Laser Scanning In Vivo Confocal Microscopy Reveals Reduced Innervation and Reduction in Cell Density in All Layers of the Keratoconic Cornea

Abstract

The exact pathophysiological processes underlying keratoconus remain an enigma. In this study, laser scanning in vivo confocal microscopy (IVCM) was used to define further the microstructural abnormalities in the keratoconic cornea and to establish the relationship with disease severity. This was a prospective, cross-sectional study comparing 52 subjects with keratoconus and 52 age-matched control subjects. Assessment included demographics, history, slit lamp biomicroscopy, computerized corneal tomography, and laser scanning IVCM. Significantly lower cell densities (in cells per square millimeter, mean +/- SD) were observed in keratoconus corneas than in normal ones: basal epithelial cells, 4340.6 +/- 595.2 vs. 5777.6 +/- 958.2 (P < 0.001), anterior keratocytes, 523.6 +/- 206.4 vs. 859.7 +/- 219.1 (P < 0.001), posterior keratocytes, 240.4 +/- 64.5 vs. 330.6 +/- 52.3 (P < 0.001), and endothelial cells 2412.2 +/- 339.5 vs. 2845.6 +/- 313.0 (P < 0.001). Subbasal nerve fiber density was 52.7% lower in keratoconus corneas than in the control (P < 0.001). Basal epithelial cell density (P = 0.001), subbasal nerve fiber density (P = 0.015), and anterior keratocyte density (P < 0.001) correlated with severity of disease. Lower subbasal nerve density also correlated with younger age at diagnosis (r = 0.397, P = 0.004). Severe disease was associated with diagnosis at a younger age (P = 0.023), a history of eye rubbing (P = 0.025), and Maori or Pacific Island ethnicity (P = 0.001). Significant microstructural abnormalities were identified at every level of the keratoconic cornea and were related to disease severity. IVCM offers a potential insight into the pathophysiology of the microstructural changes in keratoconus.