−) mice, a mouse model of nAMD, were used in this study. Vldlr−/− mice were administered metformin on postnatal day (P) 20 for 20 days (early stage of pathological change) or at 5.5 months of age for 45 days (late stage of pathological change). Retinal leakage was examined by fundus fluorescein angiography (FFA). Retinal neovascularization was assessed by lectin staining. Retinal fibrosis was assessed by Western blotting, immunofluorescence staining, and Masson’s trichrome staining.ResultsRetinal vascular leakage and neovascularization were significantly reduced in Vldlr−/− mice treated with metformin compared to those treated with the vehicle at P40. The protein levels of inflammatory factors and phospho(p)-STAT3 were decreased, and P38 and ERK signaling were suppressed in the retinas of metformin-treated Vldlr−/− mice relative to those in the control group at P40. Fibrotic markers were upregulated in the retinas of Vldlr−/− mice treated with metformin compared to those treated with the vehicle at 7 months. Levels of the inflammatory factors and p-STAT3 were increased, and PI3K/AKT, P38, and ERK signaling were upregulated in the retinas of metformin-treated Vldlr−/− mice compared to those in the control group at 7 months.ConclusionMetformin inhibits pathological retinal neovascularization but promotes fibrosis in experimental nAMD. These results provide evidence and highlight important considerations for the clinical use of metformin in different stages of nAMD.

Purpose This study aimed to investigate the effects of preservative-free latanoprost on meibomian gland function in mice and its possible mechanism. Methods Disproportionality analysis was conducted using the FAERS database to evaluate adverse reaction reports and epidemiological characteristics associated with preservative-free latanoprost. In mouse models, 0.005% preservative-free latanoprost or vehicle control was topically applied for periods ranging from 7 to 28 days. Morphological changes of the meibomian gland in mice were detected by immunohistochemistry. Immunofluorescence staining, western blotting, and/or quantitative real-time fluorescence quantitative PCR (qRT-PCR) were used to examine the expression levels of prostaglandin F2α receptor (FP), inflammatory cells and mediators, oxidative stress and signaling pathways related factors in mouse meibomian gland tissues. Results Reports of adverse reactions caused by preservative-free latanoprost increased annually in the FAERS database. Locally applied preservative-free latanoprost in mice led to an escalation of mucous secretion at the eyelid margin, accompanied by meibomian gland duct obstruction, lipid accumulation in glandular acini, an elevation in the expression levels of FP and Slco2a, and a reduction in the expression levels of PGDH within the meibomian glands. Other inflammatory markers such as CCL2, IL-1β, TNF-α, IL-6, and CXCL5 showed elevated expression levels. Notably, there was an increase in oxidative stress proteins, including NOX4, 3-NT, and 4-HNE, along with a decrease in the expression of antioxidant stress proteins, including SOD2 and Keap-1. Additionally, the Erk and NF-κB signaling pathways were significantly activated. Conclusion 0.005% preservative-free latanoprost induces meibomian gland dysfunction in mice by promoting inflammatory responses and oxidative stress.

The advent of targeted protein degradation technologies, particularly proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), is poised to revolutionize therapeutic strategies in ophthalmology. This review presents the first systematic analysis of these protein degradation platforms to address 'undruggable' targets in ocular pathologies. Harnessing distinct cellular machinery through the engagement of the ubiquitin-proteasome system and the lysosomal pathway with PROTACs and LYTACs, respectively, these heterobifunctional molecules enable the targeted elimination of disease-driving proteins implicated in ocular surface diseases, such as dry eye, and fundus diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. We review the mechanistic basis of these technologies, their translational potential in overcoming the limitations of conventional therapies, and ocular-specific challenges such as optimizing bioavailability and intraocular target selectivity. Central to this discussion is the role of advanced linker engineering in achieving spatio-temporal control of degradation activity. While barriers to ocular biodistribution and sustained delivery remain, targeted protein degradation represents a paradigm shift in ophthalmology, offering durable therapeutic effects that could significantly improve clinical outcomes and patient compliance through reduced dosing frequency.

