STUDY DESIGN

Multicenter, randomized, placebo-controlled trial

DURATION

6 months

STUDY SUBJECTS

<Major inclusion criteria:

• Age > 18 years old
• Foveal center-involving macular edema secondary to a BRVO diagnosed within 12 months before study initiation
• BCVA 20/40 to 20/400 Snellen equivalent- using ETDRS
• Mean central subfield thickness (>250 um) from 2 OCT measurements (screening and initial visit)

Major exclusion criteria:

• Previous episodes of RVO
• Afferent pupillary defect
• >10 letter improvement in BVA between screening and initial visit
• History of radial optic neurotomy or sheathotomy
• Intraocular steroids in the study eye within 3 months of initial visit
• History of PRP or sectoral PRP within 3 months of initial visit or anticipated within 4 months after initial visit
• Prior macular laser photocoagulation for ME within 4 months of initial visit
• Presence of diabetic retinopathy, wet or dry AMD
• CVA or MI within 3 months of study visit
• Prior anti VEGF treatment in study or fellow eye within 3 months of initial visit or systemic anti VEGF treatment within 6 months

RANDOMIZATION SCHEME AND INTERVENTIONS

Randomized 1:1:1

a) 0.3 mg ranibizumab monthly
b) 0.5 mg ranibizumab monthly
c) Sham injections monthly

Protocol: Patients received monthly injections for 6 months followed by a period of observation for 6 months. During the observation period, patients could receive monthly intraocular ranibizumab if they met pre-specified functional and anatomic criteria (i.e., Snellen equivalent study eye BCVA <20/40 according to the ETDRS chart or mean central subfield thickness >250 microns on OCT). Patients were evaluated at day 0 and 7, and then months 1- 6 with a full eye examination and OCT. Starting at month 3, patients were eligible for laser treatment if hemorrhages had cleared sufficiently to allow safe application of laser and the following criteria were met: Snellen equivalent BCVA <20/40 or mean central subfield thickness >250 microns, and compared with the visit 3 months before the current visit, patient had a gain of <5 letters in BCVA or a decrease of >50 microns in mean central subfield thickness

PRIMARY ENDPOINT

• Mean change from baseline BCVA at 6 months

SECONDARY ENDPOINTS:

• Mean change in BCVA over time to month 6
• Percentages of patients with > 15 letter gain from baseline to 6 months
• Percentage of patients who lost <15 letters
• Percentage of patients with CFT <250 microns at month 6
• Mean change from baseline CFT over time to month 6.

RESULTS

Study population

• 397 patients ( 134 0.3 mg ranibizumab, 131 0.5 mg ranibizumab, 132 sham injections)

PRIMARY OUTCOME:

• Statistically greater improvement in mean BCVA change in 0.3 mg and 0.5 mg compared to sham (gain of 16.6 letters, 18.3 letters vs 7.3 letters, respectfully, p < 0.0001)
• Mean vision gain was rapid: 7.5 letter gain 7 days after ranibizumab injection
• Mean improvement in BCVA was greater for patients with a BRVO < 3 months compared to > 3 months

NOTABLE SECONDARY OUTCOMES

• Greater % patients with > 15 letter gain at 6 months (significant for each ranibizumab group): 55.2% (0.3 mg), 61.1% (0.5 mg), 28.8% (sham)
• Greater % patients with < 15 letter loss: 100% (0.3 mg ), 98.5% (0.5 mg), 95.5% (sham) and significant only between 0.3 mg ranibizumab and sham
• Greater % patients with >20/40 Snellen equivalent (significant for each ranibizumab group): 67.9% (0.3 mg), 64.9% (0.5 mg), 41.7% (sham)
• Lower % patients with <20/200 vision (significant for each ranibizumab group): 1.5% (0.3 mg), 0.8% (0.5 mg), 9.1% (sham)
• Greater statistical mean reduction in CFT in the ranibizumab groups compared to sham

Adverse events
Ocular

• Retinal tear and detachment (n=1) in 0.3 mg ranibizumab group
• Endophthalmitis (n=1) in 0.5 mg ranibizumab group
• Thromboembolic events: 2 (0.5 mg group; fatal hemorrhagic stroke, nonfatal MI) vs 1 (sham- nonfatal hemorrhagic stroke)
• Intraocular inflammation: 2 (1.5%, 0.3 mg ranibizumab), 0 (0.5 mg), 4 (3.1%, sham)

CONCLUSION

Monthly 0.3 mg or 0.5 mg ranibizumab is safe and effective in treating patients with macular edema secondary to BRVOs by providing both visual and anatomic benefits