Elsevier

Ophthalmology

Volume 117, Issue 6, June 2010, Pages 1102-1112.e1
Ophthalmology

Original article
Ranibizumab for Macular Edema following Branch Retinal Vein Occlusion: Six-Month Primary End Point Results of a Phase III Study

Presented at: the Retina Congress, September 2009 and the American Academy of Ophthalmology, November 2009.
https://doi.org/10.1016/j.ophtha.2010.02.021Get rights and content

Purpose

To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO).

Design

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

Participants

A total of 397 patients with macular edema following BRVO.

Methods

Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections.

Main Outcome Measures

The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).

Results

Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7–18.5) and 18.3 (16.0–20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1–9.5) in the sham group (P<0.0001 for each ranibizumab group vs sham). The percentage of patients who gained ≥15 letters in BCVA at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups and 28.8% in the sham group (P<0.0001 for each ranibizumab group vs sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA of ≥20/40 compared with sham patients (41.7%; P<0.0001 for each ranibizumab group vs sham); and CFT had decreased by a mean of 337 μm (0.3 mg) and 345 μm (0.5 mg) in the ranibizumab groups and 158 μm in the sham group (P<0.0001 for each ranibizumab group vs sham). The median percent reduction in excess foveal thickness at month 6 was 97.0% and 97.6% in 0.3 mg and 0.5 mg groups and 27.9% in the sham group. More patients in the sham group (54.5%) received rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with BRVO.

Conclusions

Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Materials and Methods

The BRAVO 6-month, phase III, multicenter, randomized, injection-controlled study, with an additional 6-months of follow up (total 12 months), was designed to evaluate efficacy and safety of intraocular injections of ranibizumab in patients with macular edema following BRVO. The study included a 28-day screening period (days −28 to −1); a 6-month treatment period (day 0 to month 6), during which patients received monthly intraocular injections of 0.3 mg or 0.5 mg ranibizumab or sham injections;

Baseline Characteristics and Patient Disposition

Between July 2007 and November 2008, 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 (Table 2). The average age of patients was 66 years, and 53% were male. The mean time from diagnosis of BRVO to screening was 3.5 months (median, 2 months for each treatment group), with

Discussion

Although a small pilot study suggested that VEGF plays an important role in macular edema following BRVO,8 this is the first study to definitively prove that this is the case. Blocking VEGF with intraocular injections of ranibizumab has a rapid beneficial effect on visual function. There was a mean improvement of approximately 7.5 letters 1 week after the first treatment with either dose of ranibizumab. The mean improvement of between 3 and 4 lines of vision after 6 months of treatment with

Acknowledgment

Roberta M. Kelly, Genentech, Inc., provided editorial support.

References (17)

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Manuscript no. 2009-1750.

A list of study investigators is available at http://aaojournal.org

Financial Disclosure(s): The authors have made the following disclosures:

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. Genentech authors Saroj, Rundle, and Gray would like to report Equity Ownership in Roche.

Peter A. Campochiaro – Consultant, Genentech, GlaxoSmithKline, LPath, Regeneron, Potentia

Jeffrey Heier – Consultant – Genentech, Regeneron, Allergan; Support – Alimera

Leonard Feiner – Consultant – Allergan; Consultant, Lecturer – Genentech, Novartis

Sarah Gray – Employee – Genentech

Namrata Saroj – Employee – Genentech

Amy Chen Rundle – Employee – Genentech

Wendy Yee Murahasi – Employee – Genentech; Equity Owner – Roche

Roman G. Rubio – Employee – Genentech; Equity Owner – Roche

Group members listed online in Appendix 1 (available at http://aaojournal.org).

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