Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: The 24-Week Results of the VIBRANT Study

doi:10.1016/j.ophtha.2014.08.031

Ophthalmology

Volume 122, Issue 3, March 2015, Pages 538-544

Presented at: the American Academy of Ophthalmology Annual Meeting, November 2013, New Orleans, Louisiana. This was a Retina Subspecialty Day paper presentation.

https://doi.org/10.1016/j.ophtha.2014.08.031 Get rights and content

Purpose

To compare the efficacy and safety of intravitreal aflibercept injection (IAI) with macular grid laser photocoagulation for the treatment of macular edema after branch retinal vein occlusion (BRVO).

Design

The VIBRANT study was a double-masked, active-controlled, randomized, phase III trial.

Participants

Treatment-naïve eyes with macular edema after BRVO were included in the study if the occlusion occurred within 12 months and best-corrected visual acuity (BCVA) was between ≤73 and ≥24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/40–20/320 Snellen equivalent).

Methods

Eyes (1 eye per patient) received either IAI 2 mg every 4 weeks (n = 91) from baseline to week 20 or grid laser (n = 92) at baseline with a single grid laser rescue treatment, if needed, from weeks 12 through 20.

Main Outcome Measures

The primary outcome measure was the proportion of eyes that gained ≥15 ETDRS letters from baseline BCVA at week 24. Secondary end points included mean change from baseline BCVA and central retinal thickness (CRT) at week 24.

Results

The proportion of eyes that gained ≥15 ETDRS letters from baseline at week 24 was 52.7% in the IAI group compared with 26.7% in the laser group (P = 0.0003). The mean improvement from baseline BCVA at week 24 was 17.0 ETDRS letters in the IAI group and 6.9 ETDRS letters in the laser group (P < 0.0001). The mean reduction in CRT from baseline at week 24 was 280.5 μm in the IAI group and 128.0 μm in the laser group (P < 0.0001). Traumatic cataract in an IAI patient was the only ocular serious adverse event (SAE) that occurred. There were no cases of intraocular inflammation or endophthalmitis. The incidence of nonocular SAEs was 8.8% in the IAI group and 9.8% in the laser group. One Anti-Platelet Trialists' Collaboration–defined event of nonfatal stroke (1.1%) and 1 death (1.1%) due to pneumonia occurred during the 24 weeks of the study, both in patients in the laser group.

Conclusions

Monthly IAI provided significantly greater visual benefit and reduction in CRT at 24 weeks than grid laser photocoagulation in eyes with macular edema after BRVO.

Section snippets

Methods

The VIBRANT study was a phase III, multicenter, randomized, double-masked, active-controlled, 52-week trial comparing the efficacy and safety of IAI with macular grid laser photocoagulation for treatment of macular edema after BRVO. The study was conducted at 58 sites in North America and Japan (Appendix 1 provides a list of study investigators; available at www.aaojournal.org). Each respective institutional review board or ethics committee approved the study protocol. The study was carried out

Patient Disposition, Demographics, and Baseline Characteristics

We screened 281 patients; 98 were excluded because they either did not meet the inclusion/exclusion criteria (n = 92) or they withdrew consent (n = 6). Overall, 91 eyes were randomized to IAI and 92 eyes to grid laser (Table 1). All randomized eyes in both treatment groups were included in the full analysis set, except for 2 eyes in the laser group that did not have a post-baseline BCVA assessment. The safety analysis set included all randomized patients. More than 90% of patients completed the

Discussion

The treatment of macular edema after BRVO has been dominated by macular grid laser photocoagulation for nearly 30 years. In 1984, the Branch Vein Occlusion Study demonstrated in eyes with BCVA ≤20/40 due to macular edema after BRVO (with sufficient clearing of macular hemorrhages to allow safe grid laser photocoagulation) that compared with control eyes (observation only), a significantly higher percentage of eyes treated with grid laser photocoagulation had an improvement from baseline of ≥10

Acknowledgments

Editorial and administrative assistance to the authors was provided by Hadi Moini, PhD, and S. Balachandra Dass, PhD, Regeneron Pharmaceuticals, Inc.

