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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.

Publication ,  Journal Article
Maturi, RK; Glassman, AR; Josic, K; Antoszyk, AN; Blodi, BA; Jampol, LM; Marcus, DM; Martin, DF; Melia, M; Salehi-Had, H; Stockdale, CR ...
Published in: JAMA Ophthalmol
July 1, 2021

IMPORTANCE: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. OBJECTIVE: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. DESIGN, SETTING, AND PARTICIPANTS: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. INTERVENTIONS: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. MAIN OUTCOMES AND MEASURES: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. RESULTS: Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50; P < .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs 33.2% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs 14.8% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5% CI, -1.0 to 1.9 letters]; P = .47). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02634333.

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Published In

JAMA Ophthalmol

DOI

EISSN

2168-6173

Publication Date

July 1, 2021

Volume

139

Issue

7

Start / End Page

701 / 712

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Ranibizumab
  • Randomized Controlled Trials as Topic
  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Macular Edema
  • Intravitreal Injections
  • Humans
  • Female
 

Citation

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Maturi, R. K., Glassman, A. R., Josic, K., Antoszyk, A. N., Blodi, B. A., Jampol, L. M., … DRCR Retina Network, . (2021). 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, 139(7), 701–712. https://doi.org/10.1001/jamaophthalmol.2021.0606
Maturi, Raj K., Adam R. Glassman, Kristin Josic, Andrew N. Antoszyk, Barbara A. Blodi, Lee M. Jampol, Dennis M. Marcus, et al. “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 139, no. 7 (July 1, 2021): 701–12. https://doi.org/10.1001/jamaophthalmol.2021.0606.
Maturi, Raj K., et al. “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, vol. 139, no. 7, July 2021, pp. 701–12. Pubmed, doi:10.1001/jamaophthalmol.2021.0606.
Maturi RK, Glassman AR, Josic K, Antoszyk AN, Blodi BA, Jampol LM, Marcus DM, Martin DF, Melia M, Salehi-Had H, Stockdale CR, Punjabi OS, Sun JK, 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. 2021 Jul 1;139(7):701–712.

Published In

JAMA Ophthalmol

DOI

EISSN

2168-6173

Publication Date

July 1, 2021

Volume

139

Issue

7

Start / End Page

701 / 712

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Ranibizumab
  • Randomized Controlled Trials as Topic
  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Macular Edema
  • Intravitreal Injections
  • Humans
  • Female