Altered pupillary light response scales with disease severity in migrainous photophobia

Abstract

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.

A Novel Visual Psychometric Test for Light-Induced Discomfort Using Red and Blue Light Stimuli Under Binocular and Monocular Viewing Conditions

“…This might be useful for the population of migraineurs, because preliminary results suggest subgroup differences in photophobia severity between probable, episodic, and chronic migraineurs. 43 In summary, our study adds further support that lightinduced discomfort in visually normal observers is an ipRGCmediated phenomenon. We have designed a novel assessment tool as the first step toward developing a photophobia biomarker that may hold promise in refining diagnosis and revealing subgroup differences in clinical populations.…”

“…Previous psychophysical studies 2,[21][22][23]28,29,33,34,[36][37][38][39][40][42][43][44] have not used pharmacological mydriasis. Wirtschafter and Bourassa 27 investigated the effect of dilation on discomfort thresholds in a small subset of their participants (6 of 76 participants), but this experimental manipulation was not applied to their entire sample of participants.…”

“…More recent studies have adapted earlier psychophysical protocols and are faced with similar challenges. 2,22,23,33,34,[42][43][44] As a first step in quantifying pathological photophobia, we developed a psychophysical tool to quantify light-induced discomfort in visually normal participants. By incorporating the latest information on the ipRGC pathway characteristics, we examined the effects of stimulus wavelength (blue versus red light) and viewing condition (monocular versus binocular) on light-induced discomfort.…”

Pulses of Melanopsin-Directed Contrast Produce Highly Reproducible Pupil Responses That Are Insensitive to a Change in Background Radiance

“… 9 – 11 Disruption of these reflexive visual functions is seen in many clinical conditions, leading to the speculation that dysfunction in the melanopsin system is responsible. 7 , 12 – 17 Consequently, there is interest in measuring, in humans, a signal that reflects melanopsin function and testing if this signal varies between groups.…”

Pulses of melanopsin-directed contrast produce highly reproducible pupilresponses that are insensitive to a change in background radiance

“…While they represent a small fraction (~1-3%) of the total retinal ganglion cell population [1][2][3][4] , ipRGCs are critical for entrainment of circadian rhythm 5,6 , aversive responses to light 7 , light-induced lacrimation 8 , and control of pupil diameter [9][10][11] . Disruption of these reflexive visual functions is seen in many clinical conditions, leading to the speculation that dysfunction in the melanopsin system is responsible 7,[12][13][14][15][16][17] . Consequently there is interest in measuring, in humans, a signal that reflects melanopsin function and testing if this signal varies between groups.…”