Intravitreal toxicity of high-dose etanercept

Purpose: The aim of this study was to evaluate the retinal toxicity of high-dose intravitreal etanercept, a U.S. Food and Drug Administration-approved anti-inflammatory drug, in the rabbit model. Methods: Twenty (20) New Zealand albino rabbits were divided into 5 groups (n = 4); eyes in each group were intravitreally injected with one of the following doses of etanercept: 125 mu g, 250 mu g, 500 mu g, 1 mg, or 2.5 mg. One (1) 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 at days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and 14 days after injection. The animals were euthanized on day 14. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity. Results: Clinical examination, histological evaluation, and ERG results of all 5 groups demonstrated no signs of retinal toxicity. Conclusions: Intravitreal doses as high as 2.5 mg of etanercept did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent, prolonged effect than the lower doses previously recommended.