Dosing Regimens of Intravitreal Aflibercept for Diabetic Macular Edema Beyond the First Year: VIOLET, a Prospective Randomized Trial

Abstract

Introduction The purpose was to compare two flexible regimens of intravitreal aflibercept (IVT-AFL) with fixed dosing every 8 weeks, beyond the first year of treatment, in patients with diabetic macular edema (DME). VIOLET was a 100-week, randomized, Phase IIIb, non-inferiority study in patients with center-involving DME previously treated with IVT-AFL for ≥ 1 year according to the European label. Methods Patients received an initial dose of IVT-AFL at study baseline and were randomly assigned (1:1:1) to treat-and-extend (T&E), pro re nata (PRN), or fixed regimens. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline (randomization) to Week 52. Results Full analysis set comprised 458 patients (baseline mean BCVA: 72.5, 71.0, and 72.7 letters in the T&E, PRN, and fixed-dose groups, respectively). Patients received a mean (min–max) of 10.0 (2–14; T&E), 11.5 (1–25; PRN), and 12.3 (3–13; fixed) injections over 100 weeks, with 13.3 (4–23), 25.0 (3–29), and 16.1 (5–25) clinic visits, respectively. At Week 52, mean (± standard deviation) BCVA changes from baseline were + 0.5 ± 6.7 (T&E), + 1.7 ± 6.8 (PRN), and + 0.4 ± 6.7 (fixed-dosing) letters (least squares mean difference [95% confidence interval]: T&E 0.01 [− 1.46, 1.47] and PRN 0.95 (− 0.52, 2.42) letters versus fixed dosing; p < 0.0001 for both non-inferiority tests [4-letter margin]). The IVT-AFL safety profile was consistent with previous studies. Conclusion The treatment burden associated with intravitreal injections for DME is lowest with T&E regimens, but there are a range of flexible IVT-AFL dosing regimens, allowing physicians to adopt an individualized treatment plan. Trial Registration ClinicalTrials.gov identifier: NCT02818998. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02119-z.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy

“…In our study, PDME eyes constituted 33.63% of all cases, which is in line with previous reports. Due to the lack of a consensus on the definition and optimal management of PDME [ 14 , 15 ], treatment strategies such as monthly or three loading doses, pro re nata (PRN), and treat and extend (T&E) are widely used [ 26 , 27 ]. In our research, we explored PDME based on the completion of three anti-VEGF injections, consistent with current clinical practice.…”

Evaluating the Treatment of Diabetic Macular Edema with Aflibercept Based on a Regional Network of Ophthalmologic Care Givers

“…In the VIOLET study, it was shown that in patients with DME, both TER and PRN regimens achieve similar functional results. However, fewer injections were administered in the TER group, making higher patient adherence more likely [ 16 ].…”

Clinical Application of Intravitreal Aflibercept Injection for Diabetic Macular Edema Comparing Two Loading Regimens

“…A fixed bimonthly or a pro-re-nata regimen (based on strict monitoring and retreatment criteria, as stated in the DRCR.net protocol T) is recommended [ 14 ]. Treat-and-extend therapy is also a recommended regimen with non-inferior visual and anatomical improvement in DME compared to fixed dosing regimens [ 27 , 28 ], while less visual improvement was noted when the longest treatment interval was 16 weeks [ 29 ]. Despite these efforts, DME may persist.…”