Awareness of modifiable risk factors key in addressing age-related eye diseases

As the proportion of the elderly population increases around the world, the prevalence and effects of age-related eye diseases are also increasing, creating a need for greater awareness of modifiable risk factors such as nutrition and lifestyle.

According to global reports such as the World Health Organization (WHO) blindness and visual impairment project, age-related macular degeneration is the primary cause of visual impairment in industrialized countries, accounting for 19% to 30% of the total cases of low vision in developed regions. Projected data estimates a 50% increase of AMD prevalence between 2000 and 2020.

In contrast, cataract is responsible for only 2% to 3% of low-vision cases in the Americas, Europe and Western Pacific, but more than one-third of the total visual impairment in some developing regions.

Diabetic retinopathy is reported to be the cause of 6% to 10% of visual impairment in developed regions, reflecting the greater prevalence of diabetes in those areas. According to WHO projected data, the major proportion of the increase in diabetes is predicted to occur in developing countries.

From left to right, Johanna M. Seddon, MD, ScM, Sarah P. Read, PhD, and Elias Reichel, MD, collaborate on a case of age-related macular degeneration. Image: David J. McMahon, New England Eye Center

Global monitoring reports, as well as population-based studies, agree that aging is the main, unavoidable risk factor for these conditions, followed by genetic tendencies. However, there is also now a general consensus that the use of tobacco and an unbalanced diet are major, modifiable risk factors.

“A proportion of visual impairment and blindness due to age-related eye diseases could be prevented with attention to healthy lifestyles. These modifiable behaviors and preventive measures deserve increased attention and evaluation,” Johanna M. Seddon, MD, ScM, professor of ophthalmology at Tufts University School of Medicine and founding director of the Ophthalmic Epidemiology and Genetics Service at Tufts Medical Center, said.

Modifiable risk factors

Smoking is a clear-cut, well-recognized risk factor for both AMD and cataract, according to Tien Y. Wong, MBBS, PhD, director of the Singapore Eye Research Institute, National University of Singapore.

“Correlation and the magnitude of the effect are very consistent and are seen in the Western as well as in the Asian population,” he said.

The correlation is dose-dependent.

“The more you smoke, the higher the risk,” Dr. Wong said. “Studies suggest also that past smokers have a risk of developing AMD that is closer to that of nonsmokers. This is a good incentive for people to stop smoking.”

Although more difficult to assess, the correlation between eye disease and dietary factors is now also widely recognized.

“Higher intake of specific types of animal and vegetable fat (saturated, monounsaturated, polyunsaturated and trans-unsaturated), as well as a high daily consumption of processed baked goods, which are higher in some of these fats, were shown to increase the rate of AMD progression approximately twofold in a number of studies,” Dr. Seddon said. “Although most information comes from AMD studies, there are sufficient data to support a correlation also between fat intake and cataract and diabetic retinopathy.”

She said that a diet too rich in fats also increases body mass index, high cholesterol levels and high blood pressure, which are additional risk factors for eye diseases.

As far as potentially protective nutrients are concerned, research has moved in three main directions: antioxidants, lutein and zeaxanthin, and omega-3 fatty acids.

Antioxidants have been evaluated in eye disease studies in the form of vitamin and mineral supplements, but they are also found naturally in a variety of fruits and vegetables, green tea and red wine. Green vegetables such as kale, spinach, collard greens, romaine lettuce and broccoli are among the best sources of lutein and zeaxanthin and can reduce the risk of AMD, as first reported in 1994 by Dr. Seddon and colleagues. Fish, particularly salmon, tuna, mackerel and herring, is rich in omega-3 fatty acids, which also reduce the risk of AMD.

According to Sarah Parker Read, PhD, and Elias Reichel, MD, of the New England Eye Center in Boston, a number of studies have reported decreased risk of advanced AMD with increased omega-3 fatty acids.

