Blue and red light-evoked pupil responses in photophobic individuals with traumatic brain injury

Abstract

Purpose: Photophobia is a common symptom in individuals who have suffered a 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 migraineurs. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing relative pupillary responses to blue and red light.

Methods: Data was collected from 22 case subjects (mean age = 43.3±2.4; 59% female) with a prior TBI and self-reported photophobia, along with 12 control subjects (mean age = 42.6±4.5; 58% female). After a 10 min dark adaptation period, light stimuli were generated by blue (470 nm, 1x10¹³ phots/s/cm²) and red (625 nm, 7x10¹³ phots/s/cm²) LEDs. Each stimulus flashed on and off at 0.1 Hz for 30s and was delivered to the dilated left eye while the right pupil was recorded. The amplitude of normalized pupil fluctuation was quantified using Fourier fast transforms.

Results: As ipRGCs continue to fire after light offset, smaller values of the Fourier-derived pupil fluctuation are indicative of greater ipRGC contribution to the pupil responses. In either the case or the control group, the Fourier-derived pupil fluctuation was significantly (P<0.05) less for the blue (25.4±6.6 [SD], 23.8±2.4) versus red light (28.4±5.6, 28.1±3.1), consistent with the greater contribution of ipRGCs to the former stimulus. As evident in the standard deviation of the fourier-derived data, case subjects displayed greater variability in their pupil responses, especially to blue stimuli. On a 5-point scale, the case subjects rated the first blue pulse to be significantly brighter (4.3±0.1) than the second (4.0±0.2) or third pulses (3.7±0.2), and these subjective brightness grades were significantly higher that obtained from the controls for the same stimuli.

Conclusions: Similar to control subjects, case subjects showed robust ipRGC-mediated components in their pupil responses to blue light. The mean Fourier-derived amplitude of pupil fluctuation evoked by flashing blue stimuli did not differ between the two subject groups. However, greater pupil response variability in the case subjects suggests that ipRGC function may be more heterogeneous in this group. Subjectively, the case subjects reported the stimuli to be brighter than that reported by the control subjects.