Uchino Yuichi, Uchino Miki, Mizuno Miki, Shigeno Yuta, Furihata Kenichi, Shimazaki Jun
COSMOS (Corneal Subbasal Nerve and Maintenance of Ocular Surface) Study Group, Japan; Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
P-One Clinic, Keikokai Medical Corporation, 8-1 Yokamachi, Hachioji, Tokyo, 192-0071, Japan.
Exp Eye Res. 2023 May;230:109438. doi: 10.1016/j.exer.2023.109438. Epub 2023 Mar 16.
The purposes of the present study were to (1) identify the relationship between dry eye symptoms and morphological changes in corneal subbasal nerves/ocular surfaces, and (2) discover tear film biomarkers indicating morphological changes in the subbasal nerves. This was a prospective cross-sectional study conducted between October and November 2017. Adults with dry eye disease (DED, n = 43) and healthy eyes (n = 16) were evaluated based on their subjective symptoms and ophthalmological findings. Corneal subbasal nerves were observed using confocal laser scanning microscopy. Nerve lengths, densities, branch numbers, and nerve fiber tortuosity were analyzed using ACCMetrics and CCMetrics image analysis systems; tear proteins were quantified by mass spectroscopy. Compared with the control group, the DED group had significantly lower tear breakup times (TBUT) and pain tolerance capacity, and significantly higher corneal nerve branch density (CNBD) and corneal nerve total branch density (CTBD). CNBD and CTBD showed significant negative correlations with TBUT. Six biomarkers (cystatin-S, immunoglobulin kappa constant, neutrophil gelatinase-associated lipocalin, profilin-1, protein S100-A8, and protein S100-A9) showed significant positive correlations with CNBD and CTBD. The significantly higher CNBD and CTBD in the DED group suggests that DED is associated with morphological alterations in corneal nerves. The correlation of TBUT with CNBD and CTBD further supports this inference. Six candidate biomarkers that correlate with morphological changes were identified. Thus, morphological changes in corneal nerves are a hallmark of DED, and confocal microscopy may help in the diagnosis and treatment of dry eyes.
（1）确定干眼症状与角膜基底神经/眼表形态变化之间的关系；（2）发现指示基底神经形态变化的泪膜生物标志物。这是一项于2017年10月至11月进行的前瞻性横断面研究。基于主观症状和眼科检查结果，对患有干眼病（DED，n = 43）的成年人和健康眼睛（n = 16）进行评估。使用共聚焦激光扫描显微镜观察角膜基底神经。使用ACCMetrics和CCMetrics图像分析系统分析神经长度、密度、分支数量和神经纤维曲折度；通过质谱法定量泪液蛋白质。与对照组相比，DED组的泪膜破裂时间（TBUT）和疼痛耐受能力显著降低，角膜神经分支密度（CNBD）和角膜神经总分支密度（CTBD）显著升高。CNBD和CTBD与TBUT呈显著负相关。六种生物标志物（胱抑素-S、免疫球蛋白κ恒定区、中性粒细胞明胶酶相关脂质运载蛋白、原肌球蛋白-1、蛋白质S100-A8和蛋白质S100-A9）与CNBD和CTBD呈显著正相关。DED组中显著更高的CNBD和CTBD表明，DED与角膜神经形态改变有关。TBUT与CNBD和CTBD的相关性进一步支持了这一推断。确定了六种与形态变化相关的候选生物标志物。因此，角膜神经的形态变化是DED的一个标志，共聚焦显微镜检查可能有助于干眼的诊断和治疗。
