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Original Investigation
June 25, 2020

Association of Intravitreal Aflibercept With Optical Coherence Tomography Angiography Vessel Density in Patients With Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial

Author Affiliations
  • 1Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California
  • 2Department of Ophthalmology, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles
  • 3Department of Ophthalmology, Faculty of Medicine, Tanta University, Tanta, Egypt
  • 4Retina Consultants of Houston, Houston, Texas
JAMA Ophthalmol. Published online June 25, 2020. doi:10.1001/jamaophthalmol.2020.2130
Key Points

Question  What is the association of macular vessel density change with intravitreal aflibercept injection in patients with proliferative diabetic retinopathy without diabetic macular edema?

Findings  In this post hoc analysis of a randomized clinical trial of 40 patients, the macular vessel density of the superficial capillary plexus, deep capillary plexus, and choriocapillaris was not associated with a change after monthly or quarterly intravitreal injections of aflibercept during 12 months of treatment.

Meaning  The findings suggest that anti–vascular endothelial growth factor therapy may be useful for patients with retinal nonperfusion without exacerbating the nonperfusion.


Importance  Although previous studies have evaluated the association between anti–vascular endothelial growth factor therapy and macular vessel density, they were confounded by the presence of macular edema, which may be associated with artifacts and segmentation errors in optical coherence tomography angiography (OCTA).

Objective  To evaluate the association of intravitreal aflibercept with changes in macular vascular density using OCTA in patients with proliferative diabetic retinopathy without diabetic macular edema.

Design, Setting, and Participants  This post hoc analysis of a randomized clinical trial used data on 40 eyes of 40 patients with proliferative diabetic retinopathy without diabetic macular edema who were enrolled in the Intravitreal Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy (RECOVERY) clinical trial from August 1, 2016, to June 31, 2017. Three patients were lost to follow-up at month 12, and 5 patients were excluded from analysis because of poor OCTA image quality, leaving 16 patients in each cohort in the final analysis. Data analysis was performed from March 1, 2018, to January 15, 2019.

Intervention  In the RECOVERY trial, patients were randomized into cohorts receiving 2 mg of aflibercept injections monthly (n = 20) or quarterly (n = 20) and treated for 12 months.

Main Outcomes and Measures  The percentage of vascular density (in total scan and foveal and parafoveal regions) was compared before and after 12 months of therapy.

Results  The sample for this OCTA analysis included 32 eyes from 32 patients (mean [SD] age, 48.37 [12.30] years; 17 [53.1%] male). The mean (SD) total scan vascular density for the superficial vascular complex was 42.28% (4.03%; 95% CI, 40.63%-43.93%) at baseline and 39.64% (4.01%; 95% CI, 37.91%-41.37%) at month 12 (P = .69). For the deep vascular complex, the mean (SD) vascular density was 48.42% (4.99%; 95% CI, 46.36%-50.47%) at baseline and 45.69% (4.63%; 95% CI, 43.69%-47.70%) at month 12 (P = .40). For the choriocapillaris, the mean (SD) vascular density was 64.42% (3.36%; 95% CI, 63.04%-65.81%) at baseline and 62.55% (4.79%; 95% CI, 60.48%-64.62%) at month 12 (P = .16). There was no difference in vascular density parameters between monthly and quarterly injection arms at month 12.

Conclusions and Relevance  In this study, macular vascular density did not change after 12 months of intravitreal aflibercept therapy. Because nonperfusion is expected to progress in diabetic retinopathy, this finding may represent a beneficial association between anti–vascular endothelial growth factor therapy and macular vascular density.

Trial Registration  ClinicalTrials.gov Identifier: NCT02863354

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