Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy

Small fiber neuropathy (SFN) is a common feature of many inflammatory diseases, often presenting with pain and disability. SFN is diagnosed using symptoms, thermal threshold testing, and intra-epidermal nerve fiber quantification. Corneal confocal microscopy (CCM) is an ophthalmic imaging technique which non-invasively quantifies corneal nerve fiber (CNF) density, branch density and length, and has comparable diagnostic and superior ability to identify nerve regeneration compared to skin biopsy. CNF size (width and area) depends upon the number of fibers within each nerve, as well as pathology (e.g., swelling), and may provide additional sensitivity to diagnose SFN and identify nerve repair. We have compared the utility of the standard CCM variables employed to CNF size in patients with diabetic sensorimotor polyneuropathy or sarcoidosis-associated SFN, and in patients with SFN following cibinetide administration, an agent which promotes nerve repair. The results show that: 1) CNF width distribution and area depend upon neuropathy severity; 2) CNF area, density, branch density and length possess comparable discriminatory power for diagnosing neuropathy; 3) CNF area is related to length by a quadratic function which is predictive for both healthy subjects and those with SFN; 4) CNF area is a useful variable for quantifying change in CNF morphology.