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Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light: Clinical Characteristics

Hull, J.T., Czeisler, C.A. and Lockley, S.W. (2018) Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light: Clinical Characteristics Ophthalmology, 125 (8). pp. 1160-1171.

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Purpose: Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light to entrain the circadian pacemaker, a small proportion retain photic circadian entrainment, melatonin suppression, and other nonimage-forming responses to light. It is thought that these responses to light persist because of the survival of melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily to the circadian pacemaker and are functionally distinct from the rod and cone photoreceptors that mediate vision. We aimed to assess the integrity of nonimage-forming photoreception in totally visually blind patients with a range of ocular disorders. Design: Within-subject, dark-controlled design. Participants: A total of 18 totally visually blind individuals (7 females; mean age ± standard deviation = 49.8±11.0 years) with various causes of blindness, including 3 bilaterally enucleated controls. Methods: Melatonin concentrations were compared during exposure to a 6.5-hour bright white light (�7000 lux) with melatonin concentrations measured 24 hours earlier at the corresponding clock times under dim-light (4 lux) conditions. Main Outcome Measures: Area under the curve (AUC) for melatonin concentration. Results: Melatonin concentrations were significantly suppressed (defined as �33% suppression) during the bright-light condition compared with the dim-light condition in 5 of 15 participants with eyes (retinitis pigmentosa, n = 2; retinopathy of prematurity [ROP], n = 2; bilateral retinal detachments, n = 1). Melatonin concentrations remained unchanged in response to light in the remaining 10 participants with eyes (ROP, n = 3; optic neuritis/neuropathy, n = 2; retinopathy unknown, n = 2; congenital glaucoma, n = 1; congenital rubella syndrome, n = 1; measles retinopathy, n = 1) and in all 3 bilaterally enucleated participants. Conclusions: These data confirm that light-induced suppression of melatonin remains functionally intact in a minority of totally visually blind individuals with eyes. None of the bilaterally enucleated individuals or those with phthisis bulbi was responsive to light; of the remainder, half were responsive to light. Although inner retinal damage is associated with a high likelihood that nonimage-forming photoreception is absent, the impact of outer retinal damage is more ambiguous, and therefore the assessment of the presence, attenuation, or absence of nonimage-forming light responses in totally blind patients requires careful individual confirmation and cannot simply be assumed from the type of blindness. © 2018 American Academy of Ophthalmology

Item Type: Article
Authors :
Hull, J.T.
Czeisler, C.A.
Date : 2018
DOI : 10.1016/j.ophtha.2018.01.036
Uncontrolled Keywords : melatonin, biological marker, melatonin, adult, aged, Article, blindness, clinical article, clinical feature, cohort analysis, congenital glaucoma, congenital rubella syndrome, controlled study, eye enucleation, female, hormone release, human, light exposure, male, measles, middle aged, optic nerve disease, optic neuritis, photoreceptor, priority journal, retina cone, retina detachment, retina ganglion cell, retina injury, retina rod, retinitis pigmentosa, retrolental fibroplasia, white light, blindness, circadian rhythm, metabolism, pathophysiology, photostimulation, physiology, vision, visually impaired person, Adult, Aged, Biomarkers, Blindness, Circadian Rhythm, Female, Humans, Male, Melatonin, Middle Aged, Photic Stimulation, Retinal Ganglion Cells, Visual Perception, Visually Impaired Persons
Depositing User : Clive Harris
Date Deposited : 17 Jun 2020 00:51
Last Modified : 17 Jun 2020 00:51

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