Common antihypertensive drug linked to glaucoma

The use of calcium channel blockers (CCBs) may contribute to an increased risk of glaucoma despite CCBs having no effect on intraocular pressure (IOP), according to a large study.

Data from 427,480 UK Biobank participants (median age 58 years, 54.1 percent women) showed that CCB users (n=33,175) had 39-percent greater odds of glaucoma than nonusers (odds ratio [OR], 1.39, 95 percent confidence interval [CI], 1.14–1.69; p=0.001). [JAMA Ophthalmol  2023;doi:10.1001/jamaophthalmol.2023.3877]

Consistent with the main finding, macular ganglion cell–inner plexiform layer (mGCIPL) and macular retinal nerve fiber layer (mRNFL) thicknesses—both being objective structural glaucoma-related parameters—were also significantly reduced in CCB users. Specifically, mGCIPL and mRNFL were 0.34-μm (95 percent CI, −0.54 to −0.15; p=0.001) and 0.16-μm (95 percent CI, −0.30 to −0.02; p=0.03) thinner, respectively, than in non-CCB users.

On the other hand, CCB use showed no association with IOP (−0.01 mm Hg, 95 percent CI, −0.09 to 0.07; p=0.84).

The findings were consistent with those of earlier cross-sectional and longitudinal studies that showed an adverse association between CCB use and glaucoma. [Ophthalmology 2018;125:984-993; Br J Ophthalmol 2005;89:960-963; Ophthalmology 2007;114:2221-2226; Invest Ophthalmol Vis Sci 2020;61:25]

“Our analyses provide further large-scale evidence supporting those previously reported associations and suggest that the adverse association between CCB use and glaucoma risk may act via IOP-independent mechanisms,” the investigators said.

“Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care,” they added.

Detrimental or protective?

“The implication that CCBs are directly detrimental to retinal tissue is contrary to the general view of these agents being neuroprotective,” according to the investigators.

For example, CCBs exerted protection on neurons undergoing apoptosis and necrosis in in vitro studies. In several small interventional studies, CCBs were also found to help increase retrobulbar and optic nerve head blood flow, improve colour contrast sensitivity, and stabilize visual field loss in individuals with normal-tension glaucoma. [Prog Retin Eye Res 2011;30:54-71; Br J Ophthalmol 2005;89:21-25; Ophthalmology 2008;115:2049-2057]

While unclear, the apparent discrepancy may have several explanations, the investigators said. First, the in vitro studies did not account for the blood pressure-lowering ability of CCBs, and second, 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,” the investigators noted.

Indeed, in an interaction sensitivity analysis, “we observed that CCB use was associated with higher odds of glaucoma in individuals without hypertension compared with participants with hypertension, suggesting that a history of higher blood pressure may partially ameliorate the adverse association with glaucoma,” they pointed out.

However, the investigators also acknowledged that the findings might not fully account for the potential consequences of CCBs on IOP, given that the IOP assessment in the present study was limited to a single measurement. Also, there were no data on the length, frequency, or dosage of CCB use and whether the medication was taken on the day of IOP assessment.

“This warrants further investigation to determine whether the associations [between CCB use and glaucoma] are causal and to probe potential underlying biological mechanisms,” they said.