Diabetic somatic polyneuropathy (DPN) is one of the commonest long-term complications of diabetes and is a main initiating factor for foot ulceration and lower extremity amputation. Current techniques for the quantification of neuropathy either lack sensitivity (quantitative sensory testing), require expert assessment and assess only the fastest conducting myelinated fibers (electrophysiology) or are invasive (skin/nerve biopsy). Our recent work with corneal confocal microscopy (CCM) confirms that it is a rapid, non- invasive in-vivo clinical examination technique which accurately quantifies nerve damage and repair, is comparable to skin biopsy (an accepted gold standard for assessing small fiber damage), and is able to demonstrate early nerve repair after pancreas transplantation. We now propose to establish CCM as a valid surrogate for human DPN through a set of coordinated studies. First, to establish its ability to diagnose and assess progression of neuropathy we will compare CCM with other established tests of neuropathy in a cohort of patients with Impaired Glucose Tolerance (IGT) and diabetic patients with mild neuropathy over a period of 4 years. Additionally to confirm the ability of CCM to measure therapeutic efficacy, we will compare it with other FDA approved standard tests for neuropathy in patients undergoing pancreas transplantation. Finally, we will explore the role of tear nerve growth factor expression in relation to corneal nerve morphology to provide insights into the pathogenesis of corneal and hence somatic nerve fiber damage.

Public Health Relevance

Studies to accurately diagnose, assess progression and quantify repair in diabetic neuropathy have been hampered by the non-availability of a robust, reproducible and non-invasive surrogate marker of nerve damage. We propose to assess the utility of corneal confocal microscopy, a novel non- invasive surrogate of diabetic neuropathy.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Jones, Teresa L Z
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Manchester
United Kingdom
Zip Code
Ponirakis, G; Petropoulos, I N; Fadavi, H et al. (2014) The diagnostic accuracy of Neuropad for assessing large and small fibre diabetic neuropathy. Diabet Med 31:1673-80
Tavakoli, Mitra; Malik, Rayaz A (2011) Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies. J Vis Exp :
Tavakoli, M; Kallinikos, P; Iqbal, A et al. (2011) Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabet Med 28:1261-7
Tavakoli, Mitra; Marshall, Andrew; Pitceathly, Robert et al. (2010) Corneal confocal microscopy: a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy. Exp Neurol 223:245-50
Zenewicz, Lauren A; Abraham, Clara; Flavell, Richard A et al. (2010) Unraveling the genetics of autoimmunity. Cell 140:791-7