title: Stereotactic radiotherapy for neovascular age-related macular degeneration: year 2 results of the INTREPID study.
abstract: OBJECTIVE
  To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  Randomized, double-masked, sham-controlled, multicenter, clinical trial.
  
  
  METHODS
  A total of 230 participants with neovascular AMD who received ≥ 3 ranibizumab or bevacizumab injections within the preceding year and requiring treatment at enrollment.
  
  
  METHODS
  Participants received 16 Gray, 24 Gray, or sham SRT. All arms received pro re nata (PRN) ranibizumab for 12 months, with PRN bevacizumab or ranibizumab thereafter.
  
  
  METHODS
  Mean number of PRN injections; best-corrected visual acuity (BCVA); loss of <15 Early Treatment of Diabetic Retinopathy Study letters; change in optical coherence tomography central subfield thickness; and change in angiographic total lesion area and choroidal neovascularization (CNV) area.
  
  
  RESULTS
  At year 2, the 16 and 24 Gray arms received fewer PRN treatments compared with sham (mean 4.5, P = 0.008; mean 5.4, P = 0.09; and mean 6.6, respectively). Change in mean BCVA was -10.0, -7.5, and -6.7 letters for the 16 Gray, 24 Gray, and sham arms, respectively, with 46 (68%), 51 (75%), and 58 participants (79%), respectively, losing <15 letters. Mean central subfield thickness decreased by 67.0 μm, 55.4 μm, and 33.3 μm, respectively. Mean total active lesion area increased by 1.0, 4.2, and 2.7 mm(2), respectively. Mean CNV area decreased by 0.1 mm(2) in all groups. An independent reading center detected microvascular abnormalities in 6 control eyes and 29 SRT eyes, of which 18 were attributed to radiation; however, only 2 of these possibly affected vision. An exploratory subgroup analysis found that lesions with a greatest linear dimension ≤ 4 mm (the size of the treatment zone) and a macular volume greater than the median (7.4 mm(3)) were more responsive to SRT, with 3.9 PRN injections versus 7.1 in comparable sham-treated participants (P = 0.001) and mean BCVA 4.4 letters superior to sham (P = 0.24).
  
  
  CONCLUSIONS
  A single dose of SRT significantly reduces intravitreal injections over 2 years. Radiation can induce microvascular change, but in only 1% of eyes does this possibly affect vision. The best response occurs when AMD lesions fit within the treatment zone and they are actively leaking.
authors.affiliation: School of Medicine, King's College London, London, United Kingdom. Electronic address: t.jackson1@nhs.net.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Jackson
authors.affiliation: Queen's University of Belfast, Consultant in Ophthalmology, The Belfast Health and Social Care Trust, Belfast, Northern Ireland.
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.affiliation: Digital Angiography Reading Center, Great Neck, New York.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Slakter
authors.affiliation: Centre for Vision and Vascular Science, Queen's University of Belfast, Belfast, Northern Ireland.
authors.forename: Alyson
authors.initials: A
authors.lastname: Muldrew
authors.affiliation: Oraya Therapeutics, Inc, Newark, California.
authors.forename: E Mark
authors.initials: EM
authors.lastname: Shusterman
authors.affiliation: Oraya Therapeutics, Inc, Newark, California.
authors.forename: Denis
authors.initials: D
authors.lastname: O'Shaughnessy
authors.affiliation: Oraya Therapeutics, Inc, Newark, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Arnoldussen
authors.affiliation: Department of Surgery, Stanford University, Stanford, California.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Gertner
authors.affiliation: The International Drug Development Institute, Louvain-la-Neuve, Belgium.
authors.forename: Linda
authors.initials: L
authors.lastname: Danielson
authors.affiliation: Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Darius M
authors.initials: DM
authors.lastname: Moshfeghi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery; D000069579:Ranibizumab; 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 / Q000601:surgery*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab