Ranibizumab Combined With Verteporfin Photodynamic Therapy in Neovascular Age-related Macular Degeneration (FOCUS): Year 2 Results

doi:10.1016/j.ajo.2007.12.029

American Journal of Ophthalmology

Volume 145, Issue 5, May 2008, Pages 862-874.e3

https://doi.org/10.1016/j.ajo.2007.12.029 Get rights and content

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 injections 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 included changes in visual acuity (VA) and lesion characteristics 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 ranibizumab 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.

Section snippets

Study Design

FOCUS was a two-year, phase I/II, single-masked, multicenter study of ranibizumab (Lucentis; Genentech, Inc, South San Francisco, California, USA) in conjunction with verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) PDT. After up to 28 days of screening, eligible patients were randomly assigned in a 2:1 ratio to monthly intravitreal injection of ranibizumab or sham injection in one eye for 24 months. If both eyes were eligible, the eye with worse VA was the study eye unless the

Study Population

Between April 2, 2003 and January 14, 2004, 162 patients from 25 study sites in the United States were enrolled and randomly assigned to ranibizumab injection + PDT (henceforth referred to as the ranibizumab group; n = 106) or to sham injection + PDT (henceforth referred to as the PDT-alone group; n = 56). One patient randomized to ranibizumab received PDT on day zero but decided to withdraw before receiving any ranibizumab treatment and therefore was excluded from all analyses. Of the 162

Discussion

Results of this randomized, multicenter, sham injection–controlled, single-masked study comparing PDT alone vs PDT in conjunction with multiple intravitreal injections of ranibizumab indicate that the latter was superior in efficacy to PDT alone for treating predominantly classic CNV secondary to AMD. This superiority was consistent for each of the three types of efficacy outcome measures: visual acuity, anatomic characteristics of the lesions, and need for PDT retreatment.

Ninety percent of

Andrew N. Antoszyk, MD, graduated from New York Medical College in Valhalla, New York with honors (AOA). He did his ophthalmology and vitreoretinal training at the prestigious Duke University Eye Center in Durham, North Carolina under the tutelage of Professor Robert Machemer. Dr Antoszyk is currently in practice in Charlotte, North Carolina at Charlotte Eye, Ear, Nose and Throat Associates. Dr Antoszyk is a fellow in the AAO and is an associate examiner for the ABO.

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The Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON)32 was an open-label extension trial of ranibizumab for the treatment of neovascular AMD. Patients who completed the MARINA, ANCHOR, or RhuFabV2 Ocular Treatment Combining the Use of Visudyne to Evaluate Safety (FOCUS)28 trials were randomized to receive intravitreal ranibizumab injections (at the investigator’s discretion) or sham injections for 24 months. The primary outcome was adverse events, but the mean change in VA was +2.0 letters in the group receiving ranibizumab for 4 years versus −11.8 in the pooled group of those receiving sham injections for 4 years and of those receiving sham injections and then ranibizumab in HORIZON (n = 853).
To review the evidence on the safety and efficacy of anti-vascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (AMD).
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Angele A. Singh, MD, is a native of Hanover, Germany, who obtained her medical education at the University of Wurzburg. She received residency training in Ulm and Munich, Germany. After completing residency training and board certification in Ophthalmology, Dr Singh moved to the United States where she serves as a clinical scientist for Genentech, Inc in South San Francisco, California. At Genentech, she has been involved in the FOCUS, MARINA, ANCHOR, PIER, and SAILOR studies.

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Original articleRanibizumab Combined With Verteporfin Photodynamic Therapy in Neovascular Age-related Macular Degeneration (FOCUS): Year 2 Results

Purpose

Design

Methods

Results

Conclusions

Section snippets

Study Design

Study Population

Discussion

Ranibizumab for neovascular age-related macular degeneration

N Engl J Med

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

N Engl J Med

Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of two randomized clinical trials—TAP Report No. 1

Arch Ophthalmol

Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of two randomized clinical trials—TAP Report No. 2

Arch Ophthalmol

Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degenerationYear 1 results of the FOCUS Study

Arch Ophthalmol

Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovascular age-related macular degeneration

Ophthalmology

Original article
Ranibizumab Combined With Verteporfin Photodynamic Therapy in Neovascular Age-related Macular Degeneration (FOCUS): Year 2 Results