title: Retinal toxicity of commercial intravitreal tissue plasminogen activator solution in cat eyes.
abstract: 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.
  
  
  CONCLUSIONS
  Intravitreal injection of commercial tPA solution results in dose-dependent retinal toxicity in cat eyes.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan School of Medicine, Ann Arbor 48105, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hrach
authors.forename: M W
authors.initials: MW
authors.lastname: Johnson
authors.forename: A S
authors.initials: AS
authors.lastname: Hassan
authors.forename: B
authors.initials: B
authors.lastname: Lei
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
authors.forename: V M
authors.initials: VM
authors.lastname: Elner
mesh_terms: D000818:Animals; D002415:Cats; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D005654:Fundus Oculi; D007267:Injections; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000633:toxicity; D009887:Ophthalmoscopy; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000473:pathology; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000633:toxicity*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000633:toxicity*; D014822:Vitreous Body
chemical_list: D009883:Ophthalmic Solutions; D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator