Primary prevention of age related macular degeneration

Abstract

Current evidence does not support a protective role for dietary antioxidant vitamins

In this week's BMJ, Chong and colleagues present a systematic review and meta-analysis of the effectiveness of dietary antioxidants, including supplements, in the primary prevention of age related macular degeneration.¹

Age related macular degeneration is one of the most important causes of visual loss in older people. The number of people affected will increase as populations age.² Two types of age related macular degeneration exist. Geographic atrophy is a sharply demarcated area of depigmentation caused by atrophy of the retinal pigment epithelium; neovascular degeneration occurs when new blood vessels grow under the retinal pigment epithelium leading to haemorrhage and scarring. Age related macular degeneration is diagnosed in people aged 50 or more when no other obvious cause for degeneration exists.

New treatments are being developed rapidly. In the past two years, intraocular injections of agents that interfere with angiogenesis have been licensed for use in this condition.³ These bind to vascular endothelial growth factors to prevent endothelial cell proliferation and neovascularisation. Although improved treatments are always encouraging for people with age related macular degeneration, visual loss arising from the growth of new vessels is usually permanent, and no effective treatments exist for geographic atrophy. Research into why age related macular degeneration develops, with a view to preventing it, continues.

The incidence of many diseases increases exponentially with age. One common theory for the aetiology of many age related diseases, including age related macular degeneration, is that they arise as a result of the cumulative effects of oxidative stress.⁴ The systematic review by Chong and colleagues summarises the results of seven prospective studies and three randomised controlled trials evaluating the association between dietary intake of antioxidant vitamins and minerals (such as vitamin C, vitamin E, various types of carotenoids, and zinc) or dietary supplements (vitamin E and β carotene) and age related macular degeneration.¹ This is the first such review of usual dietary intake—previous reviews have considered randomised controlled trials of supplements.⁵

The prospective studies show that people with relatively high dietary intakes of antioxidant nutrients are no more or less likely to develop the condition than those with relatively low intakes. The possible exception to this is high dietary intake of vitamin E, which was associated with a 20% reduced odds of age related macular degeneration. The significance of this finding depended on which studies were included in the meta-analysis. Further studies are needed to confirm its relevance.

Dietary intake is difficult to measure accurately. In observational studies it is difficult to be sure that a fair comparison is being made, because people with different diets also differ in many other ways. In spite of these caveats, evidence of a strong protective effect of the dietary antioxidants studied was lacking. Obviously, a well balanced diet containing fruit and vegetables has many other health benefits and should still be recommended. In addition, included studies were carried out on relatively well nourished populations in the United States, Australia, and Europe, and the results may not apply to populations with different dietary intakes.

Three randomised controlled trials provide good evidence that vitamin E or β carotene supplements do not prevent age related macular degeneration (one of these trials is included in abstract form in the review but has since been published⁶). Although generally regarded as safe, vitamin supplements may have harmful effects. People who smoke may be at increased risk of lung cancer if they take β carotene,^{7 8} and vitamin E supplements may increase risk of heart failure in people with diabetes or vascular disease.⁹

While antioxidant vitamin supplements cannot be recommended as a public health measure to reduce the incidence of age related macular degeneration, people with early stage disease may benefit from supplements containing vitamin C, vitamin E, β carotene, and zinc.¹⁰ The recommended combination and doses of antioxidant vitamins and minerals is found in only a few commercial supplements and should be taken on specialist advice,¹¹ with appropriate consideration of the possible benefits and harms for the individual.

Do other options exist for primary prevention of age related macular degeneration? The strongest risk factors for this condition—age and genetic factors—are not preventable, although genetic research will provide new insights into the causes of the disease and therefore its prevention. High concentrations of polyunsaturated fats are found in the retina, but evidence for a protective effect of dietary fatty acids in this condition is inconsistent.¹² Smoking is the only preventable risk factor that has been associated with the condition in most observational studies.¹³ Currently, reducing the prevalence of smoking is probably the most effective method of reducing the population burden of this common cause of visual loss in older people.