Pulses of melanopsin-directed contrast produce highly reproducible pupilresponses that are insensitive to a change in background radiance

Abstract

PurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrallynarrowband stimuli.Methods 3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were "silent substitution" coneand melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape. ResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone-and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light. ConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups. Methods SubjectsSubjects were recruited from the community of students and staff at the University of Pennsylvania. Exclusion criteria for enrollment included a prior history of glaucoma or a negative reaction to pupil-dilating eye drops. During an initial screening session, subjects were also excluded for abnormal color vision as determined by the Ishihara plates 43 or visual acuity below 20/40 in each eye as determined using a distance Snellen eye chart. Subjects completed a brief, screening pupillometry session. We excluded at this preliminary stage subjects who were unable to provide high-quality pupil tracking data (details below). Poor data quality was found to result from difficulty suppressing blinks or from poor infra-red contrast between the pupil and iris.A total of 32 subjects were recruited and completed initial screening. Two of these subjects were excluded after screening due to poor data quality (e.g., excessive loss of data points from blinking) as determined by pre-registered criteria. Thirty subjects thus successfully completed Session 1 and provided data for analysis. These subjects were between 19-33 years of age (mean 25.93 ± 4.24 SD). Fourteen subjects identified as male, 15 female, and one declined to provide a gender identification. Of this group of 30 sub...