Extracellular Matrix and Matrix Metalloproteinase Changes in Human Corneas After Complicated Laser-Assisted In Situ Keratomileusis (LASIK)

Abstract

PURPOSE: To characterize extracellular matrix (ECM) and nine matrix metalloproteinase (MMP) changes in two corneas that underwent a complicated laser-assisted in situ keratomileusis (LASIK) procedure. METHODS: The first patient underwent bilateral LASIK. The flap on the left eye was transected in several locations and placed back. This cornea later developed edema, and the removed flap was analyzed after lamellar keratoplasty. The second patient had a LASIK flap lifted, replaced twice, and then completely removed. The epithelium grew over the stroma, but haze and severe ectasia occurred. After penetrating keratoplasty, the recipient cornea was analyzed. An autopsy cornea from a person who underwent uneventful LASIK and ten normal autopsy corneas served as controls. Corneas were analyzed by immunohistochemistry. RESULTS: Both flap regions in the treated corneas had marked alterations of ECM components and MMPs. Stromal deposits of various ECM proteins, including those normally absent in the central cornea (tenascin-C, fibrillin-1, type XIV collagen), were found. Rare myofibroblasts and inflammatory cells were present. The epithelial basement membrane (BM) was altered in both cases. The most dramatic change was poor or no staining for alpha3-alpha6 type IV collagen chains and thrombospondin. The limbal alpha1-alpha2 type IV collagen and laminin-2 (alpha2beta1gamma1) appeared in the central epithelial BM. Other components were altered to a lesser extent. The anterior stroma was positive for MMP-1 and MMP-2, and some MMP-7 was seen in the epithelium. These ECM and MMP patterns were not seen in uneventful LASIK or normal corneas. CONCLUSIONS: In the flaps of LASIK-treated corneas, fibrosed areas of anterior stroma had increased levels of MMP-1 and MMP-2 that may have caused loss of specific type IV collagen isoforms in the epithelial BM. These changes may reflect an ongoing wound healing process and contribute to the development of ectasia.