Table 1. Summary of the major Ranibizumab central retinal vein occlusion studies.
| Cruise11 | Horizon21 | Retain14 | |
|---|---|---|---|
| Objective | Assess the 12-month efficacy and safety of intraocular injections of 0.3 or 0.5 mg Ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO) | To assess long-term safety and efficacy of intraocular Ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO) | To determine long-term outcomes of patients with Ranibizumab-treated retinal vein occlusion (RVO) |
| Duration | 12 Months | 12 Months | 24 Months |
| Intervention | •Ranibizumab 0.3 mg (n=132) Every 4 weeks for 6 months then pro re nata (PRN) for another 6 months •Ranibizumab 0.5 mg (n=130) Every 4 weeks for 6 then PRN for another 6 months •Sham (n=130) Every 4 weeks for 6 months then PRN 0.5 mg Ranibizumab for 6 months | 304 patients who completed CRUISE (87%) were treated with 0.5 mg Ranibizumab PRN. Follow up every 3 months | 32 patients who completed HORIZON were injected with 0.5 mg Ranibizumab PRN Follow up was monthly for the first year and then every 3 months during the second year |
| Primary end point | Mean change from baseline BCVA letter score at month 6 | Incidence and severity of ocular and non-ocular AEs during the two year extension period | Mean improvement in best-corrected visual acuity (BCVA) and percentage of patients with edema resolution |
| Key inclusion criteria | ▪Age ≥18 years ▪Foveal center-involved Macular edema secondary to central RVO. diagnosed within 12 months prior to screening ▪BCVA 6/12 to 6/95 Snellen equivalent ▪Mean CRT ≥250 μm at screening and Day 0 | ▪304 patients who completed the 12-month CRUISE study ▪Expectation by the investigator that the patient could potentially benefit from intravitreal anti-VEGF treatment | ▪Patients who completed the Genentech-sponsored Ranibizumab RVO trials. 32 patients with CRVO. |
| Results | Mean change from baseline BCVA letter score at month 12 was 13.9 (11.2–16.5) and 13.9 (11.5–16.4) in the 0.3 mg and 0.5 mg groups, respectively, and 7.3 (4.5–10.0) in the sham/0.5 mg group (P<0.001 for each Ranibizumab group vs sham/0.5 mg) | In patients who completed month 12, the mean number of injections in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively | With a mean follow-up of 49.7 months, 14 of 32 CRVO patients (44%) had edema resolution, with 71% receiving their last injection within 2 years of treatment initiation. The mean number of injections in unresolved patients in year 4 was 5.9 Compared with patients with unresolved CRVO, patients with resolved disease had greater improvement in BCVA (25.2 vs 4.3 letters; P=0.002), and a greater percentage had a final BCVA of 6/12 or better (64.3% vs 27.8% P=0.04) |
| % of patients gained ≥15 letters | The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups | In CRVO patients, at month 12 of HORIZON, the percentage of patients who had an improvement of ≥15 letters from CRUISE baseline was 38.3% (sham/0.5 mg), 38.6% (0.3/0.5 mg), and 45.1% (0.5 mg) | At the final visit, with a mean follow-up of 51.4 months, 53.1% of the 32 CRVO patients enrolled in the RETAIN study gained 15 letters or more |
Abbreviations: BCVA, best-corrected visual acuity; BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; ETDRS, Early Treatment Diabetic Retinopathy Study; FU, follow-up; N, number; RCT, randomised controlled trial.