To construct an objective analysis system of corneal nerve tortuosity and detect the changes of corneal subbasal nerve tortuosity in patients with dry eye and diabetes.

Grade Ⅰ to Ⅳ nerve tortuosity were evaluated and 80 photos of each grade were randomly chosen from the in vivo confocal microscopy library.Nerve fibers were extracted, segmented and then analyzed by 6 tortuosity related parameters including L_C, Seg_L_C_mean, Cur_mean, Specific_p, ICM and SCC_mean.After verifying the validaty of parameters above, a cross-sectional study was conducted.Subjects were collected from June, 2018 to February, 2019 in Peking University Third Hospital, and were divided into healthy control group (28 persons 56 eyes), dry eye without diabetes group (28 patients 56 eyes), diabetes without dry eye group(24 patients 48 eyes), diabetes with dry eye group (23 patients 46 eyes). Basic and dry eye information includes sex, age, ocular surface disease index (OSDI), tear film break-up time (TBUT), Schirmer Ⅰ test (SⅠt) and corneal fluorescence staining (CFS) score.Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were detected in diabetic patients.Cochet-Bonnet examination (C-BE) was detected to evaluate corneal sensation and 2 corneal subbasal nerve photos of each eye were selected for effective tortuosity and density related parameters analysis.Data was analyzed by SPSS and diagnostic test were perfomed by MedCalc.This study followed the Declaration of Helsinki.This study protocol was approved by Ethic Committee of Peking University Third Hospital(No.IRB00006761-M2017354). Written informed consent was obtained from each subject prior to entering study cohort.

L_C, Seg_L_C_mean, Cur_mean, Specific_p, ICM and SCC_mean increased as the nerve tortuosity increased from Grade Ⅰ to Grade Ⅳ, with an overall significance among 4 groups (F=39.100, 36.367, 57.743, 4.043, 6.818, 33.493; all at P<0.01). Among the above 6 parameters, Cur_mean and L_C of any two groups were of significant difference (all at P<0.01). Twenty three to twenty eight persons were enrolled in each group of the cross-sectional study.Sex and age were comparable among 4 groups.Diagnostic criteria were met in dry eye and diabetes.Corneal sensation parameter C-BE decreased in diabetes without dry eye group and diabetes with dry eye group compared with healthy control group(all at ^AdjP<0.05), other than in dry eye without diabetes group (^AdjP≥0.05). Nerve density of diabetes without dry eye group and diabetes with dry eye group was lower compared with healthy control group(all at P<0.001), while no significant difference between dry eye without diabetes group and healthy control group(P≥0.05). Among the effective parameters of tortuosity, L_C, Cur_mean, Seg_L_C_mean and SCC_mean of dry eye without diabetes group, diabetes without dry eye group, diabetes with dry eye group were higher compared with healthy control group(all at P<0.05). Diagnostic tests of tortuosity related parameters all showed an area under curve (AUC) from 0.5 to 0.7.

L_C and Cur_mean can be used to analyze corneal nerve curvature more reliably.Compared with normal volunteers, patients of dry eye or diabetes show higher corneal subbasal nerve tortuosity.

Corneal subbasal nerve; Tortuosity; Dry eye; Diabetes