Changes in corneal morphology associated with chronic epithelial injury.

PURPOSE The purpose of this study was to evaluate the effect of chronic epithelial scrape injury on corneal morphology. METHODS The corneal epithelia in one eye of 8-week-old New Zealand White rabbits were scraped at weekly intervals. Central corneal thickness was measured by ultrasonic pachymetry before epithelial scrape each week. Control never wounded (C), chronic wounded with scrape the last week (W), and chronic wounded without scrape the last week (WW) corneas were processed for histologic analysis and transmission electron microscopy (TEM). The time intervals for histologic analysis were 4 (4 C, 2 W, 2 WW), 8 (4 C, 2 W, 2 WW), and 16 (7 C, 2 W, 5 WW) weeks. Histologic findings were monitored using hematoxylin and eosin staining, the TdT-dUTP terminal nick-end labeling (TUNEL) assay, and TEM. RESULTS Chronic wounded corneas developed marked epithelial hyperplasia and a subepithelial acellular zone. Keratocytes undergoing apoptosis were primarily detected adjacent to the acellular zone by TUNEL assay and TEM. Total central corneal thickness measured by ultrasonic pachymetry (n=7) was significantly thinner in chronically scraped eyes compared with control eyes after 8, 12, and 16 weeks (P < 0.05). Control corneas increased in total thickness over the 16 weeks of the study, but there was no significant change in total thickness of the corneas that had chronic epithelial scrape injury over this time interval. Two scraped corneas had marked decreases in total corneal thickness relative to the corneal thickness at the beginning of the study. Epithelial hyperplasia developed in all scraped corneas examined histologically after 4, 8, or 16 weeks of scraping. When central epithelial thickness measured on hematoxylin and eosin-stained sections was subtracted from the total pachymetric corneal thickness to give approximate stromal thickness, the stromal thickness was 23% lower in the chronic wounded (277+/-15 microm) compared with the unwounded (356+/-6 microm) corneas (P=0.0008) after 16 weeks of wounding. CONCLUSIONS Chronic epithelial injury induces stromal thinning and epithelial hyperplasia. These changes in cornea structure associated with chronic epithelial injury may have relevance to the pathophysiology of keratoconus.