Ranibizumab Combined With Verteporfin Photodynamic Therapy in Neovascular Age-related Macular Degeneration (FOCUS): Year 2 Results ANDREW N. ANTOSZYK, LISA TUOMI, CAROL Y. CHUNG, AND ANGELE SINGH, ON BEHALF OF THE FOCUS STUDY GROUP ● PURPOSE: To assess the efficacy and adverse-events profile of combined treatment with ranibizumab and verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration. ● DESIGN: Two-year, multicenter, randomized, single- masked, controlled study. ● METHODS: Patients received monthly intravitreal in- jections of ranibizumab 0.5 mg (n  106) or sham injections (n  56). All patients received PDT on day zero, then quarterly as needed. Efficacy assessment in- cluded changes in visual acuity (VA) and lesion charac- teristics and PDT frequency. Adverse events were summarized by incidence and severity. ● RESULTS: At month 24, 88% of ranibizumab  PDT patients had lost <15 letters from baseline VA (vs 75% for PDT alone), 25% had gained >15 letters (vs 7% for PDT alone), and the two treatment arms differed by 12.4 letters in mean VA change (P < .05 for all between- group differences). The VA benefit of adding ranibi- zumab to PDT in year one persisted through year two. On average, ranibizumab  PDT patients exhibited less lesion growth and greater reduction of CNV leakage and subretinal fluid accumulation, and required fewer PDT retreatments, than PDT-alone patients (mean  0.4 vs 3.0 PDT retreatments). Endophthalmitis and serious intraocular inflammation occurred, respectively, in 2.9% and 12.4% of ranibizumab  PDT patients and 0% of PDT-alone patients. Incidences of serious nonocular adverse events were similar in the two treatment groups. ● CONCLUSIONS: Through two years, ranibizumab  PDT was more effective than PDT alone and had a low rate of associated adverse events. (Am J Ophthalmol 2008; 145:862– 874. © 2008 by Elsevier Inc. All rights re- served.) R ANIBIZUMAB (LUCENTIS) IS A RECOMBINANT, HU- manized antibody antigen-binding fragment (Fab) that neutralizes all known active forms of vascular endothelial growth factor A (VEGF-A), a protein that is believed to play a critical role in the formation of new blood vessels. In June 2006, ranibizumab was approved by the United States Food and Drug Administration (US FDA) for treatment of all fluorescein-angiographic (FA) subtypes of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). This ap- proval was supported by two pivotal phase III studies: the MARINA (Minimally classic/occult trial of the Anti- VEGF antibody Ranibizumab In the treatment of Neovas- cular AMD) Study, which compared ranibizumab against sham treatment in patients with minimally classic or occult with no classic CNV, 1 and the ANCHOR (Anti- VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration) Study, which compared ranibi- zumab against verteporfin photodynamic therapy (PDT) in patients with predominantly classic CNV. 2 Verteporfin PDT was selected as the comparator treatment in the latter study because it has been shown to slow the progression of vision loss in patients with this typically more aggressive type of lesion 3,4 and was the standard of care at the time this study was initiated. The ANCHOR Study demon- strated that ranibizumab was clearly superior to PDT with respect to both visual acuity (VA) and anatomic (lesion size and CNV leakage) efficacy outcomes and was associ- ated with a low rate of serious ocular adverse events. These two studies were pivotal evaluations of the efficacy of ranibizumab and excluded patients who had been previ- ously treated with PDT. The two-year phase I/II study designated FOCUS (RhuFab V2 Ocular Treatment Combining the Use of Visudyne to Evaluate Safety) was designed to compare the safety, tolerability, and efficacy of ranibizumab treatment in conjunction with PDT vs PDT alone in patients with subfoveal, predominantly classic CNV secondary to AMD. Because safety was the primary outcome of interest, pa- tients who had previously been treated with PDT were not excluded. Results for the first year of FOCUS indicated that ranibizumab in conjunction with PDT had a good safety/tolerability profile and was more effective than PDT Supplemental Material available at AJO.com. Accepted for publication Dec 22, 2007. From the Charlotte Eye, Ear, Nose and Throat Associates, Charlotte, North Carolina (A.N.A.); and Genentech, Inc, South San Francisco, California (L.T., C.Y.C., A.S.). Inquiries to Andrew N. Antoszyk, Charlotte Eye, Ear, Nose and Throat Associates, 6035 Fairview Road, Charlotte, NC 28210; e-mail: ana@ ceenta.com © 2008 BY ELSEVIER INC.ALL RIGHTS RESERVED. 862 0002-9394/08/$34.00 doi:10.1016/j.ajo.2007.12.029