title: Preclinical investigations of intravitreal ziv-aflibercept.
abstract: OBJECTIVE
  To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits.
  
  
  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.
  
  
  CONCLUSIONS
  IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.
authors.forename: João Rafael
authors.initials: JR
authors.lastname: de Oliveira Dias
authors.forename: Emmerson
authors.initials: E
authors.lastname: Badaró
authors.forename: Eduardo Amorim
authors.initials: EA
authors.lastname: Novais
authors.forename: Daniel
authors.initials: D
authors.lastname: Colicchio
authors.forename: Gabrielly Maria Denadai
authors.initials: GM
authors.lastname: Chiarantin
authors.forename: Mariana Maurício
authors.initials: MM
authors.lastname: Matioli
authors.forename: Carina
authors.initials: C
authors.lastname: Verna
authors.forename: Fernando Marcondes
authors.initials: FM
authors.lastname: Penha
authors.forename: Nilana Meza Tenório
authors.initials: NM
authors.lastname: Barros
authors.forename: Carsten H
authors.initials: CH
authors.lastname: Meyer
authors.forename: Michel Eid
authors.initials: ME
authors.lastname: Farah
authors.forename: Eduardo Büchele
authors.initials: EB
authors.lastname: Rodrigues
mesh_terms: D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D004596:Electroretinography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D046529:Microscopy, Electron, Transmission; D009887:Ophthalmoscopy; D009994:Osmolar Concentration; D011817:Rabbits; D040262:Receptors, Vascular Endothelial Growth Factor / Q000633:toxicity*; D011993:Recombinant Fusion Proteins / Q000633:toxicity*; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000648:ultrastructure; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor