Objective: The aim of the study is to investigate whether corneal confocal microscopy (CCM) can be used as a rapid, reliable, automated and non-invasive method to monitor neurodegeneration in Parkinson’s disease (PD).

Background: Developing improved biomarkers of neurodegeneration in PD is vital in order to speed up the testing of novel neuroprotective agents. There is a substantial body of evidence that peripheral small fibre nerve degeneration parallels the central neurodegenerative process in PD [1][2]. Quantifying small nerve fibre degeneration in PD therefore represents a novel biomarker opportunity. Our group has pioneered automated Corneal Confocal Microscopy (CCM) as a non-invasive and reproducible method to quantify small fibre nerve degeneration. We and others have previously used CCM to demonstrate small fibre nerve degeneration in PD vs controls [3][4]. Here we present initial data aiming to assess whether progression in CCM findings can be used as a longitudinal biomarker of central neurodegeneration in PD.

Method: CCM images were obtained from PD participants and controls at baseline. CCM images were repeated for PD participants 12 months later.Images were analyzed using automated nerve analysis software, ACCMetrics (University of Manchester, UK), to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL). Independent samples t-test was used to compare CCM parameters between PD participants and controls. Paired t-test was used to compare CCM parameters at baseline and follow up in PD participants.

Results: There was a significant reduction in CNFD (mean difference: -4.286 no/mm2, p<0.05), CNBD (mean difference: -10.903 no/mm2, p<0.05) and CNFL (mean difference: -2.404 mm/mm2, p<0.05) in 77 PD patients (21F, 56M, mean age 64, mean MDS-UPDRS III:27)  compared to 27 controls (11F, 16M, mean age 62) at baseline. Over 12 months of follow up in 32 PD participants, there was a reduction in CNFD and CNFL (CNFD mean difference: -1.732 no/mm2, p<0.05; CNFL mean difference: -0.59mm/mm2, p<0.05) and no change in CNBD (mean difference: -1.181 no/mm2, p=0.265).

Conclusion: This is the first longitudinal analysis of CCM nerve measures in patients with PD and the results suggest that CCM is a potential tool for monitoring neurodegeneration in PD. This cohort of participants (77 in total) will be followed up for 24 months.

References: 1. Doppler, K. et al. Cutaneous neuropathy in Parkinson’s disease: A window into brain pathology. Acta Neuropathol. 128, 99–109 (2014). 2. Nolano, M. et al. Small fiber pathology parallels disease progression in Parkinson disease: a longitudinal study. Acta Neuropathol. 136, 501-503 (2018). 3. Kass-Iliyya, L. et al. Small fiber neuropathy in Parkinson’s disease: A clinical, pathological and corneal confocal microscopy study. Park. Relat. Disord. 21, 1454–1460 (2015). 4. Podgorny, P. J., Suchowersky, O., Romanchuk, K. G. & Feasby, T. E. Evidence for small fiber neuropathy in early Parkinson’s disease. Parkinsonism Relat. Disord. 28, 94–99 (2016).

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/corneal-confocal-microscopy-an-imaging-biomarker-of-neurodegeneration-in-parkinsons-disease/