Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation With Clinical Parameters

PURPOSE: This study quantified corneal subbasal nerve tortuosity in dry eye disease (DED) and investigated its correlation with clinical parameters by proposing an aggregated measure of tortuosity (Tagg). METHODS: The sample consisted of 26 eyes of patients with DED and 23 eyes of healthy volunteers, which represented separately the dry eye group and the control group. Clinical evaluation of DED and in vivo confocal microscopy analysis of the central cornea were performed. Tagg incorporated six metrics of tortuosity. Corneal subbasal nerve images of subjects and a validation data set were analyzed using Tagg. Spearman's rank correlation was performed on Tagg and clinical parameters. RESULTS: Tagg was validated using 1501 corneal nerve images. Tagg was higher in patients with DED than in healthy volunteers (P < 0.001). Tagg was positively correlated with the ocular surface disease index (r = 0.418, P = 0.003) and negatively correlated with tear breakup time (r = −0.398, P = 0.007). There was no correlation between Tagg and visual analog scale scores, corneal fluorescein staining scores, or the Schirmer I test. CONCLUSIONS: Tagg was validated for quantification of corneal subbasal nerve tortuosity and was higher in patients with DED than in healthy volunteers. A higher Tagg may be linked to ocular discomfort, visual function disturbance, and tear film instability. TRANSLATIONAL RELEVANCE: Corneal subbasal nerve tortuosity is a potential biomarker for corneal neurobiology in DED.