Abstract
PURPOSE: To investigate whether iron overload is associated with increased risk of ocular hypertension (OHT), primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG). METHODS: A retrospective cohort study was conducted using the TriNetX multinational database. Patients ≥ 40 years old without prior glaucoma were classified into iron overload and non-iron overload groups. Propensity score matching (1:1) was applied to balance demographics, comorbidities, and medication use. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Kaplan-Meier analyses evaluated cumulative incidence over 5 years. RESULTS: Among 63,577 matched pairs, iron overload was significantly associated with elevated risks of OHT (HR = 1.32; 95% CI, 1.06-1.66) and POAG (HR = 1.65; 95% CI, 1.32-2.06). For NTG, the HR was also above 1 (1.31), but the wide confidence interval (95% CI, 0.74-2.33) likely reflects the small number of outcome events. Stratified and sensitivity analyses, including those with ferritin > 500 ng/mL, showed consistent associations across age, sex, and comorbidity subgroups. CONCLUSIONS: Iron overload is linked to a significantly increased risk of glaucoma and ocular hypertension. These findings highlight systemic iron dysregulation as a modifiable risk factor for glaucomatous disease. TRANSLATIONAL RELEVANCE: Our findings suggest that patients with iron overload may benefit from targeted ophthalmologic referral, particularly those with visual symptoms or additional risk factors. The association between iron dysregulation and glaucoma highlights opportunities for interdisciplinary care, risk stratification using ferritin, and mechanistic research into ferroptosis-driven neurodegeneration, with implications for iron-targeted neuroprotective strategies.