A retrospective review of over 500,000 subjects found a 16% higher risk of glaucoma among subjects taking amlodipine. Click image to enlarge.

It’s been shown previously that individuals with primary open-angle glaucoma (POAG) who had taken a calcium channel blocker were at a 23% increased risk of developing glaucoma compared to those who had never taken this type of antihypertensive drug. Researchers of a recent study sought to not only confirm this but examine POAG genes that might be involved and found that due to a potentially hazardous relationship with POAG, β-blockers and diuretics may be better options for hypertensive patients at-risk of POAG. The team’s paper on the work was recently published in Clinical Hypertension.

The authors evaluated the effects of amlodipine on POAG and intraocular pressure (IOP). Three POAG-associated single-nucleotide polymorphisms were analyzed: rs9913911, an intron variant in growth arrest-specific 7 (GAS7), rs944801, an intron variant within CDKN2B-AS1, and rs2093210, an intron variant within SIX6, known to be associated with vertical cup-disc ratio, an important optic nerve head parameter that is often used to define or diagnose glaucoma.

In a retrospective review of over half a million subjects in the UK Biobank (502,494 to be exact), those who had taken amlodipine were at a 16.1% increased risk of POAG, the researcehrs found. Of the three single-nucleotide polymorphisms, rs9913911 is found in a chromosomal area previously identified by a glaucoma linkage study and subsequently by a genome-wide association study. rs944801 and rs2093210 are known to be associated with vertical cup-disc ratio, an important optic nerve head parameter that is often used to define or diagnose glaucoma.

The authors did not find an association between amlodipine and increased IOP, nor did they find one with GAS7—one of the genes that influences IOP—but CDKN2B-AS1 and SIX6, POAG genes not associated with IOP, were associated with POAG and amlodipine.

“According to certain research, calcium channel blockers may enhance choroidal and optic nerve head blood flow and slow the degradation of the visual field in open-angle glaucoma patients,” the authors wrote in their study. “According to in vitro research, calcium channel blocking lessens the extracellular matrix gene response that mechanical strain induces in lamina cribrosa cells. According to some, CCBs may cause venous dilatation, which would improve perfusion to the optic nerve head. But according to another research, using CCBs is linked to a higher risk of POAG.”

A previous study found a similar correlation between POAG and the use of calcium channel blockers, as well as a strong association with β-blockers.

“The retina may be directly affected by calcium channel blockers,” the authors explained. “In the past, calcium channel blocker use was linked to a thinner layer of macular retinal nerve giber and a thinner layer of ganglion-inner plexiform layer.”

The risk of POAG associated with amlodipine is prob­ably too low to recommend regular follow-up eye exami­nations with the medication, the authors concluded. “The risk appears to be limited to a small population with spe­cific genes. Therefore, an ophthalmological examination before amlodipine administration to all patients is prob­ably not necessary,” the authors wrote in the study. “But hypertensive patients with a fam­ily history of glaucoma or other risk factors should have at least an initial eye examination before amlodipine is begun.”