“In one meta-analysis, fish intake twice a week was associated with a reduced risk of both early and late AMD. There is no significant risk associated with taking omega-3 fatty acids, and there is a proven reduction in the incidence of cardiovascular disease and stroke,” they said.

Tien Y. Wong

Dr. Wong said the best diet for eye disease prevention is high in fiber with a good balance of vegetables and fish and an avoidance of fatty food and red meats.

“It has been shown that the Japanese diet, with high fish intake and low meat consumption, is associated with a lower rate of cardiovascular diseases and a longer life span,” he said.

The beneficial effects of physical exercise, which also helps reduce obesity, and the risks of sunlight exposure, particularly for cataract, are other known modifiable risk factors.

In diabetic retinopathy prevention, several lines of evidence support the benefits of control of blood pressure and cholesterol level through a low-salt and low-fat diet, which are as important as glucose control.

Landmark studies

Several epidemiological studies, and fewer interventional studies, have been investigating the impact of lifestyle-related factors on age-related eye diseases. In 1984, Dr. Seddon and colleagues began to explore whether diet or supplements could prevent or slow the progression of AMD and cataract.

Dr. Seddon is an investigator whose work has helped pioneer the idea of supplement use for AMD and cataract prevention.

“We hypothesized that antioxidants, like those contained in food and supplements, might block the oxidative damage to the lens and retina by daily insults such as pollution, smoking, sunlight and even normal metabolic processes,” she said. “We found that antioxidants, especially carotenoids called lutein and zeaxanthin, were protective. These are the same pigments found in the macula.”

Lutein and zeaxanthin are found in high concentrations within the macula, giving the structure its yellow color and helping to protect the retina and retinal pigment epithelium, Drs. Read and Reichel said.

“In multiple studies, increased intake of lutein and zeaxanthin has been shown to reduce the risk for advanced and intermediate AMD,” they said.

However, “current data surrounding nutritional supplements for the prevention of AMD are often inconclusive and occasionally contradictory,” Drs. Read and Reichel said. For example, a 2006 report by the U.S. Food and Drug Administration reviewed a number of studies and concluded that there was insufficient evidence to support a link between lutein and zeaxanthin and AMD risk. But because lutein and zeaxanthin lack any long-term risk, many manufacturers are currently including them in formulations, they said.

The Age-Related Eye Disease Study, which was initiated in 1990, involved 11 centers in the United States and enrolled approximately 5,000 subjects. The supplements involved in the study were vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg), and zinc oxide (80 mg) with cupric oxide (2 mg).

The group of subjects taking these supplements had a 25% reduction in risk of progression to advanced AMD over 5 years compared with controls and a 19% reduction in loss of three or more lines of vision over the same period. No effect was observed for cataract progression. These results supported the hypothesis generated earlier that antioxidants can reduce risk of AMD.

In 2006, AREDS II was started with the aim of revisiting the use of micronutrients such as lutein, zeaxanthin and omega-3 fatty acids. Results will be released in December 2012.

“Since 1985, we have conducted case-control and prospective cohort studies, evaluating single modifiable risk factors such as fat intake, smoking, body mass index and the potential benefits of specific nutrients and exercise,” Dr. Seddon said. “Significant correlations were found for both AMD and cataract in most cases.”

Two other studies, published while AREDS was in progress, found that high-dose beta-carotene supplementation significantly elevates risk of lung cancer in smokers. In addition, beta-carotene itself is not found in the retina, and its metabolism to vitamin A is tightly regulated. After the inception of AREDS, it became increasingly clear from epidemiological and biochemical studies that lutein and zeaxanthin, rather than beta-carotene, are likely to be the protective factors in carotenoid-rich fruits and vegetables.

“It is important to consider that increased intake of vitamins and minerals well above the recommended daily dose has the potential for side effects, for example, the increased risk of kidney stones from vitamin C, lung cancer in smokers from beta-carotene, increased hemorrhagic stroke risk from vitamin E and anemia from zinc,” Drs. Read and Reichel said. Therefore, it is important to suggest the use of supplementation when medically indicated.

