Age-related macular degeneration (AMD) is the major cause of visual impairment in Western countries and is the leading form of blindness in Americans over the age of 50 years. Prevalence of AMD increases with age, and it is estimated that up to one-third of individuals age 75 and older have some form of AMD (Zarbin, 2004). In the United States (US) alone, more than 8 million people carry the diagnosis (Jager, 2008) and the projected prevalence is expected to increase 50% by the year 2020 (Friedman, 2004). In China the prevalence of AMD ranges from 5.65 to 15.6% in different provinces and a ratio of 5.3:1 is observed for dry/wet AMD (Penfold, 2005).   To date, no curative therapy exists for AMD, and the condition represents a significant, unmet medical need.

AMD may be classified into early, intermediate, and advanced stages (Age-Related Eye Disease Study Report Number 3, 2000). Advanced AMD can be further classified as non-neovascular (dry, atrophic, non-exudative, non-neovascular) or neovascular (wet or exudative).

The primary pathology in AMD involves progressive deterioration of the retinal pigmented epithelium (RPE), Bruch’s membrane, and the choriocapillaris–choroid complex, which ultimately leads to loss of photoreceptor cell support (Leibowitz, 1980; Ferris, 1984; Bressler, 1988; Vingerling 1995). The RPE performs a range of critical functions important to photoreceptor maintenance including phagocytosis of outer segments, delivery of nutrients, and support of the visual pigment cycling (Zeiss, 2010).

In later stages of the disease, patchy degeneration of the photoreceptors, RPE, and underlying choriocapillaris is seen in the macula, the region of sharpest visual acuity. This degeneration eventually develops into clinically recognizable retinal areas referred to as GA. As the pathology of AMD evolves, patients experience loss of central vision that slowly progresses to blindness. The onset of GA is strongly correlated with predictable loss of visual acuity over the ensuing one to two years (Sunness, 2007).

Early clinical changes in AMD may be limited to mild visual loss or the incidental finding of drusen on ocular examination. However, as the disease progresses, patients may experience blurred vision, visual scotomas, decreased contrast sensitivity, abnormal dark adaptation, and difficulty with small print. Further insidious visual loss in patients with non-neovascular AMD occurs over months to years and can manifest as central or pericentral visual scotomas.

GA is associated with thinning of the RPE, and overlying atrophic changes in the macula result in the loss of photoreceptors (Suness, 1999). Natural history studies of GA have characterized the expected rate of visual acuity loss as a function of baseline visual acuity, and reported that a higher rate of acuity loss was associated with best-corrected visual acuity (BCVA) of > 20/50; 41% of subjects losing greater than three lines of vision at two years and 70% at four years (Sarks, 1988; Swaroop, 2007). Researchers have acknowledged that clinical trials including patient populations with this range of visual acuity will maximize the likelihood of detecting progression of disease and treatment effects (Swaroop, 2007).

Although significant progress has been made in developing novel treatments for patients with neovascular AMD, no proven treatment exists for the advanced non-neovascular or GA form of AMD. Lifestyle and dietary modifications are recommended once early AMD is recognized; including cessation of tobacco use, increased intake of antioxidants, control of hypertension, and reduction in body-mass index, but these adjustments typically have minimal impact on the disease course.