Intravitreal aflibercept for diabetic macular edema.

Abstract

PURPOSE:

A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).

DESIGN:

Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(DME) and VIVID(DME).

PARTICIPANTS:

We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.

METHODS:

Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.

MAIN OUTCOME MEASURES:

The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.

RESULTS:

Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.

CONCLUSIONS:

At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.

• Authors: Jean-François Korobelnik, Diana V Do, Ursula Schmidt-Erfurth, David S Boyer, Frank G Holz, Jeffrey S Heier, Edoardo Midena, Peter K Kaiser, Hiroko Terasaki, Dennis M Marcus, Quan D Nguyen, Glenn J Jaffe, Jason S Slakter, Christian Simader, Yuhwen Soo, Thomas Schmelter, George D Yancopoulos, Neil Stahl, Robert Vitti, Alyson J Berliner, Oliver Zeitz, Carola Metzig, David M Brown
• Journal: Ophthalmology (Ophthalmology) Vol. 121 Issue 11 Pg. 2247-54 (Nov 2014) ISSN: 1549-4713 [Electronic] United States
• PMID: 25012934 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Recombinant Fusion Proteins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• aflibercept
• Receptors, Vascular Endothelial Growth Factor

Topics

• Aged
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Diabetes Mellitus, Type 1 (complications)
• Diabetes Mellitus, Type 2 (complications)
• Diabetic Retinopathy (drug therapy, physiopathology, surgery)
• Double-Blind Method
• Female
• Humans
• Intravitreal Injections
• Laser Coagulation
• Macular Edema (drug therapy, physiopathology, surgery)
• Male
• Middle Aged
• Receptors, Vascular Endothelial Growth Factor (adverse effects, therapeutic use)
• Recombinant Fusion Proteins (adverse effects, therapeutic use)
• Tomography, Optical Coherence
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)
• Visual Acuity (physiology)