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Objective: To evaluate the postoperative effect of intracameral tPA (alteplase; Activase®, Genentech, San Francisco, CA), administered at immediate conclusion of phacoemulsification, on anterior chamber fibrin formation in dogs., Procedures: Forty-one dogs (82 eyes) undergoing bilateral phacoemulsification received 25 μg/0.1 mL intracameral tPA in one eye and 0.1 mL unmedicated aqueous vehicle in the contralateral eye immediately after corneal incision closure. Intraocular pressure (IOP) was measured, and severity of anterior chamber fibrin formation, aqueous flare, pigment precipitates on the intraocular lens (IOL) implant, posterior capsular opacification (PCO), and corneal edema were graded at approximately 1 week, 2-3 weeks, 4-6 weeks, 8-12 weeks, and greater than 3 months postoperatively., Results: Anterior chamber fibrin developed postoperatively in 68.3% of dogs (28/41) and 50% of eyes (41/82). In tPA-treated eyes, 53.7% (22/41) developed fibrin compared to 46.3% of control eyes (19/41). Some degree of postoperative ocular hypertension (POH) occurred in 53.7% of dogs (22/41) and 36.5% of eyes (30/82). In tPA-treated eyes, 34.1% (14/41) experienced POH compared to 39% of control eyes (16/41). Additional intracameral tPA injection was later required in 29.3% of both tPA-treated (12/41) and control eyes (12/41)., Conclusions: Administration of intracameral tPA at immediate conclusion of canine phacoemulsification had no clinically observable effect on anterior chamber fibrin incidence at any time point. tPA-treated eyes showed no prophylaxis against POH or secondary glaucoma compared to control eyes and received late postoperative tPA injections at the same frequency as control eyes., (© 2019 American College of Veterinary Ophthalmologists.)