title: Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective, multicenter, double-masked, randomized, active-controlled trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark. miclar01@glo.regionh.dk
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt-Erfurth
authors.forename: Paolo
authors.initials: P
authors.lastname: Lanzetta
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wolf
authors.forename: Christian
authors.initials: C
authors.lastname: Simader
authors.forename: Erika
authors.initials: E
authors.lastname: Tokaji
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Annemarie
authors.initials: A
authors.lastname: Weisberger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000503:physiopathology; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011166:Porphyrins / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D000069579:Ranibizumab; D016896:Treatment Outcome; D000077362:Verteporfin; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D000069579:Ranibizumab