title: Initiation of intravitreal aflibercept injection treatment in patients with diabetic macular edema: a review of VIVID-DME and VISTA-DME data.
abstract: BACKGROUND
  Diabetic macular edema (DME) shows a gradual and sustained functional and morphologic response to anti-vascular endothelial growth factor (VEGF) drugs, but the optimal schedule for initiation of anti-VEGF therapy is not known. This study evaluates the treatment response behavior of DME in the Phase 3 trials of intravitreal aflibercept, with 5 initial intravitreal aflibercept injections (IAI), 2 mg every 4 weeks (2q4), in the upload phase.
  
  
  METHODS
  This post hoc pooled analysis of the VISTA-DME (NCT01363440) and VIVID-DME (NCT01331681) trials evaluated the change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) during the upload phase, using pooled data from both IAI treatment groups [2q4 and 2 mg every 8 weeks (2q8)]. The mean visit-to-visit change in BCVA and CRT, and the respective rate of gainers and losers was calculated for each successive visit. A secondary analysis compared the visit-to-visit change in BCVA between the 2q4 and 2q8 treatment arms during the upload period and the first year treatment period.
  
  
  RESULTS
  The majority of eyes showed a continuing improvement of BCVA after the first IAI. The proportions of eyes gaining BCVA (≥5 letters) at each visit compared with the previous visit during the IAI 2q4 upload phase were 60 (4-weeks), 19 (8-weeks), 16 (12-weeks), 15 (16-weeks), and 14 % (20-weeks). In contrast, the proportions of eyes losing BCVA (≥5 letters) were 3 (4-weeks), 7 (8-weeks), 7 (12-weeks), 9 (16-weeks), and 8 % (20-weeks), respectively. The odds of BCVA (≥5 letters) gain/loss exceeded 1.7 at each visit (range 1.7-20). Overall, the proportion of patients with BCVA gain ≥5 letters at week 20 (compared with baseline) was 76 and 80 % in the 2q4 and 2q8 groups, respectively. The proportions of eyes showing a visit-to-visit decrease in CRT of ≥30 µm during the first 5 IAI were 77 (4-weeks), 27 (8-weeks), 21 (12-weeks), 17 (16-weeks), and 12 % (20-weeks). In the secondary analysis, the BCVA outcomes were similar for the 2q8 and 2q4 treatment arms.
  
  
  CONCLUSIONS
  The data presented here are consistent with continual functional and anatomic improvement following the fourth and fifth initial 2q4 injections, suggesting that an intensive and sufficiently long upload may be beneficial.Trial registrationVIVID-DME: Clinicaltrials.gov: NCT01331681; VISTA-DME: Clinicaltrials.gov: NCT01363440.
authors.affiliation: Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstrasse 12, 72076 Tübingen, Germany.
authors.forename: Focke
authors.identifier: 0000-0002-3873-0581
authors.initials: F
authors.lastname: Ziemssen
authors.affiliation: Organizacion Medica de Investigacion, Uruguay 725 PB, C1015ABO Buenos Aires, Argentina.
authors.forename: Patricio G
authors.initials: PG
authors.lastname: Schlottman
authors.affiliation: University of Illinois at Chicago, Illinois Eye and Ear Infirmary, 1855 W. Taylor Street, M/C 648, Chicago, IL 60612 USA.
authors.forename: Jennifer I
authors.initials: JI
authors.lastname: Lim
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstr. 5, 79106 Freiburg, Germany.
authors.forename: Hansjürgen
authors.initials: H
authors.lastname: Agostini
authors.affiliation: Division of Medical Retina and Laser Surgery, Department of Ophthalmology, University Eye Hospital Ulm, Prittwitzstr. 43, 89075 Ulm, Germany.
authors.forename: Gabriele E
authors.initials: GE
authors.lastname: Lang
authors.affiliation: Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bandello
keywords: Aflibercept; Anti-VEGF; Diabetic macular edema; Loading dose; Treatment initiation; Upload