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D.G. Dawson, T.R. Kramer, H.E. Grossniklaus, G.O. Waring, H.F. Edelhauser; Immunohistologic, Histologic, and Ultrastructural Evaluations of Corneal Wound Healing Occurring After Successful LASIK Surgery in Humans . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4878.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To chronologically evaluate the corneal cellular and extracellular wound healing process after LASIK surgery. Methods: Postmortem corneas (n=29) from 15 patients with a prior history of LASIK surgery (range = 2 months to 6 years postop (p.o.)) were received from U.S. Eye Banks. The corneas were stored in Optisol GS for 3 to 5 days before being trisected for routine histology, transmission electron microscopy (TEM), and immunofluorescent studies. Results: Light microscopy shows a 2–4 µm PAS positive lamellar scar present in all corneas. No evidence of epithelial hyperplasia is found over the flap, except at the wound margin. Keratocyte counts per high powered field are significantly increased at the peripheral lamellar scar at all p.o. times and significantly reduced in the anterior aspect of the central flap until 6 months p.o. TEM shows that the entire central and most of the peripheral lamellar scar have keratocytes near or occasionally in the region of the scar that measures 2.2 µm –9.0 µm in thickness. This hypocellular scar contains electron dense granular material mixed with a small number of normal diameter collagen fibrils that are randomly misdirected and wide–spaced. The electron dense material appears to be produced by keratocytes, both activated and quiescent types. On the other hand, the peripheral wound margin appears to heal differently as a 20 µm–50 µm in length fibrocellular scar is present in all corneas. This hypercellular scar contains keratocytes and ordered, randomly directed collagen fibrils. Additional findings at 2–6 months p.o. include extracellular spaces filled with mildly electron dense fibrillar material, foci of abnormal wide–spaced banded collagen, and occasional vacuole–laden cells containing material similar in morphology to the contents in the extracellular spaces. Immunofluorescent studies show collagen types I, V, VI, and keratin sulfate present throughout the entire lamellar scar, while alpha–smooth muscle actin is found only in keratocytes (i.e. myofibroblasts) involving the fibrotic peripheral wound margin. Conclusions: Human LASIK corneas show two types of stromal wound healing processes. The predominant wound repair process results in the production of a hypocellular scar primarily containing electron dense granular material, whereas the peripheral wound margin heals by producing a hypercellular fibrotic scar. Despite these cellular and ultrastructural differences, immunohistology suggests that both scar types consist of collagen and proteoglycan extracellular material.
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