Wei Liu

The purpose of this study was to investigate the association between serum uric acid (UA) levels and primary open-angle glaucoma (POAG), and to explore potential genetic links and causal relationships using large population-based cohorts. We analyzed data from 7443 participants in the LifeLines cohort and 90,107 participants in the UK Biobank, all aged ≥55 years. Glaucoma status was determined based on questionnaires and International Classification of Diseases (ICD) codes. Logistic regression was used to assess the association between serum UA levels and glaucoma, adjusting for demographic, clinical, and lifestyle covariates. Meta-analysis was performed to combine results across cohorts. Genetic correlation, polygenic risk score (PRS), and two-sample Mendelian randomization (MR) analyses were conducted to evaluate shared genetic architecture and causality. Higher serum UA levels were significantly associated with increased odds of glaucoma in the UK Biobank (per 0.1 mM increase, odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.02-1.11, P = 0.007 in the fully adjusted model), with consistent findings in meta-analysis. No association was observed in the LifeLines cohort. Genetic analyses revealed no evidence of shared genetic correlation or causality between UA and glaucoma. The UA PRS was not associated with glaucoma odds, and the glaucoma PRS showed no association with serum UA levels. Elevated serum UA levels were phenotypically associated with glaucoma, but genetic analyses did not support a causal link. UA may reflect systemic oxidative stress rather than directly contribute to glaucoma pathogenesis. Further studies are needed to clarify underlying mechanisms and clinical relevance.

To examine the association between serum Klotho levels and the prevalence of glaucoma, cataract, and retinal disease, and to explore the potential causal relationship between Klotho and glaucoma. Data from the 2007-2008 National Health and Nutrition Examination Survey were used, including participants aged 40 years and older. Serum Klotho levels were analyzed both as a continuous variable and by quartiles. Logistic regression analysis was performed to assess the associations between serum Klotho levels and ocular disorders. Bidirectional two-sample Mendelian randomization (MR) was used to assess a causal relationship between serum Klotho and glaucoma. A total of 2952 participants were included in the glaucoma analysis. Higher serum Klotho levels were positively associated with glaucoma risk (odds ratio [OR] = 1.05 per 100 pg/mL increase; 95% confidence interval [CI], 1.01-1.09; P = 0.006). Individuals in the highest Klotho quartile had significantly greater glaucoma risk (OR = 1.47; 95% CI, 1.07-2.03; P = 0.02). MR analyses found no evidence of a causal relationship between Klotho and glaucoma in either direction. No significant associations were observed between serum Klotho and cataract (n = 2950) or retinal disease (n = 2637). Higher circulating Klotho levels are associated with an increased prevalence of glaucoma, suggesting a more complex relationship than the previously presumed protective role of Klotho in glaucoma. The lack of genetic evidence for causality suggests this systemic-level association is unlikely to be causal, highlighting the need to investigate whether circulating Klotho reflects distinct processes from those involving its local expression within ocular tissues. These findings highlight the potential of circulating Klotho as a systemic biomarker for glaucoma risk assessment, while emphasizing that its role in ocular pathophysiology requires separate investigation of local expression and function.

Chronic kidney disease (CKD) and glaucoma are major health burdens, yet their phenotypic and genotypic relationships remain poorly understood. This population-based study aims to explore the phenotypic and genotypic relationship between CKD and glaucoma. In this cross-sectional study, European-descended individuals aged 55 years + from the Lifelines Cohort (n = 21,475; 906 CKD cases) and UK Biobank (n = 90,133; 3323 CKD cases) were analyzed. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². In Lifelines, glaucoma was defined using a previously established algorithm, which integrated self-reported glaucoma diagnosis and treatment with NEI-VFQ-25 scores. In the UK Biobank, primary open angle glaucoma cases were identified using a combination of self-reported diagnoses, treatment history, and International Classification of Diseases (ICD) codes. Logistic regression assessed the phenotypic association of CKD and eGFR with glaucoma, adjusting for demographic and clinical factors. Genetic analysis included linkage disequilibrium score regression (LDSR), polygenic risk scores (PRS), and Mendelian randomization (MR). The prevalence of glaucoma was 8.2% in Lifelines and 5.5% in the UK Biobank. In Lifelines, no association between eGFR and glaucoma was found, but eGFR quintile 5 showed increased odds of glaucoma when excluding possible cases (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.07-2.23, P = 0.02). In the UK Biobank, per 10 mL/min/1.73 m² eGFR increase was associated with higher odds of glaucoma (OR = 1.04, 95% CI = 1.02-1.07, P = 0.001), and quintile 5 exhibited increased odds regardless of whether all cases were included (OR = 1.14, 95% CI = 1.03-1.25, P = 0.01) or possible cases were excluded (OR = 1.13, 95% CI = 1.02-1.25, P = 0.02). No significant associations were found between CKD and glaucoma. LDSR showed no genetic correlations, but PRS indicated a significant association between glaucoma PRS and higher eGFR. MR revealed no causal relationship between eGFR and glaucoma. No association was found between CKD and glaucoma, but higher eGFR was associated with increased odds of glaucoma. These findings challenge the assumed link between low eGFR and glaucoma and highlight the need for further research into the underlying mechanisms and potential clinical implications of this association.

Background: Glaucoma has an insidious onset with non-specific early symptoms, often leading patients to delay in seeking help. However, postponing the first ophthalmological consultation can result in delayed diagnosis and treatment, with adverse effects on vision. This study explored the factors associated with delayed first ophthalmological consultation in patients with primary glaucoma, with the overarching aim of informing measures to reduce delayed consultation and avoid the consequent adverse outcomes.Methods: We adopted a phenomenological approach. Semi-structured interviews were conducted with patients admitted to a tertiary eye hospital in Tianjin, China, from January 2021 to April 2021. Data were analyzed by Colaizzi’s seven-step method.Results: We identified 46 patients with primary glaucoma who delayed their first ophthalmological consultation for various reasons. There were four major themes and 16 sub-themes. The major themes were as follows: (1) occult symptoms that are difficult to identify; (2) insufficient knowledge and understanding of glaucoma-related risks and harm; (3) perceived difficulties in accessing medical care; and (4) inadequate support system.Conclusion: In order to avoid patient delay and consequent irreversible damage to the visual field in patients with primary glaucoma, it is essential that medical staff identify symptoms more effectively, change habitual medical behavior of the patients, adopt a medical union model, and promote the use of a social medical support system to address practical difficulties in delivering adequate care.