A Summary of Risk Factors for AMD

by Wendy Strouse Watt, O.D.
October 2003
(Updated November 2008)
Research has revealed new risk factors in the development of age-related macular degeneration (AMD). Called epidemiological studies, they show correlations of the disease with obesity and consumption of certain dietary fats.
These discoveries are being added to the list of more commonly-known risk factors, including age, smoking, family history, gender, high blood pressure, and cardiovascular disease, all of which are summarized here. Other factors which have been identified are diabetes, exposure to blue and ultraviolet light, low consumption of fruits and vegetables, light skin color, blonde hair, blue eyes, and hyper- or hypomyopia. Information about most of these additional risks may be found elsewhere on this site.

An article published in Arch Ophthalmol. 2003 Jun;121(6):785-92. Dr. Johanna Seddon (director of epidemiology at the Massachusetts Eye and Ear Infirmary and an associate professor at Harvard Medical School and Harvard School of Public Health) was lead author of the study. They found an association with body mass index, waist circumference, and waist-hip ratio to the progression of age-related macular degeneration. Their results provide new information regarding modifiable factors for individuals with the early or intermediate stages of MD. Overall and abdominal obesity increased the risk for progression to advanced AMD, and more physical activity tended to decrease risk. These preventive measures deserve additional research and greater emphasis.
UPDATE (Nov 2008): Confirmation of these findings comes from a study by Anna Peeters, Ph.D. et al (“Changes in Abdominal Obesity and Age-Related Macular Degeneration.” Arch Ophthalmol. 2008;126(11):1554-1560.)
Researchers examined the association between changes in waist-hip ratio (WHR) and AMD. Percentage changes were noted in WHR over a period of 6 years in a total of 12,515 persons aged 45 to 64 years of age. Study subjects who had a 3% or greater reduction in WHR over the period were found to have a lower risk of AMD, particularly among those who were initially obese.

Dietary fats
Another study Dr.Seddon was involved with found that snack foods may increase risk of age-related sight loss. A study in the August 2001 issue of the Archives of Ophthalmology found that a higher intake of specific types of fat, including vegetable, monounsaturated and polyunsaturated fats, may be associated with a greater risk for advanced adult macular degeneration. Foods with higher levels of these fats overall tend to be highly processed, store-bought snack foods. Conversely, diets high in omega-3 fatty acids, which are primarily found in certain types of fish such as albacore tuna and salmon, seem to lessen the risk.

Americans have a 2 percent chance of having macular degeneration during their fifties. Approximately 10% of patients 66 to 74 years of age will have findings of macular degeneration. The prevalence increases to 30% in patients 75 to 85 years of age.

The only environmental exposure clearly associated with macular degeneration is tobacco smoking. Not only does smoking increase the risk of macular degeneration development, current or ex-smokers should not take the vitamin supplements that have beta carotene because the risk of lung cancer increases if they do so. Beta carotene vitamin supplements were recently shown to help in slowing macular degeneration in a NIH supported study.
The French POLA study (Pathologies Oculaires Liees a l’Age) looked at over 2000 subjects who lived on the French Mediterranean. The study found that both current and former smokers had the highest risk for developing macular degeneration, and that the risk of late-onset age-related macular degeneration remained elevated until 20 years after quitting smoking.
Two studies published in the Journal of the American Medical Association examined the association between cigarette smoking and the incidence of ARMD (JAMA 1996;276:1141-1146 and JAMA 1996;276:1147-1151). Smoking greater than 20-25 cigarettes per day increased the risk of developing ARMD by approximately 2.5 times when compared to non-smokers. The risks increased in a dose-dependent fashion with increasing cigarettes per day and pack-years smoked. The effects of smoking persisted even after quitting for 15-20 years.

