Abstract

The purpose of this pilot study was to investigate the light-induced pupillary and lacrimation responses mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) in migraine. Ten participants with episodic migraine and normal tear production, as well as eleven visually normal controls participated in this study. Following an initial baseline trial (no light flash), participants received seven incremental and alternating red and blue light flashes. Pupillometry recording of the left eye and a 1-min anesthetized Schirmer’s test of the right eye (using 0.5% proparacaine) were performed simultaneously. Intrinsic and extrinsic ipRGC photoactivities did not differ between migraine participants and controls across all intensities and wavelengths. Migraine participants, however, had significantly lower lacrimation than controls following the highest blue intensity. A positive correlation was found between melanopsin-driven post-illumination pupillary responses and lacrimation following blue stimulation in both groups. Our results show that participants with self-reported photophobia have normal ipRGC-driven responses, suggesting that photophobia and pupillary function may be mediated by distinct ipRGC circuits. The positive correlation between melanopsin-driven pupillary responses and light-induced lacrimation suggests the afferent arm of the light-induced lacrimation reflex is melanopsin-mediated and functions normally in migraine. Lastly, the reduced melanopsin-mediated lacrimation at the highest stimulus suggests the efferent arm of the lacrimation reflex is attenuated under certain conditions, which may be a harbinger of dry eye in migraine.

Highlights

  • Photophobia is a common and debilitating sensory disturbance characterized by light-induced ocular or cranial discomfort that can be accompanied by a subsequent increase in tear production and squinting responses [1, 2]

  • Using chromatic pupillometry to assess the intrinsically photosensitive retinal ganglion cells (ipRGCs)-mediated pupillary light reflex pathway, our pilot study demonstrated normal extrinsic and intrinsic ipRGC activity in migraine patients with photophobia

  • Our findings suggest that photophobia seen in migraine is unlikely to stem from a hypersensitized ipRGC pathway at the level of the retina, but rather downstream of that circuit

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Summary

Introduction

Photophobia is a common and debilitating sensory disturbance characterized by light-induced ocular or cranial discomfort that can be accompanied by a subsequent increase in tear production and squinting responses [1, 2]. The most common neurologic condition associated with photophobia is migraine, with 80%-90% of patients experiencing photophobia [3, 4] both during (ictally) and in between (inter-ictally) migraine attacks [5,6,7]. Light-induced lacrimation and ipRGC responses in migraine

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