Risk Of Glaucoma Research Articles

Association of lipid profile with primary open angle glaucoma in non-obese patients

Hyperlipidemia has been shown to be associated with Glaucoma as well as increased intra ocular pressure (IOP). We conducted a case control study to further study the association of Lipid profile with Primary Open Angle Glaucoma (POAG) in non-obese patients.: With the approval from Institutional Ethics Committee (ICE) and written informed consent, 100 adult patients were included in the case control study. The methods applied in the study adhered to the tenets of the declaration of Helsinki. 50 non-obese POAG patients of above 40 years aged were included as cases and another 50 without Glaucoma were taken as controls. Patients were further subjected to biochemical investigation of the serum lipid profile performed by Vitros 5600.: Mean total cholesterol, triglyceride and low-density lipoprotein (LDL) levels were found to be significantly higher in non-obese POAG cases as compared to that in controls (p<0.05), whereas mean high density lipoprotein (HDL) levels were significantly lower in non-obese POAG cases as compared to that in controls (p<0.001). The odds of high cholesterol levels to be associated with POAG in non-obese are statistically significant (p<0.001).: The study demonstrated a relationship of serum lipid levels with risk of primary open angle glaucoma.

Risk Factors for Glaucoma and Ocular Hypertension and Post-Transplant Complications in Keratoconus: A Multivariable Analysis.

Background: The purpose of this study was to investigate the risk factors for glaucoma in patients with keratoconus following keratoplasty and to identify potential factors that could affect post-transplant complications. Methods: A retrospective analysis was conducted on the medical records of 192 keratoconus patients who underwent keratoplasty. Data on treatment history, perioperative information, tissue bank data, postoperative regimens, complications, and infections were collected and analyzed. Statistical analysis was performed to identify risk factors associated with glaucoma and transplant complications. Results: There was a 41.6% incidence of glaucoma (high IOP) (p < 0.001), with the median time to glaucoma development being 314 ± 67 days post-transplant. A significant number of patients required surgical intervention, accounting for 48.05%. Our analysis revealed a 14% graft failure rate. On univariable Cox proportional hazard analysis, the following factors demonstrated statistically significant associations with the risk of glaucoma after transplantation: donor endothelial cell density, the use of a single continuous suture type, and the surgeon (performing the surgery). For many variables, the only factor that remained significant was the surgeon. Among the factors analyzed for risks of failure post-transplantation, significant associations were observed for the donor age, the time from harvest to transplant, and the surgeon. In the multivariable analysis, donor age emerged as a significant predictor of post-transplant complications. Conclusions: Risk factors such as donor endothelial cell density, suture type, surgeon, host and donor size, and host gender were found to increase the risk of developing glaucoma post-keratoplasty. Surgeon type was identified as a significant risk factor, while donor age was predictive of post-transplant complications.

Relationship Between Glaucoma and Chronic Stress Quantified by Allostatic Load Score in the All of Us Research Program

PurposeTo assess the relationship between glaucoma and allostatic load (AL), an established framework for quantifying the physiologic effects of chronic stress through measurements of systemic biomarkers. DesignRetrospective case-control study. MethodsParticipants of the National Institutes of Health All of Us (AoU) Research Program with complete AL biomarker data between December 1984 to June 2022 and with (cases) or without (controls) primary glaucoma were identified. AL scores were calculated using the adapted Seeman AL scale consisting of 10 systemic biomarkers: body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, glomerular filtration rate, albumin, C-reactive protein, and homocysteine. AL score was defined as the number of biomarkers with measurements in the highest risk quartiles. Age was calculated as the median age at time of biomarker measurements. Logistic regression analysis was performed to assess the association between the earliest possible AL score and glaucoma adjusted for race/ethnicity. Mediation analysis was performed to estimate the relationship between race/ethnicity and glaucoma mediated by AL score. ResultsThe study cohort consisted of 349 (16.1%) cases and 1,819 (83.9%) controls with 52.7% females, 2.2% Asians, 10.7% Blacks, 10.0% Hispanics, and 72.5% non-Hispanic Whites. At the earliest timepoint (median [IQR] = 6.4 [1.9-12.2] years prior to diagnosis), cases had higher AL score than controls (3 [1-4] versus 2 [1-3], respectively; p<0.001). On multivariable analysis, higher AL score (OR=1.09 per point), Black race (OR=2.58), and Hispanic ethnicity (OR=2.12) conferred higher risk of glaucoma (p≤0.02). AL score partially mediated higher glaucoma risk among Blacks (7.5%) and Hispanics (5.0%) compared to non-Hispanic Whites. On subgroup analysis, higher AL score was significantly associated with primary open angle glaucoma (POAG; OR=1.11; p=0.01) but not primary angle closure glaucoma (PACG; p=0.87). ConclusionAoU participants with glaucoma had greater AL 6.4 years prior to diagnosis, and AL score partially mediated racial/ethnic differences in glaucoma risk. These findings suggest chronic stress may increase risk for glaucoma and contribute to racial disparities in glaucoma burden.

Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus

AbstractGlaucoma is the primary factor underlying irreversible blindness. Recent studies suggest that the risk of glaucoma significantly increases in patients with systemic lupus erythematosus (SLE); however, the mechanism underlying this association remains unclear. Therefore, this study aimed to identify novel common biomarkers and potential therapeutic drugs for SLE and glaucoma. GSE27276, GSE50772, and GSE148371 datasets were sourced from the gene expression omnibus (GEO) database. An integrated analysis of the datasets for both diseases identified biomarkers and thoroughly examined their biological roles and molecular mechanisms using differential expression analysis (DEA), weighted gene co‐expression network analysis (WGCNA), gene enrichment analysis, machine learning, microRNA (miRNA) and transcription factor analyses, immune infiltration analyses, and single‐cell transcriptome analysis. Concurrently, molecular docking was used to forecast potential drugs targeting these biomarkers. Finally, reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR) was performed in human trabecular meshwork stem cells to validate the five identified biomarkers. The 10 key genes identified through DEA and WGCNA were predominantly involved in immune, inflammatory, and autophagy pathways. Additionally, machine learning identified five biomarkers, and we established associated transcription factors and miRNA regulatory networks. Immune infiltration analysis indicated an elevated presence of immune cells, including macrophages, T cells, and B cells, in both conditions. Furthermore, the DSigDB database yielded 10 potential therapeutic agents, three of which showed strong binding potential to the biomarkers via molecular docking. The RT‐qPCR results confirmed the trend in gene expression. This study uncovered a new link between SLE and primary open‐angle glaucoma, identifying biomarkers and mechanisms of immunopathogenesis for future research and treatment strategies.

Association of daily selenium intake and glaucoma: A cross-sectional study.

The association between dietary selenium intake and glaucoma remains unclear. Using data from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES), this study aimed to investigate the relationship between glaucoma and dietary selenium intake. The study included subjects aged 40 years or older who participated in the NHANES dietary intake interview and vision health questionnaire. Diagnosis of glaucoma based on self-reporting or fundus imaging. To investigate the relationship between daily selenium consumption and glaucoma, logistic regression analyses were employed. The potential linear relationship was found using smooth curve fitting. Subgroup analyses were also used. We found higher dietary selenium intake was associated with an increased risk of glaucoma (odds ratio, 1.39; 95% confidence intervals,1.07-1.81) on multivariable analysis. A linear association was found between dietary selenium intake and the occurrence of glaucoma in this population (Pnon-linearity = 0.951). Subgroup analyses showed a stable correlation between dietary selenium intake and the occurrence of glaucoma (all P for interaction > .05).This is the first study to look at the connection between dietary selenium intake and glaucoma based on the data from the 2005 to 2008 NHANES. Our findings suggested that dietary selenium intake maybe positively correlated with the risk of glaucoma in adults older than 40 years old. To find out the potential relationship between dietary selenium intake and glaucoma, More longitudinal studies are required.

BEST1 associated bestrophinopathies with angle closure and post-surgical malignant glaucoma

