Hypertension and glaucoma often go hand in hand, but what if the treatment for one increased the risk for the other? That may be the case with antihypertensive calcium channel blockers (CCBs), according to a recently published study in JAMA Ophthalmology that investigated the association of systemic CCB use with glaucoma and related traits in UK Biobank participants.1

Using calcium channel blockers (amlodipine in particular) may increase the risk of glaucoma by almost 40%. Large-scale studies are needed to learn more about this association, and publicly funded databases will play a key role in research. Photo: Accord Pharma.

CCBs decrease blood pressure by relaxing venous smooth muscle. This mechanism has been thought to increase and stabilize blood flow to the optic nerve head. Experts note, however, that there’s inconclusive evidence, with studies showing that different classes of CCBs have different and varying effects.2

The cross-sectional, population-based study1 included 427,480 UK Biobank participants (median age 58 years, 54% female), of which 7.8% were CCB users. After adjusting for key sociodemographic, medical, anthropometric and lifestyle factors, the researchers found that the use of CCBs—but not other antihypertensives—was associated with 39% increased odds of glaucoma.

Additionally, CCB use was associated with thinner macular ganglion cell inner plexiform layer and macular retinal nerve fiber layer thickness, but not with intraocular pressure (IOP). “The implication that CCBs are directly detrimental to retinal tissue is contrary to the general view of these agents being neuroprotective,” the researchers pointed out in their paper.

The researchers proposed one explanation for this discrepancy: “in vitro studies do not account for the blood pressure-lowering ability of CCBs, and the CCBs investigated in the visual field studies did not appreciably affect blood pressure in glaucoma cases. It may be that the detrimental consequences of CCBs only manifest when coupled with the hypotensive and/or vasodilatory properties of certain CCBs, such as amlodipine.”

They concluded in their JAMA Ophthalmology paper that there appears to be an “adverse association between CCB use and glaucoma, despite no apparent association with IOP.” Though a causal relationship wasn’t established, they advised that “CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.”

According to Paula Anne Newman-Casey, MD, MS, and Rithambara Ramachandran, MD, studying the unintended consequences of prescription drugs is more important than ever, given the aging population and increase in patients with multiple comorbid conditions.

In an invited commentary2 on the study by Kastner and colleagues, Drs. Newman-Casey and Ramachandran emphasized that the findings from the study “demonstrate the importance of publicly funded and publicly available big data in health care,” which encourage and enable researchers to “leverage large quantities of data to identify patterns and advance health care.”

The UK Biobank was funded with the equivalent of USD $416.9 million from the government and foundation support. The All of Us database was funded with $1.5 billion from Congress through the 21st Century Cures Act. Though neither database is nationally representative, lacking stratified random sampling and composed of a white-skewed racial/ethnic participant pool, these databases are so large that they still enable powerful statistical analysis for risk factor analysis for even less prevalent health outcomes.

Drs. Newman-Casey and Ramachandran concluded, “Continued public support for open source, cured, integrated large data sets is imperative if medicine is to become truly individually tailored, where we understand the complex interplay between an individual’s genomics, medical conditions, medications, lifestyle and social environment in order to provide more nuanced treatment recommendations at both an individual and population level.”

1. Kastner A, Stuart KV, Montesano G, et al. Calcium channel blocker use and associated glaucoma and related traits among UK Biobank participants. JAMA Ophthalmology 2023. [Epub September 7, 2023].

2. Newman-Casey PA and Ramachandran R. Power of public investment in curated big health data. Invited Commentary. JAMA Ophthalmology 2023. [Epub September 7, 2023].