A systematic review and meta‑analysis of systemic antihypertensive medications with intra‑ocular pressure and glaucoma

Author: Leung G., Grant A., Garas A.N., Li G., Freeman E.

Geographical coverage: Germany (Gutenberg), the Netherlands (Rotterdam), the United Kingdom, Singapore and the United States

Sector: Primary open-angle glaucoma

Sub‑sector: Treatment

Equity focus: Not explicitly stated

Study population: Adults with and without glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta‑analysis

Qualitative synthesis method: Not applicable

Background

Primary open‑angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. First‑line treatment involves topical ocular hypotensive medication to reduce intra‑ocular pressure (IOP) – the only modifiable risk factor. Many adults also take systemic antihypertensive medicines for high blood pressure, which can influence IOP. Evidence is mixed: low systemic blood pressure may compromise optic nerve perfusion and raise glaucoma risk, but some systemic antihypertensive classes might mask raised IOP or modify glaucoma risk. Reported effects differ across medicine classes such as β‑adrenoceptor (β) blockers (BBs), calcium‑channel blockers (CCBs), angiotensin‑converting‑enzyme inhibitors (ACE inhibitors, ACEi), angiotensin‑receptor blockers (ARBs) and diuretics. This review synthesises current evidence on the impact of systemic antihypertensive therapy on IOP and glaucoma.

Objectives

To evaluate the association between systemic antihypertensive medicines and both IOP and glaucoma risk.

Main findings

Systemic antihypertensive medicines showed heterogeneous effects on IOP and glaucoma. Eleven observational studies involving 249 295 participants met the eligibility criteria. Sample sizes ranged from 112 (prospective cohort) to 86 841 (cross‑sectional). Eight studies were assessed as low risk of bias and three as intermediate.

Meta‑analysis of four medicine classes yielded the following key results:

β‑adrenoceptor blockers (BBs): associated with lower glaucoma risk (seven studies; odds ratio [OR] 0.83, 95 % confidence interval [CI] 0.75 to 0.92; p = 0.001) and reduced IOP (three studies; β = –0.53 mm Hg, 95 % CI –1.05 to –0.02).

Calcium‑channel blockers (CCBs): associated with a slightly higher glaucoma risk (seven studies; OR 1.13, 95 % CI 1.03 to 1.24; p = 0.01) and no significant change in IOP (two studies; β = –0.11 mm Hg, 95 % CI –0.25 to 0.03).

ACE inhibitors (ACEi) and ARBs: no consistent associations with glaucoma or IOP.

Diuretics: no association with glaucoma (five studies; OR 1.00, 95 % CI 0.87 to 1.16; p = 0.95).

Methodology

The authors searched PubMed, Embase, MEDLINE and Web of Science from inception to 5 December 2022 for English‑language cross‑sectional, cohort or case‑control studies. Two reviewers independently screened records, extracted data and assessed quality with the Newcastle–Ottawa Scale. Random‑effects meta‑analysis was undertaken; heterogeneity was explored with the I² statistic. Sensitivity analyses stratified by study design and glaucoma subtype, leave‑one‑out analyses and funnel‑plot asymmetry tests were performed.

Applicability/external validity

Variability in study design, reliance on claims data and limited reporting of medicine adherence or duration constrain generalisability. Results apply chiefly to high‑income settings and to adults taking antihypertensive medicines for systemic hypertension; effects in other populations remain uncertain.

Geographic focus

The included studies were conducted in Germany, the Netherlands, the United Kingdom, Singapore and the United States.

Summary of quality assessment

We have medium confidence in the review’s conclusions. The authors restricted the search to English‑language publications, did not search reference lists or contact experts, and provided no list of excluded studies. Although individual‑study risk of bias was assessed, pooled results were not stratified by that risk. These omissions, together with reliance on observational evidence, reduce certainty in the findings.