Keratectasia After Laser In Situ Keratomileusis

Keratectasia remains one of the most troublesome complications that can arise after laser in situ keratomileusis (LASIK). Patients with this complication present with an increase in myopia and astigmatism, loss of uncorrected visual acuity, and often a loss of best-corrected visual acuity1-3 due to progressive corneal steepening that takes place centrally or inferiorly.4-6 Ectatic changes can occur as early as 1 week after LASIK,7 or they can be delayed up to several years after the initial procedure.8,9 In many cases, penetrating keratoplasty is eventually performed to manage this complication. The incidence of keratectasia after LASIK has been estimated to be 0.04% to 0.6%3,10,11; however, accurate data based on large-scale clinical studies are not available.1,5,12-14 Although a number of clinical risk factors have been reported,2,5-9,13-17 the mechanisms of post-LASIK keratectasia remain unclear. Studies of the histologic changes in post-LASIK keratectasia have demonstrated variable degrees of corneal thinning in the stromal bed and the flap. Although disruption in the Bowman layer typically observed in keratoconus has not been shown in most cases of post-LASIK keratectasia,2,8,18-20 other pathologic findings, such as macrostriae in the stromal bed, thinning of the stromal collagen lamellae, minimal scarring at the flap-stromal bed interface and lack of inflammation, and the presence of an iron ring around the steepening, have been reported.2,16,18-23 An immunohistochemical study24 on wound healing in ectatic corneas after LASIK also reported no scar tissue formation, indicated by a lack of collagen type III expression, even at the flapstromal bed interface. Keratectasia after LASIK shares similar topographic and clinical characteristics with keratoconus, a noninflammatory disease characterized by thinning of the corneal stroma, defects in the Bowman layer, and the eventual protrusion of the central cornea.25-28 Although some of the keratoconus-like histologic changes have been detected in post-LASIK keratectasia, the biochemical abnormalities found in keratoconus have not been studied in keratectasia. These biochemical alterations include decreased expression of the protease inhibitor α1-proteinase inhibitor (α1-PI) and upregulation of transcription factor Sp1.29-31 In addition, matrix metalloproteinases (MMPs), a group of enzymes that are involved in tissue remodeling, have recently been examined in keratectasia. Studies have detected MMP-3 in rare keratocytes, and MMP-10 expression was elevated in the epithelium of ectatic corneas.32 The MMP expression patterns in keratoconus remain controversial, although over-expression of MMP-1 and MMP-2 has been recently reported in keratoconus corneas.33,34 In addition, MMPs have been implicated in various other corneal conditions, including wound repair and healing, ulcerations, and diabetic corneas.35 In this study, we examined the histopathologic and biochemical characteristics of keratectasia after LASIK using light microscopy and transmission electron microscopy (TEM). Immunohistochemical analysis was also performed with antibodies against α1-PI and transcription factor Sp1. In addition, immunolocalization of major members of the MMP family, MMP-1, MMP-2, and MMP-3, was performed to determine if an MMP-mediated degradation process was involved in keratectasia after LASIK.