Corneal confocal microscopy detects small fibre neurodegeneration in Parkinson's disease using automated analysis

We studied the utility of corneal confocal microscopy (CCM) in detecting a reduction in corneal nerve parameters in a large cohort of patients with Parkinson's disease (PD) compared to controls using a fully automated potentially scalable method of analysis. We also assessed if CCM parameters are related to the severity and sub-type of PD. 98 participants with PD and 26 healthy controls underwent CCM with automated corneal nerve quantification, MDS-UPDRS III, Hoehn and Yahr scale, Montreal Cognitive Assessment, Parkinson's Disease Questionnaire-39 and PD subtype assessment. Corneal nerve fibre density (mean difference: - 5.00 no/mm², 95% confidence interval (CI) [- 7.89, - 2.12], p = 0.001), corneal nerve branch density (mean difference: - 10.71 no/mm², 95% CI [- 16.93, - 4.48], p = 0.003), corneal total branch density (mean difference: - 14.75 no/mm², 95% CI [- 23.58, - 5.92], p = 0.002), and corneal nerve fibre length (mean difference: - 2.57 mm/mm², 95% CI [- 4.02, - 1.12], p = 0.001) were significantly lower in PD participants compared to controls. There was no correlation between corneal nerve parameters and duration, severity or subtype of PD, cognitive function or quality of life. CCM with automated corneal nerve analysis identifies nerve fibre damage and may act as a biomarker for neurodegeneration in PD.