Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results

Ophthalmology. 2012 May;119(5):992-1000. doi: 10.1016/j.ophtha.2012.02.002. Epub 2012 Mar 17.


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 μm in the combination group and 107.7±11.02 μm 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.

Trial registration: NCT00433017.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / physiopathology
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Humans
  • Incidence
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / physiopathology
  • Male
  • Middle Aged
  • Photochemotherapy*
  • Photosensitizing Agents / adverse effects
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / adverse effects
  • Porphyrins / therapeutic use*
  • Prospective Studies
  • Ranibizumab
  • Treatment Outcome
  • Verteporfin
  • Visual Acuity / physiology


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin
  • Ranibizumab

Associated data