Verteporfin plus Ranibizumab for Choroidal Neovascularization in Age-related Macular Degeneration Twelve-month MONT BLANC Study Results

Purpose: To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration. Design: Prospective, multicenter, double-masked, randomized, active-controlled trial. Participants: We included 255 patients with all types of active subfoveal choroidal neovascularization. Methods: Patients were randomized 1: 1 to as-needed (pro re nata; PRN) combination (standard-fluence verteporfin 6 mg/m(2) PDT and ranibizumab 0.5 mg) or PRN ranibizumab monotherapy (sham infusion [5% dextrose] PDT and ranibizumab 0.5 mg). Patients received 3 consecutive monthly injections followed by PRN retreatments based on protocol-specific retreatment criteria. Main Outcome Measures: Mean change in best-corrected visual acuity (BCVA) from baseline to month 12, and the proportion of patients with treatment-free interval >= 3 months at any timepoint after month 2. Results: The mean change in BCVA at month 12 was +2.5 and +4.4 letters in the combination and monotherapy groups, respectively (P = 0.0048; difference: - 1.9 letters [95% confidence interval, -5.76 to 1.86], for having achieved noninferiority with a margin of 7 letters). The proportion of patients with a treatment-free interval of >= 3 months at any timepoint after month 2 was high, but did not show a clinically relevant difference between the treatment groups. Secondary efficacy endpoints included the mean number of ranibizumab retreatments after month 2 (1.9 and 2.2 with combination and monotherapy, respectively [P = 0.1373]). The time to first ranibizumab retreatment after month 2 was delayed by 34 days (about 1 monthly visit) with combination (month 6) versus monotherapy (month 5). At month 12, mean +/- standard error central retinal thickness decreased by 115.3 +/- 9.04 mu m in the combination group and 107.7 +/- 11.02 mu m in the monotherapy group. The mean number of verteporfin/sham PDT treatments was comparable in the 2 groups (combination, 1.7; monotherapy, 1.9). The safety profiles of the 2 groups were comparable, with a low incidence of ocular serious adverse events. Conclusions: The combination PRN treatment regimen with verteporfin PDT and ranibizumab was effective in achieving BCVA gain comparable with ranibizumab monotherapy; however, the study did not show benefits with respect to reducing the number of ranibizumab retreatment over 12 months. The combination therapy was well tolerated