ABSTRACT Introduction Mutations in BEST1 gene have been linked to the development of refractory angle closure glaucoma (ACG). This study aims to delineate the clinical characteristics, genetic mutations, and disease progression in patients with autosomal recessive bestrophinopathy (ARB) and autosomal dominant Best vitelliform macular dystrophy (BVMD) who are presented with treatment-resistant ACG. Methods This retrospective analysis encompasses a comprehensive ophthalmic assessment, retinal imaging, and mutational profiling of six patients diagnosed with bestrophinopathy and concurrent ACG, with a particular emphasis on the risk of post-glaucoma filtration surgery malignant glaucoma (MG). Exome sequencing was conducted utilizing a next-generation sequencing (NGS) based gene panel. Results The cohort included five patients with ARB and one with BVMD, with a mean (±SD) age at ACG diagnosis of 35.1 ± 6.9 years. NGS analysis revealed homozygous BEST1 variants in four patients (ARB; cases 1–4) and a heterozygous BEST1 variant in one patient (BVMD; case 5). One patient (ARB; case 6), despite a recessive pedigree, showed a single heterozygous variant, suggesting the presence of an undetected heterozygous variant indicative of compound heterozygous autosomal recessive inheritance. A novel non-frameshift deletion (c.841_843delTTC; p.Phe281del) was identified in case 2. Surgical intervention was required due to uncontrolled glaucoma in all cases except case 4. All five cases that underwent glaucoma filtration surgery developed MG, which was effectively managed with combined iridozonulo-hyaloido-vitrectomy (IZHV) and pars plana vitrectomy (PPV). Cases 5 and 6, harboring a heterozygous pathogenic variant (c.241 G>A; p.Val81Met), experienced refractory MG and corneal decompensation necessitating multiple interventions. Conclusion Genomic analysis plays a pivotal role in the management of bestrophinopathies with ACG. Characterization of mutational types facilitates prognostication and enables timely interventions. IZHV with PPV emerges as a promising standalone or adjunctive procedure for the management of glaucoma among patients with BEST1 mutations and ACG.

Influence of dexamethasone-induced matrices on the TM transcriptome

Pathologic bidirectional interactions between the extracellular matrix (ECM) and cells within the human trabecular meshwork (hTM) contribute to ocular hypertension. An in vitro model is needed to study these cell-matrix interactions and their effect on outflow homeostasis. This study aimed to determine whether pathogenic ECM derived from dexamethasone (DEX)-treated hTM cultures induces clinically relevant glaucoma-like changes in healthy hTM cells at the transcriptional level. Corneoscleral rims from non-glaucoma donors were used to isolate primary hTM cells after validation according to the consensus recommendations for TM culture. Normal hTM cells (n = 5) were plated on a coverslip and treated with 100 nM DEX or ethanol for four weeks. These cultures were then decellularized, plated with primary hTM cells, and allowed to grow for another 72 h. RNA was extracted from these hTM cells for stranded total RNA-Seq. Sequencing libraries prepared using the Zymo-Seq RiboFree Total RNA library kit were pooled and sequenced using Illumina NovaSeq 6000. After quality control, sequence reads were aligned to the human genome build hg19. Differential expression (DE) analyses were performed using paired multi-factorial ANOVA. The expression of several DE genes associated with glaucoma (ANGPTL2, PDE7B, C22orf23, COL4A1, ADAM12, IFT122, SEMA6C) was validated using EvaGreen-based Droplet Digital PCR (ddPCR) assays. Gene ontology analyses of the DE genes were performed using the PANTHER and NDEx IQA databases, and functional analyses were performed with the DAVID Bioinformatics software. Using a cutoff of p-value <0.05 and fold change ≥2.0, our differential analysis identified 267 up- and 135 down-regulated genes in DEX-induced ECM-treated cells compared to the control. These differentially expressed genes were found to play a significant role in pathways such as cytokine and oxidative stress-induced inflammation, integrin signaling, matrix remodeling, and angiogenesis. These findings were further supported by previously performed proteomics studies using the same model. Using ddPCR, we validated the expression of seven genes associated with the risk of primary open-angle glaucoma. These results not only provide support for the pathogenic ECM model of steroid-induced glaucoma, but also demonstrate that the pathologic changes induced by this model are indeed found at the transcriptional level. These findings further demonstrate that matrix changes significantly influence cell expression profiles, which enable further understanding of the molecular mechanisms underlying glaucomatous changes in the TM. However, future studies with a larger and more diverse set of samples and longer time points are needed to confirm the utility of this model for mechanistic studies.

Impact of Environmental Factors on Glaucoma Progression: A Systematic Review.

