This study included adults with diabetic macular oedema, who had at least one eye with a best corrected visual-acuity letter score (range 0 to 100) of 78 (approximate Snellen equivalent, 20/32) to 24 (20/320). One eye was randomised to intravitreal injection with aflibercept (dose of 2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg). The study drugs were injected at baseline and then every 4 weeks unless visual acuity was 20/20 or better with a central subfield thickness below the eligibility threshold and there was no improvement or worsening in response to the past two injections. The median number of injections administered was 9 in the aflibercept group and 10 in both the bevacizumab and ranibizumab groups.
The primary outcome was the mean change in visual acuity from baseline to 1 year, with adjustment for baseline visual acuity. The improvement seen with aflibercept was larger than that seen for bevacizumab or ranibizumab (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), but the relative effect was found to vary according to initial visual acuity (p<0.001 for interaction).
Subgroup analyses showed no difference between groups in terms of mean visual acuity gain in those patients with a baseline visual acuity of 20/40 or better (improvement of around 8 letters in each group). However, in eyes with a baseline visual acuity of 20/50 or worse, there was an advantage seen with aflibercept (mean improvement of 19 letters) over bevacizumab (12 letters) or ranibizumab (14 letters), despite a similar number of overall injections (median 10 for aflibercept and ranibizumab and 11 for bevacizumab).
The author of a related editorial notes that the majority of patients with diabetic macular oedema present with a visual acuity of 20/40 or better; as there were no significant differences in safety or efficacy among drugs in this patient subgroup, cost will be a major consideration when choosing therapy.
Although a post hoc analysis identified more cardiovascular events in patients treated with ranibizumab (17% vs. 9% with aflibercept and bevacizumab; P=0.01), it is thought that this may be a chance finding and continued surveillance is warranted.
NICE guidance (TA274; April 2013) recommends ranibizumab as an option for treating visual impairment due to diabetic macular oedema only if the eye has a central retinal thickness of 400 micrometres or more at the start of treatment and the manufacturer provides it with the discount agreed in the patient access scheme. Guidance on aflibercept for macular oedema is currently in development (expected June 2015). NICE will not be appraising bevacizumab in this indication as it is unlicensed.