To evaluate the safety and bioavailability of intravitreal ziv-aflibercept (IVZ) in experimental model.

Thirty–two eyes of 16 male rabbits received one IVZ injection under anesthesia and the operating microscope. All right and left eyes respectively received 1.25 and 0.626mg/0.05ml of ziv-aflibercept. Then, rabbits were randomly allocated to four groups (4 rabbits in each group) at 24 hours, 7, 14, and 30 days. The rabbits were euthanized at 24 hours, 7, 14, and 30 days and the eyes were enucleated. Indirect ophthalmoscopy, vitreous and aqueous sampling and electrophysiological recordings were obtained before euthanization. Histological examination was performed after enucleation. Vitreous samples were evaluated by enzyme-linked immunosorbent assay (ELISA) to measure the concentration of ziv-aflibercept

No serious drug-related ocular inflammation and toxicity or systemic adverse events were identified. ERG findings showed no difference to the baseline measurements. Remained vitreous concentration of ziv-aflibercept injection for the 0.626 mg/ml group were 0.0360, 0.0335, 0.0309, and 0.0264 (± 0.01 mg/ml) and for the 1.25 ( mg/ml) group were 0.0406, 0.0371, 0.0321, and 0.0287 (± 0.01 mg/ml), at 1, 7, 14, and 30 days after injection respectively.

IVZ at concentrations of 1.25 and 0.625 mg/0.05mL proved to be safe in the experimental model. It seems that IVZ may be well tolerated. These short-term results suggest that intravitreal ziv-aflibercept could be a cost effective therapeutic option for the treatment of retinal vascular diseases. However, the long-term safety and efficacy of intravitreal ziv-aflibercept remain unknown.