Glaucoma, a leading cause of irreversible vision loss, is characterized by progressive degeneration of retinal ganglion cells. Intraocular pressure (IOP) remains a well-established risk factor, but recent research suggests environmental and lifestyle factors may also play a role. This review aimed to evaluate the current evidence on the impact of environmental factors on glaucoma progression. We conducted a systematic review following PRISMA guidelines, searching various databases for studies on environmental factors and glaucoma progression. Our review identified several key findings. IOP remains the most crucial modifiable risk factor. Aerobic exercise and mindfulness practices may lower IOP and provide neuroprotection. Lifestyle modifications like smoking cessation and balanced diets were also emphasized. Studies suggest air pollution exposure, particularly PM2.5, may be associated with an increased risk of glaucoma. However, the studies were primarily observational, and more research is needed to establish causality and elucidate underlying mechanisms. This review highlights the multifaceted nature of glaucoma, emphasizing the interplay between established risk factors (IOP) and emerging environmental influences (air pollution). Environmental factors hold promise as potential targets for glaucoma prevention and management strategies. Future research should focus on well-designed studies to investigate causal relationships and biological mechanisms.

51169 The Risk of Glaucoma in Patients with Psoriasis: A population-based retrospective cohort study

51169 The Risk of Glaucoma in Patients with Psoriasis: A population-based retrospective cohort study

Associations of different types of statins with the risk of open-angle glaucoma: a systematic review and network meta-analysis.

Previous studies implied that different types of statins may pose divergent impacts on the risk of glaucoma onset. This study aimed to comprehensively evaluate the effects of various statins on the risk of glaucoma occurrence. PubMed, Cochrane CENTRAL, Embase, and Web of Science were searched from February 1994 to February 2024. We included studies that investigated the effects of various types of statins, fibrates, ezetimibe, cholestyramine, niacin, PCSK9 inhibitors, omega-3 fatty acids, and any cholesterol-lowering medications on glaucoma onset or progression. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) and the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-1) tool were used to assess the quality of randomized controlled trials (RCTs)and non-RCTs, respectively. The frequentist network meta-analysis framework was utilized to evaluate the comparative effectiveness, with the random effects model applied. This network meta-analysis comprised 12 studies, encompassing 262,217 individuals and including cholesterol-lowering medications such as statins, fibrates, ezetimibe, cholestyramine, niacin, and omega-3 fatty acids. Our findings demonstrate that comparing to the placebo, rosuvastatin (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.03 to 1.46), simvastatin (RR, 1.21; 95% CI, 1.02 to 1.43), and pravastatin (RR, 1.20; 95% CI, 1.01 to 1.43) increased the risk of glaucoma onset with statistical significance. Rosuvastatin, simvastatin, and pravastatin were each associated with a significantly increased risk of glaucoma onset. We advise medical practitioners to exercise caution when prescribing these specific statins for patients who are at risk of developing glaucoma. What is known Previous studies have suggested a link between statins and the risk of developing glaucoma. However, there is still ongoing debate regarding the specific effects of each type of statin on the onset of glaucoma. What is new This network meta-analysis comprehensively evaluated the effects of various statins on the risk of glaucoma onset. Rosuvastatin, simvastatin, and pravastatin were associated with a significantly increased risk of glaucoma onset.

Comparative Effects of GLP-1 Receptor Agonists and Metformin on Glaucoma Risk in Type 2 Diabetes Patients

PurposeTo compare effects of glucagon-like peptide-1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension, and the need for first-line glaucoma treatments in patients with type 2 diabetes. DesignA retrospective cohort study was conducted using electronic medical records (EMR) data from the from an international electronic health record network, covering a period from May 2006 to May 2024. ParticipantsPatients diagnosed with type 2 diabetes mellitus (T2DM) who were treated with either GLP-1 receptor agonists or metformin. MethodsData from 120 healthcare organizations across 17 countries were analyzed. Patient outcomes were assessed at 1, 2, and 3 years. Propensity score matching (PSM) was used to balance covariates such as demographics, comorbidities, and medication usage. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. Main Outcome MeasuresIncidence of POAG, ocular hypertension, and the need for first-line treatments including beta-blockers, prostaglandin analogues, brimonidine, brinzolamide, dorzolamide, netarsudil, and laser trabeculoplasty. ResultsAfter PSM, both groups included 61,998 patients at the 1-year follow-up, 27,414 at the 2-year follow-up, and 14,100 at the 3-year follow-up. Patients treated with GLP-1 receptor agonists had a significantly decreased risk of developing POAG compared to those on metformin at 1 year (RR 0.59, 95% CI 0.39-0.88), 2 years (RR 0.50, 95% CI 0.32-0.78), and 3 years (RR 0.59, 95% CI 0.37-0.94). Similar protective effects were observed for ocular hypertension with risk reductions of 56% at 1 year (RR 0.44, 95% CI 0.31-0.62), 57% at 2 years (RR 0.43, 95% CI 0.30-0.62), and 49% at 3 years (RR 0.51, 95% CI 0.34-0.75). The risk of first-line therapy initiation was also lower in the GLP-1 receptor agonists group at 1 year (RR 0.63, 95% CI 0.53-0.74), 2 years (RR 0.71, 95% CI 0.59-0.85), and 3 years (RR 0.75, 95% CI 0.62-0.91). ConclusionsGLP-1 receptor agonists are associated with a significantly lower incidence of POAG, ocular hypertension, and the need for first-line glaucoma treatments compared to metformin in patients with type 2 diabetes. These findings highlight the potential ocular benefits of GLP-1 receptor agonists and their expanding role in the clinical management of diabetic patients.

