Safety of Intravitreal Zoledronic Acid, an Anti-angiogenic Bisphosphonate, in a Rat Model

Purpose: To determine the safety of intravitreal zoledronic acid (ZA) in the rat eye. Methods: Twenty eyes of 20 pigmented rats were randomized into five groups to receive an intravitreal injection of 8, 4, 2 and 1 micrograms (mcg) of ZA, or balanced salt solution (BSS). One week and one month after the injections, all eyes were evaluated for intraocular inflammation. Electroretinography (ERG) was performed before, and one week and one month after the injections. All eyes were enucleated one month after the injection for histologic examination. Results: No significant inflammatory response was observed in any eye. No significant decrease in ERG amplitude (a & b waves) was observed one week and one month after intravitreal ZA injection, as compared to baseline, BSS-treated eyes or non-injected fellow eyes. Histologic examination of the retinal pigment epithelium and neurosensory retina were unremarkable in all groups. Additionally, no significant increase in immune reactivity for glial fibrillary acidic protein was noted in any eye. Conclusion: Based on clinical, histopathologic and ERG findings in this experimental study, up to 8 mcg of intravitreal zoledronic acid seems to be safe in the rat eye.