Clinical applications of confocal microscopy to corneal innervation

Abstract

In vivo corneal confocal microscopy (IVCM) is a non‐invasive ophthalmic imaging technique that provides images of the cornea at the cellular level. Despite the uses in ocular surface pathologies, in the last decades IVCM has been used to provide more knowledge in refractive surgery wound healing (LASIK and PRK), dry eye disease, and in some corneal infections (amoebas and filamentous fungi). The observation of the corneal cells, both normal and inflammatory, and the possibility of quantification of the corneal nerve density and quality with manual or automated tools, makes IVCM have a significant potential to improve the diagnosis and prognosis in several systemic and corneal conditions. Neuropathic pain has multiple aetiologies, but a major feature is small fibre dysfunction or damage. IVCM has been utilized to show small nerve fibre loss in patients with diabetic and other neuropathies. IVCM has comparable diagnostic utility to intraepidermal nerve fibre density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fibre loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease, and dementia. Patients with small fibre neuropathy have IVCM nerve changes. In conclusion, IVCM has good diagnostic and prognostic capability and fulfils the criteria as an end point for clinical trials in corneal, and peripheral and central neurodegenerative diseases.