Risk Factors of AMD
Cigarette Smoking. An increased incidence of neovascular and atrophic AMD has been consistently demonstrated among smokers (Thornton 2005; Chakravarthy 2010).
The macular pigment (MP) optical density in 34 cigarette smokers was compared against the MP optical density in 34 non-smokers matched for age, sex, and dietary patterns. It was found that tobacco users had significantly less MP than control subjects. Further, smoking frequency (cigarettes per day) was inversely related to MP density (Hammond 1996).
In a study investigating the relationship between smoking and the risk of developing AMD in Caucasians, 435 cases with end stage AMD were compared to 280 controls. The authors demonstrated a strong association between the risk of both dry and wet form AMD and the amount of cigarette smoking. More specifically, for subjects with 40 pack years (number of pack years = packs smoked per day [x] years as a smoker) of smoking, the odds ratio (probability of the condition occurring) was 2.75 compared with non-smokers. Both types of AMD showed a similar relation; smoking more than 40 pack years of cigarettes was associated with an odds ratio of 3.43 for dry AMD and 2.49 for wet AMD. Stopping smoking was associated with reduced odds of AMD. Also, the risk in those who had not smoked for over 20 years was comparable to non-smokers. The risk profile was similar for males and females. Passive smoking exposure was also associated with an increased risk of AMD in non-smokers (Khan 2006).
Oxidative Stress. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, high proportion of polyunsaturated fatty acids, and exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress. Furthermore, there is strong evidence suggesting that lipofuscin (a photoreactive substance) is derived, at least in part, from oxidatively damaged photoreceptor outer segments (Drobek-Slowik 2007). While naturally occurring antioxidants typically manage this, environmental factors and stress can decrease circulating antioxidants. For example, levels of the endogenous antioxidant glutathione decrease as people age, making the lens nucleus and retina susceptible to oxidative stress (Babizhayev 2010).
Vitamin C, normally highly concentrated in the aqueous humor and corneal epithelium, helps absorb damaging ultraviolet radiation, protect the basal layer of the epithelium, and prevent AMD (Brubaker 2000). L-carnosine and vitamin E also mitigate oxidative stress and free-radical damage (Babizhayev 2010).
Inflammation. Injury and inflammation to the pigmented layer of the retina (retinal pigment epithelium or RPE) as well as the choroid cause an altered and abnormal diffusion of nutrients to the retina and RPE, possibly precipitating further RPE and retinal damage (Zarbin 2004). Animal studies show that oxidative stress-induced injury to the RPE results in an immune-mediated chronic inflammatory response, drusen formation, and RPE atrophy (Hollyfield 2008).
Research has identified specific genetic changes, which can lead to an inappropriate inflammatory response and set the stage for AMD onset (Augustin 2009). Other studies looking at whether inflammatory markers predicted AMD risk found that higher levels of C-reactive protein (CRP) were predictive of AMD after controlling for genotype, demographic and behavioral risk factors (Seddon 2010; Boekhoorn 2007).
Phototoxicity. Another risk factor for AMD is phototoxicity caused by exposure to blue and ultraviolet (UV) radiation, both of which adversely affect the functioning of RPE cells. Cultured human RPE cells are susceptible to apoptotic cell death induced by Ultraviolet B (UVB) irradiation. Absorption of UV light by the innermost layer of the choroid can largely prevent the cytotoxic effect. (Krohne 2009). Exposure to sunlight without protective sunglasses is a risk factor for AMD (Fletcher 2008).
Hypertension. A study of 5,875 Latino men and women identified a pronounced risk for wet AMD if diastolic blood pressure was high, or if individuals had uncontrolled diastolic hypertension (Fraser-Bell 2008). Prolonged treatment of hypertension with a thiazide diuretic, however, was associated with a more significant incidence of neovascular AMD, possibly due to the known phototoxic effects of thiazide diuretics (De la Marnierre 2003).
Low Carotenoid Intake. Insufficient intake of the following carotenoids is linked to AMD: lutein, zeaxanthin, and meso-zeaxanthin. Lutein, zeaxanthin, and meso-zeaxanthin are carotenoids present in the retina and positively affect MP density (Ahmed 2005). Lutein and zeaxanthin help to prevent AMD by maintaining denser MP, resulting in less retinal tearing or degeneration (Stahl 2005). The therapeutic efficacy of lutein and zeaxanthin in AMD is significant, according to the Lutein Antioxidant Supplementation Trial (LAST), which showed improvement in several symptoms accompanying AMD (Richer 2004).
Low Vitamin B Intake. Several studies show that low levels of certain B vitamins are associated with an increased risk for AMD. The Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS) in 5,442 female health professionals showed that daily supplementation with folic acid, B6 and B12 resulted in significantly fewer AMD diagnoses compared to placebo (Christen 2009).
High Fat Intake. Higher intake of specific types of fat, rather than total fat, may be associated with a greater risk of advanced AMD. Diets high in omega-3 fatty acids, fish and nuts were inversely associated with AMD risk when intakes of linoleic acid (an omega-6 fatty acid) was low (Tan 2009).
A French study found that high total fat, saturated fat and monounsaturated fat intake were all associated with an increased risk of developing AMD (Delcourt 2007). Eating red meat 10 or more times per week appears to increase risk for developing early AMD, while eating chicken more than 3 times per week may confer protection against the disease (Chong 2009a).
High trans fat consumption has been linked to an increased prevalence of late (more advanced) AMD in a study of 6,734 individuals. In the same study, olive oil consumption offered a protective effect (Chong 2009b).
Ethnicity. Studies in the USA indicate that a higher percentage of Caucasian-Americans get macular degeneration compared to African-Americans (Klein 2011).