Combination Intravitreal Ranibizumab 0.5mg and Verteporfin PDT versus Verteporfin PDT Alone in the FOCUS Study of Neovascular Age-Related Macular Degeneration (AMD)

Abstract

Purpose:: The FOCUS study compared the safety and efficacy of monthly intravitreal injections of ranibizumab combined with verteporfin photodynamic therapy (PDT) with verteporfin PDT alone in patients with subfoveal, predominantly classic CNV secondary to AMD.

Methods:: In this Phase I/II, multicenter, randomized, single-masked, controlled study, patients were randomized 2:1 to receive either monthly ranibizumab 0.5mg (n=106) or sham (n=56). Verteporfin PDT was initially performed 7 days before ranibizumab or sham and then every 3 months as needed in both arms.

Results:: At 24 months, 87.5% of combination-treated patients had lost <15 letters, compared to 75% of the PDT-only arm (p=0.04). Mean VA had improved in the combination-treated group by 4.6 letters over baseline, compared to a loss of 7.8 letters in the PDT-only group (p<0.0001). The VA benefit was seen as early as 7 days and was maintained throughout the study. In addition, 24.8% of combination-treated patients improved mean VA by >15 letters, compared to 7.1% in the control group (p=0.006), and only 30.5% of patients progressed to 20/200 vision with combination, compared to 50% with PDT alone (p=0.006). On average, after the initial verteporfin PDT, a mean 0.4 additional verteporfin treatments were required in the combination group, compared to an additional 3.0 verteporfin treatments in the PDT-only group. The higher incidence of intraocular inflammation identified at 12 months was significantly reduced following a protocol amendment changing ranibizumab from a lyophilized to the liquid formulation (Lucentis^TM), and increasing the interval between the two treatments in the combination arm to 28 days.

Conclusions:: At 24 months, combination therapy reduced vision loss of >15 letters compared to verteporfin PDT alone, increased mean VA over baseline, reduced progression to 20/200 and the need for PDT retreatment. The change from the lyophilized to the liquid formulation of ranibizumab and increased interval between treatments resulted in significant reduction of intraocular inflammation.

Clinical Trial:: www.clinicaltrials.gov nct0056823

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • photodynamic therapy