Can corneal confocal microscopy be used as an imaging biomarker for neurodegeneration in children and adults with metabolic disease?

Gad, Hoda (2024) Can corneal confocal microscopy be used as an imaging biomarker for neurodegeneration in children and adults with metabolic disease? Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Corneal Confocal Microscopy (CCM) is a non-invasive ophthalmic imaging technique to quantify small nerve fibre morphology in patients with diabetic neuropathy and other metabolic peripheral neuropathies. This thesis establishes that CCM is indeed a robust imaging technique which can identify early subclinical and clinical neuropathy in children with Type 1 diabetes mellitus (T1DM) and adults with T1DM and Type 2 diabetes mellitus (T2DM). We demonstrate the utility of CCM in detecting neuropathy not only in patients with established neuropathy, but also in patients with diabetes without neuropathy. We also demonstrate a precise relationship between glycemic variability and hypoglycaemia with corneal nerve loss in patients with T1DM and T2DM. This thesis provides further evidence for the utility of CCM as a surrogate endpoint of early small fibre neuropathy by demonstrating nerve damage in obese children with acanthosis nigricans (AN) (a sign of insulin resistance) and obese adults with and without T2DM. We also show nerve regeneration in individuals with obesity without T2DM after 3 months of treatment with the once weekly Glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide.