Calcium Channel Blockers Again Linked to Glaucoma

Patients on calcium channel blockers (CCBs) had a higher likelihood of glaucoma than their counterparts, according to a population-based, cross-sectional study.

Examining data on more than 400,000 participants in the U.K. Biobank revealed that use of CCBs was associated with a 39% greater odds of glaucoma after adjusting for various factors, including the use of other antihypertensives (OR 1.39, 95% CI 1.14-1.69, P=0.001), reported Alan Kastner, MD, MSc, of Clínica Oftalmológica Pasteur in Santiago, Chile, and colleagues in JAMA Ophthalmology.

This association was not observed with diuretics, RAS inhibitors, or beta-blockers, and the researchers also found evidence that CCBs may boost the risk of glaucoma by thinning layers of the retina.

The risk isn’t severe enough to pull patients off CCBs who don’t already have glaucoma or who have stable disease, co-author Anthony Khawaja, MBBS, PhD, of University College London, told MedPage Today. But it’s worth considering alternate medications in patients who are taking the drugs and suffering from worsening glaucoma, he said.

“For these patients, we need to think about other factors than eye pressures, as they are getting worse despite all we can do for the eye pressure,” he said. “If these patients are on CCBs, I discuss the imperfect evidence we have with the patient and their general physician for consideration of changing their antihypertensives.”

Previous research has linked CCBs to glaucoma, Khawaja said, but the authors of the new study sought to take a look at a larger data set. “We wanted to not only look at the association between CCBs and glaucoma overall in the general population, but also look at the relationship with physical parameters that are important in glaucoma — intraocular pressure [IOP] and the thickness of the inner retina.”

Kastner and colleagues focused on 427,480 U.K. Biobank participants (recruited from 2006 to 2010) who had undergone eye exams (mean age 58 years, 54.1% women, 94.8% white). Overall, 26.7% had hypertension and 7.8% were taking CCBs (n=33,175).

Glaucoma was rare regardless of whether patients were taking CCBs or not (0.4% vs 0.2%, respectively).

Among 41,023 subjects with appropriate data on optical coherence tomography (OCT)-derived inner retinal layer thickness, CCB users had a significantly thinner inner retina compared with non-users (-0.16 μm, 95% CI -0.30 to -0.02 μm, P=0.03), “an important parameter that helps in the diagnosis of glaucoma,” Khawaja said.

Macular ganglion cell-inner plexiform layers were also thinner in CCB users (-0.34 μm, 95% CI -0.54 to -0.15 μm, P=0.001).

“Interestingly, CCB users did not have a significantly different eye pressure than non-users,” Khawaja said. “This suggests that while CCBs have an impact on glaucoma, it is not via raised intraocular pressure and may be via more direct effects on the optic nerve.”

In an invited commentary, Paula Anne Newman-Casey, MD, MS and Rithambara Ramachandran, MD, of the University of Michigan at Ann Arbor, said the study authors have “elegantly analyzed” the relationship between CCBs and glaucoma. “Half of the adult population in the U.S. has hypertension, so the topic of how antihypertensive medications impact glaucoma and eye pressure is highly relevant to ophthalmologists in the U.S.,” they wrote.

The commentary authors added that “there has been controversy about the use of calcium channel blockers as a potential treatment for normal-tension glaucoma, and there has been contradictory evidence surrounding the use of CCBs and its impact on IOP and open-angle glaucoma.”

It’s not clear how CCBs might increase the risk for glaucoma, said Khawaja.

“We have not proved cause and effect. If there is a true effect, we believe it will be via direct effects on the optic nerve rather than via changes in eye pressure,” he said. “We know that calcium channels are very important for optic nerve function, and also for the function of cells surrounding the optic nerve head which offer support. But further basic science research is needed to probe any possible causal pathways.”

What about other blood pressure drugs? “So far, we have not found consistent evidence that other antihypertensives individually affect risk,” Khawaja said. “Oral beta-blockers certainly lower eye pressure and may reduce risk. There is some evidence that too low a blood pressure may be harmful, but the cause-effect relationship remains uncertain.”

In their study, the research team found no association between glaucoma and use of other antihypertensive agents:

• Diuretics: OR 1.03 (95% CI 0.84-1.28)
• RAS inhibitors: OR 1.12 (95% CI 0.93-1.34)
• Systemic beta-blockers: OR 0.93 (95% CI 0.74-1.18)

Kastner and co-authors noted various limitations, such as the lack of non-white subjects and the lack of information about duration and doses of CCBs.

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