Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

Abstract

Chronic pain may affect 30-50% of the world's population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

Keywords: Sjogren’s syndrome; autoimmune neuropathies; autoimmunity; confocal microscopy (CM); cornea; sarcoidosis; skin biopsy; small fiber neuropathy (SFN).

Figure 1

Layer-by-layer image of the healthy cornea. (a)—superficial epithelial cells, (b,c)—sub-basal nerve plexuses, (d,e)—stroma, and (f)—endothelium.

Figure 2

The sub-basal nerve plexus in (a)—healthy volunteer with normal nerve fibers, (b)—patient with diabetic neuropathy with reduced nerve fibers, and (c)—patient with diabetes and Charcot neuro-osteoarthropathy with a severe loss of nerve fibers.