Altered pupillary light response scales with disease severity in migrainous photophobia

Background: Autonomic dysfunction and light sensitivity are core features of the migraine attack. Growing evidence also suggests changes in these parameters between attacks. Though sensory and autonomic responses likely interact, they have not been studied together across the spectrum of disease in migraine. Methods: We performed digital infrared pupillometry while collecting interictal photophobia thresholds (PPT) in 36 migraineurs (14 episodic; 12 chronic; 10 probable) and 24 age and sex-matched non-headache controls. Quantitative pupillary light reflexes (PLR) were assessed in a subset of subjects, allowing distinction of sympathetic vs parasympathetic pupillary function. A structured questionnaire was used to ascertain migraine diagnosis, headache severity, and affective symptoms. Results: Photophobia thresholds were significantly lower in migraineurs than controls, and were lowest in chronic migraine, consistent with a disease-related gradient. Lower PPT correlated with smaller dark-adapted pupil size and larger end pupil size at PPT, which corresponded to a reduced diameter change. On PLR testing, measures of both parasympathetic constriction and sympathetic re-dilation were reduced in migraineurs with clinically severe migraine. Conclusions: In summary, we show that severity of photophobia in migraine scales with disease severity, in association with shifts in pupillary light responses. These alterations suggest centrally mediated autonomic adaptations to chronic light sensitivity.