title: Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis.
abstract: OBJECTIVE
  To systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD).
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Medline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs).
  
  
  RESULTS
  Of 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI -0.25 to 2.46,P=0.17 and 0.63 letters, 95% CI -0.26 to 1.52,P=0.17, respectively). There was a significant improvement in mean CRT following switching (-61.90 µm, 95% CI -77.10 to -46.80,P<0.001 and -50.00 µm, 95% CI -63.20 to -36.80,P<0.001 at 6 and 12 months, respectively).
  
  
  CONCLUSIONS
  Pooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.
authors.affiliation: Sydney Retina Clinic & Day Surgery; Sydney Institute of Vision Science, Sydney; Save Sight Institute, Department of Ophthalmology, University of Sydney, Camperdown, NSW, Australia.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Spooner
authors.affiliation: Sydney Retina Clinic & Day Surgery; Sydney Institute of Vision Science, Sydney.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hong
authors.affiliation: Sydney Retina Clinic & Day Surgery; Sydney Institute of Vision Science, Sydney; Save Sight Institute, Department of Ophthalmology, University of Sydney, Camperdown, NSW, Australia.
authors.forename: Wijeyanthy
authors.initials: W
authors.lastname: Wijeyakumar
authors.affiliation: Sydney Retina Clinic & Day Surgery; Sydney Institute of Vision Science, Sydney; Save Sight Institute, Department of Ophthalmology, University of Sydney, Camperdown, NSW, Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Chang
keywords: aflibercept; anti-vascular endothelial growth factor; macular degeneration; meta-analysis; treatment resistance