Purpose

To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease.

Design

Cross-sectional study.

Participants

Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of −6 decibels or better on automated perimetry.

Methods

Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography.

Main Outcome Measures

Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson’s correlation analysis.

Results

Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm²/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG.

Conclusions

Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.

中文翻译：

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早期原发性开角型青光眼患者对全视野色刺激的瞳孔反应减少。

目的

评估彩色瞳孔测定法揭示早期原发性开角型青光眼（POAG）患者的瞳孔对光的异常反应的能力，并测试瞳孔缩小度与疾病中视神经损伤的结构特征是否相关。

设计

横断面研究。

参加者

早期POAG患者46例（63.4±8.3岁，男性63％，华裔87％）和90例年龄相匹配的健康对照组（61.4±8.6岁，男性34％，华裔89％）。在自动视野检查中，POAG患者的视野平均偏差（VFMD）为-6分贝或更好。

方法

使用配备有发光二极管照明系统的改良型Ganzfeld穹顶，每位参与者分别在蓝光（462 nm）下单眼暴露2分钟，然后在红光（638 nm）下另外2分钟暴露。对数增加光刺激强度，以评估固有光敏性视网膜神经节细胞（ipRGCs）的外部和内部响应的组合。光诱发的水平瞳孔直径变化是使用红外瞳孔成像单眼评估的。

主要观察指标

计算基线调整的，光诱导的瞳孔收缩幅度，并为每种刺激构建单独的辐照-响应曲线。使用线性混合模型分析比较各组之间以及整个光强度的瞳孔收缩幅度。使用Pearson相关分析评估瞳孔测量参数与青光眼不同结构和功能特征之间的线性关系。

结果

与处于中度至高辐照度（≥11 Log光子/ cm ² / s）的蓝色（P  = 0.003）和红色（P <0.001）光的对照组相比，早期POAG患者的光诱发的瞳孔收缩减少。 对于POAG患者，瞳孔最大收缩幅度与视网膜神经纤维层厚度（RNFL）厚度相关（蓝色：r  = 0.51，P <0.001；红色：r  = 0.45，P = 0.002），但与对照组无关。相反，早期POAG患者的瞳孔测量参数与视野得分无关。

结论

患有早期POAG的患者对中，高强度蓝光和红光的瞳孔反应减弱。这种与波长无关的功能改变与RNFL的结构变薄有关，并且可能是疾病早期阶段表达黑素蛋白的ipRGC的功能障碍或丧失的结果。