Periodic intravitreal aflibercept injections may reduce the likelihood of developing proliferative diabetic retinopathy (PDR) or vision-reducing center-involved diabetic macular edema (DME) in people with moderate-to-severe nonproliferative diabetic retinopathy (NPDR), according to research published in JAMA Ophthalmology.
Protocol W (ClinicalTrials.gov identifier NCT02534333) was conceived as a long-term study to determine if there is a benefit to aflibercept spanning a 2- and 4-year period for the prevention of either PDR or center-involved DME in eyes with moderate to severe NPDR.
Researchers collected data between 2016 and 2020 and included adults with type 1 or type 2 diabetes with severe NPDR across 64 clinical sites in the United States. All eyes were randomly assigned 1:1 to receive either 2 mg of intravitreal aflibercept or sham injections.
The primary study outcome was the development of either center-involved DME with vision loss or PDR.
The cohort included 399 eyes from 328 participants (aflibercept n=200, sham n=199). Median participant age was 57 years (interquartile range, 51 to 64 years) and 57.6% of participants were men. At baseline, 17% of eyes had moderate NPDR, 31.6%, and 27.3% had moderately severe NPDR (DRSS level 47A and 47B-D, respectively), and 24.1% of eyes had severe NPDR. Median baseline visual acuity letter score was 88 (Snellen equivalent, 20/20).
In each group, 84.7% and 87.4% of participants (aflibercept and sham, respectively), completed their 2-year visit (mean 10±3 total visits).
Among patients who completed their 2-year visit, DR severity improved by 2 steps or more from baseline in 44.8% and 13.7% of eyes in the aflibercept and sham groups, respectively (adjusted odds ratio [aOR], 5.91; 97.5% CI, 3.19-10.95). Severity of DR worsened by 2 or more steps in 5.2% and 12.4% of eyes in each group, respectively (aOR, 0.37; 95% CI, 0.13-1.01), and compared with baseline, mean central subfield thickness at 2 years decreased by 6±27 µm and 1±28 µm (adjusted mean difference, -4 µm).
Mean change in visual acuity during the study period was -0.9±5.8 and -2.0±6.1 letters in the aflibercept and sham groups, respectively (adjusted mean difference, 0.5 letters). After 2 years, 75% and 71.7% of eyes in each group had a visual acuity of 20/20 or better, and no eyes had a visual acuity of 20/200 or worse.
Within the group of participants who completed the 2-year visit, mean number of aflibercept injections was 8±1.2 total; a mean of 7.7±0.7 injections were given for prevention alone. The mean number of sham injections was 7.4±1.1.
In the aflibercept group, there were 3 documented cases of endophthalmitis resulting from preventive injections out of a total of 2406 total injections in both study and nonstudy eyes. Rates of cardiovascular or cerebrovascular adverse events were not different between the 2 groups.
Study limitations include potential bias in the results due to the number of patients lost to follow-up and the use of a treatment algorithm based on DRCR Retina Network investigator consensus, which may differ when another anti-VEGF agent or treatment approach is used.
“Through 2 years, preventive treatment with aflibercept did not confer visual benefit, on average, compared with initial observation and intravitreal anti-VEGF therapy given only after PDR or DME development,” the research says. “The 4-year results will be critical to assess whether PDR and DME prevention with aflibercept results in long-term [visual acuity] benefit.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Maturi RK, Glassman AR, Josic K, et al; for the DRCR Retina Network. Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the Protocol W randomized clinical trial. JAMA Ophthalmol. Published online March 30, 2021. doi:10.1001/jamaophthalmol.2021.0606