A recent meta-analysis published in Ophthalmology examined associations of four categories of systemic medications—antihypertensives, lipid-lowering drugs, antidepressants and antidiabetic agents—with glaucoma prevalence and IOP in 11 population-based cohort studies of the European Eye Epidemiology consortium. The team found significant associations between use of calcium channel blockers, one class of antihypertensive studied, and increased glaucoma prevalence. However, nonselective and selective beta-blockers were associated with lower IOP. Use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications was not associated with glaucoma prevalence or lower IOP.

Researchers based in Europe have identified a potentially harmful association between use of calcium channel blockers and glaucoma prevalence.
Researchers based in Europe have identified a potentially harmful association between use of calcium channel blockers and glaucoma prevalence. Photo: Teva Pharmaceuticals. Click image to enlarge.

A total of 143,240 participants were included in the glaucoma analyses and 47,177 participants in the IOP analyses. Antihypertensive drugs assessed included beta-blockers, diuretics, calcium channel blockers, alpha-agonists, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Associations with antidiabetic medications were examined in diabetic participants only.

In the meta-analyses, use of calcium channel blockers was associated with a higher prevalence of glaucoma (odds ratio [OR]: 1.23). This association was stronger for monotherapy of calcium channel blockers with direct cardiac effects (OR: 1.96). Use of systemic beta-blockers was associated with a lower IOP (-0.33mm Hg). Monotherapy of both selective (-0.45mm Hg) and nonselective (-0.54mm Hg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (-0.30mm Hg) but not when used as monotherapy.

“It is possible that systemic beta-blockers do not reduce the risk of glaucoma per se, but limit the detection of glaucoma given that elevated IOP is often a trigger for diagnosing glaucoma,” the authors noted in their paper. “The blood pressure-lowering effect of systemic beta-blockers may thus balance out the IOP-lowering effect on glaucoma risk, explaining the null association between use of systemic beta-blockers and glaucoma prevalence.”

The researchers also found that nocturnal systemic hypotension may be associated with increased risk of glaucoma progression. “This may thus explain the association between calcium channel blockers and increased glaucoma prevalence, if calcium channel blockers are preferentially taken at bedtime,” they proposed.

Because time of medication use was not known in the studies examined, they were not able to provide evidence for this hypothesis.

“A potentially harmful association of calcium channel blockers for glaucoma is particularly noteworthy, as this is a commonly prescribed class of medication,” the researchers concluded in their paper. “If further studies confirm a causal nature for this association, this may inform alternative treatment strategies for hypertensive patients with, or at risk of, glaucoma.”

Vergroesen JE, Schuster AK, Stuart KV, et al. Association of systemic medication use with glaucoma and intraocular pressure: the E3 Consortium. Ophthalmology. May 5, 2023. [Epub ahead of print].