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B. J. Song, H. Cai, N. Gomes, S. Chang, J. C. Tsai, M. Forbes, L. V. Del Priore; Ocular Safety of Serial Intravitreal Injections of Recombinant Human Erythropoietin: A 7 Month Study in Rabbits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5605. doi: https://doi.org/.
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Previous studies have demonstrated that recombinant human erythropoietin (rhEPO) is therapeutic in various rodent models of glaucoma and retinal degeneration. Treatment of such chronic diseases may require repeat intravitreal injections of rhEPO, but there is no data regarding the safety of repeat intravitreal injections, particularly in nonrodent species. The purpose of this study is to evaluate the long-term effects of monthly intravitreal injections of rhEPO in a higher species.
Sixteen New Zealand white rabbits were randomly divided into one of 4 groups: control (no injection), saline injection, or rhEPO injections of 500 U and 1000 U (N=4 per group). The right eye of each animal was injected at one month intervals over a period of 7 months. Eyes were followed ophthalmoscopically and with electroretinography (ERG) at 1 day prior, and 1 week, 1 month, and 6 months after the initial injection. Intraocular pressure (IOP) was measured using a Tonopen-XL at the conclusion of each ERG. Following the final ERG, animals underwent fluorescein angiography and sacrifice one week later. Scotopic and photopic ERG amplitude and implicit times were analyzed by calculating a ratio of the experimental right eye to the contralateral eye to control for interexperiment variability. Angiograms were graded for the presence of neovascularization from 0 to +4 by a masked observer. Statistical analysis of ERG and IOP data was carried out using two-way ANOVA.
Fifteen animals were used for this experiment (1 rabbit was excluded due to the development of a traumatic cataract). Between all groups and time points, there were no statistically significant differences in the computed right eye:left eye ratios for the scotopic or photopic ERG components (p>0.05). Differences in IOP were not statistically significant between groups or time points (p>0.05). No evidence of neovascularization or fluorescein leakage was seen on angiography. While artifactual retinal detachment was seen in all groups on histological analysis of stained sections by a masked observer, there were no visible differences in retinal architecture or thickness in the rhEPO groups when compared to uninjected controls.
Monthly 0.1 ml intravitreal injections of rhEPO at a dose of up to 1000 U over 7 months is well-tolerated and does not cause adverse effects on retinal function, architecture, or vasculature in a rabbit model.
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