Everest Study

In Brief Purpose: To assess the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Methods: In this multicenter, double-masked, primarily indocyanine green angiography–guided trial, 61 Asian patients were randomized to verteporfin PDT (standard fluence), ranibizumab 0.5 mg, or the combination. Patients were administered with verteporfin PDT/placebo and initiated with three consecutive monthly ranibizumab/sham injections starting Day 1, and re-treated (Months 3–5) as per predefined criteria. The primary endpoint was the proportion of patients with indocyanine green angiography–assessed complete regression of polyps at Month 6. Secondary endpoints included mean change in best-corrected visual acuity at Month 6 and safety. Results: At Month 6, verteporfin combined with ranibizumab or alone was superior to ranibizumab monotherapy in achieving complete polyp regression (77.8% and 71.4% vs. 28.6%; P < 0.01); mean change ± standard deviation in best-corrected visual acuity (letters) was 10.9 ± 10.9 (verteporfin PDT + ranibizumab), 7.5 ± 10.6 (verteporfin PDT), and 9.2 ± 12.4 (ranibizumab). There were no new safety findings with either drug used alone or in combination. Conclusion: Verteporfin PDT combined with ranibizumab 0.5 mg or alone was superior to ranibizumab monotherapy in achieving complete regression of polyps in this 6-month study in patients with symptomatic macular polypoidal choroidal vasculopathy. All treatments were well tolerated over 6 months. EVEREST, the first, multicenter, double-masked, primarily indocyanine green angiography–guided randomized controlled trial for symptomatic macular polypoidal choroidal vasculopathy, demonstrated superiority of verteporfin photodynamic therapy combined with ranibizumab or alone over ranibizumab monotherapy in achieving complete regression of polyps at Month 6. Best-corrected visual acuity improved in all treatment arms.