title: Epimacular brachytherapy for neovascular age-related macular degeneration (CABERNET): fluorescein angiography and optical coherence tomography.
abstract: OBJECTIVE
  To report the fluorescein angiography (FA) and optical coherence tomography (OCT) results of a clinical trial of epimacular brachytherapy (EMBT) used for the treatment of neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  Pivotal multicenter, active-controlled, randomized clinical trial.
  
  
  METHODS
  A total of 494 participants with treatment-naïve, neovascular AMD.
  
  
  METHODS
  Participants with classic, minimally classic, and occult lesions were randomized to receive (a) EMBT and 2 mandated monthly ranibizumab injections followed by pro re nata (PRN) ranibizumab or (b) 3 mandated monthly ranibizumab injections followed by mandated quarterly plus PRN ranibizumab. Participants underwent FA at screening and at months 1, 6, 12, 18, and 24. Optical coherence tomography scans were undertaken monthly for 24 months. The FA and OCT images were analyzed at respective independent reading centers.
  
  
  METHODS
  Change at 24 months in mean FA total lesion size and choroidal neovascularization (CNV) size and change in mean OCT centerpoint thickness.
  
  
  RESULTS
  The mean (standard deviation) changes in FA total lesion size in the EMBT and control arms were +1.9 (8.7) and -3.0 (7.2) mm(2), respectively, with a mean change in total CNV size of +0.4 (8.4) and -4.7 (6.5) mm(2), respectively. Mean (standard deviation) changes in OCT centerpoint thickness were -144 (246) and -221 (185) μm, respectively. Retrospective subgroup analyses showed no significant difference between treatment arms in mean centerpoint thickness in some subgroups, including eyes with classic lesions. The control arm showed a significantly larger reduction in mean total lesion size and mean CNV size than the EMBT arm in all subgroups analyzed. Nine eyes in the EMBT arm showed features consistent with mild, nonproliferative radiation retinopathy, but with a mean gain of 5.0 Early Treatment Diabetic Retinopathy Study letters.
  
  
  CONCLUSIONS
  Both FA and OCT suggest that EMBT with PRN ranibizumab results in an inferior structural outcome than quarterly plus PRN ranibizumab. Some subgroup analyses suggest that classic lesions may be more responsive than occult lesions, although generally both subgroups are inferior to ranibizumab. A non-vision-threatening radiation retinopathy occurs in 2.9% of eyes over 24 months, but longer follow-up is needed.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: King's College London, London, United Kingdom. t.jackson1@nhs.net
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Jackson
authors.forename: Pravin U
authors.initials: PU
authors.lastname: Dugel
authors.forename: Judith D
authors.initials: JD
authors.lastname: Bebchuk
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Smith
authors.forename: Robert
authors.initials: R
authors.lastname: Petrarca
authors.forename: Jason S
authors.initials: JS
authors.lastname: Slakter
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Jaffe
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Nau
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D003131:Combined Modality Therapy; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology; D000069579:Ranibizumab; D012160:Retina / Q000473:pathology / Q000528:radiation effects; D013326:Strontium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology; D014821:Vitrectomy; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D013326:Strontium Radioisotopes; D000069579:Ranibizumab