In vivo confocal microscopy of corneal nerves: analysis and clinical correlation

Abstract

Corneal confocal microscopy is a growing technique for the study of the cornea at the cellular level, providing images comparable to ex vivo histochemical methods. In vivo confocal microscopy (IVCM) has an enormous potential, being a noninvasive procedure that images the living cornea, to study both its physiological and pathological states. Corneal nerves are of great interest to clinicians and scientists due to their important roles in regulating corneal sensation, epithelial integrity, proliferation, wound healing, and for their protective functions. IVCM enables the noninvasive examination of corneal nerves, allowing the study of nerve alterations in different ocular diseases, after corneal surgery, and in systemic diseases. To date, the correlation of sub-basal corneal nerves and their function has been studied in normal eyes, keratoconus, dry eye, contact lens wearers, and in neurotrophic keratopathy, among others. Further, the effect of corneal surgery on nerves has been studied, demonstrating the regenerative capacity of corneal nerves and the recovery of sensation. Moreover, IVCM has been applied in the diagnosis of peripheral diabetic neuropathy and the assessment of progression in this systemic disease. The purpose of this review is to describe the principles, applications, and clinical correlation of IVCM in the study of corneal nerves in different ocular and systemic diseases.

FIGURE 1

Normal corneal sub-basal nerve plexus and after herpes simplex keratitis with two types of confocal microscopes. (A) Normal sub-basal nerve plexus. Slit scanning confocal microscopy (SSCM) Confoscan 4. (B) Herpes simplex keratitis with severe sensation loss. Note the decrease in total nerve count, length, and branching. SSCM. (C) Normal sub-basal nerve plexus. Laser scanning confocal microscopy (LSCM) HRT3/RCM. (D) Herpes simplex keratitis with severe sensation loss. Note the decrease in nerves density and branching. LSCM.

FIGURE 2

Corneal sub-basal nerve plexus in Infectious keratitis. (A) Slit scanning confocal microscopy (Confoscan 4). Decrease in nerve density. (B) Laser scanning confocal microscopy (HRT3/RCM). Decrease in nerve density and increase in dendritic cells.