There Is Significant Within-Subject Variation in the Time from Light Stimulus to Maximum Pupil Constriction Among Healthy Controls

<b>Background</b>: Handheld quantitative pupilometers (QPs) measure each phase of the pupillary light reflex (PLR) and provide a summary score based on these values. One phase of the PLR is the period of time from the onset of light exposure to the maximum constriction of the pupil, also known as time to maximum constriction (tMC). Although tMC has been found to vary significantly among patients with neurological injury, there are no studies reporting tMC in healthy controls. This study addresses this gap. <b>Methods</b>: Subjects in this prospective observational study were healthy controls who provided paired (left and right eye) QP readings during four separate observations over the course of 2 days. The tMC was derived by determining the smallest observed pupil size during videos filmed at 30 frames per second, and we assessed within-subject variability using the coefficient of variance and intraclass correlation coefficient (ICC). <b>Results</b>: Fifty subjects provided 380 QP readings (190 left eye and 190 right eye). Subjects primarily identified as female (80%), non-Hispanic (86%), white (62%), and <40 years old (74%). The mean tMC was 1.0 (0.14) seconds (s) for the left eye and 1.0 (0.17) s for the right eye; the coefficient of variance ranged from 11.6% to 18.8% and the ICC ranged from 0.25 to 0.40. For the between-subject comparisons across the four observation periods, the left and right eye mean differences ranged from 0.001 to 0.063 and the ICC ranged from 0.12 to 0.52. <b>Conclusions</b>: The tMC values vary significantly in healthy controls. Changes in pupil function as a clinical biomarker of intracranial pathology are not fully understood. Identifying clinical correlations of tMC variation may provide insight for the prognostication and treatment of neurocritically ill patients.