Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts; Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts.
Ophthalmology. 2018 Aug;125(8):1160-1171. doi: 10.1016/j.ophtha.2018.01.036. Epub 2018 Apr 4.
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.
Within-subject, dark-controlled design.
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.
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.
Area under the curve (AUC) for melatonin concentration.
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.
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.
尽管大多数完全失明的个体由于光无法使生物钟同步而表现出非同步的昼夜节律，但一小部分人仍保留光对生物钟的同步作用、褪黑素的抑制以及其他对光的非成像反应。据认为，这些对光的反应之所以持续存在，是因为含有黑色素的视网膜神经节细胞（ipRGCs）的存活，这些细胞主要投射到生物钟，并且与介导视觉的杆状和锥状光感受器在功能上不同。我们旨在评估各种眼部疾病导致的完全失明患者中非成像光感受的完整性。
自身对照，暗室控制设计。
共 18 名完全失明的个体（7 名女性；平均年龄±标准差=49.8±11.0 岁），失明原因各不相同，包括 3 名双侧眼球摘除的对照者。
在暴露于 6.5 小时明亮白光（~7000lux）下时比较褪黑素浓度，并在相应的时钟时间在暗光（4lux）条件下测量 24 小时前的褪黑素浓度。
褪黑素浓度的曲线下面积（AUC）。
与暗光条件相比，15 名有眼参与者中有 5 名（色素性视网膜炎，n=2；早产儿视网膜病变[ROP]，n=2；双侧视网膜脱离，n=1）在明亮光条件下褪黑素浓度明显受到抑制（定义为抑制≥33%）。其余 10 名有眼参与者（ROP，n=3；视神经炎/神经病，n=2；视网膜病变原因不明，n=2；先天性青光眼，n=1；先天性风疹综合征，n=1；麻疹性视网膜病变，n=1）以及所有 3 名双侧眼球摘除者的褪黑素浓度对光没有反应。
这些数据证实，在少数有眼的完全失明个体中，光诱导的褪黑素抑制仍然具有功能性。没有任何双侧眼球摘除者或眼球萎缩者对光有反应；其余的，一半对光有反应。尽管内视网膜损伤与非成像光感受器缺失的可能性高度相关，但外视网膜损伤的影响则更为模糊，因此，在完全失明的患者中评估非成像光反应的存在、衰减或缺失需要仔细的个体确认，而不能简单地从失明的类型来推断。
