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 1250 and 626 µg/0.05ml of ziv-aflibercept. Then, rabbits were randomly allocated to four groups (4 rabbits in each group) at 24, 168, 336, and 720 hours. The rabbits were euthanized at predesignate intervals and the eyes were enucleated. Indirect ophthalmoscopy, vitreous 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 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 vitreal concentration of ziv-aflibercept injection for the 626 µg/ml group were 416, 349, 124, 41.2, and 18.1 (±10 µg/ml ) and for the 1250 ( µg/ml ) group were 833, 737, 284, 87.3, and 38.2 (± 10 µg/ml ), at 0, 24, 168, 336, and 720 hours after injection respectively. The vitreous concentration of aflibercept was analyzed by one-compartment model. The area under curve from time 0 to the end point (AUC last) was 147637.2 hours × µg/ml for the full dose group (1250 µg/0.05ml ) and 68498.4 hours × µg/ml for the half dose group (625 µg/0.05ml ). The assessed vitreous half-life (T 1/2) of ziv-aflibercept was 113 hours in both groups.

IVZ at concentrations of 1250 and 625 µg/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.