Reflexive Eye Closure in Response to Cone and Melanopsin Stimulation

Abstract

Objective:To quantify interictal photophobia in migraine with and without aura using reflexive eye closure as an implicit measure of light sensitivity, and to assess the contribution of melanopsin and cone signals to these responses.Methods:Participants were screened to meet criteria for one of three groups: headache-free (HAf) controls, migraine without aura (MwoA), and migraine with visual aura (MwA). MwoA and MwA participants were included if they endorsed ictal and interictal photophobia. Exclusion criteria included impaired vision, inability to collect usable pupillometry, and history of either head trauma or seizure. Participants viewed light pulses that selectively targeted melanopsin, the cones, or their combination during recording of orbicularis oculi electromyography (OO-EMG) and blinking activity.Results:We studied twenty participants in each group. MwA and MwoA groups reported increased visual discomfort to light stimuli (Discomfort rating, 400% contrast, MwA: 4.84 [95% CI: 0.33, 9.35]; MwoA: 5.23 [0.96, 9.50]) as compared to HAf controls (2.71 [0, 6.47]). Time course analysis of OO-EMG and blinking activity demonstrated that reflexive eye closure was tightly coupled to the light pulses. The MwA group had greater OO-EMG and blinking activity in response to these stimuli (EMG activity, 400% contrast: 42.9%Δ [28.4, 57.4]; Blink activity, 400% contrast: 11.2% [8.8, 13.6]) as compared to the MwoA (EMG activity, 400% contrast: 9.9%Δ [5.8, 14.0]; Blink activity, 400% contrast: 4.7% [3.5, 5.9]) and HAf control (EMG activity, 400% contrast: 13.2%Δ [7.1, 19.3]; Blink activity, 400% contrast: 4.5% [3.1, 5.9]) groups.Conclusions:Our findings suggest that the intrinsically-photosensitive retinal ganglion cells (ipRGCs), which integrate melanopsin and cone signals, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Moreover, we find a dissociation between implicit and explicit measures of interictal photophobia depending on a history of visual aura in migraine. This implies distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which the amplification of ipRGC signals elicit implicit and explicit signs of visual discomfort.

Comparison of deep learning-assisted blinking analysis system and Lipiview interferometer in dry eye patients: a cross-sectional study

“…It was previously reported that there is a functional relation between the visual cortex and the trigeminal nociceptive system, and flash light stimulation activated the visual cortex and triggered nociceptive blink reflex pronouncedly in healthy subjects [ 41 ]. Moreover, exposure to intense luminance could activate trigeminal nerve activity, increase parasympathetic outflow to the eye and cause ocular discomfort [ 42 , 43 ]. Therefore, it is quite possible that the flashlight from Lipiview exerts an impact on the subjective comfort and interferes with the spontaneous blinking process.…”

Blue Light—Ocular and Systemic Damaging Effects: A Narrative Review

“…Melanopsin expression in different human and mice trigeminal branches, especially in the ophthalmic one, could also contribute to photophobia [ 85 , 86 ]. This function is still debatable as several authors did not find a significant effect [ 54 , 87 ].…”

“…The study conducted by Kaiser et al [ 54 ] found a clear dissociation between explicit and implicit measures of photophobia in subjects experiencing interictal light discomfort. The authors used the method of silent substitution stimulation to target melanopsin, cones, or both while the central 5° of the visual field was blocked to minimize the effects of macular pigment.…”

Visual hypersensitivity in patients treated with anti‐calcitonin gene–related peptide (receptor) monoclonal antibodies

“…Up to 90% of patients with migraine report photophobia during a migraine headache (ictal) 9 and about 60% report it outside of migraine attacks (interictal) 10 . There is evidence for both a central (i.e., hyperexcitability of the visual cortex) 6,23 and a peripheral (i.e., differences in retinal rod responses) 24,25 origin for photophobia. The limitation of many studies researching visual sensitivity in migraine is that they focus solely on photophobia; however, visual hypersensitivity in patients with migraine comprises a much broader concept.…”