Laird Harrison

September 09, 2017

BARCELONA, Spain — For patients with diabetic macular edema, aflibercept 2.0 mg (Eylea, Regeneron) is better than ranibizumab 0.5 mg (Lucentis, Genentech/Roche), with or without laser photocoagulation, for the first 12 months of treatment, results from a new meta-analysis show.

"When you treat diabetic macular edema with aflibercept, you get better visual acuity," said investigator Jean-François Korobelnik, MD, from the University of Bordeaux in France.

Aflibercept was more effective regardless of whether the protocol for administering ranibizumab was as-needed or treat-and-extend, he told Medscape Medical News.

Previous studies have shown similar results, but questions have remained about the significance of the dose of ranibizumab and the role of laser photocoagulation, and few prospective clinical trials have directly compared vascular endothelial growth factor (VEGF) inhibitors.

Other meta-analyses have aggregated data from studies of different therapies, but their results could have been biased because of the differences in the way the studies were conducted, said Dr Korobelnik. Also, correlations between trial-level variables are not necessarily equivalent to correlations between patient-level variables, he explained.

For their meta-analysis, the investigators used raw data on individual patients from multiple studies, which allowed them to adjust for baseline differences in best-corrected visual acuity. Dr Korobelnik presented the findings here at the 17th EURETINA Congress.

The investigators used best-corrected visual acuity as the key treatment modifier; other potential modifiers, such as severity of diabetic retinopathy and previous treatment with VEGF inhibitors, were shown to be nonsignificant in previous trials.

The meta-analysis included the following trials:

  • Diabetic Retinopathy Clinical Research Protocols (DRCR) I, J, and T






  • RIDE

  • RISE




In all the trials that included aflibercept, the protocol for that drug was a 2-mg intravitreal injection every 4 weeks for the first 5 injections, followed by 2 mg every 8 weeks. None of the trials combined aflibercept with laser photocoagulation.

The ranibizumab protocol varied from trial to trial, and sometimes included laser photocoagulation.

The change in best-corrected visual acuity favored aflibercept, no matter which treatment it was compared with or whether baseline visual acuity was adjusted for. The result was also the same whether the comparison was mean letters of visual acuity gained or the odds ratio of gaining 10 letters or 15 letters, and whether aggregate data or patient-level data from the studies were used.

The mean difference in letters gained was significantly better when aflibercept was compared with laser photocoagulation alone, with as-needed ranibizumab 0.5 mg, and with treat-and-extend ranibizumab with or without laser photocoagulation.

Table. Superiority of Aflibercept Over Other Treatments at 1 Year

Comparison Treatment Adjusted Difference in Letters Gained 95% Confidence Interval
Laser photocoagulation 10.27 8.79–11.74
As-needed ranibizumab 0.5 mg 4.95 3.09–6.83
Treat-and-extend ranibizumab 0.5 mg 4.90 2.06–7.72
In combination with laser photocoagulation
  As-needed ranibizumab 0.5 mg 5.77 3.81–7.74
  Treat-and-extend ranibizumab 0.5 mg 3.65 0.94–6.35


The study supports 12-month results from the most significant trial comparing VEGF inhibitors for diabetic macular edema — DRCR Protocol T — in which aflibercept was shown to be better than ranibizumab 0.3 mg, the dose on the label in the United States, Dr Korobelnik reported.

In Europe, the standard dose of ranibizumab is 0.5 mg, and some authorities, including the EURETINA guidelines, have questioned whether the results would have been different if aflibercept had been compared with a higher dose of ranibizumab, Dr Korobelnik added.

We clearly saw that, in many cases, aflibercept appears to be superior to ranibizumab. Dr Paris Tranos

"I think it's a very thorough, very rigorous meta-analysis," said session comoderator Paris Tranos, PhD, from Ophthalmica in Thessaloniki, Greece.

"We clearly saw that, in many cases, aflibercept appears to be superior to ranibizumab," he told Medscape Medical News.

However, this study does not show long-term differences beyond 12 months. In Protocol T, the superiority of aflibercept over ranibizumab that was seen at 12 months had faded by 24 months ( Ophthalmology. 2016;123:1351-1359).

Dr Korobelnik reports being a consultant for Alcon, Allergan, Bayer, Boehringer-Ingelheim, Kanghong, Krys, Novartis, Roche, Thea, and Zeiss. Dr Tranos has disclosed no relevant financial relationships.

European Society of Retina Specialists 17th EURETINA Congress. Presented September 8, 2017.

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