RESUMEN
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 overgrowth. 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 µm) than in controls (8.11 ± 3.31 µm; P < .001). The thickness of peripheral stromal nerves (12.6 ± 3.1 µm) was similar to that of controls (14.86 ± 5.60 µm; 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 µm) did not differ from that of the controls (4.0 ± 0.61 µm; 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.