title: Ziv-aflibercept in macular disease.
abstract: OBJECTIVE
  Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis.
  
  
  METHODS
  Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA.
  
  
  RESULTS
  There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab.
  
  
  CONCLUSIONS
  Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept.
  
  
  BACKGROUND
  NCT02173873.
authors: Departments of Ophthalmology, American University of Beirut, and Rafic Hariri University Hospital, Beirut, Lebanon.
authors: Ahmad M
authors: AM
authors: Mansour
authors: Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
authors: Sara I
authors: SI
authors: Al-Ghadban
authors: Departments of Ophthalmology, American University of Beirut, and Rafic Hariri University Hospital, Beirut, Lebanon.
authors: Muhammad H
authors: MH
authors: Yunis
authors: Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
authors: Marwan E
authors: ME
authors: El-Sabban
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000191:economics / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000191:economics / Q000627:therapeutic use*; D058471:Subretinal Fluid; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Angiogenesis; Drugs; Macula; Neovascularisation