Clinical Studies:
VISTA/VIVID
Citation: Korobelnik J-F, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247-2254. doi:10.1016/j.ophtha.2014.05.006
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Objective
To compare visual acuity outcomes at 52 weeks between intravitreal aflibercept and macular laser photocoagulation in eyes with diabetic macular edema (DME)
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STUDY DESIGN
Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(United States) and VIVID(Europe, Japan, and Australia)
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DURATION
12 months
STUDY SUBJECTS
Major inclusion criteria:
- Adult patients with type 1 or 2 diabetes mellitus with DME (retinal thickening involving the 1 mm CST (>300 microns in VIVID) with visual acuity between 24 and 73 ETDRS letters (20/40 – 20/320)
Major exclusion criteria:
- Previous treatment with anti-VEGF within 90 days, laser photocoagulation within 90 days, any intraocular surgery within 90 days, any history of VR surgery, active PDR, TRD, myopia >8D, macular scar, A1c >12, BP >160/95
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:1:1 to
(a) aflibercept 2 mg every 4 weeks
(b) aflibercept 2 mg every 8 weeks after 5 monthly loading doses
(c) macular laser photocoagulation at baseline
Retreatment criteria for PRN group: monthly evaluation and treatment if ≥ 5 letter decrease in vision or disease activity (IRF, SRF, sub-RPE fluid)
RESULTS (52 weeks)
Study population
- 466 patients – VISTA; 406 patients – VIVID
- VISTA had a higher percentage of African American patients, VIVID had a higher percentage of Asian patients, otherwise similar demographics between the 3 cohorts
Visual acuity end-points
- Mean change in visual acuity (Q4, Q8, and Laser respectively): :+12.5±9.5 vs +10.7±8.2 vs +0.2±12.5 letters (P < 0.0001) in VISTA, and +10.5±9.5 vs +10.7±9.3 vs +1.2±10.6 letters (P < 0.0001) in VIVID
- Gain > 10 letters (Q4, Q8, and Laser respectively): 64.9% and 58.3% versus 19.5% (P < 0.0001) in VISTA, and 54.4% and 53.3% versus 25.8% (P < 0.0001) in VIVID
- Gain > 15 letters (Q4, Q8, and Laser respectively): 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
- Eyes with >2 step improvement in DRSS (Q4, Q8, and Laser respectively): 33.8% and 29.1% versus 14.3% (P < 0.01) in VISTA and (33.3% and 27.7% versus 7.5% (P < 0.001) in VIVID
National Eye Institute Visual Function Questionnaire
- Change in near score: Only the Q4 cohort saw a significant benefit compared to the laser cohort
- Change in distance score: Scores similar across the 3 cohorts
Angiographic end-points on OCT
- Change in CST from baseline (Q4, Q8, and Laser respectively): −185.9±150.7, −183.1±153.5, and−73.3±176.7 μm, (P < 0.0001) in VISTA and −195.0±146.6, −192.4±149.9, and −66.2±139.0 μm, (P < 0.0001) in VIVID
Adverse events
- Antiplatelet Trialists’ Collaboration criteria (ATCC) events: 3.1% (Q4), 3.5% (Q8), 2.8% (laser)
- No difference in any other adverse events
CONCLUSIONS
Aflibercept had superior functional and anatomic endpoints over laser with similar efficacy between q4 and q8 week dosing