Is the Incidence of Age-Related Macular Degeneration Declining?

William C. Ou; Charles C. Wykoff, MD, PhD


January 18, 2018

The Age of Chronic Disease

The year 2018 marks the 100th anniversary of the infamous "Spanish flu" pandemic that claimed the lives of over 20 million people worldwide. The landscape of medicine in that time was markedly different from today. The intervening century has seen the advent of vaccinations, antibiotics, and a variety of pharmacologic and technological advances, all of which have made it much more unlikely that such an event will be seen again.[1]

Indeed, it is becoming clear that the 21st century will be defined not by infectious diseases but rather by those that come from within: cardiovascular disease, diabetes, cancer, and other chronic diseases with complex pathogenesis and management.[2]

One of these diseases is age-related macular degeneration (AMD), a leading cause of visual impairment in the developed world.[3] AMD most commonly occurs in patients older than 50 years and involves damage to the macula, which provides central vision crucial for tasks like reading.

Among patients with AMD, the most common cause of blindness is the late-stage neovascular (wet) form. Wet AMD is characterized by choroidal neovascularization, in which abnormal blood vessels grow under and into the retina, leading to exudation, fibrosis, and vision loss.

AMD Risk Factors: Nature and Nurture

The risk factors for AMD include both genetic and environmental influences.

Broadly, non-Hispanic white patients are at highest risk of developing AMD,[4] as are individuals with a family history of the disease. Rather than a classic Mendelian inheritance pattern, more than 30 genetic polymorphisms have been associated with risk of developing AMD. Two well-established loci are the CFH locus, which codes for complement factor H—a regulator of the complement cascade of the innate immune system, and the ARMS2/HTRA1 locus.[5,6,7] An illustrative example was provided in a 2005 analysis from investigators for the Age-Related Eye Disease Study (AREDS), who identified a specific CFH allele that conferred a 7.4-fold increase in AMD risk in homozygotes.[6]

AMD risk may also be influenced by a variety of environmental factors, including smoking,[8] obesity,[9] and diet.[10]

Additionally, AREDS and AREDS2 found that supplementation with a specific formula of antioxidants and minerals may reduce risk for progression from intermediate-stage AMD to late-stage disease.[11,12]


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