Nicotinamide Supplementation and Primary Open-Angle Glaucoma in Patients With Ocular Hypertension

Importance Ocular hypertension (OHT) is a primary risk factor for primary open-angle glaucoma (POAG), and systemic nicotinamide has emerged as a potential metabolic prophylactic intervention to prevent conversion; however, real-world evidence is lacking. Objective To determine whether systemic nicotinamide supplementation, with potential neuroprotective properties, is associated with reduced risk of POAG diagnosis and delayed need for medical or surgical escalation in patients with OHT. Design, Setting, and Participants This cohort study evaluated deidentified electronic medical record data from a federated research network of 67 US health care organizations between March 2006 and March 2026. Nicotinamide supplementation was the sole exposure of interest and was specified a priori. Propensity score matching (1:1) was used to balance baseline covariates. Patients with a primary diagnosis of OHT and at least 1 prior health care encounter were included, excluding those with history of open-angle glaucoma, laser therapy, or glaucoma topical therapies. Exposures Documented systemic nicotinamide exposure, compared with a control group having no history of nicotinamide or niacin use. Main Outcomes and Measures The primary outcome was risk of POAG diagnosis. Secondary outcomes included initiation of first-line topical glaucoma therapy and requirement for laser trabeculoplasty. Hazard ratios (HRs) and 95% CIs were estimated using time-to-event analyses. Results The propensity score-matched sample included 2920 patients (1460 in each cohort; nicotinamide group: mean [SD] age, 54.4 [19.6] years, 846 [57.9%] female; control group: mean [SD] age, 54.9 [18.8] years, 869 [59.5%] female). Over a mean (SD) follow-up of 3.7 (1.7) years, POAG diagnosis occurred in 51 patients in the nicotinamide group (3.5%) compared with 132 patients in the control group (9.0%) (HR, 0.34; 95% CI, 0.25-0.47; P  < .001), representing an absolute risk reduction of 5.5% in the nicotinamide cohort (95% CI, 3.8-7.3). Topical intraocular pressure–lowering therapy was initiated in 198 patients in the nicotinamide group (13.6%) compared with 309 patients in the control group (21.2%) (HR, 0.57; 95% CI, 0.48-0.68; P  < .001). Laser trabeculoplasty was performed in 12 patients in the nicotinamide group (0.8%) vs 28 patients (1.9%) in the control group (HR, 0.38; 95% CI, 0.19-0.74; P  = .003). Conclusions and Relevance In this cohort study, systemic nicotinamide exposure was associated with a reduced risk of disease development in patients with OHT. By potentially delaying POAG diagnosis and decreasing the rate of subsequent prescribed interventions, nicotinamide represents a potential adjunctive strategy complementary to standard therapy, warranting further prospective investigation.