title: An exploratory study of the safety, tolerability and bioactivity of a single intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic macular oedema.
abstract: OBJECTIVE
  The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO).
  
  
  METHODS
  Five subjects with DMO, foveal thickness > or =250 microm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT.
  
  
  RESULTS
  Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 microm. At 4 weeks after injection, the median excess FTH was 59 microm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 microm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters).
  
  
  CONCLUSIONS
  A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.
authors.affiliation: The Wilmer Eye Institute, 600 North Wolfe Street, Maumenee #719, Baltimore, MD 21287, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: Do
authors.forename: Q D
authors.initials: QD
authors.lastname: Nguyen
authors.forename: S M
authors.initials: SM
authors.lastname: Shah
authors.forename: D J
authors.initials: DJ
authors.lastname: Browning
authors.forename: J A
authors.initials: JA
authors.lastname: Haller
authors.forename: K
authors.initials: K
authors.lastname: Chu
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.forename: J M
authors.initials: JM
authors.lastname: Cedarbaum
authors.forename: R L
authors.initials: RL
authors.lastname: Vitti
authors.forename: A
authors.initials: A
authors.lastname: Ingerman
authors.forename: P A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D000368:Aged; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007267:Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012160:Retina / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000187:drug effects; D014822:Vitreous Body
chemical_list: D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor