12-month data from the BOLT study provides supporting evidence for the use of bevacizumab in patients with clinically significant DME.
Dr Phil Hykin (principal investigator), Dr Michel Michaelides, and a team of co-investigators at the department of medical retina at Moorfields Eye Hospital in London have undertaken a two-year study that compares repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy in patients with centre-involving clinically significant diabetic macular oedema (CSME). The 12-month data have been recently published in full in the journal Ophthalmology.1
Previous uncontrolled and retrospective studies of ivB have indicated that intravitreal bevacizumab may assist managing nonischemic DME.5,6 Others yielded more reliable data suggesting ivB benefits for patients with chronic diffuse DME,7,8 and in 2007 Soheilian et al., undertook a three-arm trial in treatment-naïve patients with CSME that showed that a single ivB injection produced better outcomes when compared with macular laser therapy.9
Dr Michaelides explains what they set out to achieve: "Our trial was designed as a prospective, single centre, randomized two-year trial. The patient cohort had CSME and had all received at least one macular laser treatment (MLT) beforehand. We wanted to compare how effective repeated ivB was with four monthly modified ETDRS MLT. Report 1 is our assessment of macular perfusion at 4 months with fundus fluorescein angiography in both study arms.10 Report 2 is our findings at the end of 12 months.1 "
A total of 80 eyes of 80 patients were enrolled in the study in the age range of 40-86 years, the mean age being 64.2 comprising 25 females and 55 males. Patients were split into 2 groups randomly, 38 to the laser group and 42 to the bevacizumab group. They were stratified for BCVA so that both groups would have comparable mean baseline BCVA.
Those patients in the laser arm had MLT and were reviewed every 4 months (with a minimum of 1 treatment and maximum of 4 treatments in the first 12 months). The bevacizumab arm was reviewed every 6 weeks and received a minimum of 3 injections and maximum of 9 in the first 12 months.
What we found
"Our results highlighted that after 12 months bevacizumab had a far greater treatment effect than the modified ETDRS MLT. The bevacizumab group achieved a median gain of 8 ETDRS letters compared with a loss in the laser group of 0.5 ETDRS letters. It was calculated that the odds of gaining more than 10 ETDRS letters over 12 months was five times greater in the drug group than in the laser group. After 12 months the mean ETDRS BCVA achieved in the drug group was 61.3 and in the laser arm 50.0. There were no safety concerns identified at 12 months.
"Our findings are comparable with those of the DRCRNet and RESOLVE studies,11 " said Dr Michaelides. "The implications of this are that we anticipate that treating people with CSME with repeated ivB before irreversible damage has been done will mean they can enjoy improved visual outcomes in the future and that with the more rapid reduction in macular oedema may mean improved longer-term visual acuity. Our 2-year outcome data will be presented at Euretina September 2010."
1. M. Michaelides, et al. Ophthalmology 2010; 117:1078-1086.
2. Early Treatment Diabetic Retinopathy Study Research Group. Arch. Ophthalmol. 1985;103(12):1796–1806.
3. M.R. Hee, et al. Arch. Ophthalmol. 1995;113:1019–1029.
4. Diabetic Retinopathy Clinical Research Network. Ophthalmology 2007;114:525–536.
5. E.J. Chung et al. Retina 2008;28:957-63.
6. J.F. Arevalo et al. Ophthalmology 2009;116:1488-97.
7. C. Haritoglou et al. Retina 2006;26:999-1005.
8. D. Kook et al. Retina 2008;28:1053-60.
9. M. Soheilian et al. Retina 2007;27:1187-95.
10. M. Michaelides et al. Retina 2010;30:781-86.
11. Diabetic Retinopathy Clinical Research Network. Ophthalmology. 2010;117:1064-1077.