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Charles J. Hrach, MD; Mark W. Johnson, MD; Adam S. Hassan, MD; Bo Lei, MD; Paul A. Sieving, MD, PhD; Victor M. Elner, MD, PhD

Arch Ophthalmol. 2000;118:659-663.

Background  We previously reported retinal toxic reactions in rabbit eyes receiving intravitreal injections of commercial tissue plasminogen activator (tPA) in concentrations greater than or equal to 50 µg/0.1 mL, and recent clinical experience suggests that intravitreal tPA solution may produce toxic effects in human eyes. We therefore investigated the dose-dependent retinal toxicity of intravitreal commercial recombinant tPA solution in cat eyes, which have a vascularized inner retina and vitreous volume similar to that of human eyes.

Methods  Commercial tPA in L-arginine solution was injected into the mid vitreous cavity of normal cat eyes in doses of 25, 50, 75, and 100 µg/0.1 mL and 200 µg/0.2 mL. Control (fellow) eyes received an equal volume of sterile saline solution. After injection, eyes were evaluated by ophthalmoscopy and electroretinography for 14 days and then enucleated for histopathological evaluation.

Results  Fundus pigmentary alterations were observed in eyes receiving doses greater than or equal to 50 µg/0.1 mL. Changes were centered in the area around the injection site, and the area's size increased in proportion to the dosage. Mean electroretinography B-wave amplitude measured at 14 days was significantly reduced in eyes receiving greater than or equal to 50 µg of tPA in a dose-dependent fashion. Light microscopy of the involved areas showed loss of photoreceptor elements with necrosis and proliferation of the retinal pigment epithelium.

Conclusion  Intravitreal injection of commercial tPA solution results in dose-dependent retinal toxicity in cat eyes.

Clinical Relevance  Because cat eyes are similar to human eyes regarding retinal vascularity and vitreous volume, intravitreal injections of commercial tPA (with L-arginine vehicle) in concentrations greater than 25 µg/0.1 mL are potentially unsafe in human eyes.

From the Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan School of Medicine, Ann Arbor.
None of the authors have any proprietary interest in any product or company described in this article.

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