Laird Harrison

September 10, 2017

BARCELONA, Spain — Ranibizumab treats proliferative diabetic retinopathy more effectively than laser photocoagulation, researchers reported here at the 17th EURETINA Congress.

The finding challenges lasers as the standard of care, opening the door to wider use of anti-vascular endothelial growth factor (VEGF) drugs, Gabrielle Lang, MD, from the University of Ulm, Germany, told Medscape Medical News.

"VEGF inhibitors are a good option to treat proliferative diabetic retinopathy as monotherapy," she said. "I think clinicians will be able to use it."

Although laser treatments can slow the progression of proliferative diabetic retinopathy, they often cause some permanent vision loss. A handful of preliminary studies have suggested effectiveness of anti-VEGF drugs, which are widely used in the related condition of diabetic macular edema.

A previous trial, Protocol S of the Diabetic Retinopathy Clinical Research Network (DRCDnet), showed that ranibizumab was "noninferior" to laser treatment, as reported by Medscape Medical News . That trial did not include a group who received a combination treatment of laser and ranibizumab.

In the new study, carried out at multiple sites in Germany, patients with diabetic retinopathy were divided into three groups. Thirty-five patients received ranibizumab 0.5 mg (protocol), 35 received panretinal photocoagulation, and 36 received a combination of the two treatments.

The three groups were similar in age, sex, HbA1c, type of diabetes, duration of diabetes, best-corrected visual acuity, and central subfield retinal thickness.

The patients visited the clinic monthly for the first year, and the researchers followed up with them for another year after that. In the first year, six patients dropped out from the ranibizumab-only group, nine from the laser-only group, and eight from the combination treatment group.

The patients were all 18 years of age and older with best-corrected visual acuity of at least 20 ETDRS letters (Snellen equivalent 20/400) and HbA1c of at least 12%.

The laser-only group received a mean of 1928 laser burns, whereas the combination group received 1670. The ranibizumab group received a mean of 5.2 injections, and the combination group received a mean of 5.1.

The ranibizumab group got better results than the other two groups, and the differences in neovascularization, central subfield retinal thickness, and best-corrected visual acuity were all statistically significant.

Table. Mean Change in 12 Months

Outcome Ranibizumab Laser Both
Neovascularization (mm2) −3.8 −0.9 −2.6
Central subfield retinal thickness (μm) −5.3 35.4 17.6
Best-corrected visual acuity (EDTRS letters) 1.1 −3.7 −1.1

In the ranibizumab-only group, there were three serious adverse events: a retinal hemorrhage, a reduced visual acuity, and a vitreous hemorrhage. In the laser-only group, there were four serious adverse events: a cataract, a vitreous hemorrhage, and two vitrectomies. And in the combination group, there were six, including two cases of retinal or macular edema, a retinal detachment, a vitreous hemorrhage, and two vitrectomies.

Each of the groups suffered 1 Anti-Platelet Trialists Collaboration event.

Protocol S

This trial added to the information provided by Protocol S because Protocol S included patients with diabetic macular edema, and these patients needed more injections. "We wanted to know the efficacy in patients without diabetic macular edema," said Dr Lang.

After her presentation, Pravin Dugel, MD, from the University of Southern California in Los Angeles, pointed out that the treatment was less intensive in this trial than in Protocol S. "Why do you think there was such a big difference in visual acuity?" he asked.

"We know this from the old days of diabetic retinopathy study, that one complication is macular edema resulting in vision loss," Dr Lang responded. "So this is due to the thickening of the retina with panretinal laser."

The other comoderator, Ramin Tadayoni, MD, PhD, from Paris-Sorbonne University in France, told Medscape Medical News the study was useful in confirming the Protocol S findings. "We always need at least two studies," he said. "This is a very critical issue."

Still, some clinicians may find it difficult to switch completely from laser to anti-VEGF therapy, he said. "The real question we ask ourselves is the applicability to real life." Anti-VEGF treatments may require patients to return for intravitreal injections indefinitely, Dr Tadayoni pointed out. In contrast, they might need only a single laser treatment.

Dr Lang told Medscape Medical News that it is not clear yet how long patients with diabetic retinopathy will continue to need anti-VEGF injections to keep the disease in check. "It's a good chance they don't need that much," she said.

The study was funded by Novartis. Dr Lang is a consultant for Novartis. Dr Dugel has relationships with 44 medical companies, including stock ownership in Clearside Biomedical, Digisight, Aerpio, Alimera, Annidis, Macusight, Ophthotech, PanOptica, and TrueVision. Dr Tadayoni is an advisor to all the companies selling anti-VEGF agents.

17th EURETINA Congress. Presented September 9, 2017.

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