An analysis of 2-year data from the DRCR Retina Network's Protocol W study indicates anti-VEGF treatments can delay progression of NPDR to proliferative diabetic retinopathy but was not linked to improvements in visual acuity.
A recent clinical study examining the effect of early treatment with anti-VEGF injections among patients with diabetic retinopathy has returned mixed results.
Despite early results suggesting prophylactic treatment could prevent the progression of diabetic retinopathy, further analysis indicated this approach did not lead to improvements in visual acuity among these patients at 2 years.
"While it is possible that preventive injections of anti-VEGF drugs may help protect vision in the longer-term, we saw no effect on vision at two years," said Raj Maturi, MD, Indiana University, the protocol chair for the study, in a statement. "These 2-year results suggest that close monitoring and routine treatment when complications develop are key to preventing vision loss from diabetic retinopathy."
With mountains of data demonstrating use of the agents in treatment for a slew of ophthalmic conditions, investigators sought to learn more about the use of anti-VEGF agents as a prophylactic treatment among patients with nonproliferative diabetic retinopathy to prevent progression to proliferative diabetic retinopathy. To do so, part of the DRCR Retina Network Protocol W study was designed with the intent of assessing at the effects of anti-VEGF use in patients with moderate to severe NPDR without center-involved diabetic macular edema (CI-DME).
Conducted between January 15, 2016 and May 28, 2020, this portion of Protocol W enrolled 328 adults (399 eyes) with moderate to severe NPDR and randomly assigned them to 2.0 mg of aflibercept injections or sham given at baseline, months 1, 2, and 4, and again every 4 months through 2 years. For the purpose of analysis, treatment was deferred if the eye had mild NPDR or better between years 2 and 4. Of note, aflibercept was administered in both groups if CI-DME with vision loss or high-risk proliferative diabetic retinopathy developed. Investigators noted vision loss was defined as a loss of 10 or mote letter at 1 visit or a loss of 5-9 letters at 2 consecutive visits and the inclusion criteria of moderate to severe NPDR was defined as a score of 43-53 using the Early Treatment Diabetic Retinopathy Study severity level.
The study population had a median age of 57 (IQR, 51-64) years, 57.6% were men, and 46.7% were White. Of the 399 eyes included I the suited, 17% had moderate NPDR, 31.6% had moderately severe NPDR (DRSS level 47A), 27.3% had moderately severe NNPDR (DRSS level 47B-D), and 24.1% had severe NPDR. The mean baseline visual acuity letter score was 88 in both the aflibercept and sham group.
At the end of 2 years, the cumulative probability of developing CI-DME with vision loss of proliferative diabetic retinopathy was 43.5% among those in the sham arm and 16.3% among those receiving aflibercept. Analyses indicated risk for either outcome was reduced 68% with use of aflibercept (HR, 0.32; 97.5% CI, 0.21-0.50; P <.001).
When assessing individual components of the primary end point, investigators found the probability of developing PDR was 13.5% among those receiving aflibercept and 33.2% among those in the sham arm. For CI-DME with vision loss, the probability was 4.1% among those receiving aflibercept and 14.8% among those in the sham arm. Additionally, the adjusted mean difference in change from baseline visual acuity was 0.5 letters favoring the aflibercept group (0.5; 97.5% CI, -1.0 to 1.9; P=.47).
"Although we did not see any difference in visual outcomes at two years, the four-year follow-up is going to be very important," said Jennifer Sun, MD, MPH, chair of Diabetes Initiatives for the DRCR Retina Network, in the aforementioned statement. "We look toward the four-year data to see whether reducing rates of diabetic retinopathy worsening will lead to long-term improvement in visual outcomes."
This study, “Effect of Intravitreous Anti–Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy,” was published in JAMA Ophthalmology.