EFFECT OF CAFFEINE CONSUMPTION ON INTRAOCULAR PRESSURE AND RISK OF GLAUCOMA: A SYSTEMATIC REVIEW

INTRODUCTION AND OBJECTIVES Glaucoma is one of the leading causes of blindness worldwide with intraocular pressure (IOP) as its main risk factor. Several studies have investigated the association between IOP and caffeine consumption with mixed results. This study aims to review whether caffeine consumption increases IOP thus, increases the risk of glaucoma. METHODS A comprehensive literature search was performed in 4 databases, including Pubmed, Proquest, ScienceDirect, and Cochrane. Last search was conducted on March 20, 2023. We include human studies investigating caffeine impact on IOP and/or glaucoma risk published in English with full text available from 2013 to 2023. The risk of bias was assessed with RoB 2.0 for crossover studies, NIH for cross-sectional and case-control studies. We present our results according to PRISMA guidelines. RESULT A total of 130.012 participants from 7 different studies were included in this review. Three crossover, 3 cross-sectional, and 1 case-control study were evaluated. This study involved a multi-racial population although Caucasian predominated. Five out of 7 studies exhibited a significant association (all p values &lt;0.05) between caffeine consumption and increased risk of developing glaucoma. CONCLUSION Caffeine consumption generally shows a significant impact on developing risk of glaucoma and has been shown to increase IOP in acute settings, reported up to 90 minutes after consumption/ingestion. Limitations of this study include a small number of crossover participants and a high variability of participants (young healthy individuals and glaucoma patients). Further research is advised to investigate the association between caffeine consumption in a longer follow-up time and a more specific population.

Improvement in signs and symptoms of severe dry eye disease after dual therapy with high-potency steroids and 0.05% cyclosporine

Objective To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). Materials and methods This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. Results In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). Conclusions Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.

Evaluating the risk of new-onset glaucoma in chronic kidney disease patients: a nationwide cohort study

BackgroundA better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019.MethodThis retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan–Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported.ResultsSeven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26–1.32], p < 0.001). Kaplan–Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13–1.21] for females vs. aHR 1.39 [CI:1.35–1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37–1.62]; 50–59: aHR 1.48 [CI: 1.40–1.56]; 60–69: aHR 1.30 [CI: 1.25–1.6]; 70–79: aHR 1.21 [CI: 1.17–1.26]; > 80: aHR 1.29 [CI: 1.21–1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001).ConclusionsOur cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients.Trial registrationDue to the retrospective nature of the study, no registration was necessary.

Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes

BackgroundAge-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes.MethodsInstrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates.ResultsThe results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E−04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (β = −0.190 year, 95% CI −0.374 to −0.008, P = 0.041). The EEA of HannumAge (β = −0.85 μm, 95% CI −1.57 to −0.14, P = 0.019) and HorvathAge (β = −0.63 μm, 95% CI −1.18 to −0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (β = 0.06 μm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05).ConclusionThe present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.

Development of a novel scoring system for glaucoma risk based on demographic and laboratory factors using ChatGPT-4.

