Adult patients with hypertension who received systemic alpha-2 adrenergic receptor agonists may have had a lower likelihood of developing glaucoma-related diagnoses compared with those treated with systemic beta-blockers.
In a multicenter, retrospective cohort study, investigators used de-identified electronic health records from the TriNetX Analytics Platform, which includes data from more than 130 million patients across 67 US health care organizations, to evaluate new diagnoses over 1-, 3-, and 5-year follow-ups among patients aged 40 years or older with hypertension who had received at least four prescriptions for systemic alpha-2 agonists or beta-blockers. Patients with preexisting ocular hypertension or primary open-angle glaucoma, concomitant exposure to the comparator drug, or inadequate ophthalmic follow-up were excluded. After propensity score matching, the analysis included 4,152 patients in each treatment group.
The outcomes included incident ocular hypertension and primary open-angle glaucoma. The investigators performed adjusted Cox proportional hazards analyses using the full cohort to assess whether the findings remained consistent following adjustment for demographic, clinical, medication, laboratory, socioeconomic, and health care utilization factors.
Across the adjusted analyses, systemic alpha-2 agonist use was consistently associated with a lower odds of both ocular hypertension and primary open-angle glaucoma compared with beta-blocker use. In the propensity score–matched analysis, primary open-angle glaucoma developed in 2% of patients receiving alpha-2 agonists compared with 3% of those receiving beta-blockers at 3 years and in 2% vs. 4%, respectively, at 5 years. Ocular hypertension rates were similar during earlier follow-up but were lower among alpha-2 agonist users at 5 years (2% vs. 4%).
The findings were consistent across both the propensity score–matched and adjusted analyses, supporting an association between systemic alpha-2 agonist use and lower risks of glaucoma-related diagnoses. The investigators noted that the observations warranted further prospective and mechanistic study before changes in clinical practice are implemented.
The study had several important limitations. As an observational analysis of electronic health records, it could not establish causality, and residual confounding and confounding by indication remained possible despite extensive adjustment. The database did not include detailed ophthalmic measures such as intraocular pressure, optic nerve imaging, corneal thickness, or visual field testing. Drug adherence could not be confirmed. Diagnoses were based on diagnostic codes, and the findings may not be generalizable beyond this US health care population.
"The consistent reduction in hazard across multiple outcomes and time frames, coupled with biologically plausible mechanisms involving both [intraocular pressure] modulation and vascular-neuroprotective pathways, supports further exploration of this association," wrote lead study author Ibrahim Abboud, of the University of California, Riverside School of Medicine, and colleagues.
The study authors reported no conflicts of interest.
Source: BMJ Open Ophthalmology
