The REVEAL Study: Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy in Asian Patients with Diabetic Macular Edema.

OBJECTIVE: The primary study hypothesis was that ranibizumab 0.5 mg monotherapy or combined with laser is superior to laser monotherapy based on mean average change in best-corrected visual acuity (BCVA) over 12 months in Asian patients with visual impairment resulting from diabetic macular edema (DME). DESIGN: A 12-month, randomized, double-masked, multicenter, laser-controlled, phase III study. PARTICIPANTS: Three hundred ninety-six patients aged ≥18 years, with type 1 or 2 diabetes mellitus, BCVA of 78-39 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and visual impairment resulting from DME. METHODS: Patients were randomized to ranibizumab + sham laser (n = 133), ranibizumab + active laser (n = 132), or sham injection + active laser (n = 131). Ranibizumab/sham injections were administered on day 1 and continued monthly. As of month 3, monthly injections were continued if stable vision was not reached. Treatment was reinitiated if BCVA decreased because of DME progression. Active/sham laser was administered on day 1 and thereafter according to ETDRS guidelines. MAIN OUTCOME MEASURES: Average change in BCVA from baseline to months 1 through 12, central retinal subfield thickness (CRST), and safety over 12 months. RESULTS: Ranibizumab monotherapy or combined with laser was superior to laser in improving mean average change in BCVA from baseline to months 1 through 12 (+5.9 and +5.7 vs +1.4 letters). At month 12, greater proportion of patients gained ≥15 letters with ranibizumab and ranibizumab + laser compared with laser (18.8% and 17.8% vs 7.8%). Mean CRST reduced significantly from baseline to month 12 with ranibizumab (-134.6 µm) and ranibizumab + laser (-171.8 µm) versus laser (-57.2 µm). Patients received a mean of 7.8 and 7.0 ranibizumab injections in the ranibizumab and ranibizumab + laser arms, respectively, and 1.5-1.9 active laser across treatment arms over 12 months. Conjunctival hemorrhage was the most common ocular, whereas nasopharyngitis and hypertension were the most common nonocular adverse events. Ranibizumab was not associated with any cases of cerebrovascular hemorrhage and cerebrovascular ischemia. No death related to study treatment was reported. CONCLUSIONS: Ranibizumab monotherapy or combined with laser showed superior BCVA improvements over laser treatment alone in Asian patients with visual impairment resulting from DME. No new ocular or nonocular safety findings were observed and treatment was well tolerated over 12 months.

EXTEND II: an open-label phase III multicentre study to evaluate efficacy and safety of ranibizumab in Chinese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To evaluate the efficacy and safety of monthly ranibizumab 0.5 mg in Chinese patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD). METHODS: A 12-month open-label single-arm multicenter phase III study that included treatment-naïve (study eye) patients with primary/recurrent subfoveal CNV secondary to AMD. Patients (N = 114) aged ≥50 years with best-corrected visual acuity (BCVA) of 73-24 letters were treated with monthly ranibizumab for 12 months. Main outcomes were mean BCVA change from baseline to month 4 (primary endpoint) and over time to month 12, effects of ranibizumab treatment on retinal structure (months 4 and 12), and safety. RESULTS: Ranibizumab led to significant improvements in mean BCVA ± standard error (SE) at both months 4 and 12 versus baseline (+9.5 ± 1.10 letters, 95 % confidence interval [CI] 7.3-11.7, and +12.7 ± 1.14 letters, 95 % CI 10.4-14.9, respectively, both P < 0.0001). Ranibizumab prevented loss of vision (≥0 letters BCVA gain) in 91.2 % of patients. Mean central retinal thickness ± SE reduced from baseline to month 12 (-119.9 ± 12.97 µm, 95 % CI -145.59 to -94.20, P < 0.0001). No new safety findings were reported in this study. CONCLUSION: Ranibizumab administered monthly over 12 months was effective in improving BCVA and was well-tolerated in Chinese nAMD patients.