乌鸦传媒

VANCOUVER -- Almost 60% of patients with nonproliferative diabetic retinopathy (NPDR) had at least a two-step improvement in retinopathy score when treated with an anti-VEGF agent, results of a randomized trial showed.

Fewer than 5% of patients developed vision-threatening complications during 6 months of treatment with aflibercept (Eylea). By comparison, 6% of patients in a sham-injection control group had a two-step improvement in the Diabetic Retinopathy Severity Scale (DRSS), and a fourth of them developed vision-threatening complications.

The findings added to evidence that earlier intervention in diabetic retinopathy can help preserve vision for more patients, speakers said here at the meeting.

"What's your threshold for initiating treatment for patients with diabetic retinopathy?" asked Charles C. Wykoff, MD, PhD, of Retina Consultants of Houston. "I think we all can agree that patients with center-involved macular disease with visual acuity loss, as well as those with high-risk proliferative diabetic retinopathy, warrant intervention."

"But other points in the transition can be more ambiguous: Non-center involved DME [diabetic macular edema], center-involved DME without visual acuity loss, and non-high-risk proliferative diabetic retinopathy all allow room for debate. What about nonproliferative disease, specifically those eyes without proliferation and without DME? There is relatively little data available to guide discussions for this large population of nearly 3 million people across the United States."

Location on the DRSS has prognostic information, Wykoff continued. Eyes with a DRSS score of 47 or 53 (moderate/severe NPDR) have a high risk of progression to proliferative disease over the subsequent 1 to 2 years. Even in the absence of DME, diabetic retinopathy can significantly affect vision and quality of life, he said.

The clinical ambiguity formed the basis for the randomized trial. Investigators in five countries enrolled 402 patients with NPDR without DME and a DRSS score of 47 or 53. Patients were randomized to two dosing schedules of intravitreal aflibercept (2 mg every 8 or 16 weeks) or to a sham injection group. The primary endpoint was the proportion of patients with ≥2-step improvement in DRSS score from baseline to 24 weeks. Results of the two aflibercept groups were combined for the primary-outcome analysis.

The study population had a mean age of 56, mean HbA1c of 8.5%, and mean diabetes duration of 14 years. Baseline best-corrected visual acuity averaged 82-83 letters, and mean central retinal thickness was 246-249 µM. Three fourths of the patients had DRSS level 47 disease severity.

The 24-week analysis showed that 58.4% of the aflibercept groups had at least a two-step improvement in DRSS as compared with 6% of the sham control group (P<0.0001). Separate analyses of the aflibercept groups showed that 61.5% of the 8-week group and 55.2% of the 16-week group met the primary endpoint (P<0.0001 for each versus sham).

Mean central retinal thickness increased by 4.7 µM in the sham group and decreased by 19.4 µM in the aflibercept groups (P<0.0001).

Wykoff reported that 25.6% of patients in the sham group developed vision-threatening complications, including PDR/anterior segment neovascularization (13.5%) or center-involving DME (14.4%). The aflibercept groups had a cumulative rate of 4.5%, including 3.7% in the 8-week group and 5.2% in the 16-week group.

The decision to initiate treatment for patients with DRSS scores of 47 or 53 should continue to be individualized, said Wykoff. "The PANORAMA trial provides excellent prospective data to guide the decisions and the discussion."

Another presentation provided additional data to support decisions about earlier anti-VEGF therapy for diabetic retinopathy. Michael Elman, MD, of Elman Retina Group in Glen Burnie, Maryland, summarized findings from a subgroup analysis of the phase III, randomized, sham-controlled and trials, which evaluated ranibizumab in a mixed group of patients with mild/moderate NPDR, moderate/severe NPDR, or PDR. The objective of the analysis was to determine two-step improvement rates at 24 months across the groups of patients with different baseline disease severity.

The primary finding was that patients with moderate/severe NPDR derived the greatest benefit from anti-VEGF therapy. In that subgroup, comprising a third of the 750 patients in the two trials combined, about 80% attained a two-step improvement in disease severity with either of the two doses of ranibizumab evaluated in the two trials. The rates were 10%-15% in the patients with mild/moderate NPDR and 31%-36% in the subgroup with PDR.

Across the range of baseline disease severity from 10-75, substantially more patients achieved at least a two-step improvement versus the sham group, Elman reported. Patients without DME at baseline derived greater benefit thank those with DME.

"You can see significant improvement in the PDR group; about a third of them will improve by two or more steps," said Elman. "The sweet spot is in the group with moderate to severe NPDR, where you know that many of these patients will be high risk for progression."

At the very least, the data make a compelling case for treating one eye, he added. "If it were my eye, I would argue that I want that eye treated."