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Aflibercept treatment resulted in statistically significant anatomic improvement, but no improvement in visual acuity among patients with NPDR without CI-DME at 4 years of analysis.
An investigation into aflibercept for the prevention of vision-threatening complications of nonproliferative diabetic retinopathy (NPDR) suggests the therapy as a preventive strategy may not be warranted for NPDR eyes without center-involved diabetic macular edema (CI-DME).1
Compared to sham, the initiation of intravitreal aflibercept for NPDR eyes without CI-DME only if vision-threatening complications developed was linked to statistically significant anatomic improvements, but no improvements in visual acuity at the Protocol W trial's fourth year of analysis.
“The results of this study indicate that the anatomic benefit from early anti-VEGF treatment does not result in improved visual acuity, and so it may not be worth the risk and inconvenience to the patient of repeat preventive injections for NPDR,” said Jennifer Sun, MD, MPH, Joslin Diabetes Center, Harvard Medical School, and chair of diabetes initiatives, DRCR Retina Network in a statement.2
Within the analysis, the DRCR Retina Network team identified no notable benefit of early treatment for subgroups based on baseline Diabetic Retinopathy Severity Scale (DRSS), noncentral DME, race and ethnicity, or sex.
At the trial’s 2-year analysis, the anti-vascular endothelial growth factor (anti-VEGF) therapy was shown to reduce diabetic retinopathy severity, lower the incidence of vision-impairing CI-DME, and reduce the risk of progression to proliferative diabetic retinopathy (PDR) in 200 eyes compared with sham. Within two years, data show the probability of developing CI-DME with vision loss or PDR was approximately 16% (aflibercept) compared to 43% (sham).1
However, despite the anatomic benefits reported, the trial’s findings did not demonstrate an associated visual acuity benefit over two years with 2.0 mg aflibercept therapy. The 4-year analysis ultimately reinforced the 2-year mark’s findings, indicating no statistical difference in either visual acuity or rates of vision loss between the two groups.
The trial enrolled 399 eyes between January 2016 and March 2018 across 64 locations in the United States and Canada. The participant population had a mean age of 56 years and was 42.4% female. According to the data, the 4-year cumulative probability of developing PDR or CI-DME was 33.9% with aflibercept compared to 56.9% with sham (adjusted hazard ratio [aHR], 0.40; 97.5% confidence interval [CI], 0.28 to 0.57; P <.001).1
The probability of developing PDR within four years was 27.9% for eyes in the aflibercept group versus 49.0% for eyes in the sham group, according to the trial. Trial data show the probability of developing CI-DME with vision loss was 11.3% for eyes in the aflibercept group and 19.1% for eyes in the sham group.1
The findings also express a decrease in visual acuity by a mean of 2.7 letters for eyes in the aflibercept group versus 2.4 letters for eyes in the sham group (adjusted mean difference, -0.5 [97.5%, -2.3 to 1.3]; P = .52) from baseline to 4 years. Moreover, 13.1% of eyes in the aflibercept group versus 12.7% in the sham group reported 10 or more letters worse than baseline (adjusted OR, 1.11 [97.5%, 0.55 to 2.22]; P - .74) at four years.
Among those who completed all four years of study, eyes assigned to the aflibercept group received a mean of 13.0 injections, and 79.6% received at least one injection in year 4. Of eyes randomly assigned to sham, 40.3% who completed all four years initiated aflibercept treatment. The probability of anti-VEGF initiation for PDR or CI-DME within four years was 18.7% with aflibercept and 40.7% with sham.
Investigators cited the treatment and visit burden, as well as the increased risk of complications with each additional injection, that would likely increase the overall burden for eyes receiving early anti-VEGF.1
“This study indicates that monitoring patients regularly for vision-threatening diabetes complications and treating eyes only as needed is the best approach,” said Raj Maturi, MD, Indiana University School of Medicine and Retina Partners Midwest, in a statement.2
1. Maturi RK, Glassman AR, Josic K, et al. Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy. JAMA. 2023;329(5):376–385. doi:10.1001/jama.2022.25029
2. NIH/NATIONAL EYE INSTITUTE. Early anti-VEGF treatment of diabetic retinopathy yields no benefit to visual acuity. EurekAlert! https://www.eurekalert.org/news-releases/978565. Published February 7, 2023. Accessed February 7, 2023.