The Role of Corneal Confocal Microscopy in Parkinson's Disease and Atypical Parkinsonism

Abstract

Several neuropathological studies have demonstrated alpha synuclein deposition and small fibre denervation in skin biopsies of participants with Idiopathic Parkinson’s disease (PD), suggesting the possibility of using small fibre loss as a biomarker in idiopathic PD. Whilst estimation of nerve fibre density with a skin biopsy offers an objective means of quantifying small fibre pathology, it is invasive, time-consuming, costly and not repeatable. Corneal Confocal Microscopy (CCM) has been shown to be a valid technique to detect small fibre neuropathy non-invasively and reliably. Cross sectional studies in small cohorts of PD participants have demonstrated corneal nerve loss in PD participants compared to healthy controls. This thesis aims to further investigate the role of CCM as a biomarker in PD by using larger sample sizes, comparing manual and automated analysis techniques, assessing longitudinal change in CCM parameters and comparing corneal nerve morphology between participants with PD, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). This thesis established that CCM using automated analysis detects corneal nerve loss in PD participants. Manual and automated analysis have good correlation. The longitudinal study did not demonstrate any significant change in CCM parameters after 12 months but found that PD participants with the most corneal nerve damage at baseline had greater motor progression after 12 months. A comparison of corneal nerve loss between PD, MSA and PSP participants showed differential nerve loss, with marked changes seen in PD and MSA and less nerve loss in PSP. CCM may be a useful tool in identifying PD participants who are faster motor progressors to enrich clinical trials and differentiate between PD, PSP and MSA participants.

Date of Award	31 Dec 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Christopher Kobylecki (Supervisor) & Monty Silverdale (Supervisor)