No Laser on First-line Anti-VEGF for Diabetic Macular Edema

Damian McNamara

September 10, 2016

COPENHAGEN — More patients with diabetic macular edema achieved improvements in visual impairment with ranibizumab monotherapy than with a combination of ranibizumab plus laser therapy or with laser therapy alone, according to a post hoc analysis of the RESTORE core and extension studies.

It is best to start with monotherapy with the anti-vascular endothelial growth factor (anti-VEGF), "and not add laser early on," said investigator Paul Mitchell, MD, PhD, from the University of Sydney in Australia.

"Doing laser at baseline is not helpful; it reduced the likelihood of achieving better vision in the long term in these two studies," he explained. "Whether laser later in the protocol is useful has not been answered in any major study."

Dr Mitchell presented results from the analysis here at the European Society of Retina Specialists 16th EURETINA Congress.

In the 12-month phase 3 double-blind RESTORE core study, 343 patients were randomized to one of three groups: ranibizumab monotherapy plus sham laser; ranibizumab plus active laser; or a sham injection plus active laser.

In the 24-month open-label RESTORE extension study, 240 of these patients were treated with ranibizumab, laser, or both at the discretion of the investigators.

The primary end point of the studies — vision of at least 20/40 — was chosen "because this is the level of vision required in most countries for driver's license attainment," Dr Mitchell explained.

Table 1. Percent of Patients With at Least 20/40 Vision

Treatment Group Baseline, % 12 Months, % Change, %
Ranibizumab 46.1 73.0 +26.9
Laser 38.2 44.5 +6.3
Ranibizumab plus laser 38.1 61.9 +23.8


Treatment received during the core study had an effect on the achievement of at least 20/40 vision in the extension study.

At 36 months, this threshold was achieved by 78.3% of the ranibizumab monotherapy group. "So there was actually a progressive improvement," Dr Mitchell reported.

The threshold was also achieved by 67.1% of the ranibizumab-plus-laser group and 60.0% of the laser-only group. In each group, approximately one-third of the people who had not achieved at least 20/40 vision at 12 months had done so by 36 months.

One year is not the end of the story.

"This is quite important information; 1 year is not the end of the story," said Dr Mitchell.

Predicting the Future

A goal of the post hoc analysis was to identify baseline predictors of future vision of at least 20/40. "It's important to identify these predictors because it could help guide treatment and inform the risk–benefit ratio of different options," he explained.

Table 2. Baseline Predictors of at Least 20/40 Vision at 12 Months

Predictor P Value
Baseline vision of at least 20/40 <.001
Ranibizumab 0.5 mg monotherapy <.001
Ranibizumab 0.5 mg plus laser combination therapy .001
Duration of diabetes of less than 10 years .005
Central retinal subfield thickness  
   <300 µm .017
   300–400 µm .004


But a completely different scenario was reported by session moderator Ahmed Abu El-Asrar, MD, PhD, from King Saud University in Riyadh, Saudi Arabia.

"According to our experience in a diabetes population, I have never seen a patient who responded to ranibizumab alone, especially when they have retinal ischemia," he told Medscape Medical News.

"Of course we give anti-VEGF, but they only respond after laser therapy. So we give the laser up-front. This strategy gives long-term stability of macular edema," he explained.

Obviously, "more research is needed," said Dr El-Asrar after discussing the differences between his experience and results from the post hoc analysis with Dr Mitchell.

Dr Mitchell is a consultant and receives grants from Novartis. Dr El-Asrar has disclosed no relevant financial relationships.

European Society of Retina Specialists 16th EURETINA Congress. Presented September 9, 2016.

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