Sleep and circadian phenotype in people without cone-mediated vision: a case series of fiveCNGB3and twoCNGA3patients

Abstract

Light exposure entrains the circadian clock through the intrinsically photosensitive retinal ganglion cells, which sense light in addition to the cone and rod photoreceptors. In congenital achromatopsia (prevalence 1:30–50,000), the cone system is non-functional, resulting in severe light avoidance and photophobia at daytime light levels. How this condition affects circadian and neuroendocrine responses to light is not known. In this case series of genetically confirmed congenital achromatopsia patients (n = 7; age 30–72 years; 6 women, 1 male), we examined survey-assessed sleep/circadian phenotype, self-reported visual function, sensitivity to light and use of spectral filters that modify chronic light exposure. In all but one patient, we measured rest-activity cycles using actigraphy over 3 weeks and measured the melatonin phase angle of entrainment using the dim-light melatonin onset. Due to their light sensitivity congenital achromatopsia patients used filters to reduce retinal illumination. Thus, congenital achromatopsia patients experienced severely attenuated light exposure. In aggregate, we found a tendency to a late chronotype. We found regular rest-activity patterns in all patients and normal phase angles of entrainment in participants with a measurable dim-light melatonin onset. Our results reveal that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment, even when survey-assessed sleep and circadian phenotype indicated a tendency for a late chronotype and sleep problems in our congenital achromatopsia cohort.

Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults

“…In sum, most of the available laboratory data suggest that melanopic EDI is a reliable index that provides a good approximation of the apparent spectral sensitivity of human circadian and acute nonvisual responses to ocular light exposure. In particular, for the extended exposures to polychromatic light that are relevant to everyday living environments, existing evidence indicates that any additional contributions from cones (or rods; whose spectral sensitivity is close to melanopsin [ 34 , 96 , 97 ]) do not compromise the predictive value of melanopic EDI.…”

“…The contribution of rods to such responses is an interesting topic for research in its own right. Nonetheless, including a rod component in any such future metrics is unlikely to substantially improve the accuracy with which they recreate the spectral sensitivity of the relevant response(s), since the very similar spectral sensitivity profiles of rods and melanopsin render effective irradiance for these 2 opsins highly correlated [ 97 ]. Conversely, cone spectral sensitivity is quite distinct from melanopsin and has the potential to substantially refine metrics for circadian and neurophysiological responses.…”

pyActigraphy: Open-source python package for actigraphy data visualization and analysis

“…Such analysis package would also help to reduce error rates by alleviating the burden of manual data processing that hampers the processing of large-scale actigraphy data sets. So far, the pyActigraphy package has successfully been used to compute non-parametric rest-activity rhythm variables [56,57], to automatically detect sleep periods…”

Current Insights into Optimal Lighting for Promoting Sleep and Circadian Health: Brighter Days and the Importance of Sunlight in the Built Environment

“…Further consideration is necessary to determine what the exact light dosing should be at peak times of midday exposure for the typical population and what accommodations, if any, are required for children or subgroups with environmental sensitivities. 139 As already mentioned, there is no general “Recommended Dietary Allowance” for light analogous to the daily nutrient intake recommendations maintained by the US Institute of Medicine or health authorities in other countries.…”