title: Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT): A Phase 3 Randomized Controlled Trial.
abstract: To assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD).
  
  
  
  Phase 3 randomized controlled trial.
  
  
  
  Patients (n = 363) with neovascular AMD already receiving intravitreal ranibizumab injections.
  
  
  
  Either pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n = 224) or ongoing PRN ranibizumab monotherapy (n = 119).
  
  
  
  The coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB.
  
  
  
  The mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P = 0.068). The mean VA change was -4.8 letters in the EMB arm and -0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups, -6.6 to -1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P = 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm(2) versus 0.4 mm(2) in the ranibizumab arm (P = 0.27). The CNV size decreased by 0.5 mm(2) in the EMB arm and by 1.3 mm(2) in the ranibizumab arm (P = 0.27). The OCT foveal thickness decreased by 1.0 μm in the EMB arm and by 15.7 μm in the ranibizumab arm (P = 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable.
  
  
  
  These results do not support the use of EMB for chronic, active, neovascular AMD. Safety is acceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned.
authors.affiliation: School of Medicine, King's College London, London, United Kingdom; Department of Ophthalmology, King's College Hospital, London, United Kingdom. Electronic address: t.jackson1@nhs.net.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Jackson
authors.affiliation: Department of Ophthalmology, King's College Hospital, London, United Kingdom.
authors.forename: Riti
authors.initials: R
authors.lastname: Desai
authors.affiliation: School of Medicine, King's College London, London, United Kingdom; Department of Ophthalmology, King's College Hospital, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simpson
authors.affiliation: School of Medicine, King's College London, London, United Kingdom; Department of Ophthalmology, King's College Hospital, London, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Neffendorf
authors.affiliation: School of Medicine, King's College London, London, United Kingdom; Department of Ophthalmology, King's College Hospital, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Petrarca
authors.affiliation: Statistics Collaborative, Inc, Washington, DC.
authors.forename: Kelly
authors.initials: K
authors.lastname: Smith
authors.affiliation: Statistics Collaborative, Inc, Washington, DC.
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.affiliation: School of Medicine, King's College London, London, United Kingdom; Department of Engineering and Physics, King's College Hospital, London, United Kingdom.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Lewis
authors.affiliation: Department of Ophthalmology, Maidstone Hospital, Maidstone, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Membrey
authors.affiliation: Bristol Eye Hospital, Bristol, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Haynes
authors.affiliation: Hull and East Yorkshire Eye Hospital, Hull, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Costen
authors.affiliation: Sunderland Eye Infirmary, Sunderland, United Kingdom, and the Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: David H W
authors.initials: DH
authors.lastname: Steel
authors.affiliation: Central Angiographic Reading Centre, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Alyson
authors.initials: A
authors.lastname: Muldrew
authors.affiliation: Central Angiographic Reading Centre, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D002908:Chronic Disease; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008266:Macula Lutea; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology; D000069579:Ranibizumab / Q000627:therapeutic use; D012160:Retina / Q000528:radiation effects; D016879:Salvage Therapy; D013326:Strontium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014821:Vitrectomy; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy*
chemical_list: D020533:Angiogenesis Inhibitors; D013326:Strontium Radioisotopes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab