To determine the relative contribution of melanopsin and cone stimulation to discomfort from light in migraineurs.

Under daylight conditions, human vision has contributions from both the classical cone photoreceptors and the more recently characterized melanopsin-containing retinal ganglion cells. The extent to which each class of photoreceptor contributes to the sensation of visual discomfort in the intact retina has not been described. Using modulations of the spectral content of light to independently target the melanopsin and cone photopigments, we tested if people with migraine experience discomfort from either or both of these stimuli.

Based on responses to the Penn Online Evaluation of Migraine, subjects between the age of 25 and 40 years old were enrolled into two cohorts: headache-free controls and migraineurs who reported interictal light sensitivity. In a pre-registered study (, subjects viewed pulses of varying spectral contrast (100, 200, and 400%) designed to produce isolated stimulation of the cones, melanopsin, or both (light flux). Subjects were asked to rate the degree of discomfort on a 0 to 10 scale for each light pulse. The 9 stimuli were presented 24 times each in a randomized order. Simultaneous measurements of pupil response and squint were also made, but are not described here.

Five control and ten migraine subjects have completed the study (out of a planned total enrollment of 120). Controls did not report discomfort for any of the stimuli (median rating of 1 for all stimuli). Migraineurs reported increasing discomfort with increasing contrast for all three stimulus types (median ratings for the 100, 200, and 400% stimuli for cones: 2, 3.5, 5.5; melanopsin: 1, 3, 5; and light flux: 2.5, 4, 6).

Targeted stimulation of cones and melanopsin produce visual discomfort in migraineurs, suggesting that both photoreceptor classes contribute to light sensitivity in migraine.