Widely prescribed calcium channel blockers (CCBs) may increase the risk of progression to severe primary open-angle glaucoma (POAG), according to a large retrospective cohort study published in Investigative Ophthalmology & Visual Science.
Researchers from the Mayo Clinic and collaborating institutions analyzed electronic health record data from more than 7,400 patients with mild to moderate POAG using the TriNetX US Collaborative Network.
After propensity score matching, the investigators found that both dihydropyridine calcium channel blockers (dCCBs) and nondihydropyridine calcium channel blockers (ndCCBs) were associated with significantly higher rates of progression to severe glaucoma compared with matched controls not taking the drugs.
CCBs are among the most commonly prescribed cardiovascular medications worldwide, frequently used to treat hypertension, angina, and coronary artery disease. The drugs work by regulating calcium influx into vascular and cardiac tissue, although their ocular effects have remained debated for decades.
While some earlier studies have suggested that CCBs may improve optic nerve perfusion through vasodilation and potentially exert neuroprotective effects, other studies have linked the medications to worsening glaucoma progression and retinal nerve fiber layer thinning.
To explore the issue further, the researchers identified patients diagnosed with mild or moderate POAG between 2004 and 2024 and stratified them according to CCB use. The study excluded patients taking beta-blockers, ACE inhibitors, or angiotensin receptor blockers to reduce confounding from other antihypertensive therapies.
After matching for age, sex, race, ethnicity, and hypertension status, the study included 3,039 patients taking dCCBs, 684 taking ndCCBs, and matched control groups not receiving calcium channel blockers.
Progression rates differed substantially between cohorts – 3.5 percent of dCCB users progressed to severe POAG compared with 2.1 percent of matched controls. The effect was even more pronounced among ndCCB users, where 6.9 percent progressed versus 1.9 percent of controls.
Overall, dCCB use was associated with a 67 percent higher relative risk of progression to severe POAG, while ndCCBs carried more than a threefold increased risk. Direct comparison between the two drug classes also suggested that ndCCBs may pose a greater glaucoma risk than dCCBs.
The biological explanation for this risk remains unclear. The study authors discuss several possible mechanisms, including blood flow diversion in ischemic tissues caused by CCB-induced vasodilation, extracellular matrix changes within the lamina cribrosa due to mechanical strain, and IOP-independent neurodegenerative mechanisms.
The investigators caution that their study does not establish causation. Limitations included reliance on ICD-10 coding, lack of detailed intraocular pressure and visual field data, and inability to assess medication adherence or duration of therapy. Residual confounding from systemic disease severity also remains possible.
Nevertheless, the authors state that their findings “warrant further investigation to elucidate the underlying mechanisms linking CCB exposure to glaucoma progression,” with those patients taking CCBs being monitored more frequently to identify any early disease progression.
