Intravitreal toxicity of high-dose etanercept.
OBJECTIVE
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 microg, 250 microg, 500 microg, 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.
Kivilcim
Muhamet
M
Department of Ophthalmology, University of Arizona, Arizona Health Sciences Center, Tucson, AZ 85711, USA.
Peyman
Gholam A
GA
Kazi
Abdul Ahad
AA
Dellacroce
John
J
Ghobrial
Randa N
RN
Monzano
Roberta
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D004594:Electrophysiology; D004596:Electroretinography; D000068800:Etanercept; D007074:Immunoglobulin G / Q000633:toxicity*; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D014822:Vitreous Body / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D000068800:Etanercept