Use of calcitonin gene-related peptide (CGRP) inhibitors to treat migraine is associated with a reduced risk for glaucoma, new research showed.

In a multinational retrospective study of nearly 74,000 adults with migraine, those who received CGRP inhibitors had a 25% lower risk for glaucoma within 3 years of first use than those who received non-CGRP inhibitors, with the risk reduction especially strong in women and older adults.

In subtype analyses of specific treatments, CGRP inhibitors were linked to reduced glaucoma risk vs amitriptyline, lisinopril, metoprolol, propranolol, topiramate, valproate, and venlafaxine.

“Further studies are needed to confirm these results, but the findings may help us better understand both migraine and glaucoma,” co-investigator Chien-Hsiang Weng, MD, Brown University Warren Alpert Medical School, Providence, Rhode Island, said in a release.

The findings were published online on May 6 in Neurology. 

Eye Health Benefits

Previous research has shown an association between migraine and increased glaucoma risk. Both conditions affect the blood flow in the brain in response to stimuli, and because CGRP inhibitors are known to help regulate both blood vessel contraction and nervous system inflammation, researchers wanted to investigate whether the use of these drugs might affect glaucoma risk, Weng noted. 

The study included data from the Global Collaborative Network of the TriNetX for 73,644 adults (mean age, 43 years; 81% women) across 30 countries. All had been diagnosed with migraine and received treatment medications between 2018 and 2024. All participants were followed for up to 3 years. 

Medications used by participants in the CGRP inhibitor group (n = 36,822) included the monoclonal antibodies (mAbs) — fremanezumab, galcanezumab, erenumab, or eptinezumab — or the small-molecule CGRP receptor antagonists (gepants) — rimegepant and atogepant.

Medications taken by CGRP inhibitor-naive participants (n = 36,822) included amitriptyline, candesartan, flunarizine, lisinopril, metoprolol, nadolol, propranolol, topiramate, valproate, and venlafaxine. 

Generalizable Findings?

Results showed that 153 glaucoma events occurred in the CGRP inhibitor group (0.4%) over 3 years, while 223 events occurred in the CGRP inhibitor-naive group (0.6%). The use of CGRP inhibitors was associated with a significantly lower risk for glaucoma development vs nonuse of CGRP inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.61-0.92). 

The risk was also reduced for those who used CGRP inhibitors compared to those who used the anti-seizure medications valproate (HR, 0.54) and topiramate (HR, 0.73), the beta-blockers metoprolol and propranolol (HR, 0.76 for both), the ACE inhibitor lisinopril (HR, 0.49), and the antidepressants amitriptyline (HR, 0.69) and venlafaxine (HR, 0.68). 

Additionally, a stronger link between the use of CGRP inhibitors and reduced glaucoma risk was found in women (HR, 0.72), participants aged 45 years or older (HR, 0.77), and those diagnosed with chronic migraine (HR, 0.66) or migraine without aura (HR, 0.62).

Among those who used CGRP inhibitors, there was a reduced risk for glaucoma for those who used mAbs (HR, 0.77) but not for those who used gepants.

Sensitivity analysis of glaucoma subtypes showed CGRP inhibitors were linked to a lower risk for ocular hypertension (HR, 0.62) but not for primary open-angle glaucoma, compared with non-CGRP inhibitors. 

The investigators noted that the large and real-world design, multinational patient population, and rigorous approach to propensity score-matching were all study strengths.

“This enhances the generalizability of our findings,” they wrote.

The study was funded by the Taichung Veterans General Hospital in Taiwan. The investigators reported no relevant financial relationships.