Retinal toxicity of commercial intravitreal tissue plasminogen activator solution in cat eyes

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

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)659-663
Number of pages5
JournalArchives of Ophthalmology
Issue number5
StatePublished - May 2000
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology


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