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

Arch Ophthalmol. 2000 May;118(5):659-63. doi: 10.1001/archopht.118.5.659.


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 microg/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 microg/0.1 mL and 200 microg/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 microg/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 microg 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 microg/0.1 mL are potentially unsafe in human eyes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cats
  • Cell Division
  • Dose-Response Relationship, Drug
  • Electroretinography / drug effects
  • Fundus Oculi
  • Injections
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / toxicity
  • Ophthalmoscopy
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / pathology
  • Plasminogen Activators / administration & dosage
  • Plasminogen Activators / toxicity*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / toxicity
  • Retina / drug effects*
  • Retina / pathology
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / toxicity*
  • Vitreous Body


  • Ophthalmic Solutions
  • Recombinant Proteins
  • Plasminogen Activators
  • Tissue Plasminogen Activator