We developed a scoring system for assessing glaucoma risk using demographic and laboratory factors by employing a no-code approach(automated coding) using ChatGPT-4. Comprehensive health checkup data were collected from the Korea National Health and Nutrition Examination Survey. Using ChatGPT-4, logistic regression was conducted to predict glaucoma without coding or manual numerical processes, and the scoring system was developed based on the odds ratios (ORs). ChatGPT-4 also facilitated the no-code creation of an easy-to-use risk calculator for glaucoma. The ORs for the high-risk groups were calculated to measure performance. ChatGPT-4 automatically developed a scoring system based on demographic and laboratory factors, and successfully implemented a risk calculator tool. The predictive ability of the scoring system was comparable to that of traditional machine learning approaches. For high-risk groups with 1-2, 3-4, and 5 + points, the calculated ORs for glaucoma were 1.87, 2.72, and 15.36 in the validation set, respectively, compared with the group with 0 or fewer points. This study presented a novel no-code approach for developing a glaucoma risk assessment tool using ChatGPT-4, highlighting its potential for democratizing advanced predictive analytics, making them readily available for clinical use in glaucoma detection.

Comparing glaucoma risk in children receiving low-dose and high-dose glucocorticoid treatment after cataract surgery.

Treatment with glucocorticoids following paediatric cataract surgery is crucial to prevent inflammation, but may lead to secondary glaucoma, and hypothalamic-pituitary-adrenal axis suppression. We wish to compare glaucoma outcomes following high-dose and low-dose glucocorticoid treatment after paediatric cataract surgery. This cohort study included Danish children undergoing cataract surgery before 10 years of age, receiving either a low-dose or high-dose postoperative glucocorticoid treatment. Case identification and collection of a standardized dataset were retrospective, from 1 January 2010 to 31 December 2016, and prospective thereafter, until 31 December 2021. High-dose treatment included 0.5-1.0 mg subconjunctival depot dexamethasone or methylprednisolone, followed by 6-8 drops of dexamethasone for 1 week, tapered by one drop weekly. Low-dose treatment included 6 drops for 3 days, followed by 3 drops for 18 days. Sustained (>3 months) ocular hypertension or glaucoma was compared between the two groups. Overall, 267 children (388 eyes) were included in the study. Ninety-five children (133 eyes) had received high-dose treatment and had a median follow-up time of 89 months (IQR: 57.2-107.4), while 173 children (255 eyes) had received the low-dose treatment and had a median follow-up time of 40.5 months (IQR: 22.9-60.4). Survival curves showed a lower risk of glaucoma in the low-dose group for children with axial lengths ≥18 mm. Low-dose glucocorticoid treatment was associated with a lower risk of glaucoma in children with axial lengths ≥18 mm. The same effect was not observed in children with shorter eyes. High-dose glucocorticoid should be limited in children undergoing cataract surgery.

Central corneal thickness and the risk of primary open-angle glaucoma: a Mendelian randomisation mediation analysis

BackgroundThe association of central corneal thickness (CCT) with primary open-angle glaucoma (POAG) remains uncertain. Although several observational studies assessing this relationship have reported an inverse association between CCT and POAG,...

Loneliness and social isolation are associated with an increased risk of glaucoma: a UK Biobank cohort study

BackgroundLoneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma.MethodsA total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs.ResultsDuring a median follow-up of 13.1 (interquartile range: 12.3–13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04–1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01–1.16; P = 0.033) were associated with an increased risk of glaucoma.ConclusionsIn this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.

Integrating Genetics in Glaucoma Screening.

As additional glaucoma genes are identified and classified, polygenic risk scores will be refined, facilitating early diagnosis and treatment. Ensuring genetic research is equitable to prevent glaucoma blindness worldwide is crucial. To review the progress in glaucoma genetics over the past 25 years, including the identification of genes with varying contributions to the disease and the development of polygenic risk scores. Over the last 2 and a half decades, glaucoma genetics has evolved from identifying genes with Mendelian inheritance patterns, such as myocilin and CYP1B1, to the discovery of hundreds of genes associated with the disease. Polygenic risk scores have been developed, primarily based on research in Northern European populations, and efforts to refine these scores are ongoing. However, there is a question regarding their applicability to other ethnic groups, especially those at higher risk of primary open angle glaucoma, like individuals of African ancestry. Glaucoma is highly heritable and family history can be used for cascade clinical screening programs, but these will not be feasible in all populations. Thus, cascade genetic testing using well-established genes such as myocilin may help improve glaucoma diagnosis. In addition, ongoing investigations seek to identify pathogenic genetic variants within genes like myocilin. The expanding availability of genetic testing for various diseases and early access to genetic risk information necessitates further research to determine when and how to act on specific genetic results. Polygenic risk scores involving multiple genes with subtle effects will require continuous refinement to improve clinical utility. This is crucial for effectively interpreting an individual's risk of developing glaucoma and preventing blindness.