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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zhou reported receiving grants from Regeneron during the conduct of the study. Dr Wykoff reported receiving grants and personal fees from Adverum, Allergan, Chengdu Kanghong, Clearside Biomedical, Genentech/Roche, Kodiak, Novartis, Regeneron, and Regenxbio; receiving grants from Opthea, Samsung, and Xbrane Biopharma; and receiving personal fees from Bayer and Alimera Sciences outside the submitted work. Dr Sadda reported receiving personal fees from Amgen, Allergan, Novartis, Roche/Genentech, Merck, 4DMT, Regeneron, Optos, Centervue, and Hedelberg and receiving nonfinancial support from Carl Zeiss Meditec, Nidek, and Topcon outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Baseline Optical Coherence Tomography Angiography (OCTA) of a Patient With Proliferative Diabetic Retinopathy From the Monthly Group

En face OCTA vessel density maps at the level of the superficial vascular complex (A), deep vascular complex (B), and choriocapillaris (C) are shown.

Figure 2.. Optical Coherence Tomography Angiography (OCTA) of the Same Patient at 12 Months After Aflibercept Injection

En face OCTA vessel density maps at the level of the superficial vascular complex (A), deep vascular complex (B), and choriocapillaris (C) are shown. During 1 year, there was no change in central macular vessel density in the eyes of patients with proliferative diabetic retinopathy and no diabetic macular edema treated with monthly or quarterly aflibercept therapy.