Effects of Mild Traumatic Brain Injury (mTBI) on Retinal Structure, Function, and Pupillary Light Responses

Abstract

Purpose: Evaluate the sensitivity and light adaptation characteristics of ipRGC-mediated PLR and how they are altered in the dark and under different backgrounds with direct pupil stimulation in patients with mTBI.

Methods: Direct pupillary light reflex (PLR) to blue light (peak λ = 440nm, FWHM = 20nm) was measured from the dominant eye, the other eye was fully occluded, of 12 control adult subjects (ages 42.2 ± 17.0 years) and 12 chronic mTBI patients (ages 35.4 ± 12.8 years) using LiveTrack pupilometer module and an infrared camera (30Hz) inside a LED-driven Ganzfeld system (Espion V6 ColorDome, Diagnosys LLC, Lowell, MA). The study consisted of two protocols: (1) The intensity series included 19 steps of increasing intensity ranging from 0.001 to 198 cd/m2, was completed first in sequence after 5 minutes of initial dark adaptation, and 2 minutes between test flashes. A test blue flash stimulus with a duration of 1 second was used, and the pupil response were recorded for 7.5 seconds. Between each successive step, 2 minutes of dark adaption was allowed. (2) The background intensity series, consisted of 7 steps, ranging from 0 to 10 cd/m2, was completed thereafter with test flash of 120 cd/m2 on top of the background. Pupil diameter measurements were made following 5 minutes of initial dark-adaptation, and first on a dark background with a 120 cd/m2 test flash for a duration of 1 second. The subjects adapted for 2 minutes to each subsequent background intensity. The same bright, blue test flash of 120 cd/m2 was used on top of each background intensity. The 6-second post-illumination pupil response (PIPR) amplitudes were extracted at 6 seconds after stimulus offset, and averaged over a 100ms window (i.e., between 6950ms and 7050ms). The peak or maximal pupil constriction amplitude was measured at the trough from baseline. A stimulus intensity response was plotted for the PIPR and peak percent reduction from baseline across all 19 intensities. The intensity series PIPR and peak data was fitted to the Naka-Rushton equation of the form V(I) = (Vmax * In) / (In + Kn) to derive the saturated amplitude (Vmax), slope (n) and semisaturation constant (K). The values of the fit parameters were compared between control and mTBI groups. For the background series, the baseline pupil diameter, PIPR, and peak parameters were extracted from the 7 steps and compared between controls and mTBI patients. Wilcoxin rank sum test was used to compare the corresponding parameters between mTBI and controls. P values less than 0.05 were considered statistically significant.

Results: The PIPR was significantly reduced in mTBI patients relative to controls through both the intensity and background series, indicating a reduction in luminance gain of ipRGCs. In addition, the baseline pupil diameter following 2 or 5-minutes of dark-adaptation and at the end of 2-minutes of light adaptation over a 5-log unit range of background intensities (0.0001-10 cd/m2) was larger (i.e., less constriction) for mTBI patients, suggesting an underlying pathophysiology of the ipRGCs, reaffirming the dysfunction of the luminance gain control.

Conclusions: The reduction in the PIPR and the larger baseline pupil responses in patients with mTBI insinuated an underlying pathophysiology that may reflect a dysfunction of ipRGC and its luminance gain control mechanism especially when exposed to long duration light stimuli. Therefore, evaluating the baseline diameter at 2 minutes following light exposure on a series of background intensities may prove to be clinically more useful for identifying retinal abnormalities in mTBI.