Elsevier

Ophthalmology

Volume 118, Issue 8, August 2011, Pages 1594-1602
Ophthalmology

Original article
Sustained Benefits from Ranibizumab for Macular Edema Following Branch Retinal Vein Occlusion: 12-Month Outcomes of a Phase III Study

Portions of these data were presented at: the American Association for Research in Vision and Ophthalmology, May 2–6, 2010, Fort Lauderdale, Florida; World Ophthalmology Congress, June 5–9, 2010, Berlin, Germany; American Society of Retina Specialists, August 28–September 1, 2010, Vancouver, British Columbia; Retina Society, September 23–26, 2010, San Francisco, California; American Academy of Ophthalmology, October 16–19, 2010, Chicago, Ilinois.
https://doi.org/10.1016/j.ophtha.2011.02.022Get rights and content

Purpose

Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO).

Design

Prospective, randomized, sham injection-controlled, double-masked, multicenter trial.

Participants

A total of 397 patients with macular edema after BRVO.

Methods

Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met.

Main Outcome Measures

The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed.

Results

Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5–18.4) and 18.3 (15.8–20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6–14.6) in the sham/0.5 mg group (P < 0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified.

Conclusions

At month 12, treatment with ranibizumab as needed during months 6–11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design

The BRAVO study was a 12-month, phase III, multicenter, randomized trial that included a 6-month, injection-controlled treatment period followed by a 6-month observation period, designed to evaluate the efficacy and safety of intraocular injections of ranibizumab in patients with macular edema following BRVO. The details of BRAVO methodology have been reported5 and are briefly summarized in this article. During the treatment period (day 0 to month 5), patients received monthly intraocular

Patient Characteristics and Disposition

A total of 397 patients were randomized to receive intraocular injections of 0.3 mg (n = 134) or 0.5 mg (n = 131) ranibizumab or sham injections (n = 132) at 93 centers in the United States. Patient demographics and baseline ocular characteristics were similar across treatment groups. The mean time from diagnosis of BRVO to screening was 3.5 months (median, 2 months for each treatment group), with a duration of ≤3 months in 65% of patients. Mean baseline BCVA letter score was 54.6 letters

Discussion

During the initial treatment period, monthly intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid visual and anatomic improvements in patients with BRVO. The mean gain in BCVA ETDRS letter score was 7.5 by day 7 and 16.6 (0.3 mg) and 18.3 letters (0.5 mg) at month 6. Beginning at month 6 and throughout the observation period, patients continued to be examined monthly and could receive intraocular injections of ranibizumab if ETDRS refracted BCVA was ≤20/40 or mean CST was ≥250

Acknowledgment

The authors thank Roberta Kelly of Genentech, Inc., for editing, formatting, and preparing the figures.

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Manuscript no. 2010-1760.

Financial Disclosure(s): The author(s) have made the following disclosure(s): David M. Brown: Eli Lilly, Schering Plough, Thrombogenics (financial support); Genentech, Novartis (consultant, lecturer, financial support); Allergan, Alcon, Regeneron, Molecular Partners, Paloma, Steba Biotech, Alimera, Heidelberg, Zeiss (consultant, financial support). Peter A. Campochiaro: Alimera, Genzyme, Molecular Partners, Oxford Biomedical, Alcon, Genentech, GlaxoSmithKline (financial support); Genentech, GlaxoSmithKline, LPath, Regeneron, Bristol-Myers Squibb (not current), Pfizer (consultant). Robert Bhisitkul: Genentech, Allergan (lecturer, financial support); Dow Pharmaceuticals (lecturer); Active Site, Santen (consultant). Allen C. Ho: Genentech (consultant, lecturer). Sarah Gray: Genentech (employee); Roche (equity owner). Namrata Saroj: Genentech (employee); Roche (equity owner). Anthony P. Adamis: Genentech (employee); Roche (equity owner). Roman G. Rubio: Genentech (E); Roche (equity owner). Wendy Yee Murahashi: Genentech (employee); Roche (equity owner).

Funding: Genentech, Inc., South San Francisco, California, provided support for the study and participated in study design; conducting the study; and data collection, management, and interpretation.

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