Alterations of corneal extracellular matrix after multiple refractive procedures: a clinical and immunohistochemical study.
OBJECTIVE
To describe the clinical course and alterations of the corneal extracellular matrix (ECM) and basement membrane (BM) in a cornea after hexagonal keratotomy, transverse keratotomies, and keratomileusis.


METHODS
Frozen sections of this cornea and of 12 normal corneas were studied by immunofluorescence with specific antibodies. The patient history was analyzed to allow a clinical correlation.


RESULTS
In the treated cornea, keratotomy scars and subepithelial fibrosis with neovascularization were seen. Around and beneath the epithelial plugs and along the keratotomy scars, deposits of types III, VI, VIII, and XIV collagen; fibrillin-1; fibronectin; and tenascin-C were found, together with short streaks of types IV (alpha 1-alpha 2) and VII collagen, laminin-1 and -5, entactin, and perlecan. alpha 3-alpha 4 Type IV collagen chains were abnormally absent from the BM around the epithelial plugs. At the edges of the keratomileusis flap, subepithelial fibrosis areas were found, with abnormal deposits of eight different collagen types, perlecan, fibronectin, fibrillin-1, and tenascin-C. The major part of the flap interface did not show ECM abnormalities. ECM alterations outside the scarred areas included the appearance of tenascin-C in the stroma and of alpha 1-alpha 2 type IV collagen in the epithelial BM, and the disappearance of fibronectin from Descemet's membrane.


CONCLUSIONS
Five years after surgery, the treated cornea still presented BM abnormalities at sites of keratotomy scars and epithelial plugs. Several ECM components were abnormally expressed outside the scarred areas, consistent with an ongoing fibrosis in the treated cornea.
Maguen
E
E
Ophthalmology Research Laboratories, Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Alba
S A
SA
Burgeson
R E
RE
Butkowski
R J
RJ
Michael
A F
AF
Kenney
M C
MC
Nesburn
A B
AB
Ljubimov
A V
AV
D000368:Aged; D001251:Astigmatism / Q000601:surgery*; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016039:Corneal Transplantation; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D006801:Humans; D007646:Keratotomy, Radial; D053685:Laser Therapy; D008297:Male; D009216:Myopia / Q000601:surgery*; D012189:Retrospective Studies
D016326:Extracellular Matrix Proteins