The Morphologic Characteristics of Corneal Nerves in Advanced Keratoconus as Evaluated by Acetylcholinesterase Technique

PURPOSE: To study the morphologic characteristics of corneal nerves in patients with advanced keratoconus using the acetylcholinesterase technique in corneal whole mounts. DESIGN: Prospective, observational case series. METHODS: Fourteen corneal buttons from 14 keratoconic patients (9 males and 5 females; mean age, 34.3 years) who had undergone keratoplasty for advanced keratoconus and 6 corneal buttons from 6 normal corneas were included. Whole mounts were stained for acetylcholinesterase and were scanned with a novel digital pathology scanning microscope. RESULTS: Seventy-one percent of keratoconic corneas demonstrated central stromal nerve changes, which included thickening, tortuosity, nerve spouting, and over-growth. The nerve changes ranged from early to extensive and could be separated into 3 different grades. The central stromal nerves were abnormally thicker (18.9 +/- 14.7 mu m) than in controls (8.11 +/- 3.31 mu m; P < .001). The thickness of peripheral stromal nerves (12.6 +/- 3.1 mu m) was similar to that of controls (14.86 +/- 5.60 mu m; P = .072). Subbasal nerves showed changes in the form of loss of radial orientation and increased tortuosity, especially at the cone apex. At the cone base, a concentric arrangement of subbasal nerves was found in 43% of cases. Localized thickenings of subbasal nerves also were observed at their origin from the bulbous terminations of sub-Bowman nerves. The terminal bulbs, too, were enlarged. The mean diameter of the subbasal nerves in keratoconus (4.11 +/- 0.60 mu m) did not differ from that of the controls (4.0 +/- 0.61 mu m; P = .422). CONCLUSIONS: This study provides additional histologic evidence of the involvement of corneal nerves in keratoconus and suggests further that they may play a role in the pathophysiologic factors and progression of the disease. (Am J Ophthalmol 2011;152:364-376. (C) 2011 by Elsevier Inc. All rights reserved.)