Objective: To analyze the characteristic changes of corneal nerve fibers in patients with Parkinson's disease (PD) by corneal confocal microscopy (CCM) and investigate the association of corneal nerve fiber parameters with disease severity and motor symptoms. Methods: Forty-two patients with PD were recruited from the Department of Neurology, Henan University People's Hospital from June 2018 to October 2019. Meanwhile, 40 healthy controls who visited the hospital for physical examination at the same period were enrolled. Corneal nerve fibers in both eyes of all participants were detected by using CCM. The differences of corneal nerve fibers were comparatively analyzed between PD group and healthy controls. Associations of corneal nerve parameters with clinical characteristics such as course of disease, Hoehn and Yahr stage (H-Y stage), unified Parkinson disease rating scale (UPDRS), levodopa equivalent daily dosage (LEDD) were analyzed by using partial correlations. The receiver operating characteristic (ROC) curve was used to analyze the capability of corneal nerve fibers for distinguishing patients with PD from healthy controls. Results: Corneal nerve fiber density (CNFD) in PD group ((19±3)/mm2) was significantly decreased compared with healthy controls ((28±4)/mm2) (t=10.798, P<0.001). However, corneal nerve branch density (CNBD) was significantly increased in PD group ((25±11)/mm2) compared with healthy controls ((18±6)/mm2) (t=-3.427, P=0.001). Meanwhile, corneal nerve fiber length (CNFL) was decreased in PD group ((11.0±2.5) mm/mm2) in comparison with healthy controls ((12.5±1.6) mm/mm2) (t=3.139, P=0.002). ROC curve analysis revealed that CNFD could discriminate PD patients from healthy controls, with an area under the curve of 0.961 3 (95%CI: 92.42-99.84, P<0.000 1). CNFD was negatively correlated with H-Y stage and UPDRS-Ⅲ (r=-0.501 and -0.399, both P<0.05). CNBD was significantly negatively associated with H-Y stage, UPDRS-Ⅲ and UPDRS-Total (r=-0.622, -0.394 and -0.354, respectively, all P<0.05). CNFL was negatively correlated with H-Y stage, UPDRS-Ⅲ and UPDRS-total (r=-0.574, -0.484 and -0.422, respectively, all P<0.05). Conclusion: Small nerve fiber injuries exist in PD patients. Corneal nerve fibers negatively correlates with motor symptoms. CNFD have a good discriminative power to distinguish PD patients from healthy controls and may serve as a marker for PD.
目的： 通过角膜共聚焦显微镜（CCM）检测帕金森病（PD）患者的角膜神经纤维变化，同时探讨角膜神经纤维与疾病严重程度和运动症状的关系。 方法： 收集2018年6月至2019年10月在河南大学人民医院神经内科门诊就诊和住院治疗的年龄40~80岁PD患者42例，作为PD组，并收集同时期来医院体检的40~80岁的40名健康中老年人作为健康对照组，受试者双眼均行CCM检查。对比分析PD组与健康对照组的角膜神经差异，采用相关分析评估PD患者角膜神经纤维与病程、H-Y分期（H-Y）、统一帕金森病评定量表（UPDRS）、左旋多巴每日等效剂量（LEDD）的关系，采用受试者工作特征曲线分析角膜神经纤维能否作为PD诊断的标志物。 结果： PD患者的角膜神经纤维密度（CNFD）［（19±3）支/mm2］低于健康对照组［（28±4）支/mm2］（t=10.798，P<0.001）。PD患者的角膜神经分支密度（CNBD）［（25±11）支/mm2］高于健康对照组［（18±6）支/mm2）］（t=-3.427，P=0.001）。PD患者的角膜神经纤维长度（CNFL）［（11.0±2.5） mm/mm2］少于健康对照组［（12.5±1.6） mm/mm2）］（t=3.139，P=0.002）。CNFD具有较好的诊断PD的敏感度和特异度，其受试者工作特征曲线下面积为0.961 3（95%CI：92.42~99.84，P<0.000 1）。PD运动症状受累较重侧角膜神经纤维与受累较轻侧间差异无统计学意义（P>0.05）。偏相关分析显示CNFD与H-Y、UPDRS-Ⅲ呈负相关（r分别为-0.501，-0.399，均P<0.05）。CNBD与H-Y、UPDRS-Ⅲ、UPDRS-总分负相关（r分别为-0.622、-0.394、-0.354，均P<0.05）。CNFL与H-Y、UPDRS-Ⅲ、UPDRS-总分负相关（r分别为-0.574、-0.484、-0.422，均P<0.05）。 结论： PD患者存在小神经纤维损伤， 随着疾病严重程度的增加，小神经纤维的代偿能力下降。角膜神经纤维与运动严重程度负相关。CNFD诊断PD有较高的敏感度，可能作为诊断PD的标志物。.