title: Routine versus As-Needed Bevacizumab with 12-Weekly Assessment Intervals for Neovascular Age-Related Macular Degeneration: 92-Week Results of the GMAN Trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD) using 2 different treatment regimens in which patients were assessed clinically at up to 12-week intervals.
  
  
  METHODS
  Randomized, controlled, noninferiority trial.
  
  
  METHODS
  A total of 331 patients with nAMD.
  
  
  METHODS
  Patients were treated with 1.25 mg intravitreal bevacizumab and followed up to 92 weeks. They were randomized into 2 arms. All patients received 3 loading doses 4 weeks apart and thereafter were assessed every 12 weeks until the end of the study. One arm received a routine treatment at each 12-week assessment, and the other arm was treated at these assessments on an as-needed basis. After the loading doses, patients in either arm who showed signs of disease activity had an additional assessment after 6 weeks and at that visit had top-up treatments on an as-needed basis.
  
  
  METHODS
  Mean best-corrected visual acuity (BCVA) at 92 weeks.
  
  
  RESULTS
  At 92 weeks, patients who had treatments every 12 weeks had superior BCVA to those treated on an as-needed basis every 12 weeks (P = 0.008), with the regular treatment arm gaining a mean BCVA of 5.5 letters and the as-needed treatment arm gaining 0.6 letters. The regular treatment arm of the study showed significantly improved outcomes with respect to 5-, 10-, and 15-letter changes in BCVA from baseline compared with the as-needed treatment arm, as well as superior reading speed. In patients who completed the study, up to but not including week 92, the mean number of treatments was 10.8 for the regular treatment arm and 9.1 for the as-needed treatment arm.
  
  
  CONCLUSIONS
  A treatment regimen with regular bevacizumab injections every 12 weeks after loading doses supplemented with as-needed top-up treatments produced a stable improvement in BCVA from baseline. The improvement in BCVA was broadly similar to that obtained in other studies using anti-vascular endothelial growth factor drugs with more frequent assessments and treatments.
authors.affiliation: Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Centre for Ophthalmology & Vision Sciences, and Centre for Advanced Discovery & Experimental Therapeutics (CADET), Institute of Human Development, University of Manchester, Manchester, United Kingdom.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Mahmood
authors.affiliation: Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Roberts
authors.affiliation: Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Centre for Ophthalmology & Vision Sciences, and Centre for Advanced Discovery & Experimental Therapeutics (CADET), Institute of Human Development, University of Manchester, Manchester, United Kingdom.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Aslam
authors.affiliation: Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Parkes
authors.affiliation: Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Barugh
authors.affiliation: Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Centre for Ophthalmology & Vision Sciences, and Centre for Advanced Discovery & Experimental Therapeutics (CADET), Institute of Human Development, University of Manchester, Manchester, United Kingdom. Electronic address: Paul.Bishop@manchester.ac.uk.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Bishop
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; 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* / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab