Calcium Channel Blocker Use Associated with Higher Prevalence of Glaucoma

Anthony P. Khawaja, MBBS, PhD

Credit: UCL Institute of Ophthalmology

A new meta-analysis has identified a potentially harmful association between the use of calcium channel blockers (CCBs) and prevalence of glaucoma in more than 140,000 people across 8 European countries.¹

The investigative team, led by Anthony P. Khawaja, MBBS, PhD, UCL Institute of Ophthalmology, additionally indicated that non-selective and selective beta blockers were associated with lower intraocular pressure (IOP), while a suggestive association was found between the use of high-ceiling diuretics and lower IOP.

“Our findings confirm the known IOP-lowering effect of systemic beta-blockers, quantifying the effect on a population level, and identify other potential systemic medication modifiers of glaucoma risk,” investigators wrote.¹ “While our novel findings require further studies to determine whether the associations are causal, these findings will be of interest to physicians carrying for glaucoma patients with systemic comorbidities.”

Despite being the leading cause of irreversible visual loss worldwide, elevated IOP is currently the only modifiable risk factor for glaucoma onset and progression. Systemic medication classes are known to or thought to modulate glaucoma risk; however, for many of these associations, there have been inconsistent findings and few studies have accounted for polypharmacy or important confounders, according to investigators.²

Here, Khawaja and colleagues looked to examine the association of commonly used systemic medications with glaucoma prevalence and IOP across 11 independent population-based cohorts in the European Eye Epidemiology (E3) Consortium. Participants were recruited between 1991 - 2017 from France, Germany, Greece, the Netherlands, Norway, Portugal, Russia, and the United Kingdom. A total of 143,240 participants from 11 studies from the E3-consortium were included in the glaucoma analyses, compared to 47,177 participants from 10 studies included in the IOP analyses.

Investigators analyzed the associations of 4 categories of systemic medications (antihypertensive medications: beta-blockers, diuretics, CCBs, alpha-agonists, angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs); lipid-lowering medications; antidepressants; antidiabetic medications) with glaucoma prevalence and IOP.

The team performed multivariable logistic regression analysis with glaucoma status as the dependent variable and medication use as a binary exploratory variable for the glaucoma analyses. For the IOP analyses, investigators performed multivariable linear regression models with IOP as the dependent variable. Glaucoma prevalence ranged from 0.9 - 8.7% in the study population, with greater prevalence in the oldest group.

In the meta-analyses of maximally adjusted multivariable models, investigators found the use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% CI, 1.08 - 1.39). They noted the association was stronger for the use of selective CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 - 3.12). However, the use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not clearly associated with glaucoma prevalence.

Meanwhile, the use of systemic beta-blockers was associated with a lower IOP (Beta, -0.33 mmHg; 95% CI, -0.57 to -0.08). When assessing hypertensive use as monotherapy, both non-selective beta-blockers (Beta, -0.54 mmHg; 95% CI, -0.94 to -0.15) and selective beta-blockers (Beta, -0.45 mmHg; 95% CI, -0.74 to -0.16) were associated with lower IOP.

Investigators indicated a suggestive association between the use of high-ceiling diuretics and lower IOP (Beta, -0.30 mmHg; 95% CI, -0.47 to -0.14), but monotherapy of high-ceiling diuretics was not significantly associated with lower IOP. They additionally noted the use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not associated with IOP.

“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,” investigators noted.¹

References

1. Vergroesen JE, Schuster AK, Stuart KV, et al. Association of systemic medication use with glaucoma and intraocular pressure: the E3 Consortium [published online ahead of print, 2023 May 5]. Ophthalmology. 2023;S0161-6420(23)00306-8. doi:10.1016/j.ophtha.2023.05.001
2. Kim J, Kennedy Neary MT, Aschard H, et al. Statin Use in Relation to Intraocular 552 Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK 553 Biobank. Investigative Ophthalmology & Visual Science 2022;63(5):31-