Purpose To characterize a novel NR2E3 mutation pair (p.R311Q/p.R97H) in Enhanced S-cone syndrome (ESCS) and its clinical trajectory. Methods A 20-year-old male with progressive nyctalopia and recurrent macular edema underwent comprehensive evaluation including spectral-domain OCT, full-field ERG, pattern/flash VEP, and whole-exome sequencing with familial segregation analysis. Results Multimodal imaging revealed bilateral macular schisis with cystoid edema but absent pigmentary changes. Electrophysiology confirmed diagnostic hallmarks: extinguished rod responses, LA/DA waveform superimposition (S-cone dominance), and reduced 30Hz flicker amplitudes. Genetic analysis identified compound heterozygous variants affecting functional domains (p.R97H in DBD; p.R311Q in LBD), previously unreported in ESCS. Anti-VEGF therapy provided transient anatomical improvement without sustained benefit. Conclusion This report (1) expands the NR2E3 mutational spectrum with novel DBD/LBD variants, (2) demonstrates that vision loss correlates with secondary edema rather than primary photoreceptor degeneration.

The clinical evidence linking medications to retinal detachment (RD) remains limited. This study utilises real-world data from the U.S. FDA Adverse Event Reporting System (FAERS) to identify drugs associated with RD and characterise their classifications. A disproportionality analysis was performed on over 17 million FAERS reports. Drugs with statistically significant disproportionate RD reporting were identified and categorised by therapeutic class, signal strength, latency period, subgroup factors (e.g., off-label use, age, gender, subtypes, regions), and sensitivity analysis. Thirty drugs showed significant associations with RD, including ophthalmic agents, anticancer therapies, corticosteroids, and erectile dysfunction medications. Signal strength varied: pilocarpine, encorafenib, and ocriplasmin exhibited the highest signal strength, while prednisolone and bevacizumab showed lower strength. Latency periods differed significantly: erectile dysfunction drugs had the longest median latency (365 days), whereas anticancer drugs had the shortest (14 days). Subgroup analyses revealed elevated RD signal strength with off-label use and distinct susceptibility patterns: younger adults (<65) and males had higher signal strength for specific drug classes (e.g., ophthalmic agents), while older adults (>65) were more susceptible to RD with corticosteroids. Subtype analysis highlighted drug-specific associations with exudative, tractional, and rhegmatogenous RD. Sensitivity analysis restricted to healthcare professional reports further confirmed the robustness of the findings. This study provides a stratified list of medications with disproportionate reporting signals for RD. Further high-quality epidemiological and mechanistic studies are warranted to validate the potential causality associations between these medications and RD.

Background Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. Methods The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. Results Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). Conclusions This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

To investigate the sensitivity and potential application of steady-state flash visual evoked potentials (SSFVEP) in assessing the visual function of fundus diseases with vitreous hemorrhage. 18 patients diagnosed with monocular vitreous hemorrhages in the fundus were examined the flash visual evoked potentials (FVEP) and SSFVEP in both eyes. The difference in the P2-wave amplitude of FVEP and the average amplitude of SSFVEP waveform between the diseased eyes and those without vitreous hemorrhage were statistically compared. There was no significant difference in the waveform of FVEP between both eyes. The amplitude of P2-wave from FVEP of the diseased eye was slightly lower than that without vitreous hemorrhage. However, the difference was not statistically significant (P = 0.111). The waveform of SSFVEP in the eye without vitreous hemorrhage showed a towering shape, while that of the diseased eye was flat. The average amplitude of SSFVEP in the diseased eye was statistically lower than that without vitreous hemorrhage (P = 0.036). The difference ratio of SSFVEP amplitude between both eyes was significantly greater than that of FVEP amplitude (P = 0.028). In some fundus diseases with vitreous hemorrhage, SSFVEP had a higher sensitivity than FVEP, providing a novel potential application for visual function assessment.