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S. Esquenazi, J.C. He, H.E. Bazan, N.G. Bazan; Prevention of Experimental Post-Lasik Diffuse Lamellar Keratitis (LDK) by a Novel Platelet-Activating Factor Receptor Antagonist . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1403.
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Purpose: Platelet-activating factor (PAF) delays corneal epithelial wound healing and induces keratocyte apoptosis (IOVS, 43:1422, 2002). PAF actions are can be inhibited by antagonists that block the PAF receptor, therefore, we have tested the hypothesis that a novel PAF antagonist may prevent LDK after LASIK treatment in a rabbit model Methods: Left eyes of New Zealand rabbits were pretreated with a peribulbar injection of 0.5 ml of the PAF receptor antagonist LAU 0901 (2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester) dissolved in 20 hydroxypropyl B cyclodextrin (30 µg/µl). Two rabbits were pretreated with a peribulbar injection of 0.5 ml of cyclodextrin alone and served as controls. A flap (160 µm thick) was created in both eyes of all rabbits using the Moria CB disposable-head microkeratome and the -2 suction ring. Pseudomonas endotoxin (0.2 ml) was applied to the corneal midstromal bed to trigger a diffuse lamellar keratitis reaction, then the flap was replaced in both eyes. The left eyes were additionally treated with 1 drop of LAU 0901 four times a day. Rabbits were killed at postoperative days 1, 2, 3, 5, and 8, corneas were photographed, and immunohistochemical analysis was performed. Results: Corneas not treated with LAU 0901 and controls showed a severe sterile inflammatory response in the flap interface and adjacent stroma characterized from day 1 by loss of keratocytes, infiltration with PMNs and monocytes, and the presence of epithelial cells. Corneas of rabbits treated with LAU 0901 showed minimal loss of keratocytes in the interface, minimal inflammatory cell infiltration, and minimal presence of epithelial cells, from day 1 until the end of the study, day 8. Conclusions: Induction of DLK can be blocked by a PAF receptor antagonist in rabbit eyes undergoing LASIK surgery. We postulate that treatment with LAU-0901 blocks keratocyte apoptosis, the release of cytokines, and migration of inflammatory cells, and allows the migration of fibroblasts and myofibroblasts to the wound site, which would explain the absence of inflammatory response and adequate healing of the flap interface and adjacent stroma.
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