PURPOSE

To evaluate corneal sensitivity and corneal nerve morphology among patients with Wolfram syndrome (WFS).

DESIGN

An observational clinical case series with confirmatory experiments.

METHODS

We included a group of 12 patients with biallelic mutations in the WFS1 gene and a control group composed of 30 individuals with type 1 diabetes (T1D). All participants (n = 42) underwent a complete ophthalmic examination, esthesiometry, and retinal nerve fiber layer assessment using optical coherence tomography. Morphologic assessment of corneal neuropathy by in vivo corneal confocal microscopy was conducted in 11 patients with WFS (both eyes) and 1 WFS patient (1 eye) as well as in 24 patients with T1D (both eyes in 6 patients and 1 eye in 18 patients). Additionally, corneas from Wfs1KO mice and their wild-type littermates were subjected to laser scanning confocal microscopy.

RESULTS

Corneal sensitivity was significantly reduced in patients with WFS compared with patients with T1D (4.50 cm [interquartile range, 3.50–5.50 cm] vs 6.00 cm [interquartile range, 6.00–6.00 cm]; P < 10^–5). Additionally, corneal nerve fiber and branch density as well as nerve fiber length were low among patients with WFS. Corneal sensitivity correlated with macular average thickness (R = 0.6928; P = .039) and best-corrected visual acuity (R = –0.61; P = .002) in the WFS group. Similarly, Wfs1 knockout mice also presented corneal neurodegeneration changes when corneal nerve fiber density and length were measured using laser scanning confocal microscopy.

CONCLUSIONS

Decreased corneal sensitivity and corneal nerve degeneration are observed in WFS. Corneal sensitivity is linked with the degree of disease progression as measured by visual acuity and retinal thinning.

中文翻译：

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神经元变性导致角膜敏感性降低是 Wolfram 综合征的新临床特征

目的

评估 Wolfram 综合征 (WFS) 患者的角膜敏感性和角膜神经形态。

设计

带有验证性实验的观察性临床病例系列。

方法

我们纳入了一组 12名 WFS1基因双等位基因突变的患者和一个由 30 名 1 型糖尿病 (T1D) 患者组成的对照组。所有参与者 ( n  = 42) 都使用光学相干断层扫描进行了完整的眼科检查、感觉测量和视网膜神经纤维层评估。通过体内角膜共聚焦显微镜对 11 名 WFS 患者（双眼）和 1 名 WFS 患者（1 眼）以及 24 名 T1D 患者（6 名患者的双眼和 18 名患者的 1 眼）进行角膜神经病变的形态学评估）。此外，对来自 Wfs1KO 小鼠及其野生型同窝小鼠的角膜进行了激光扫描共聚焦显微镜检查。

结果

与 T1D 患者相比，WFS 患者的角膜敏感性显着降低（4.50 cm [四分位距，3.50–5.50 cm] vs 6.00 cm [四分位距，6.00–6.00 cm]；P < ^10–5）。此外，WFS 患者的角膜神经纤维和分支密度以及神经纤维长度较低。WFS 组的角膜敏感性与黄斑平均厚度 (R = 0.6928; P  = .039) 和最佳矫正视力 (R = –0.61; P  = .002) 相关。同样，当使用激光扫描共聚焦显微镜测量角膜神经纤维密度和长度时，Wfs1 敲除小鼠也出现角膜神经变性变化。

结论

在 WFS 中观察到角膜敏感性降低和角膜神经变性。角膜敏感性与通过视力和视网膜变薄测量的疾病进展程度有关。