Family history of macular degeneration
Macular degeneration appears to be hereditary in some families but not in others. Since macular degeneration affects most patients later in life, it is difficult to study successive generations in a family. Approximately one fourth of all late-stage macular degeneration appears to have a genetic basis. The lifetime risk of developing late-stage macular degeneration is 50% for people who have a relative with macular degeneration vs 12% for people who’s relatives do not have macular degeneration (4x the risk). People who have first-degree relatives with late-stage macular degeneration develop macular degeneration at an increased rate at a relatively young age. (Arch Ophthalmol.1998;116:1646-51)

There are more women than men who have MD. It may be due to the fact that women live longer. The Age-Related Eye Disease Study, or AREDS, enrolled 4500 patients aged 60 to 80 years. It was found that women, those with a history of arthritis, and those with a lower likelihood of having a history of angina were found to be at risk of intermediate forms of age-related macular degeneration.

High blood pressure
Recently published data shows that people with previously controlled hypertension (blood pressure less than 160/95) were approximately twice as likely, and persons with uncontrolled hypertension (blood pressure more than 160/95) were approximately three times as likely, to develop wet macular degeneration than persons with normal blood pressure (Ophthalmology 2003;110: 636-643). In the Age-Related Eye Disease Study persons with hypertension were 1.5 times as likely to have wet macular degeneration compared with persons without hypertension. In general, higher systolic pressure and higher pulse pressure are associated with higher risk of wet macular degeneration.
A blood pressure reading of 140/80, means that the systolic blood pressure is 140 and your diastolic pressure is 80. The pulse pressure is calculated as systolic blood pressure minus diastolic blood pressure. In this example, the pulse pressure would be 60 (140 minus 80). (The pulse pressure would be high if the systolic pressure is high and the diastolic pressure is low). Higher pulse pressure and lower diastolic blood pressure may be markers for degenerative changes occurring in eyes that are at risk for wet macular degeneration development.
Physical activity such as brisk walking, jogging, and bicycling long enough to work up a sweat when performed regularly (more than 3 times a week) reduces macular degeneration. A sedentary lifestyle may result in obesity, which has been inconsistently found to be associated with macular degeneration.

Cardiovascular disease
A history of heart disease or stroke and atherosclerosis (hardening of the arteries) is associated with a higher incidence of macular degeneration.
High levels of blood serum cholesterol are associated with an increased tendency to develop macular degeneration. A study published in the Archives of Ophthalmology in March of 2000 that looked at 600 patients in the metropolitan New York area found that neovascular, or “wet,” macular degeneration was associated with a history of high blood pressure, and with elevated cholesterol levels. Dry macular degeneration was not related to either high blood pressure or high cholesterol.
A new study is underway titled “Cardiovascular Risk Factors and AMD.” The purpose is to explore new research that has suggested that risk factors causing heart disease may also play a role in AMD. Two substances normally found in the blood, homocysteine and C-reactive protein, when elevated, have been shown to be risk factors for the development of cardiovascular disease. Dr. Andrew Vine, director of the Retina Service at the Kellogg Eye Center and collaborator with the AMD Genetic Study, is interested in understanding if these same two substances, when elevated, may be risk factors for the development of AMD. Contact: Jacqueline Stader, COT,CCRC, Clinical Research Coordinator, (734) 763-7249, email; [email protected]. Address: Retina Clinic, U-M Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105.

Alzheimer’s disease
Finally, a correlation has also been drawn between Alzheimer’s disease and AMD. The authors of “Is age-related maculopathy associated with Alzheimer’s Disease?” (American Journal of Epidemiology 1999;150:963-968) examined this relationship in a prospective population-based study in the Netherlands.
From 1990 to mid-1993, 1,438 individuals aged 75 years or older were screened for the presence of age-related maculopathy and Alzheimer’s disease, and follow-up examinations were conducted from mid-1993 to the end of 1994. Subjects with advanced age-related maculopathy at baseline showed an increased risk of incident Alzheimer’s disease (relative risk = 2.1), but this risk decreased after additional adjustment for smoking and atherosclerosis (relative risk = 1.5). These findings suggest that the neuronal degeneration occurring in age-related maculopathy and Alzheimer’s disease may, to some extent, have a common pathogenesis.