Systemic α₂-agonist use and lower hazard of glaucoma compared with β-blockers: a cohort study

Systemic antihypertensive medications may influence glaucoma-related outcomes through intraocular pressure-dependent and vascular mechanisms. While topical α₂-agonists are established glaucoma therapies, the association between systemic α₂-agonists and glaucoma hazard remains unexamined; we compared their hazard with systemic β-blockers in adults with hypertension.

We conducted a multicentre retrospective cohort study using deidentified electronic health records. Adults aged ≥40 years with hypertension and chronic exposure to systemic α₂-agonists or β-blockers were included. Patients with pre-existing ocular hypertension (OHT), primary open-angle glaucoma (POAG), concomitant comparator use, or inadequate ophthalmic follow-up were excluded. We balanced cohorts using propensity score matching (PSM) and assessed the hazard of OHT and POAG at 1, 3, and 5 years. Cox models estimated adjusted HRs (aHRs) with 95% confidence intervals (CIs).

Patients treated with α₂-agonists (n=4186) were matched to those treated with β-blockers (n=360 399), resulting in 4152 patients per group after PSM. In Cox models (on the unmatched cohorts) adjusted for demographics, comorbidities, medications, laboratory and biometric measures, socioeconomic indicators and selected procedures, α₂-agonist exposure was associated with a lower hazard of OHT (aHR (95% CI) 0.582 (0.473 to 0.716), 0.559 (0.468 to 0.669) and 0.534 (0.450 to 0.634)) and POAG (aHR (95% CI) 0.359 (0.300 to 0.429), 0.333 (0.282 to 0.392) and 0.334 (0.286 to 0.390)) at 1-year, 3-year, and 5-year follow-up, respectively (all p<0.001).

Systemic α₂-agonist use was associated with a substantially lower hazard of glaucoma-related diagnoses compared with systemic β-blocker use. These findings are limited by the observational design, potential residual confounding, and reliance on diagnostic coding. These results warrant further investigation in prospective mechanistic studies and randomised clinical trials.