Presented by

Dr. Bruce A. Perkins

The real-world variability in clinical presentation of diabetic distal symmetric polyneuropathy (or “diabetic neuropathy”) and complexities in its measurement have severely hindered the development of therapies. As diabetic neuropathy remains asymptomatic for years, and though it may involve injury to different anatomical nerve types that show variable clinical manifestations between individuals, it is generally understood that injury occurs first to the small, thinly- or un- myelinated, fibres that make up the pain and temperature sensory fibres as well as the autonomic fibres. At face value this offers an opportunity to identify early in the course of its natural history the asymptomatic, peripheral nerve-specific injury. While perhaps less relevant as a clinical endpoint for trials, for which late foot complications such as ulcer and amputation are most relevant, and in turn these late complications include the loss of protective sensation from neuropathy as only one of three component causes (along with inadequacies vascular supply and general foot care), it offers the opportunity to identify therapies that have specific impact on peripheral nerves. Of the two morphologic measures of peripheral small nerve fibres (intra-epidermal nerve fibre density from skin biopsy and non-invasive imaging of corneal nerves through confocal microscopy, CCM), I will discuss the large-scale cohort efforts that have aimed to determine the ability of CCM to identify current and predict future onset of diabetic neuropathy, and recent trials implementing CCM. I will frame these findings within perspective on Phase 2 and Phase 3 clinical trials for diabetic and other forms of peripheral neuropathy.