The migraine eye: distinct rod-driven retinal pathways' response to dim light challenges the visual cortex hyperexcitability theory

Abstract

Migraine-type photophobia, most commonly described as exacerbation of headache by light, affects nearly 90% of the patients. It is classified as one of the most disabling symptoms that accompany an attack. Using subjective psychophysical assessments, we showed recently that migraine patients are more sensitive to all colors of light during the ictal than during the interictal phase and that control subjects do not experience pain when exposed to different colors of light. Based on these findings, we suggested that color preference is unique to migraineurs (as it was not found in control subjects) rather than migraine phase (as it was found in the ictal and interictal phases). To identify the origin of this photophobia in migraineurs, we compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger (by 14-19% in the light-adapted and 18-34% in the dark-adapted flash ERG) in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual Correspondence-Rami Burstein, CLS-649,

Exploring the Link Between Dry Eye and Migraine: From Eye to Brain

“… 50 Beyond these two pathways, other postulated, but less well studied pathways in photophobia involve the hypothalamus, retinal rod and cone cells, and the iris. 47 , 51 , 52 …”

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

“…Our results also argue against a change in the sensitivity of melanopsin or the cones in migraine under photopic conditions. There have been varying reports of alteration of cone electroretinogram responses in people with migaine 79,80 , although these studies are also difficult to interpret given possible differences in retinal irradiance between the studied groups 81 .…”

“…Because we placed an artificial pupil between the stimulus and the pharmacologically dilated pupil of the observer, our stimuli illuminated only a small area of the cornea, and minimally the iris. There has also been interest in the contribution of the rods to photophobia in migraine 80 , and there is evidence that the rods provide inputs to ipRGCs 84 . We sought to minimize the influence of the rods upon our measurements by modulating our stimuli around a photopic background.…”

Fear of light: On the cause and remediation of photophobia

“…Figure 3 Spectral transmission of the FL41 lens. 43 original reports have changed their position, arguing that in migraine photophobia the cones 55 and the rods 56 are involved. Although the ipRGCs might play a role in sensitivity to bright light, 57 it is difficult to see how their activity can explain the sensitivity to flicker, 58 pattern 59 and colour 25 that occurs in migraine.…”

“…Since 2010, there have been five reviews of photophobia, 49–53 generally accepting the idea that the ipRGCs play a role, a seductive viewpoint given that the ipRGCs are the only photoreceptors that encode absolute light levels. 54 Yet the authors responsible for the original reports have changed their position, arguing that in migraine photophobia the cones 55 and the rods 56 are involved. Although the ipRGCs might play a role in sensitivity to bright light, 57 it is difficult to see how their activity can explain the sensitivity to flicker, 58 pattern 59 and colour 25 that occurs in migraine.…”