Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration

Abstract

T h e n e w e ng l a n d j o u r na l o f m e dic i n e n engl j med 363;17 nejm.org october 21, 2010 1648 This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the authors' clinical recommendations. A n ophthalmologist refers a 66-year-old man for consultation with a retinal specialist. The patient has had blurred and distorted vision in his right eye for the past 2 weeks. Examination reveals drusen beneath the retina in both eyes. His right eye also has a subretinal hemorrhage just temporal to the center of the macula, as well as subretinal fluid (Fig. 1A). A fluorescein angio-gram shows subfoveal neovascularization (Fig. 1B). Optical coherence tomography reveals fluid beneath and within the layers of the retina (Fig. 1C). The retinal specialist diagnoses neovascular age-related macular degeneration (AMD) and recommends intraocular injections of ranibizumab. The Cl inic a l Probl em AMD is the leading cause of blindness in the United States. All patients initially have a form of the disorder called dry AMD, characterized by the development and accumulation of drusen, which are localized deposits of extracellular material that appear as yellow spots in the retina on ophthalmoscopy. As dry AMD progresses, focal areas of atrophy of the retinal pigment epithelium appear. Wet, or neovascu-lar, AMD then develops in some patients with established dry AMD. Wet AMD is characterized by the growth of abnormal vessels beneath the retinal pigment epi-thelium and between the retinal pigment epithelium and the overlying retina. The Eye Diseases Prevalence Research Group estimates that in the year 2000, a total of 1.2 million residents of the United States had neovascular AMD, 973,000 had dry AMD with atrophy of the retinal pigment epithelium, and 7.3 million had large drusen (≥125 µm in diameter) and were therefore at increased risk for atrophy or neovascularization. The same group estimates that these numbers will increase by more than 50% by the year 2020 as a result of aging of the population. 1 Many patients with AMD have moderate vision loss, between 20/50 and 20/100 in the better eye. These patients have quality-of-life measurements that are 32% below normal, similar to those among patients with severe angina or hip fractures. 2 A person with very severe neovascular disease may have 20/800 vision in the better eye and will have a reduction in quality of life of 60%, similar to that of a patient who is bedridden with a catastrophic stroke. 2 AMD is estimated to cost the United States $30 billion a year. 2 Pathoph ysiol o gy a nd Effec t of Ther a py Despite decades of intensive investigation, the molecular mechanisms underlying the pathogenesis of AMD are still obscure. It is likely that in most patients, a num-The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITAETSBIBLIOTHEK REGENSBURG on April 7, 2022. For personal use only. No other uses without permission.