In the latest article in our Clinical Therapeutics series, “Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration,” Drs. James Folk and Edwin Stone present the case vignette of a 66-year-old man with a 2-week history of blurred and distorted vision in his right eye. A retinal specialist diagnoses neovascular age-related macular degeneration (AMD) and recommends treatment with ranibizumab. The article includes a video that demonstrates their technique of intraocular injection of ranibizumab.
Age-related macular degeneration is the leading cause of blindness in the United States. In the year 2000, 1.2 million residents of the United States were estimated to have neovascular AMD; of these, 973,000 had dry AMD with atrophy of the retinal pigment epithelium, and 7.3 million had large drusen (greater than/equal to 125 micrometers in diameter), and were therefore at increased risk of developing atrophy or neovascularization.
• How does AMD affect quality of life?
Many people with AMD have moderate vision loss, between 20/50 and 20/100 in their better eye. These persons have quality of life measurements that are 32% below normal, similar to those who suffer from severe angina or hip fractures. A person with very severe neovascular disease may have 20/800 vision in the better eye and will have a 60% reduction in the quality of life, similar to someone who is bedridden after a catastrophic stroke.
• What is the pathophysiology of AMD?
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 retinal pigment epithelium atrophy appear. “Wet” or neovascular AMD then develops in some patients with established dry AMD. Wet AMD is characterized by the growth of abnormal vessels beneath the retinal pigment epithelium, and between the retinal pigment epithelium and the overlying retina.
Morning Report Questions
Q: What is the mechanism of action of ranibizumab?
A: Ranibizumab is the Fab fragment of a recombinant, humanized, monoclonal antibody that binds to all forms of VEGF-A. The inhibition of VEGF-A reduces the permeability of the neovascular vessels as well as their further growth.
Q: How effective is ranibizumab for the treatment of age-related macular degeneration?
A: Only 4% of patients treated with 0.5 mg of ranibizumab and 5% of those treated with 0.3 mg lost 15 letters of vision at 1 year, as compared with 36% of patients treated with laser-activated verteporfin. Forty percent of the 0.5-mg ranibizumab group and 36% of the 0.3-mg group gained 15 letters of vision, as compared with only 6% in the verteporfin group. In a different study, at 1 year, only 5% of patients treated with either 0.3 mg or 0.5 mg of ranibizumab had lost 15 letters of vision (about three lines on a standard eye chart), as compared with 38% of controls. Thirty-four percent of the patients treated with 0.5 mg and 25% treated with 0.3 mg, actually gained 15 letters of vision, as compared with only 5% of controls.
Figure 1. Clinical Characteristics of Neovascular Age-Related Macular Degeneration.