Blue and Red Light-Evoked Pupil Responses in Photophobic Subjects with TBI.

PURPOSE: Photophobia is a common symptom in individuals suffering from traumatic brain injury (TBI). Recent evidence has implicated blue light-sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs) in contributing to the neural circuitry mediating photophobia in migraine sufferers. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing pupillary responses to blue and red light. METHODS: Twenty-four case participants (mean age 43.3; 58% female), with mild TBI and self-reported photophobia, and 12 control participants (mean age 42.6; 58% female) were in this study. After 10 minutes of dark adaptation, blue (470 nm, 1 × 10 phots/s/cm) and red (625 nm, 7 × 10 phots/s/cm) flashing (0.1 Hz) light stimuli were delivered for 30 seconds to the dilated left eye while the right pupil was recorded. The amplitude of normalized pupil fluctuation (constriction and dilation) was quantified using Fourier fast transforms. RESULTS: In both case and control participants, the amplitude of pupil fluctuation was significantly less for the blue light stimuli as compared to the red light stimuli, consistent with a contribution of ipRGCs to these pupil responses. There was no significant difference in the mean pupil fluctuation amplitudes between the two participant groups, but case participants displayed greater variability in their pupil responses to the blue stimulus. CONCLUSIONS: Case and control participants showed robust ipRGC-mediated components in their pupil responses to blue light. The results did not support the hypothesis that ipRGCs are "hypersensitive" to light in TBI participants with photophobia. However, greater pupil response variability in the case subjects suggests that ipRGC function may be more heterogeneous in this group.

The Effect of Refractive Error on Melanopsin-Driven Pupillary Responses.

Purpose: Human and animal studies suggest that light-mediated dopamine release may underlie the protective effect of time outdoors on myopia development. Melanopsin-containing retinal ganglion cells may be involved in this process by integrating ambient light exposure and regulating retinal dopamine levels. The study evaluates this potential involvement by examining whether melanopsin-driven pupillary responses are associated with adult refractive error. Methods: Subjects were 45 young adults (73% female, 24.1 ± 1.8 years) with refractive errors ranging from -6.33 D to +1.70 D. The RAPDx (Konan Medical) pupillometer measured normalized pupillary responses to three forms of square-wave light pulses alternating with darkness at 0.1 Hz: alternating long wavelength (red, peak at 608 nm) and short wavelength (blue, peak at 448 nm), followed by red only and then blue only. Results: Non-myopic subjects displayed greater pupillary constriction in the blue-only condition and slower redilation following blue light offset than subjects with myopia (P = 0.011). Pupillary responses were not significantly different between myopic and non-myopic subjects in the red-only condition (P = 0.15). More hyperopic/less myopic refractive error as a continuous variable was linearly related to larger increases in pupillary constriction in response to blue-only stimuli (r = 0.48, P = 0.001). Conclusions: Repeated light exposures to blue test stimuli resulted in an adaptation in the pupillary response (more constriction and slower redilation), presumably due to increased melanopsin-mediated input in more hyperopic/less myopic adults. This adaptive property supports a possible role for these ganglion cells in the protective effects of time outdoors on myopia development.

Observer-perceived light aversion behaviour in photophobic subjects with traumatic brain injury.

BACKGROUND: Photophobia is a common sequela of traumatic brain injury (TBI). Diagnostic tools for this debilitating condition are lacking. This investigation sought to determine whether masked observers can distinguish subjects with TBI-associated photophobia from matched controls based on video recordings of their ocular responses to light stimulation. METHODS: Cohorts of students (n = 20), photophobic TBI subjects (n = 28) and their matched control subjects (n = 12) were recruited. A custom pupillometer delivered bright (1013 -1014 photons/s/cm2 ), flashing (0.10 Hz) red (625 nm) and blue (470 nm) light stimuli to subjects, and consensual pupil light responses were recorded. Using a five-point scale, masked observers later graded light aversion behaviour in the pupil video recordings obtained from the student cohort based on observed blinking, tearing and squinting. A grading scale was developed and used by masked observers to grade light aversion behaviour in videos obtained from subjects with post-TBI photophobia and the matched controls. These subjects also scored their perceived discomfort during each light pulse using a five-point scale. RESULTS: The subjects in the TBI cohort scored both the blue and red flashing stimuli as evoking more discomfort, relative to control subjects, consistent with their reported photophobia. There was strong agreement among the masked observers for their grades of light aversion behaviour in the videos of ocular light stimulation (interclass correlation co-efficient = 0.78; 29 per cent perfect concordance). However, the median grades for the videos obtained from the TBI subject cohort were not significantly different from those for the control group. CONCLUSIONS: Clinicians cannot diagnose TBI-related photophobia based solely on video recordings of ocular responses to light. The need remains for an objective test to diagnose and manage this prevalent post-TBI symptom.