Correlation Between Epithelial Ingrowth and Basement Membrane Remodeling in Human Corneas After Laser-Assisted In Situ Keratomileusis

Objective: To further investigate the hypothesis that epithelial ingrowth in human corneas after laser-assisted in situ keratomileusis (LASIK) correlates with basement membrane remodeling, as suggested by the presence of matrix metalloproteinase 9 around epithelial cells in the lamellar scar. Methods: Immunohistochemical analysis and transmission electron microscopy were applied to human postmortem corneas with post-LASIK epithelial ingrowth. Results: Epithelial ingrowth into the flap margin was observed in 8 of 18 corneas (44%). Matrix metalloproteinase 9 immunolocalized around ingrown epithelium in 6 of these 8 corneas (75%). There was a positive correlation between the presence of matrix metalloproteinase 9 at the wound margin and discontinuities in the basement membrane, as determined by laminin and beta(4) integrin immunofluorescence. Transforming growth factor beta 2 was present into the stroma of some corneas with epithelial ingrowth and interrupted basement membrane, suggesting some degree of epithelial-stromal interaction. Transmission electron microscopy confirmed large areas of remodeled basement membrane along ingrown epithelial cells. Conclusions: The neo-basement membrane components underlying the ingrown cells in human corneas with epithelial ingrowth after LASIK appear to be partially disassembled. Epithelial-stromal interaction over time may be related to prolonged wound healing remodeling, which calls into question the stability of the flap.