Association Between Vitamin D Deficiency and Systemic Outcomes in Patients with Glaucoma: A Real-World Cohort Study

Background: Glaucoma is an age-related optic neuropathy frequently accompanied by systemic comorbidities. Vitamin D deficiency (VDD) has been associated with cardiovascular and renal diseases in the general population, yet its relationship with long-term systemic outcomes in glaucoma remains unclear. This study evaluated the association between baseline vitamin D status and subsequent mortality and cardiorenal events in patients with primary glaucoma. Methods: We conducted a retrospective cohort study using deidentified electronic health records from the TriNetX U.S. Collaborative Network, a federated network of participating healthcare organizations. Adults (≥18 years) with incident primary glaucoma (2005-2020) and a serum 25-hydroxyvitamin D (25(OH)D) test within 12 months prior to diagnosis were categorized as VDD (<30 ng/mL) or vitamin D adequacy (VDA; ≥30 ng/mL). After 1:1 propensity score matching across 47 demographic, clinical, medication, and laboratory variables, 11,855 patients per group were followed for up to 5 years. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), and renal function decline (eGFR < 60 mL/min/1.73 m²). Analyses incorporated Kaplan-Meier curves, Cox models, landmark tests, sensitivity analyses, and competing risk methods. Results: Among the 35,100 eligible patients, the matched cohorts demonstrated higher 5-year risks associated with VDD for all-cause mortality (HR 1.104; 95% CI 1.001-1.217), MACE (HR 1.151; 95% CI 1.078-1.229), and AKI (HR 1.154; 95% CI 1.056-1.261), whereas the risks of renal function decline did not differ (HR 0.972; 95% CI 0.907-1.042). Risk divergence emerged within the first year of follow-up and persisted through the 5-year observation period. Conclusions: In patients with primary glaucoma, vitamin D deficiency was associated with higher long-term risks of mortality and cardiorenal complications, but not renal function decline. Taken together, the results are consistent with vitamin D status serving as a marker of broader systemic vulnerability in glaucoma and highlight the need for prospective studies to further clarify its prognostic significance.