Epidemiology and Risk Factors Overview
Global Burden
Age-related macular degeneration(AMD) poses a significant global burden. It usually affects middle-aged and older people, with prevalence increasing with advancing age. It is estimated that 10% to 20% of individuals older than 65 years have some form of AMD, and it is predicted to affect 288 million people globally by 2050. The prevalence of AMD is highest among white people, intermediate in Asian and Hispanic people and lowest among Black people. Geographic atrophy (GA) is accountable for approximately 5 million to 8 million cases of AMD worldwide. The global prevalence of GA is estimated at 0.44%. In the United States, about 1 million people are affected by GA, with 160,000 new cases occurring each year. In Germany, between 400,000 and 450,000 people live with GA; in France, it is estimated that there are approximately 265,000 patients with the condition; in Italy, an estimated 170,000 individuals have dry AMD (including GA); while in Spain, the prevalence is estimated…
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Global Burden
Age-related macular degeneration (AMD) poses a significant global burden. It usually affects middle-aged and older people, with prevalence increasing with advancing age. It is estimated that 10% to 20% of individuals older than 65 years have some form of AMD, and it is predicted to affect 288 million people globally by 2050. The prevalence of AMD is highest among white people, intermediate in Asian and Hispanic people and lowest among Black people. Geographic atrophy (GA) is accountable for approximately 5 million to 8 million cases of AMD worldwide. The global prevalence of GA is estimated at 0.44%. In the United States, about 1 million people are affected by GA, with 160,000 new cases occurring each year. In Germany, between 400,000 and 450,000 people live with GA; in France, it is estimated that there are approximately 265,000 patients with the condition; in Italy, an estimated 170,000 individuals have dry AMD (including GA); while in Spain, the prevalence is estimated at 155,000 patients with GA. A recent national study in Spain showed the overall prevalence of AMD in that population to be 7.6%, with 1,161 out of 9,129 (12.7%) patients with AMD having GA.
Aging is a significant risk factor for developing GA. One study that pooled findings from North America, Europe and Australia found that, compared to people aged 55 to 69 years, the risk for developing any type of AMD increased by more than eightfold in people aged 70 to 79 years, and more than 30 times in those aged 80 to 86 years. In Europe, the incidence of GA was shown to increase fourfold every decade between the ages of 50 and 80 years. In this population, it is estimated that GA affects 0.16% of patients who are aged 60 years, compared to up to 2.91% in patients who are aged 80 years. In the United States, the prevalence of GA is 0.28% in patients aged 60 to 64 years and 0.98% in those who are aged 70 to 74 years. The correlation between increasing age and GA remains evident even in populations where prevalence rates are lower. In Asia, the prevalence of GA is estimated at 0.09% for people aged 60 to 69 years, and 0.29% in those aged at least 70 years.
The development and progression of AMD is strongly influenced by genetic factors. Genome-wide association studies (GWAS) found that the prevalence of late AMD and the progression of GA are closely tied to certain gene variations. To date, 103 genes have been associated with the development of AMD, with 34 of them contributing to late AMD progression. Three genes, complement factor H (CFH), high-temperature requirement factor A1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2), have been identified to have the highest population attributable risk for advanced AMD prevalence. The CFH gene is located on chromosome 1. It encodes the CFH protein, which is a key regulator of the complement system – a multiprotein system that plays a crucial role in immune defense (see the Pathophysiology subsection). Different genetic variants in the CFH gene can result in complement system dysregulation, potentially leading to AMD development or progression. However, some CFH alleles have been linked to potential AMD-protective effects. Alleles of the HTRA1 and AMRS2 genes, tightly linked on chromosome 10, are highly associated with an increased risk of GA incidence and more rapid GA expansion. The pathophysiological roles of these and other major loci associated with the development of dry and wet AMD are shown in Figure 1-2.
Cigarette smoking is another risk factor strongly associated with developing AMD, including GA. It represents a key development-contributing factor in at least 27% of AMD cases. One study showed that smoking up to 25 cigarettes a day can lead to a 100% increase in the risk of developing AMD. This risk does not seem to decrease significantly after quitting smoking. In The Age-Related Eye Disease Study 1 and 2 (AREDS and AREDS2), one of the largest studies exploring the natural history and risk factors of AMD, a significant association between smoking status and faster GA expansion was observed. Among smokers, GA was found to progress at a numerically faster rate (0.33 mm/year) compared to nonsmokers (0.27 mm/year).
Certain dietary and lifestyle patterns have also been shown to influence the likelihood of developing AMD. For instance, irregular exercise, a higher BMI and obesity have all been associated with the progression from early to advanced stages of AMD. In contrast, a well-balanced diet can significantly benefit eye health and play a crucial role in lowering the risk of AMD. Long-chain polysaturated fatty acids, vitamins C, D and E, zinc and carotenoids are known to promote macular health. The AREDS studies investigated their impact on AMD progression, and found that the risk of developing advanced AMD was reduced when these nutritional factors were taken as daily supplementation (for more information, see Treatment Options and Therapies).These studies showed that the adherence to a Mediterranean-like diet was strongly associated with a decreased risk of GA progression and slower GA lesion growth. Higher fish intake was associated with the strongest protection against GA. Additionally, protective effects were observed with consumption of whole grains and whole fruits, as well as with limited alcohol intake.

References
- Abdelsalam A, Del Priore L, Zarbin MA. Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol. 1999;44(1):1-29.
- Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-2015.