Association Between Chronic Oral Nitrate Use and the Risk of Ocular Hypertension and Open-Angle Glaucoma

Abstract

Purpose: To evaluate the association between the use of oral nitrates and the risk of developing ocular hypertension (OHT) and open-angle glaucoma (OAG) in patients with chronic ischemic heart disease (IHD). Design: Retrospective clinical cohort study. Subjects: Patients aged ≥40 with a diagnosis of chronic IHD identified in the TriNetX U.S. Collaborative Network from January 1, 2005, to January 1, 2023 Methods: This study utilized deidentified patient data from the TriNetX database. Patients aged ≥40 years with a diagnosis of chronic IHD were categorized into two cohorts: those prescribed oral nitrates (≥4 renewal prescriptions) (index event) and those without nitrate prescriptions. Exclusion criteria included a prior diagnosis of glaucoma or OHT or those who had nitrates for indications other than IHD. Propensity score matching (PSM) (1:1 nearest neighbor, caliper 0.1) was performed to balance demographic, clinical, and socioeconomic factors. We performed Cox proportional hazards model to calculate the adjusted hazards ratio (aHR) and 95% confidence intervals (CIs).The primary endpoints were the risks of developing OAG, primary open-angle glaucoma (POAG), OHT, and the initiation of first-line glaucoma treatments over 1-, 3-, and 5-year follow-up periods from the index event. Main Outcome Measures: OAG, POAG, OHT, and the initiation of first-line glaucoma treatments. Results: After PSM, each cohort included 30,937 patients. Nitrate use was associated with a significantly lower risk of OAG at 3 years (aHR, 0.82; 95% CI, 0.71-0.95) and 5 years (aHR, 0.68; 95% CI, 0.58-0.79). Similarly, the risk of POAG was reduced at 3 years (aHR, 0.78; 95% CI, 0.67-0.92) and 5 years (aHR, 0.67; 95% CI, 0.57-0.79). However, no significant association was observed between nitrate use and OHT at any time point. Patients in the nitrate group were also less likely to require first-line glaucoma therapy at 1 year (aHR, 0.72; 95% CI, 0.63-0.81), 3 years (aHR, 0.78; 95% CI, 0.71-0.85), and 5 years (aHR, 0.83; 95% CI, 0.75-0.91). Conclusions: The use of oral nitrates was associated with a reduced risk of OAG and POAG over long-term follow-up, while no effect was observed on OHT development.