Preclinical investigations of intravitreal ziv-aflibercept

Ophthalmic Surg Lasers Imaging Retina. Nov-Dec 2014;45(6):577-84. doi: 10.3928/23258160-20141118-15.


Background and objective: To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits.

Materials and methods: Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay.

Results: All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept.

Conclusion: IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.

MeSH terms

  • Angiogenesis Inhibitors / toxicity*
  • Animals
  • Cell Line
  • Cell Survival
  • Drug Evaluation, Preclinical
  • Electroretinography
  • Humans
  • Intravitreal Injections
  • Male
  • Microscopy, Electron, Transmission
  • Ophthalmoscopy
  • Osmolar Concentration
  • Rabbits
  • Receptors, Vascular Endothelial Growth Factor / toxicity*
  • Recombinant Fusion Proteins / toxicity*
  • Retina / drug effects*
  • Retina / physiopathology
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / ultrastructure
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor