Abstract
Purpose: :
To evaluate the retinal toxicity of high–dose intravitreal etanercept in the rabbit model. Etanercept, a US Food and Drug Administration–approved antiinflammatory drug that is used in the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, and psoriatic arthritis, may be an alternative or adjunct drug for the treatment of uveitic diseases, including Behcet’s disease.
Methods: :
All animals were treated in accordance with the ARVO guidelines on the care and use of animals in research. Twenty New Zealand albino rabbits were divided into five groups (n=4) to evaluate five doses of intravitreally injected etanercept: 125 µg, 250 µg, 500 µg, 1 mg, and 2.5 mg. One eye in each animal was used for the study dose; the fellow eye was injected with buffered sterile saline as a control. All animals were examined using indirect ophthalmoscopy and slit–lamp biomicroscopy before and after intravitreal injection and on days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and on day 14 postinjection, before the animals were euthanized. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity.
Results: :
Clinical examination, histological evaluation, and ERG results of all five groups demonstrated no signs of retinal toxicity.
Conclusions: :
High doses of up to 2.5 mg of etanercept injected intravitreally did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent and prolonged effect than the lower doses that were previously recommended.
Keywords: drug toxicity/drug effects • inflammation