0028 Post Illumination Pupil Response is Associated with Circadian Timing in Healthy Adults

Abstract Introduction Greater variability in day-to-day sleep timing (i.e., sleep regularity) is associated with later circadian phase, potentially through increased variability in the timing of light exposure across the day. In humans, the circadian timing system is entrained via light exposure transmitted from the eye to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). The post-illumination pupillary response (PIPR) is one method used to measure the light-based activity of ipRGCs and has been shown to be greater in individuals with later sleep timing. However, the extent to which PIPR may be impacting circadian timing and sleep regularity is unclear. We therefore assessed the association between circadian timing, sleep regularity, and PIPR in healthy adults. Methods Eighteen ostensibly healthy volunteers (12F; aged mean±SD 29±7y) underwent an in-laboratory stay that began with a PIPR assessment followed by ~8h evening salivary melatonin collection in dim-lighting ( 5lux). Following the in-laboratory stay, participants recorded a daily sleep-wake diary for ~14-days to capture sleep regularity. PIPR was determined using a blue- and red-light stimulus following a 10-minute dark adaptation period and quantified as the percentage change between baseline pupil diameter and the pupil diameter 6-seconds post-stimulus. Circadian phase was determined via salivary dim-light melatonin onset (DLMO; 3pg/ml threshold) and sleep regularity was assessed using the standard deviation (SD) of diary-determined sleep onset across the ~14 days. The associations between DLMO, SD sleep onset, and PIPR were assessed using unadjusted linear models. Results On average, participants had a DLMO of 20:10±1:04, sleep onset of 24:05±1:34, and a SD sleep onset timing of 1.11±0.47h. Later DLMO was associated with greater PIPR sensitivity (effect: 4.2%; p=0.014); however, there was no significant association between SD sleep onset timing and PIPR (p=0.7). Conclusion We found that a later circadian phase was associated with a greater sensitivity to light in healthy adults, with no significant relationship between sleep regularity and light sensitivity. While directionality of the significant relationship is unclear, these findings may suggest that sleep regularity has limited impact on light sensitivity and thus the observed delayed phase via irregular sleep schedules may be driven by a different mechanism (i.e., differing light exposure patterns). Support (if any)