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−
Summary
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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