Randomized Trial of Beta-Carotene and Macular Degeneration
Randomized Trial of Beta-Carotene and Macular Degeneration
To determine whether 50 mg of beta-carotene taken every other day reduces the risk of
 developing age-related macular degeneration (AMD) among male U.S. physicians who were aged 40
 to 84 in 1982.

 To investigate the possible relationship of AMD with other antioxidants, including selenium
 and vitamins A, C, and E.

 To identify potential risk factors for development of AMD. Possible risk factors include
 height, systemic hypertension, cardiovascular disease, blood cholesterol, cigarette smoking,
 iris and skin color, sunlight exposure, body mass index, diabetes, and alcohol intake.
Macular degeneration, a major cause of blindness in the United States, is the leading cause
 of new cases of blindness in people aged 65 and older. The National Eye Institute estimates
 that each year an additional 165,000 people, mainly in the older age groups, develop macular
 disease. Among all people with macular degeneration, approximately 116,000 are affected by
 the neovascular form of the disease. Although laser treatment is an effective treatment for
 patients with certain forms of neovascular membranes (exudative AMD), for most patients there
 is no available treatment.

 The pathogenesis of AMD is only partly understood, and its etiology remains obscure. The
 Retinal and Choroidal Diseases Panel of the National Advisory Eye Council has stated that
 "none of the fundamental causes of any type of macular disease is known, and none can be
 prevented." Thus, this panel recommended that one of the NEI's program development priorities
 should be to "initiate epidemiologic studies of macular diseases to identify possible
 causative, protective, or aggravating factors."

 This trial is part of the Physicians Health Study, sponsored by the National Heart, Lung, and
 Blood Institute (NHLBI) of the National Institutes of Health, with funding for eye
 epidemiologic data evaluations provided by the NEI. It is an ongoing, randomized,
 placebo-controlled trial of aspirin in the prevention of cardiovascular mortality and of
 beta-carotene in the prevention of cancer. Following randomization, each of the 22,071
 physicians enrolled was assigned to one of four groups to take either aspirin or its placebo
 and beta-carotene or its placebo. Followup questionnaires are sent 6 and 12 months after
 randomization and every 12 months thereafter. The average length of followup is now greater
 than 12 years.

 The hypothesis that beta-carotene levels are inversely related to AMD is supported by
 experimental studies on the relationship between antioxidants and retinal morphology and
 function. There is increasing evidence that visible and ultraviolet light can damage the
 retina through production of superoxide radicals. Antioxidants (including beta-carotene,
 vitamins A, E, and C, and selenium) protect against oxidative damage by acting as scavengers
 for the superoxide radicals.

 Epidemiologic data from the first National Health and Nutrition Examination Survey (NHANES-1)
 are also consistent with a link between antioxidants and AMD; the frequency of consumption of
 fruits and vegetables rich in vitamin A (beta-carotene) was negatively correlated with AMD
 after adjustment for demographic and medical factors.

 Data from this study will determine whether one 50-mg beta-carotene capsule taken on
 alternate days protects against the development of AMD and whether additional risk factors
 emerge after simultaneous controlling for other potential confounding factors.

 Reported diagnoses of AMD are confirmed by medical record review. The primary analysis will
 be a comparison of incidence of reported AMD in the beta-carotene and placebo groups. The Cox
 proportional hazards model will also be used to determine whether there is a difference in
 time to diagnosis of AMD between the two groups.
When the Physicians Health Study was established in the early 1980s by the NHLBI to collect
 data on a stable population at risk for heart attack, only male physicians were studied
 because males were thought to be at higher risk than females for ischemic heart problems.
 The study population consists of 22,071 male U.S. physicians who were aged 40 to 84 years
 in 1982. The subjects have no history of myocardial infarction, cancer, kidney disease,
 renal disease, or any other contraindication to the use of aspirin or beta-carotene,
 including regular use of corticosteroids.