Objective: The aim of the study is to use automated analysis of corneal confocal microscopy (CCM) images to allow rapid and reliable quantification of corneal nerve degeneration in patients with idiopathic Parkinson’s disease (IPD).

Background: One of the major challenges in Parkinson’s disease drug development is how to accurately monitor neuronal loss and hence the efficacy of new drugs. There are concerns about the sensitivity and inter- and intra-rater reliability with clinical scales such as the UPDRS. Several neuropathological studies(1) have demonstrated pathological changes in small nerve fibers in skin biopsies of patients with IPD, opening up the possibility of using measures of small fiber loss to monitor disease progression and degeneration in IPD. Whilst estimation of nerve fiber density with a skin biopsy offers an objective means of quantifying small fiber pathology, it is an invasive, time-consuming and costly procedure and not repeatable. CCM has been shown to be a valid technique to detect small fiber neuropathy non-invasively and reliably. We have previously demonstrated changes in CCM parameters in IPD patients compared to controls (2). This study uses automated analysis of CCM parameters to demonstrate a difference in small fiber nerves between IPD patients and controls

Methods: Images were analyzed using automated nerve analysis software, ACCMetrics (University of Manchester, UK), to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal total branch density (CTBD), corneal nerve fiber area (CNFA) and corneal nerve fiber width (CNFW).

Results: 27 IPD patients (17 male, 10 female, mean age 64 years) and 27 controls (16 male, 11 female, mean age 60 years) were enrolled in the study. All CCM parameters except CNFW were significantly (p<0.05) lower compared to controls (CNFD mean difference: -4.062 no/mm2, p =0.049; CNBD mean difference: -12.46 no/mm2, p =0.006; CNFL mean difference: -2.89 no/mm2, p =0.008; CTBD mean difference: -17.73 no/mm2, p= 0.004; CNFA mean difference: -0.001 no/mm2, p=0.034).

Conclusions: Automated CCM analysis detects extensive small fiber damage in patients with IPD, which may allow the assessment of neurodegeneration and regeneration. We are performing a longitudinal study to assess changes in CCM parameters in patients with IPD over time.

References: 1. Donadio V, Incensi A, Leta V, Giannoccaro MP, Scaglione C, Martinelli P, et al. Skin nerve a-synuclein deposits:A biomarker for idiopathic Parkinson disease. Neurology. 2014;82(15):1362–9. 2. Kass-Iliyya L, Javed S, Gosal D, Kobylecki C, Marshall A, Petropoulos IN, Ponirakis G, Tavakoli M, Ferdousi M, Chaudhuri K, Jeziorska M, Malik R, Silverdale M. Small fiber neuropathy in Parkinson’s disease: A clinical, pathological and corneal confocal microscopy study. Park Relat Disord. 2015;21(12):1454–60.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/non-invasive-automated-corneal-nerve-quantification-reveals-neurodegeneration-in-parkinsons-disease-a-potential-novel-imaging-biomarker/