期刊
OPHTHALMOLOGY
卷 125, 期 8, 页码 1160-1171出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ophtha.2018.01.036
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资金
- Cephalon Inc
- Mary Ann & Stanley Snider via Combined Jewish Philanthropies
- National Football League Charities
- Optum
- Philips Respironics, Inc
- ResMed Foundation
- San Francisco Bar Pilots
- Schneider Inc
- Sysco
- Cephalon, Inc
- Jazz Pharmaceuticals
- Takeda Pharmaceuticals
- Teva Pharmaceuticals Industries, Ltd
- Sanofi-Aventis, Inc
- Sepracor, Inc
- Wake Up Narcolepsy
- Bose Corporation
- Boston Celtics
- Boston Red Sox
- Columbia River Bar Pilots
- Institute of Digital Media and Child Development
- Klarman Family Foundation
- Samsung Electronics
- Quest Diagnostics, Inc
- Vanda Pharmaceuticals
- Zurich Insurance Company, Ltd
- Biological Illuminations LLC
- F. Lux Software LLC
- BHP Billiton
- Informa Exhibitions
- Teague
- National Institute of Neurological Disorders and Stroke [R01 NS40982, R01 NS040982]
- Wellcome Trust, United Kingdom [060018/B/99/Z]
- National Center for Research Resources [M01-RR02635]
- Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR025758]
- Cephalon Clinical Fellowship in Circadian Medicine, Division of Sleep Medicine, Harvard Medical School
- National Heart, Lung and Blood Institute fellowship in the program of training in Sleep, Circadian and Respiratory Neurobiology at Brigham and Women's Hospital [T32 HL079010]
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 (similar to 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. (C) 2018 by the American Academy ofOphthalmology. This is an open access article under the CCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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