John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Diabetic macular oedema is a common complication of diabetes, in which damage to the blood vessels at the back of the eye leads to swelling. Lucentis, Eylea and Avastin are three antiangiogenic drugs that can be injected into the eye to treat the blood vessels and reduce the swelling. In June 2017, Gianni Virgili from the University of Florence in Italy, and colleagues, updated their Cochrane review of these drugs and used a network meta-analysis to compare their effects.

Gianni: Antiangiogenic therapy using anti-vascular endothelial growth factor, or anti-VEGF, therapy, has become the standard treatment to try to improve vision in patients with diabetic macular oedema. These drugs have largely replaced laser treatment, which was used for several decades. They are injected directly into the eye and several drugs are available, including Lucentis, Eylea and Avastin as mentioned by John. However, Avastin is not yet licensed for use with diabetic macular oedema.
For this latest version of our review, we found 24 studies of anti-VEGF and lasers. One large, publicly funded trial had compared the three drugs directly and another small trial compared ranibizumab with bevacizumab; providing us with a small amount of direct randomised evidence. We augmented this with the indirect evidence from all other trials in the network meta-analysis, allowing us to estimate the differences in effects between the drugs more precisely.
This showed that people treated with anti-VEGFs were about three times more likely to improve vision compared to those treated with lasers. About three in 10 people experienced improved vision if treated with anti-VEGF, compared to only one in 10 if treated with lasers. Comparing the drugs, about one in 10 more people treated with Eylea would improve vision at one year, compared with Lucentis and Avastin, which had similar effects. However, the difference in average visual acuity between Eylea and Lucentis or Avastin was only half-to-one line, which is relatively small in terms of clinical importance.
There were too few trials with data at two years after treatment to conduct a network meta-analysis for that length of follow-up, but the trial comparing Lucentis, Eylea and Avastin found little difference in vision improvement between the drugs at two years. Alongside this, the trialists found that differences in vision improvement were not clinically important even at one year for people with diabetic macular oedema who still had good vision.
With regard to adverse effects, there was no suggestion of any differences between anti-VEGF and lasers or between the different antiVEGF drugs, but cardiovascular events were rare in the trials and could not be investigated precisely.
In conclusion, our extensive systematic review and network meta-analysis found that the currently available anti-VEGFs are all safe and effective treatments for diabetic macular oedema. Future research should investigate the effects of the treatments when used in routine clinical practice over the long term, given that there tend to be fewer injections and clinical examinations in these settings than in the trials.

John: If you would like to read about the two dozen trials in Gianni’s review and their network meta-analysis, you can access the full version online by going to Cochrane library dot com and searching for 'diabetic macular oedema and network meta-analysis'.