PMID- 23490327 OWN - NLM STAT- MEDLINE DCOM- 20131119 LR - 20220408 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 120 IP - 9 DP - 2013 Sep TI - Stereotactic radiotherapy for neovascular age-related macular degeneration: 52-week safety and efficacy results of the INTREPID study. PG - 1893-900 LID - S0161-6420(13)00150-4 [pii] LID - 10.1016/j.ophtha.2013.02.016 [doi] AB - PURPOSE: To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (nvAMD). DESIGN: Randomized, double-masked, sham-controlled, multicenter, clinical trial. PARTICIPANTS: Two hundred thirty patients with onset of nvAMD within 3 years who received 3 or more injections of ranibizumab or bevacizumab within the preceding year and who needed continuing ranibizumab or bevacizumab treatment. INTERVENTIONS: Participants were randomized 2:1:2:1 to 16 Gy plus pro re nata (PRN) ranibizumab, sham 16 Gy plus PRN ranibizumab, 24 Gy plus PRN ranibizumab, or sham 24 Gy plus PRN ranibizumab, respectively. MAIN OUTCOME MEASURES: The primary efficacy end point was the mean number of ranibizumab injections at 52 weeks. Secondary end points were change in mean best-corrected visual acuity (VA), loss of fewer than 15 Early Treatment Diabetic Retinopathy Study letters, gain of 0 or more and 15 or more letters, and change in angiographic total lesion size and choroidal neovascularization (CNV) lesion size. RESULTS: Both the 16-Gy and 24-Gy SRT arms received significantly fewer ranibizumab treatments compared with the sham arms: mean number of treatments, 2.64 (median, 2), 2.43 (median, 2), and 3.74 (median, 3.5), respectively (P = 0.013 and P = 0.004, respectively, vs. sham). Change in mean VA was -0.28, +0.40, and -1.57 letters for the 16-Gy, 24-Gy, and sham arms, respectively. The 16-Gy, 24-Gy, and sham arms lost fewer than 15 letters in 93%, 89%, and 91% of eyes, respectively, with 53%, 57%, and 56% gaining 0 or more letters, respectively, and 4% gaining 15 letters or more in all arms. Mean total angiographic lesion area changed by -1.15 mm(2), +0.49 mm(2), and +0.75 mm(2), respectively; mean CNV lesion area decreased by 0.16 mm(2), 0.18 mm(2), and 0.10 mm(2), respectively. Optical coherence tomography central subfield thickness decreased by 85.90 mum, 70.39 mum, and 33.51 mum, respectively. The number of adverse events (AEs) and number of serious AEs (SAEs) were similar across arms. No AEs were attributed to radiation. No SAEs occurred in the study eye. CONCLUSIONS: A single dose of SRT significantly reduces ranibizumab retreatment for patients with nvAMD, with a favorable safety profile at 1 year. Whereas chronic nvAMD typically results in loss of VA over time, SRT is associated with relatively well-preserved VA over 1 year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. CI - Copyright (c) 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Jackson, Timothy L AU - Jackson TL AD - King's College London, London, United Kingdom. FAU - Chakravarthy, Usha AU - Chakravarthy U FAU - Kaiser, Peter K AU - Kaiser PK FAU - Slakter, Jason S AU - Slakter JS FAU - Jan, Ernest AU - Jan E FAU - Bandello, Francesco AU - Bandello F FAU - O'Shaughnessy, Denis AU - O'Shaughnessy D FAU - Gertner, Michael E AU - Gertner ME FAU - Danielson, Linda AU - Danielson L FAU - Moshfeghi, Darius M AU - Moshfeghi DM CN - INTREPID Study Group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20130313 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - ZL1R02VT79 (Ranibizumab) SB - IM MH - Aged MH - Angiogenesis Inhibitors/*administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects MH - Combined Modality Therapy MH - Double-Blind Method MH - Female MH - Fluorescein Angiography MH - Humans MH - Intravitreal Injections MH - Male MH - *Radiosurgery/adverse effects MH - Ranibizumab MH - Retreatment MH - Tomography, Optical Coherence MH - Treatment Outcome MH - Visual Acuity/physiology MH - Wet Macular Degeneration/diagnosis/*drug therapy/physiopathology/*surgery FIR - Krankenhaus, Hanusch IR - Krankenhaus H FIR - Findl, Oliver IR - Findl O FIR - Chen, Yen-An IR - Chen YA FIR - Tatzreiter, Sophie IR - Tatzreiter S FIR - Netzhautklinik, Vienna IR - Netzhautklinik V FIR - Stur, Michael IR - Stur M FIR - Vogl, Karin IR - Vogl K FIR - Kolar, Petr IR - Kolar P FIR - Vyslouzilova, Daniela IR - Vyslouzilova D FIR - Kralove, Hradec IR - Kralove H FIR - Studnicka, Jan IR - Studnicka J FIR - Dusova, Jaroslava IR - Dusova J FIR - Breznayova, Jana IR - Breznayova J FIR - Rehak, Jiri IR - Rehak J FIR - Chrapek, Oldrich IR - Chrapek O FIR - Jirkova, Barbora IR - Jirkova B FIR - Vlacil, Ondrej IR - Vlacil O FIR - Jan, Ernest IR - Jan E FIR - Hejsek, Libor IR - Hejsek L FIR - Nemec, Pavel IR - Nemec P FIR - Rejmont, Leos IR - Rejmont L FIR - Benesova, Zaneta IR - Benesova Z FIR - Hamouz, Jan IR - Hamouz J FIR - Pokorna, Jitka IR - Pokorna J FIR - Pokorna, Stanislava IR - Pokorna S FIR - Veith, Miroslav IR - Veith M FIR - Dubska, Zora IR - Dubska Z FIR - Kousal, Bohdan IR - Kousal B FIR - Dithmar, Stefan IR - Dithmar S FIR - Pollithy, Stefanie IR - Pollithy S FIR - Bartz-Schmidt, K U IR - Bartz-Schmidt KU FIR - Peters, Tobias IR - Peters T FIR - Wilhelm, Barbara IR - Wilhelm B FIR - Hoh, Helmut IR - Hoh H FIR - Kontopoulos, Theodoros IR - Kontopoulos T FIR - Bandello, Francesco IR - Bandello F FIR - Introini, Ugo IR - Introini U FIR - Milesi, Jacopo IR - Milesi J FIR - Triolo, Giacinto IR - Triolo G FIR - Chakravarthy, Usha IR - Chakravarthy U FIR - Gillvray, Karen IR - Gillvray K FIR - Kelly, Lisa IR - Kelly L FIR - Williams, Michael IR - Williams M FIR - Ghanchi, Faruque IR - Ghanchi F FIR - Cole, Mick IR - Cole M FIR - Doyle, Edward IR - Doyle E FIR - Olayinka, Osoba IR - Olayinka O FIR - Jackson, Timothy L IR - Jackson TL FIR - Aslam, Tariq IR - Aslam T FIR - IT, Dip IR - IT D FIR - Lotery, Andrew IR - Lotery A FIR - Narendran, Nirodhini IR - Narendran N FIR - Yang, Yit IR - Yang Y EDAT- 2013/03/16 06:00 MHDA- 2013/11/20 06:00 CRDT- 2013/03/16 06:00 PHST- 2012/09/20 00:00 [received] PHST- 2013/02/13 00:00 [revised] PHST- 2013/02/13 00:00 [accepted] PHST- 2013/03/16 06:00 [entrez] PHST- 2013/03/16 06:00 [pubmed] PHST- 2013/11/20 06:00 [medline] AID - S0161-6420(13)00150-4 [pii] AID - 10.1016/j.ophtha.2013.02.016 [doi] PST - ppublish SO - Ophthalmology. 2013 Sep;120(9):1893-900. doi: 10.1016/j.ophtha.2013.02.016. Epub 2013 Mar 13.