Stereotactic radiotherapy for neovascular age-related macular degeneration: Year 2 results of the INTREPID study

T.L. Jackson, U. Chakravarthy, J.S. Slakter, A. Muldrew, E.M. Shusterman, D. O'Shaughnessy, M. Arnoldussen, M.E. Gertner, L. Danielson, D.M. Moshfeghi

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30 Citations (Scopus)


Purpose: To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (AMD). Design: Randomized, double-masked, sham-controlled, multicenter, clinical trial. Participants: 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. Main Outcome Measures: 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 mm, 55.4 μm, and 33.3 μm, respectively. Mean total active lesion area increased by 1.0, 4.2, and 2.7 mm2, respectively. Mean CNV area decreased by 0.1 mm2 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 mm3) 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. © 2015 by the American Academy of Ophthalmology.
Original languageEnglish
Pages (from-to)138-145
Issue number1
Early online date07 Sep 2014
Publication statusPublished - Jan 2015

Bibliographical note

cited By 18


  • bevacizumab
  • ranibizumab
  • angiogenesis inhibitor
  • monoclonal antibody
  • vasculotropin A
  • VEGFA protein, human, age related macular degeneration
  • angiography
  • Article
  • central macular thickness
  • controlled study
  • double blind procedure
  • external beam radiotherapy
  • eye photography
  • fluorescence angiography
  • human
  • major clinical study
  • microangiopathy
  • microvascularization
  • multicenter study
  • optical coherence tomography
  • optical coherence tomography device
  • priority journal
  • radiation dose
  • radiation injury
  • radiotherapy
  • randomized controlled trial
  • sham procedure
  • stereotactic radiotherapy
  • stereotactic treatment
  • subretinal neovascularization
  • treatment duration
  • treatment response
  • vision
  • visual acuity
  • X ray system
  • aged
  • antagonists and inhibitors
  • clinical trial
  • female
  • intravitreal drug administration
  • male
  • middle aged
  • multimodality cancer therapy
  • physiology
  • radiosurgery
  • treatment outcome
  • very elderly
  • wet macular degeneration, Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Fluorescein Angiography
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Radiosurgery
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Visual Acuity
  • Wet Macular Degeneration


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