Recombinant hirudin prophylaxis of experimental postoperative intraocular fibrin formation
Purpose: Postoperative fibrin formation is common after vitreous surgery for the complications of proliferative diabetic retinopathy and proliferative vitreoretinopathy. We tested the efficacy of a directly acting antithrombin agent, recombinant desulphatohirudin variant 1 (™Revasc), in preventing postoperative fibrin formation in a rabbit model. Methods: In a prospective study, we performed standard fragmatome lensectomies and core vitrectomies on Dutch Belted rabbits in a masked fashion. In Group 1 there were 10 control eyes with lactated Ringer's infusion and 10 eyes with 10 ug/cc of recombinant hirudin mixed in the infusate. In Group 2 there were 15 control eyes and 40 treated eyes that received the drug via a limbal paracentesis at the end of the surgery. The doses used were 0.02 ug, 2 ug, 10 ug, 50 ug, and 200 ug, with eight eyes at each dose. The amounts of postoperative fibrin and hemorrhage were graded in a masked fashion using slit lamp examination and indirect ophthalmoscopy on postoperative days one through five and seven. Results: In Group 1 the mean grade of early postoperative fibrin formed was significantly less in the treated eyes compared to the controls. None of the treated eyes developed intraoperative bleeding or postoperative vitreous hemorrhage. In Group 2 there was significantly less early postoperative fibrin formed in the eyes treated with a dose of ™Revasc ≥ 2 ug versus the controls. There was increased postoperative hemorrhage in eyes treated with 50 ug and 200 ug of ™Revasc (which is 25-100 times greater than the minimum effect dose) versus the controls. Conclusions: Intraocular recombinant desulphatohirudin variant 1 is an effective inhibitor of postoperative fibrin formation with either of the two routes of administration tested. A tendency towards increased postoperative bleeding was noted with injections at doses 25-100x the minimum effective dose.
Nasir, MA; Toth, CA; Mittra, RA; Ho, CL
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