ESTABLISHING CORNEAL CONFOCAL MICROSCOPY AS A SURROGATE ENDPOINT FOR THE ASSESSMENT OF DIABETIC PERIPHERAL NEUROPATHY

Abstract

Corneal confocal microscopy (CCM) has been utilised to study corneal nerves, epithelium, stroma and the endothelium in a variety of normal and disease states and has been suggested as a surrogate imaging endpoint for assessing peripheral neuropathies. It can detect early damage of small nerve fibres, stratify the severity of diabetic neuropathy and assess progressive degeneration and nerve regeneration after therapeutic intervention. The studies in this thesis have investigated central and inferior corneal nerve alteration, quality of life (QoL) and neuropathic pain symptoms in patients with and without painful diabetic neuropathy (DN). Furthermore, to establish the aetiology of corneal nerve damage, corneal keratocyte density and risk factors for corneal nerve damage have been assessed in patients with diabetes. This thesis demonstrates that implementing a standardized protocol for CCM image selection results in high intra- and inter-observer reproducibility. Furthermore, there was a reduction in corneal keratocyte density in patients with and without DN which was associated with corneal nerve loss. There is an association between CCM parameters, QoL, patient's mood and severity of neuropathic pain and symptoms. CCM also detects greater corneal nerve loss in patients with painful compared to painless DN with more prominent corneal nerve damage in the inferior whorl (IW) compared to the central cornea in patients with DN. A longitudinal study also showed a significant reduction in the inferior whorl length (IWL) with minimal alteration in more proximal corneal nerves in the central cornea, suggesting that IWL may be preferable to study small fibre neuropathy in longitudinal studies of patients with DN.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Rayaz Malik (Supervisor), Handrean Soran (Supervisor) & Andrew Marshall (Supervisor)