title: Intravitreal toxicity of high-dose etanercept.
abstract: 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.
authors.affiliation: Department of Ophthalmology, University of Arizona, Arizona Health Sciences Center, Tucson, AZ 85711, USA.
authors.forename: Muhamet
authors.initials: M
authors.lastname: Kivilcim
authors.forename: Gholam A
authors.initials: GA
authors.lastname: Peyman
authors.forename: Abdul Ahad
authors.initials: AA
authors.lastname: Kazi
authors.forename: John
authors.initials: J
authors.lastname: Dellacroce
authors.forename: Randa N
authors.initials: RN
authors.lastname: Ghobrial
authors.forename: Roberta
authors.initials: R
authors.lastname: Monzano
mesh_terms: 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*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D000068800:Etanercept