Intravitreal recombinant human erythropoietin: A safety study in rabbits

Purpose: To evaluate the ocular safety of varying doses of a single intravitreal injection of the candidate neuroprotective agent, recombinant human erythropoietin (rhEPO). Methods: Thirty New Zealand rabbits were divided into one of six groups: untreated controls, intravitreal saline injection, and intravitreal injections of rhEPO (100 U, 250 U, 500 U, or 1000 U). Electroretinography (ERG) was performed one day prior to injection and on post-injection days 3, 7, 14, and 21. Fluorescein angiography was done on post-injection day 28 and graded for the presence of neovascularization by a masked observer. Animals were sacrificed for histologic examination 30 days after injection. Results: Except for the rhEPO 500 U group on day 21, there were no statistically significant differences in the amplitude or implicit time of the ERGs between groups or at different timepoints. Fluorescein angiography showed no evidence of neovascularization. Light microscopy showed no apparent abnormalities in retinal morphology or evidence of retinal damage compared to control groups. Conclusion: A single 0.1-ml intravitreal injection of rhEPO at a dose of up to 1000 U does not appear to cause adverse effects on retinal vasculature, retinal anatomy, or ERG function in albino rabbits.