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: See Editorial on page 443.

: Supplementary material is available at www.aaojournal.org.

: The VIBRANT Study Investigator list available at www.aaojournal.org.

: Financial Disclosure(s): Sponsored by Regeneron Pharmaceuticals, Inc., Tarrytown, NY. The sponsor participated in the design and conduct of the study, analysis of the data, and preparation of the manuscript.

: The authors have made the following disclosures: P.A.C.: Consultant (for which Johns Hopkins University receives remuneration) – Genentech, Regeneron Pharmaceuticals, Inc., Aerpio; Consultant (for which there is personal remuneration) – AbbVie, Advanced Cell Technology (DSMC), Alimera, Applied Genetic Technologies Corporation, Eleven, Kala; Research funding – Genentech, Regeneron Pharmaceuticals, Inc., Aerpio, Allergan, Genzyme, Oxford BioMedica, Roche; Equity – Graybug.

: W.L.C.: Consultant, Research Funding, Lecture Fees – Genentech, Regeneron Pharmaceuticals, Inc., Roche.

: D.S.B.: Advisory Board Member – Alcon, Allergan, Neurotech; Consultant – Alcon, Allegro, Allergan, Bausch & Lomb, Bayer, GlaxoSmithKline, KalVista, Neurotech, Novartis, Regeneron Pharmaceuticals, Inc., Roche, Santen, ThromboGenics; Research Funding – Alcon, Genentech, Pfizer, Regeneron Pharmaceuticals, Inc.; Lecture Fees – Allergan, Genentech.

: J.S.H.: Consultant – Acucela, Aerpio, Alcon, Allegro, Allergan, Bayer, Endo Optiks, Forsight Vision, Genzyme, Heidelberg Engineering, Kala Pharmaceuticals, Liquidia, Merz, Neurotech, Notal Vision, Ohr Pharmaceutical, Oraya, Regeneron Pharmaceuticals, Inc., Sanofi, Stealth Peptides, ThromboGenics, Xcovery; Research Funding – Acucela, Aerpio, Alcon, Alimera, Genentech, Genzyme, Kato, Lpath, Notal Vision, Novartis, Ohr Pharmaceutical, Ophthotech, QLT, Regeneron Pharmaceuticals, Inc.

: D.M.B.: Consultant – Allergan, Bayer, Genentech, Genzyme, Heidelberg Engineering, Notal Vision, Novartis, QLT, Regeneron Pharmaceuticals, Inc., ThromboGenics; Research Funding – Abbott, Acucela, Alimera, Allergan, Ampio, Genentech, Genzyme, GSK, Novartis, Ophthotech, Pfizer, pSivida, Quark, QLT, Regeneron Pharmaceuticals, Inc., Santen, ThromboGenics, XOMA. Travel Support – Regeneron Pharmaceuticals, Inc.

: R.V.: Employee – Regeneron Pharmaceuticals, Inc.

: H.K.: Employee – Regeneron Pharmaceuticals, Inc.

: A.J.B.: Employee – Regeneron Pharmaceuticals, Inc.

: K.E.: Employee – Regeneron Pharmaceuticals, Inc.

: K.W.C.: Employee – Regeneron Pharmaceuticals, Inc.

: Y.S.: Employee – Regeneron Pharmaceuticals, Inc.

: Y.C.: Employee – Regeneron Pharmaceuticals, Inc.

: J.A.H.: Consultant – Advanced Cell Technologies, Alcon, Genentech, KalVista, Merck, Regeneron Pharmaceuticals, Inc., Second Sight, ThromboGenics.

View full text

Original articleIntravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: The 24-Week Results of the VIBRANT Study

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Methods

Patient Disposition, Demographics, and Baseline Characteristics

Discussion

Acknowledgments

Ophthalmology

Mol Ther

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study

Arch Ophthalmol

Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study

Arch Ophthalmol

Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study

Ophthalmology

Original article
Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: The 24-Week Results of the VIBRANT Study