Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials

Abstract

Purpose: This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME).

Methods: PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater.

Results: A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001).

Conclusions: Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.

Keywords: VISTA; VIVID; anti-VEGF therapy; diabetic macular edema; diabetic retinopathy; intravitreal aflibercept; proliferative diabetic retinopathy.

Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs Do, Gordon, and Suñer have no proprietary interest in the study drug. Dr Do is a consultant to Allergan, Asclepix, Boehringer Ingelheim, Clearside, Genentech, Kodiak Sciences, and Regeneron Pharmaceuticals, Inc, and has received research funding from Asclepix, Boehringer Ingelheim, Genentech, and Regeneron Pharmaceuticals, Inc. Dr Gordon has received research funding from Alcon, Alimera, Allergan, Genentech, the National Institutes of Health (NIH), Novartis, Regeneron Pharmaceuticals, Inc, Santen Pharmaceutical Co, Ltd, and Topco. Dr Suñer is a consultant to Alimera, Allergan, Genentech, Novartis, and Regeneron Pharmaceuticals, Inc; a speaker for Alimera, Genentech, and Regeneron Pharmaceuticals, Inc; and an investigator for Alimera, Allergan, Genentech, Kodiak Pharmaceuticals, Inc, and Regeneron Pharmaceuticals, Inc. Drs Reed, Moini, and Du are salaried employees and shareholders of Regeneron Pharmaceuticals, Inc. Dr Gibson was a salaried employee of Regeneron Pharmaceuticals, Inc, at the time these analyses were performed. Dr Shah is a consultant to and investigator for Regeneron Pharmaceuticals, Inc, and an investigator for Alcon, Allergan, Apellis, Ellex, Genentech, NIH, and Novartis.

© The Author(s) 2022.

Figures

Figure 1.

Distribution of incidences of PDR events by baseline DRSS score through week 100. Full analysis set. Observed case, with data censored from the time of rescue therapy. PDR event defined as PDR (DRSS score ≥ 61), PRP, or vitrectomy. Abbreviations: DRSS, Diabetic Retinopathy Severity Scale; IAI, intravitreal aflibercept injection; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation. aP = .0451 compared with eyes with baseline DRSS score 47 in the laser control group (difference: 10.9% [95% CI, 0.2 to 21.5]). bP = .0095 compared with eyes with baseline DRSS score 53 in the laser control group (difference: −11.9% [95% CI, −20.8 to −2.9]).

Figure 2.

Cumulative incidence of PDR events through week 100 by baseline DRSS score of: (A) ≤ 53 and (B) 47 or 53. PDR event defined as PDR (DRSS score ≥ 61), PRP, or vitrectomy. Abbreviations: DRSS, Diabetic Retinopathy Severity Scale; IAI, intravitreal aflibercept injection; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation.

Figure 3.

Proportion of eyes with a baseline DRSS score of 43 or greater who achieved a DRSS score of 35 or less through week 100. Abbreviations: DRSS, Diabetic Retinopathy Severity Scale; IAI, intravitreal aflibercept injection. *P = .0023 compared with laser control. **P < .0001 compared with laser control.