Visual Hypersensitivity Positively Associated With Patient Outcomes in CGRP-Treated Individuals With Migraine


Visual hypersensitivity decreased after 3 months of treatment, with a clear association with clinical response to treatment regarding migraine days.

Gisela Terwindt, MD, professor of neurology at Leiden University Medical Center

Gisela Terwindt, MD

Data from a prospective study published in Headache revealed possible links between visual hypersensitivity and individuals with migraine treated with anti-calcitonin gene related peptide (CGRP) receptor antibodies. All told, 3 months after patients received treatment, findings showed a positive association between reductions in monthly migraine days (MMDs) and decrease in visual hypersensitivity.

In total, the single-center study featured 105 patients on 70 mg of erenumab (Aimovig; Amgen) and 100 on225 mg of fremanezumab (Ajovy; Teva Pharmaceuticals) who completed a 3-month follow-up. Coming into the study, patients completed the Leiden Visual Sensitivity Scale (L-VISS) before starting treatment (T0) and 3 months after treatment initiation (T1). Using a daily e-diary, treatment effectiveness was measured in the final 3 weeks of the 3-month period and 4 weeks before baseline.

Senior investigator Gisela Terwindt, MD, professor of neurology at Leiden University Medical Center, and colleagues hypothesized that treatment with anti-CGRP antibodies would diminish visual hypersensivity in patients with migraine. Baseline characteristics of the cohort showed mostly females (erenumab: 85%; fremanezumab: 82%), with approximately 60% of patients having migraine without aura. In addition, more patients on fremanezumab were diagnosed with chronic migraine (59% vs 49%).

After 3 months of treatment, both mean ictal and interictal L-VISS scores slightly decreased, going from 20.1 (±7.7) to 19.2 (±8.1)(P = .042) and from 11.8 (±6.6) to 11.1 (±7.0)(P = .050), respectively. As noted, there was a positive association between the reduction in MMD and the decrease in interictal L-VISS (ß = 0.2; 95% CI, 0.0-0.3; P = .010) and the reduction in ictal L-VISS (ß = 0.3; 95% CI, 0.1-0.5; P = .001).

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"Visual hypersensitivity is one of the most debilitating features of migraine,” the study authors wrote. "Even if the migraine headache is successfully treated, many patients with migraine still report this as one of the most bothersome symptoms associated with migraine. Even though we found a significant decrease in visual hypersensitivity, this reduction was relatively small and dependent on the reduction in migraine."

"Considering previously reported L-VISS scores in patients with migraine and healthy controls, it is not expected that visual hypersensitivity resolves completely, even when patients convert from chronic migraine to episodic migraine; however, as photophobia is one of the most bothersome symptoms of a migraine attack, every decrease could already be relevant in the total burden experienced during a migraine attack," they added.

Among the 63 individuals who saw a more than 50% reduction in MMDs, the mean ictal L-VISS decreased from 19.0 (±8.2) to 16.5 (±9.4)(P = .002) and mean interictal L-VISS decreased from 10.1 (±6.4) to 8.8 (±6.6)(P = .021). Those with less than a 50% reduction (n = 126) saw no change in mean ictal L-VISS (P = .911) or interictal L-VISS (P = .482) scores after 3 months. In a response predictor analysis, absolute reduction in MMD in response to treatment with either therapy seemed not associated with interictal L-VISS (P = .069).

While the visual hypersensitivity score did not decrease in patients with less than 50% reduction in MMDs in response to treatment with erenumab, a different study demonstrated that the CGRP-mediated trigeminovascular activity is inhibited in these less than 50% responders.2 "This suggests that the decrease in visual hypersensitivity is not directly related to trigeminal nerve blockage but may be a secondary effect of decrease in migraine days,” Terwindt et al wrote. "This would fit the data that mAbs targeting CGRP are large molecules that cannot easily pass the blood–brain barrier, and most likely work via a peripheral site of action."

1. Vries Lentsch SD, Perenboom MJL, Carpay JA, MaassenVanDenBrink A, Terwindt GM. Visual hypersensitivity in patients treated with anti-calcitonin gene-related peptide (receptor) monoclonal antibodies. Headache. 2023;63(7):926-933. doi:10.1111/head.14531
2. de Vries LS, Al-Hassany L, Ferrari MD, et al. CRGP-mediated trigeminovascular reactivity in migraine patients treated with erenumab. J Neurol Neurosurg Psychiatry. 2022;93:911-912
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