title: Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-Related Macular Degeneration: 12-Month Safety and Efficacy Outcomes.
abstract: OBJECTIVE
  To prospectively assess the safety and efficacy of intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD).
  
  
  METHODS
  This prospective, non-randomized clinical trial included 49 patients with treatment-resistant nAMD who received 2 mg intravitreal aflibercept as 3 monthly loading doses, followed by injections every 2 months over 12 months. Inclusion criteria included active nAMD on fluorescein angiography at baseline and persistent intra- or subretinal fluid on optical coherence tomography (OCT) for ≥ 6 months prior to baseline with a minimum of 4 injections of bevacizumab and/or ranibizumab. Patients were assessed monthly for best-corrected visual acuity (BCVA), central retinal thickness (CRT) measured with OCT and occurrence of adverse events. Retinal pigment epithelium atrophy (RPEA) was assessed at baseline and at 12 months.
  
  
  RESULTS
  Mean BCVA improved by 4.7 letters (95% CI: 2.1-7.3, p < 0.001) and CRT decreased by 97.2 µm (95% CI: 54.4-140.1, p < 0.001) at 12 months compared to baseline. Median RPEA area increased by 0.48 mm2 (range = -0.1 to 19.9, p < 0.001). There was 1 arterial thromboembolic event and 2 cases of submacular haemorrhage.
  
  
  CONCLUSIONS
  In this cohort of treatment-resistant nAMD patients, intravitreal aflibercept was effective in improving vision and reducing exudation. Early visual and anatomic outcomes may predict longer-term response to treatment, but further assessment is required.
authors.affiliation: Sydney Institute of Vision Science, Sydney, N.S.W., Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Chang
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Broadhead
authors.forename: Thomas
authors.initials: T
authors.lastname: Hong
authors.forename: Nichole
authors.initials: N
authors.lastname: Joachim
authors.forename: Adil
authors.initials: A
authors.lastname: Syed
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Schlub
authors.forename: Levente
authors.initials: L
authors.lastname: Toth
authors.forename: Tunde
authors.initials: T
authors.lastname: Peto
authors.forename: Meidong
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy*
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