Four-year results show no vision gains with preventive aflibercept in NPDR
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Four-year outcomes of the DRCR Retina Network Protocol W study showed that preventive aflibercept vs. sham treatment in eyes with moderate to severe NPDR leads to anatomic improvement but no gain in visual acuity.
The results, published in JAMA, confirmed the findings of the previous primary analysis at 2 years.
Image: Adobe Stock.
“This study indicates that monitoring patients regularly for vision-threatening diabetes complications and treating eyes only as needed is the best approach,” Raj K. Maturi, MD, protocol chair for the 4-year study, said in a press release issued by the National Eye Institute of the National Institutes of Health.
The study, funded by the NEI, included 399 eyes of 328 participants with severe nonproliferative diabetic retinopathy (NPDR) in at least one eye. Preventive aflibercept intravitreal injections were administered in 200 eyes at 1, 2 and 4 months and then every 4 months over 2 years. This schedule was maintained unless the disease improved to mild NPDR or better. Sham injections were administered in 199 eyes over the same period. Aflibercept treatment was initiated in any eye that developed high-risk proliferative diabetic retinopathy or center-involved diabetic macular edema (CI-DME).
Over the 4-year study, 33.9% of eyes receiving preventive treatments showed disease progression compared with 56.9% of those in the sham group, but there was no evident benefit on vision. Visual acuity decreased from baseline to 4 years by a mean of 2.7 letters for eyes in the aflibercept group vs 2.4 letters for eyes in the sham group. The mean number of injections over the 4 years of the study was 11 in the preventive treatment group and three in the sham group.
The authors concluded that aflibercept as a preventive strategy may not be generally warranted for patients with NPDR without CI-DME.
“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,” Jennifer K. Sun, MD, MPH, chair of diabetes initiatives for the DRCR Retina Network, said in the release.
Reference:
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Once again, kudos are due to the DRCR Retina Network for organizing, funding and overseeing clinical trials that help answer important clinical questions about how to best care for our patients with retinal diseases.
In this study, Protocol W, eyes with moderate to severe nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema were randomized to an aflibercept “preventive” arm, with aflibercept given in three loading doses followed by every 4 months, vs. a sham “observation” arm, which only received treatment if a vision-threatening complication (VTC) such as proliferative diabetic retinopathy (PDR) or DME developed. We had previously seen the 2-year results, which showed that prophylactic treatment with aflibercept reduced the incidence of VTCs from 43% to 16% but, importantly, had no impact on visual acuity vs. treating these eyes once the complications had developed.
One of the big questions after 2 years was, would we see a difference in the longer-term outcomes that was not apparent in the first 2 years? Might prophylaxis, over time, actually lead to fewer injections by preventing the cat from getting out of the bag, so to speak? The Protocol W 4-year outcomes help address these questions: There was no difference in visual acuity between the two arms, and the prophylactic aflibercept arm received nearly four times as many injections (11 vs. 3) over this time period. Interestingly, the difference in the rate of VTCs narrowed in years 3 and 4, with 34% of patients in the preventive arm developing PDR or DME vs. 57% in the sham group. This suggests to me that — at least for one-third of patients — every 4 month aflibercept was insufficient suppression. We saw a similar effect in PANORAMA with patients backsliding in year 2 when they were switched from an every 8 week arm to as-needed treatment. Managing patients with diabetic retinopathy — whether with anti-VEGF agents or with observation — requires an individualized approach.
These data help reassure us that following moderate and severe NPDR patients closely (so we can detect DME and/or PDR in their milder stages), and treating these vision-threatening complications when they develop, is a reasonable strategy.
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