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Retinal toxicity of commercial intravitreal tissue plasminogen activator solution in cat eyes
C J Hrach1, M W Johnson, A S Hassan
1Department of Ophthalmology and Visual Sciences, University of Michigan School of Medicine, Ann Arbor 48105, USA.
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.
Insights
Intravitreal injection of tissue plasminogen activator (tPA) causes dose-dependent retinal toxicity in cats. Concentrations above 25 microg/0.1 mL may be unsafe for human eyes.
Area of Science:
- Ophthalmology
- Retinal research
- Toxicology
Background:
- Previous reports indicated retinal toxic reactions from intravitreal tissue plasminogen activator (tPA) in rabbits.
- Clinical observations suggest intravitreal tPA may cause toxic effects in human eyes.
Purpose of the Study:
- To investigate the dose-dependent retinal toxicity of intravitreal commercial recombinant tPA solution in cat eyes.
- To assess the safety of tPA concentrations for potential human use based on feline models.
Main Methods:
- Commercial tPA was injected into cat eyes at varying doses (25–200 microg).
- Control eyes received sterile saline.
- Eyes were evaluated using ophthalmoscopy, electroretinography, and histopathology for 14 days.
Main Results:
- Retinal pigmentary alterations and dose-dependent reductions in electroretinography B-wave amplitude were observed at doses ≥50 microg/0.1 mL.
- Histopathology revealed photoreceptor loss, necrosis, and retinal pigment epithelium changes.
- The size of affected areas correlated with tPA dosage.
Conclusions:
- Intravitreal tPA administration leads to dose-dependent retinal toxicity in feline eyes.
- Commercial tPA concentrations exceeding 25 microg/0.1 mL may pose a risk to human eyes due to similarities in retinal vascularity and vitreous volume.