Lack of Association between LOXL1 Variants and Pigment Dispersion Syndrome/Pigmentary Glaucoma: A Meta-Analysis.

The phenotypic similarities between exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and pigment dispersion syndrome (PDS)/pigmentary glaucoma (PG), particularly their association with material deposition in the eye's anterior segment, have prompted investigations into genetic commonalities. This study focuses on the LOXL1 gene, conducting a comprehensive meta-analysis of three candidate gene association studies. We analyzed three single nucleotide polymorphisms (SNPs) of LOXL1: rs1048661, rs3825942, and rs2165241. Our results reveal nominal significance for the exonic SNPs rs1048661 and rs3825942 (p ≤ 0.01), but show no significant association for the intronic SNP rs2165241 (p = 0.83) with PDS/PG. There was homogeneity across study cohorts (I2 = 0), and sensitivity analyses and funnel plots confirmed a lower likelihood of bias in our findings. The lack of a statistically significant association between LOXL1 variants and PDS/PG at p < 0.05 was attributable to the insufficient statistical power of the pooled data, which ranged from 5% to 37% for the three SNPs. This study suggests no association between LOXL1 variants and PDS/PG. Further validation and exploration of XFS/XFG-associated genes in larger and more diverse cohorts would be helpful to determine the genetic correlation or distinctiveness between these conditions.

Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights.

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion and trabecular meshwork changes, resulting in increased intraocular pressure and potential glaucomatous optic neuropathy. This review summarizes recent progress in PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) and susceptibility loci identified from genome-wide association studies (GSAP and GRM5/TYR). Areas for future research are also identified, especially the development of efficient model systems. While substantial strides have been made in understanding the genetics of PDS/PG, our review identifies key gaps and outlines the future directions necessary for further advancing this important field of ocular genetics.

Dual-Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease.

Dry eye disease (DED) is a major ocular pathology worldwide, causing serious ocular discomfort and even visual impairment. The incidence of DED is gradually increasing with the high-frequency use of electronic products. Although inflammation is core cause of the DED vicious cycle, reactive oxygen species (ROS) play a pivotal role in the vicious cycle by regulating inflammation from upstream. Therefore, current therapies merely targeting inflammation show the failure of DED treatment. Here, a novel dual-atom nanozymes (DAN)-based eye drops are developed. The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer. The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS, inhibiting NLRP3 inflammasome activation, decreasing proinflammatory cytokines expression, and suppressing cell apoptosis. Consequently, the DAN effectively alleviate ocular inflammation, promote corneal epithelial repair, recover goblet cell density and tear secretion, thus breaking the DED vicious cycle. Our findings open an avenue to make the DAN as an intervention form to DED and ROS-mediated inflammatory diseases.

ASSOCIATION OF DIABETIC MACULAR EDEMA WITH QUALITY OF LIFE IN PATIENTS WITH TYPE 2 DIABETES: The Fushun Diabetic Retinopathy Cohort Study.

PURPOSE: To report the vision-related quality of life in patients with diabetic macular edema (DME) in a population-based study. METHODS: In this cross-sectional study, we analyzed 1,659 subjects with type 2 diabetes. Questionnaires were administered to assess the patient's vision-related quality of life. Diabetic macular edema severity was graded according to the established protocols. A subject's DME score ranged from 1 (no DME in either eye) to 7 (severe bilateral DME) using predefined criteria. RESULTS: Composite 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores for participants with DME were 88.9 (interquartile range [IQR]: 76.2-94.9) compared with 92.0 (IQR: 82.7-96.0) for those without DME ( P < 0.001). Locally weighted scatterplot smoothing plots depicted a consistent decline in composite NEI-VFQ-25 scores corresponding to the escalation of bilateral DME severity: starting from 88.59 for no DME in either eye, progressing through 86.65, 85.83, 85.31, 84.91, 83.85, and culminating at 82.71 for bilateral severe DME. Notably, the locally weighted scatterplot smoothing plots highlighted significant NEI-VFQ-25 composite score reduction at unilateral mild DME (slope m = -1.94). CONCLUSION: Significant changes in vision-related quality of life manifest in the early stage of DME. Therefore, early identification and intervention for these patients are crucial clinical objectives.

Undiagnosed diabetic retinopathy in Northeast China: prevalence and determinants.

Objective: To report the prevalence and contributing factors of undiagnosed diabetic retinopathy (DR) in a population from Northeastern China. Subjects/Methods: A total of 800 subjects from the Fushun Diabetic Retinopathy Cohort Study were enrolled. A questionnaire assessing incentives and barriers to diagnosis of DR was administered. Logistic regression was used to identify clinical and sociodemographic factors associated with undiagnosed DR. In a prespecified subgroup analysis, we divided patients into vision-threatening diabetic retinopathy (VTDR) and non-VTDR (NVTDR) subgroups. Results: Among 800 participants with DR, 712 (89.0%) were undiagnosed. Among 601 with NVTDR, 566 (94.2%) were undiagnosed. Among 199 with VTDR, 146 (73.4%) were undiagnosed. The risk factors affecting the timely diagnosis of NVTDR and VTDR exhibit significant disparities. In multivariate models, factors associated with undiagnosed VTDR were age over 60 years (OR = 2.966; 95% CI = 1.205-7.299; P = 0.018), duration of diabetes over 10 years (OR = 0.299; 95% CI = 0.118-0753; P = 0.010), visual impairment or blindness (OR = 0.310; 95% CI = 0.117-0.820; P = 0.018), receiving a reminder to schedule an eye examination (OR = 0.380; 95% CI = 0.163-0.883; P = 0.025), and the belief that "people with diabetes are unlikely to develop an eye disease" (OR = 4.691; 95% CI = 1.116-19.724; P = 0.035). However, none of the factors were associated with undiagnosed NVTDR (all P ≥ 0.145). Conclusion: Our research has uncovered a disconcerting trend of underdiagnosis in cases of DR within our population. Addressing determinants of undiagnosed DR may facilitate early detection.

Genome-Wide Associations and Confirmatory Meta-Analyses in Diabetic Retinopathy.

The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p < 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis.

The Association of the Prevalence of Depression in Type 2 Diabetes Mellitus with Visual-Related Quality of Life and Social Support.

AIM: To report the prevalence of depression and its association with vision-related quality of life and social support in a type 2 diabetes mellitus (T2DM) population. METHODS: Patients were recruited from a community-based study, Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), conducted between July 2012 and May 2013 in China. Depression was assessed using the Centre for Epidemiological Studies Depression Scale (CES-D). Vision-related quality of life was evaluated using the Visual Function Questionnaire-25 (VFQ-25). Social support was captured with the Social Support Rating Scale (SSRS). Generalized linear models were used to estimate the individual and joint association of VFQ-25 composite score (VFQCS) and SSRS score (SSRSS) with depression. RESULTS: A total of 1618 subjects (60.9% female) aged 61.69 ± 8.72 years in an urban district of Jiangjun Street, Fushun City, Liaoning province, Northeast China from July 2012 to May 2013 were recruited, of which, 23.36% (95% CI: 21.30-25.42%) were identified with depression. Every 14.1 increase in VFQ-25 composite score decreased the risk of depression by half (OR = 0.5; 95% CI: 0.4-0.6); with the elevation of 10.0 SSRS score the risk of depression decreased by 40% (OR = 0.6; 95% CI: 0.5-0.7). Patients with the VFQCS less than 91.3 and SSRSS less than 38.0 had 5.9 times more risk of depression (OR = 5.9; 95% CI: 3.6-9.7). Age (over 60 years) (OR = 0.6; 95% CI: 0.4-0.9) and medical history of cardiovascular disease (OR = 1.7; 95% CI: 1.1-2.5) were independently correlated with depression symptom. CONCLUSION: The prevalence of depression is high among patients with T2DM in urban district in northeast China. Vision-related quality of life and social support scores are significantly associated with depression. Measures should be taken to screen depressive symptoms in patients with type 2 diabetes patients. These patients need to be intervened with appropriate and effective treatment as early as possible. Meanwhile, behavioral health specialists should guide the patient to get and use social support sources effectively.

EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma.

Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Anti-fibrosis potential of pirarubicin via inducing apoptotic and autophagic cell death in rabbit conjunctiva.

This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 µmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 µmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 µmol/L MMC, both 7.5 µmol/L and 15 µmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 µmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 µmol/L prevented postoperative conjunctival fibrosis in an animal model.

Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis.

The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.

Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis.

As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to "hyperglycaemia" and "ROP". Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, P<0.0001). Comparing with the control, subjects in the ROP group had a significantly longer duration of hyperglycemia (Standardized mean difference [SMD] = 1.21, P< 0.0001), and higher mean glucose level. (SMD = 0.88, P = 0.0004) However, when combining the adjusted OR (after adjustment for birth weight, gestational age and other factors) provided from individual studies, only borderline significant association were observed on duration of hyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association.

[Advances in near work-induced transient myopia].

The possible mechanism of myopia remains controversial while gene and environment are two generally acknowledged factors underlie the development of human myopia. Near work which is a primary, environmentally based factor in the development and progression of permanent myopia (PM) may take effect via near work-induced transient myopia (NITM). In this review, the definition, measuring procedure and relative evaluation parameters of NITM as well as its characteristics, methods for reducing NITM and its possible mechanisms reported in the literature will be summarized.