ONLINE FIRST CLINICAL TRIALS SECTION EDITOR: ANNE S. LINDBLAD, PhD A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema 24-Month Data: Report 3 Ranjan Rajendram, MD, FRCOphth; Samantha Fraser-Bell, PhD, FRANZCO; Andrew Kaines, FRANZCO; Michel Michaelides, MD, FRCOphth; Robin D. Hamilton, DM, FRCOphth; Simona Degli Esposti, MD; Tunde Peto, MD, PhD; Catherine Egan, FRANZCO; Catey Bunce, DSc; Richard David Leslie, MD, FRCP; Philip G. Hykin, MD, FRCOphth Objective: To report the 2-year outcomes of the BOLT study, a prospective randomized controlled trial evalu- ating intravitreous bevacizumab and modified Early Treat- ment Diabetic Retinopathy Study (ETDRS) macular la- ser therapy (MLT) in patients with persistent clinically significant macular edema (CSME). Methods: In a 2-year, single-center, randomized con- trolled trial, 80 patients with center-involving CSME and visual acuity of 20/40 to 20/320 were randomized to re- ceive either bevacizumab or MLT. Main Outcome Measures: Primary outcome: differ- ence in ETDRS best-corrected visual acuity (BCVA) be- tween arms. Secondary outcomes: mean change in BCVA, proportion gaining at least 15 and at least 10 ETDRS let- ters, losing fewer than 15 and at least 30 letters, change in central macular thickness, ETDRS retinopathy sever- ity, and safety outcomes. Results: At 2 years, mean (SD) ETDRS BCVA was 64.4 (13.3) (ETDRS equivalent Snellen fraction: 20/50) in the bevacizumab arm and 54.8 (12.6) (20/80) in the MLT arm (P = .005). The bevacizumab arm gained a median of 9 ETDRS letters vs 2.5 letters for MLT (P = .005), with a mean gain of 8.6 letters for bevacizumab vs a mean loss of 0.5 letters for MLT. Forty-nine percent of patients gained 10 or more letters (P =.001) and 32% gained at least 15 letters (P = .004) for bevacizumab vs 7% and 4% for MLT. Percentage who lost fewer than 15 letters in the MLT arm was 86% vs 100% for bevacizumab (P = .03). Mean reduction in central macular thickness was 146 μm in the bevacizumab arm vs 118 μm in the MLT arm. The median number of treatments over 24 months was 13 for bevacizumab and 4 for MLT. Conclusions: This study provides evidence supporting longer-term use of intravitreous bevacizumab for persis- tent center-involving CSME. Application to Clinical Practice: Improvements in BCVA and central macular thickness seen with bevaci- zumab at 1 year were maintained over the second year with a mean of 4 injections. Trial Registration: eudract.ema.europa.eu Identifier: 2007-000847-89 Arch Ophthalmol. 2012;130(8):972-979. Published online April 9, 2012. doi:10.1001/archophthalmol.2012.393 M ODIFIED E ARLY Treatment Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) has been the mainstay of treatment for clinically significant diabetic macular edema (CSME) for the past 3 decades and reduces the risk of moderate visual loss by approximately 50% (from 24% to 12%) at 3 years; however, visual acu- ity (VA) improves (a 15-letter gain at 3 years) in less than 3% of patients, and better treatments have been sought. 1 The BOLT study (n=80) was con- ducted to evaluate repeated intravitreal be- vacizumab administration (1.25 μg/50 μL) vs modified ETDRS MLT in patients with persistent CSME. At 12 months, the bev- acizumab (Avastin; Genentech USA, Inc) arm gained a median of 8 ETDRS letters, whereas the MLT arm lost a median of 0.5 Author Affiliations are listed at the end of this article. ARCH OPHTHALMOL / VOL 130 (NO. 8), AUG 2012 WWW.ARCHOPHTHALMOL.COM 972 ©2012 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a University College London User on 01/03/2014