Can Migraine Drugs Guard Against Glaucoma? CGRP Inhibitors Show Promise

People who used calcitonin gene-related peptide (CGRP) inhibitor drugs to prevent migraine had a lower risk of glaucoma, a retrospective study showed.

Among 74,000 migraine patients, those taking CGRP inhibitors for migraine prevention had a 25% lower risk of incident glaucoma within 3 years compared with those using other migraine prophylaxis (HR 0.75, 95% CI 0.61-0.92), reported Chien-Hsiang Weng, MD, MPH, of Brown University in Providence, Rhode Island, and co-authors.

Only monoclonal antibody CGRP inhibitors — fremanezumab (Ajovy), galcanezumab (Emgality), eptinezumab (Vyepti), or erenumab (Aimovig) — were associated with a lower glaucoma risk, Weng and colleagues wrote in Neurology.

Risk of glaucoma was not lower with the two CGRP receptor antagonists included in the study, atogepant (Qulipta) or rimegepant (Nurtec).

“Glaucoma is a leading cause of blindness, and evidence has linked migraine with an increased risk of glaucoma, with both conditions affecting the capacity of the blood vessels in the brain to alter blood flow in response to stimuli,” Weng said in a statement. “Since CGRP inhibitors help regulate blood vessel contraction and inflammation in the nervous system, there has been hope that these drugs could benefit eye health in people at risk of glaucoma.”

CGRP inhibitors may affect glaucoma risk through intraocular pressure (IOP) regulation and neuroinflammation, the researchers hypothesized.

“The blood-aqueous barrier of the ciliary processes is a major determinant of aqueous humor formation. Animal studies have demonstrated that intracameral administration of CGRP disrupted the blood-aqueous barrier and increased IOP, which may lead to an increased risk of glaucoma,” Weng and co-authors wrote.

“This hypothesis is supported by our findings, which show a reduced risk of ocular hypertension in the CGRP inhibitor group compared with the non-CGRP inhibitor group. In addition to IOP modulation, CGRP contributes to inflammatory signaling cascades in both migraine and ocular tissues,” they added. “Studies have shown that neurogenic inflammation can accelerate retinal ganglion cell loss and optic nerve damage, even in the absence of elevated IOP.”

Weng and colleagues evaluated electronic health records of 73,644 adult migraine patients who received preventive drugs from May 2018 — when the FDA approved the first CGRP blocker, erenumab — through 2024 in the TriNetX global collaborative network. Most data came from the U.S.

The researchers categorized patients into a CGRP inhibitor group (those taking erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant, or rimegepant) or a non-CGRP inhibitor group (those taking valproate, topiramate, flunarizine, candesartan, lisinopril, metoprolol, propranolol, nadolol, amitriptyline, or venlafaxine).

Participants had an initial prescription for a migraine preventive drug and at least one refill within 6 months. Crossovers were not allowed: the non-CGRP inhibitor group included only individuals who never used CGRP inhibitors.

The groups were propensity score matched on demographic and clinical variables and followed for up to 3 years to monitor incident glaucoma. Each group had 36,822 migraine patients. In the CGRP inhibitor group, the mean age was 42.5 years and the average follow-up was 1.77 years. In the non-CGRP inhibitor group, the mean age was 42.6 years and the average follow-up was 1.97 years.

During the study, 0.42% of participants in the CGRP inhibitor group and 0.61% of those in the non-CGRP inhibitor group had incident glaucoma. The reduced risk of glaucoma persisted even when CGRP inhibitors were compared specifically with beta-blockers, Weng and co-authors said. Sensitivity analyses yielded consistent findings.

Migraineurs taking CGRP inhibitors had a lower risk of ocular hypertension (HR 0.62, 95% CI 0.42-0.91) but not primary open-angle glaucoma (HR 1.58, 95% CI 0.85-2.40) compared with non-CGRP inhibitor users, the researchers noted.

Residual confounding, such as migraine severity or patient adherence, may have influenced outcomes, they acknowledged. The study also was limited by a lack of granular ophthalmic data like serial IOP measurements or optic nerve imaging, which precluded analyses of how inhibiting CGRP might mediate IOP changes.

“Further studies are needed to confirm these results, but the findings may help us better understand both migraine and glaucoma,” Weng said.

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