Purpose.: The post-illumination pupil response (PIPR) has been quantified using four metrics, but the spectral sensitivity of only one is known; here we determine the other three. To optimize the human PIPR measurement, we determine the protocol producing the largest PIPR, the duration of the PIPR, and the metric(s) with the lowest coefficient of variation. Methods.: The consensual pupil light reflex (PLR) was measured with a Maxwellian view pupillometer. Experiment 1: Spectral sensitivity of four PIPR metrics (plateau, 6 seconds, area under curve early and late recovery) was determined from a criterion PIPR to a 1-second pulse and fitted with vitamin A1 nomogram (??max = 482 nm). Experiment 2: The PLR was measured as a function of three stimulus durations (1 second, 10 seconds, 30 seconds), five irradiances spanning low to high melanopsin excitation levels (retinal irradiance: 9.8a??14.8 log quanta.cma??2.sa??1), and two wavelengths, one with high (465 nm) and one with low (637 nm) melanopsin excitation. Intra- and interindividual coefficients of variation (CV) were calculated. Results.: The melanopsin (opn4) photopigment nomogram adequately describes the spectral sensitivity of all four PIPR metrics. The PIPR amplitude was largest with 1-second short-wavelength pulses (a?￥12.8 log quanta.cma??2.sa??1). The plateau and 6-second PIPR showed the least intra- and interindividual CV (a?¤0.2). The maximum duration of the sustained PIPR was 83.0 ?± 48.0 seconds (mean ?± SD) for 1-second pulses and 180.1 ?± 106.2 seconds for 30-second pulses (465 nm; 14.8 log quanta.cma??2.sa??1). Conclusions.: All current PIPR metrics provide a direct measure of the intrinsic melanopsin photoresponse. To measure progressive changes in melanopsin function in disease, we recommend that the PIPR be measured using short-duration pulses (e.g., a?¤1 second) with high melanopsin excitation and analyzed with plateau and/or 6-second metrics. Our PIPR duration data provide a baseline for the selection of interstimulus intervals between consecutive pupil testing sequences.
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