Cheng Jun, Liu Chang, Yu Mingyi, Lee Isabelle Xin Yu, Wang Xinyue, Hsu Victor Wei-Tse, Takahashi Aya, Mehta Jodhbir S, Zhou Lei, Tong Louis, Liu Yu-Chi
Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Eye Disease, China; School of Ophthalmology, Shandong First Medical University, China.
Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore; Cornea and Refractive Surgery Group, Singapore Eye Research Institute, Singapore.
Ocul Surf. 2025 Aug 14;38:230-241. doi: 10.1016/j.jtos.2025.08.002.
To investigate the imaging, clinical, and tear proteomic profiles between neuropathic corneal pain (NCP) and dry eye disease (DED), and to identify potential imaging and molecular biomarkers for the differentiation of NCP from DED.
This cross-sectional study included 54 NCP patients (105 eyes), 53 DED patients (106 eyes), and 54 healthy controls (108 eyes). All subjects were evaluated with ocular surface assessment, ocular pain assessment survey (OPAS), and in-vivo confocal microscopy to characterize corneal nerves, microneuromas (MNs), immune cells, and epithelial cells. Tear quantitative proteomics were analyzed.
The percentage of presence of MNs, the number, total area, total perimeter, and average area of MNs were significantly higher in the NCP group than the other two groups. NCP patients had significantly higher corneal nerve fiber width. MNs parameters were significantly correlated with the OPAS scores (r = 0.20 to 0.48, all P < 0.05). Particularly, in peripheral NCP, both MNs total area and perimeter exhibited a significant correlation with the OPAS eye pain intensity (r = 0.55-0.57, both P < 0.05). Combinations of MNs parameters and OPAS scores had high diagnostic efficacy for NCP with an area under the curve (AUC) of 0.916. A total of 129 significantly differential proteins were identified, such as up-regulated vinculin and down-regulated DLG associated protein 4 in NCP, as well as up-regulated S100A12 and matrix metallopeptidase 9 in DED. These dysregulated proteins were linked to neuron apoptosis, inflammatory response, and synaptic transmission.
NCP patients present with different imaging features, clinical characteristics and proteomic profiles, compared with DED patients. These can be used as differentiating indicators.
研究神经性角膜疼痛（NCP）和干眼疾病（DED）之间的影像学、临床及泪液蛋白质组学特征，识别用于区分NCP与DED的潜在影像学和分子生物标志物。
这项横断面研究纳入了54例NCP患者（105只眼）、53例DED患者（106只眼）和54名健康对照者（108只眼）。所有受试者均接受眼表评估、眼痛评估调查（OPAS）以及共聚焦显微镜活体检查，以对角膜神经、微神经瘤（MNs）、免疫细胞和上皮细胞进行特征描述。对泪液进行定量蛋白质组学分析。
NCP组中MNs的存在百分比、MNs的数量、总面积、总周长和平均面积均显著高于其他两组。NCP患者的角膜神经纤维宽度显著更高。MNs参数与OPAS评分显著相关（r = 0.20至0.48，均P < 0.05）。特别是在周边NCP中，MNs的总面积和周长均与OPAS眼痛强度显著相关（r = 0.55 - 0.57，均P < 0.05）。MNs参数与OPAS评分的组合对NCP具有较高的诊断效能，曲线下面积（AUC）为0.916。共鉴定出129种显著差异蛋白，如NCP中上调的纽蛋白和下调的Dlg相关蛋白4，以及DED中上调的S100A12和基质金属肽酶9。这些失调的蛋白与神经元凋亡、炎症反应和突触传递有关。
与DED患者相比，NCP患者具有不同的影像学特征、临床特征和蛋白质组学特征。这些可作为鉴别指标。
