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    Early Anti-VEGF Fails to Improve VA in NPDR

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    When is it appropriate to use aflibercept for patients with nonpro­liferative diabetic retinopathy (NPDR) but no center-involved diabetic mac- ular edema (CI-DME)? Results from the Protocol W indicate that the best strategy is to regularly monitor patients and initiate treatment with aflibercept (Eylea) only when vision-threatening complications develop.1

    The researchers investigated the effects of early aflibercept on VA and the rate of vision-threatening complica­tions in patients with moderate to severe NPDR. Although anti-VEGF treatment reduced the risk of progres­sion to proliferative DR and CI-DME with vision loss, the preventive in­jections failed to produce better VA outcomes than sham treatment.

    Mild nonproliferative diabetic retinopathy.

    TOO EARLY TO TREAT. Based on the study’s findings, this patient with mild NPDR should not be treated prophylactically with aflibercept. This image was originally published in the ASRS Retina Image Bank. Carolyn Daley. Mild Nonproliferative Diabetic Retinopathy. Retina Image Bank. 2019; Image Number 28819. © The American Society of Retina Specialists.

    Study rationale. Although anti- VEGF agents are used in patients with proliferative diabetic retinopathy and CI-DME with vision loss, some physicians use them for prophylaxis in patients with NPDR, said Raj Maturi, MD, at Indiana University School of Medicine and Retina Partners Midwest in Indianapolis. Dr. Maturi also served as protocol chair for the study.

    Study specifics. This multicenter study involved 328 adults (399 eyes) with moderate to severe NPDR without CI-DME. Half of the eyes were injected with aflibercept, the other half with sham. All eyes received injections at one, two, and four months after enroll­ment, and then every four months for the rest of the first two years. Preventive treatment with aflibercept was given every four months until the four-year mark except in those whose NPDR im­proved to mild disease. This allowed the researchers to assess the rate of disease progression and the difference in VA between the two groups.

    Risk of progression. The researchers found that the four-year cumulative risk of developing proliferative DR or CI-DME with vision loss was lower in the anti-VEGF group than in the sham group (33.9% vs. 56.9%; p < .001).

    Anatomic benefit and VA. The anti-VEGF therapy slowed disease pro­gression, as measured by the diabetic retinopathy severity scale. However, no differences in VA emerged between the two groups after four years.

    Monitoring is essential. Given these findings, ophthalmologists are advised to regularly monitor patients and promptly treat those who progress to proliferative disease or develop DME, Dr. Maturi said. At this time, however, prophylactic treatment is “not gener­ally warranted” for patients who have NPDR without CI-DME, the investiga­tors wrote.

    Christos Evangelou, PhD


    1 Maturi RK et al. JAMA. 2023;329(5):376-385.


    Relevant financial disclosures: Dr. Maturi—None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Breazzano DRCR Network: S; Eyepoint: S; Ocuterra: S; Ophthea: S; Oxurion: S.

    Dr. Klink Dutch Research Council: S; European Union: S; Friends Foundation of the Netherlands Institute for Neuroscience: S; Human Brain Project: S.

    Dr. Maturi Allegro: C,S; Allergan: C,S; Allgenesis: C; AiViva: C; Boehringer Ingelheim: S; Clearside: S; Eli Lilly: C; Dutch Ophthalmic: C; Gemini: S; Genentech: S; Graybug: S; Gyroscope: S; KalVista: S; Jaeb Center for Health Research: C; NeuroTech: C; NGM Biopharmaceuticals: S; Novartis: C; Opthea: S; Ribomic: S; Samsung Bioepis: S; Santen: S; Senju: S; ThromboGenics: S; Unity: C,S.

    Dr. Moulton NEI: S; U.S. Department of Veterans Affairs: S.

    Disclosure Category



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    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
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