Benign Prostatic Hyperplasia Pharmacotherapy and Incident Ocular Surface Disease: Comparative Risk of Alpha-Blockers Versus 5-Alpha Reductase Inhibitors.

OBJECTIVE: To compare the risk of incident ocular surface disease (OSD) among men treated with alpha-blockers versus 5-alpha reductase inhibitors (5-ARIs) for benign prostatic hyperplasia (BPH). METHODS: A retrospective cohort study using data from a de-identified electronic health record database was performed. Adult men diagnosed with BPH taking either an alpha-blocker or a 5-ARI were included, along with untreated BPH controls. OSD was defined using ICD-10-based concept sets for dry eye and related tear-film disorders. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards regression adjusting for age, diabetes, autoimmune disease, hypertension, hyperlipidemia, and PDE5i use. RESULTS: Among 2,538 treated men (2,303 alpha-blocker; 235 5-ARI), 235 OSD events occurred. Compared with alpha-blockers, 5-ARI use was associated with lower OSD risk in unadjusted (HR 0.47; 95% CI 0.27-0.82; p=0.008) and adjusted analyses (HR 0.37; 95% CI 0.19-0.65; p=0.001). Kaplan-Meier analysis demonstrated greater OSD-free survival among 5-ARI users (p=0.008). In a three-group model including untreated patients, alpha-blocker use was associated with increased OSD risk versus no treatment (HR 3.77; 95% CI 2.34-6.06), while 5-ARI use was not (HR 1.31; 95% CI 0.67-2.82). CONCLUSIONS: Alpha-blockers were associated with increased OSD risk relative to untreated patients. Compared with alpha-blockers, 5-ARI use was associated with lower OSD risk and was not significantly different from untreated controls. These findings may inform therapeutic decision-making, particularly in men at risk for OSD.