Abstract

Melanopsin-containing retinal ganglion cells play an important role in the non-image forming effects of light, through their direct projections on brain circuits involved in circadian rhythms, mood and alertness. Individual differences in the functionality of the melanopsin-signaling circuitry can be reliably quantified using the maximum post-illumination pupil response (PIPR) after blue light. Previous protocols for acquiring PIPR relied on the use of mydriatics to dilate the light-exposed eye. However, pharmacological pupil dilation is uncomfortable for the participants and requires ophthalmological expertise. Hence, we here investigated whether an individual’s maximum PIPR can be validly obtained in a protocol that does not use mydriatics but rather increases the intensity of the light stimulus. In 18 participants (5 males, mean age ± SD: 34.6 ± 13.6 years) we evaluated the PIPR after exposure to intensified blue light (550 µW/cm2) provided to an undilated dynamic pupil. The test-retest reliability of the primary PIPR outcome parameter was very high, both between day-to-day assessments (Intraclass Correlation Coefficient (ICC) = 0.85), as well as between winter and summer assessments (ICC = 0.83). Compared to the PIPR obtained with the use of mydriatics and 160 µW/cm2 blue light exposure, the method with intensified light without mydriatics showed almost zero bias according to Bland-Altman plots and had moderate to strong reliability (ICC = 0.67). In conclusion, for PIPR assessments, increasing the light intensity is a feasible and reliable alternative to pupil dilation to relieve the participant’s burden and to allow for performance outside the ophthalmological clinic.

Highlights

  • The suprachiasmatic nucleus (SCN) in the hypothalamus encompasses the endogenous biological clock, which drives physiological, endocrine, and behavioral rhythms with a periodicity of about24 h [1]

  • We previously showed that these post-illumination pupil response (PIPR) measurements have very high within-subject test-retest reliability [16]

  • Retinal illuminance during blue light was estimated based on the mean pupil diameter during blue light to be 18850 Td in 160My+, 1545 Td in 160My−, and 4897 Td in 550My−

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Summary

Introduction

The suprachiasmatic nucleus (SCN) in the hypothalamus encompasses the endogenous biological clock, which drives physiological, endocrine, and behavioral rhythms with a periodicity of about24 h [1]. The daily environmental light-dark cycle serves as the main synchronizer to entrain these so called circadian rhythms to an exact 24-h cycle in order to remain in phase with the 24-h period of a day on Earth [2]. Photosensitive retinal ganglion cells (ipRGCs) play a key role in this circadian photoentrainment [3,4]. IpRGCs express the photopigment melanopsin which enables them to intrinsically decode ambient light levels [3,5]. Through direct connections between ipRGCs and the brain, the integrated intrinsic and extrinsic information on environmental light is transferred from the retina to downstream non-image forming brain regions, with the SCN as one of the main targets [8]

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