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

摘要

PurposeAlthough 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.DesignWithin-subject, dark-controlled design.ParticipantsA total of 18 totally visually blind individuals (7 females; mean age 齭tandard deviation9.8?.0 years) with various causes of blindness, including 3 bilaterally enucleated controls.MethodsMelatonin 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 (4ux) conditions.Main Outcome MeasuresArea under the curve (AUC) for melatonin concentration.ResultsMelatonin concentrations were significantly suppressed (defined as e33% 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.ConclusionsThese 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.