Geometrical Features of Sub-basal Corneal Whorl-like Nerve Patterns in Dry Eye Disease: An In Vivo Confocal Microscopy Study

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PurposeTo investigate the geometrical feature of the whorl-like corneal nerve in dry eye disease (DED) across different severity levels and subtypes, and to preliminarily explore its diagnostic ability. DesignCross-sectional study. ParticipantsThe study included 29 healthy subjects (51 eyes) and 62 DED patients (95 eyes). MethodsAll subjects underwent comprehensive ophthalmic examinations, dry eye tests, and in vivo confocal microscopy to visualize the whorl-like corneal nerve at the inferior whorl (IW) region and the straight nerve at the central cornea. The structure of the corneal nerve was extracted and characterized using the fractal dimension (CNDf), multi-fractal dimension (CND0), tortuosity (CNTor), fiber length (CNFL), and numbers of branching points (CNBP). Main outcome measuresThe characteristics of quantified whorl-like corneal nerve metrics in different groups of severity and subtype defined by symptoms and signs of DED. ResultsCompared to the healthy controls, the CNDf, CND0, and CNFL of the IW decreased significantly as early as grade 1 DED (P<0.05), while CNTor increased (P<0.05). These parameters did not change significantly in the straight nerve. As the DED severity increased, CNDf and CNFL in the whorl-like nerve further decreased in grade 3 DED compared to grade 1. Significant nerve fiber loss was observed in aqueous-deficient DED compared to evaporative DED (P<0.05). Whorl-like nerve metrics correlated with ocular discomfort, tear film break-up time, tear secretion and corneal fluorescein staining, respectively (P<0.05). Furthermore, merging parameters of whorl-like and linear nerve showed an area under the curve value of 0.910 in diagnosing DED. ConclusionsGeometrical parameters of IW could potentially allow optimization of the staging of DED. Reliable and objective measurements for the whorl-like cornea nerve might facilitate patient stratification and diagnosis of DED.