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.

中文翻译：

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眼睛暴露于白光对完全视觉盲者的褪黑激素分泌的抑制作用

目的

尽管由于光线无法带走昼夜节律起搏器，大多数完全失明的人表现出不带昼夜节律，但是一小部分保留了光性昼夜节律，褪黑激素抑制以及其他对光无图像形成的反应。据认为，由于含黑色素的内在光敏性视网膜神经节细胞（ipRGCs）的存活，这些对光的反应持续存在，该细胞主要投射至昼夜节律起搏器，并且在功能上不同于介导视力的杆状和锥状光感受器。我们旨在评估患有一系列眼疾的全盲患者的非成像光接收的完整性。

设计

主题内，黑暗控制的设计。

参加者

共有18位完全失明的人（7位女性；平均年龄±标准差= 49.8±11.0岁），有多种导致失明的原因，其中包括3名双侧摘除眼镜的对照。

方法

将褪黑激素浓度在暴露于6.5小时的白光（约7000 lux）下与在暗光（4 lux）条件下在相应的时钟时间提前24小时测得的褪黑素浓度进行了比较。

主要观察指标

褪黑激素浓度曲线下的面积（AUC）。

结果

与昏暗状态相比，在15名有眼的参与者中，褪黑素浓度在暗光条件下显着受到抑制（定义为≥33％抑制）（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）。其余10名有眼的参与者对光的反应褪黑激素浓度保持不变（ROP，n = 3;视神经炎/神经病，n = 2;视网膜病变未知，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），并且在所有3例双侧摘除双眼的参与者中。

结论

这些数据证实，光诱导的褪黑激素抑制在少数完全有视觉盲的人的眼睛中保持功能完整。没有双侧去核个体或患有鳞茎鳞茎的个体对光没有反应。其余的一半对光有反应。尽管内部视网膜损伤与缺乏无图像形成的光接收的可能性较高相关，但外部视网膜损伤的影响更为模糊，因此，对完全盲患者的无图像形成的光反应的存在，衰减或不存在进行了评估。需要仔细的个人确认，不能简单地从盲人的类型中推断出来。