“We recommend the AREDS formulation only in patients with high-risk disease (category 3 or 4). Smokers, or those with a history of smoking, are placed on a formulation that does not contain beta-carotene,” Drs. Read and Reichel said.

Supplementation can be expensive, they said, and patients in this age group are taking multiple medications, so they suggest simplifying the regimen by using a multivitamin that also contains the AREDS formulation.

Dr. Wong is a co-author of a series of landmark community-based studies that have systematically documented the frequency, causes and impact of low vision and major eye diseases. The studies have examined subjects in three different ethnic groups, Malay, Chinese and Indian, in Singapore. This series of studies is the single largest epidemiological study of eye disease worldwide, involving more than 10,000 participants.

Results of the Singapore Malay Eye Study have already been published. A total of 3,280 Asian Malay adults aged 40 to 80 years were examined to evaluate the association between several lifestyle-related risk factors and AMD, diabetic retinopathy and cataract.

Smoking was confirmed to play a significant role in progression from early AMD to late AMD. It was also confirmed to be associated with earlier onset nuclear cataract, with one in six nuclear cataract cases attributable to smoking in younger-than-average male subjects, according to the study.

“One of the key major differences with Western populations is that in Asia, there is a significantly higher proportion of male than female smokers,” Dr. Wong said. “In the Singapore Malay Eye Study, 93% of current smokers were men. A similar preponderance of male smokers was found in the Funagata study in Japan, where the prevalence of late AMD was also significantly higher in men.”

While apparently falling in Europe, the U.S. and Australia, smoking rates in Asia have been rising and could become a major problem in the future, he said. An estimated 50% to 70% of adult men are reported to be smokers in some Asian countries, compared with less than 30% in some developed countries, including England and Australia.

In the same population, the prevalence of diabetic retinopathy was 35.4% and was associated in 80% to 90% of the cases with poor glycemic and blood pressure control. Higher total cholesterol levels were also associated with the condition.

Increasing awareness

According to a 2005 global survey commissioned by AMD Alliance International and more recent local studies, awareness of AMD and associated risk factors has increased, compared with a 1999 survey, but is still low. The highest levels of AMD awareness were in the U.S. (30%), Canada (25%) and Australia (21%).

In Europe, the U.K. (16%), Germany (14%) and France (13%) had awareness levels that were in the middle range, while in Spain, the Netherlands and Italy, less than 10% of respondents were familiar with the disease.

Wanda Hamilton

An even lower percentage of awareness was found in Hong Kong (4%) and Japan (6%), the only Asian countries included in the survey.

“The low level of awareness in some European countries might be due to a higher reliance on families and friends, which makes seeking information and institutional support less imperatively necessary,” Wanda Hamilton said. “In Asian countries, awareness may be lower because of the lower AMD prevalence. AMD in Japan is categorized as a rare disease.”

Ms. Hamilton is former CEO at AMD Alliance International and currently group director of fundraising at the Royal National Institute of Blind People, U.K.

She said regular eye examinations are important to treating blinding eye diseases and conditions early and effectively because they can help lead to early diagnosis and treatment.

Subjects also must know about modifiable risk factors and how they can put themselves at less risk for developing eye diseases. A lack of awareness of the main modifiable risk factor — smoking — was shown in the AMD Alliance International report. Only 32% of respondents who were aware of AMD named smoking as a risk factor. Unprotected exposure to sunlight was named by 32% and lack of vitamins and nutrients by 36%. A major exception was Australia, where 77% of respondents were aware that smoking can harm their sight. Australia is one of the few countries in the world to mount a major advertising campaign with graphic pictures to illustrate the harmful effects of smoking on eye health.

Ms. Hamilton said that increasing awareness of potentially blinding eye diseases and correlated risk factors should be at the forefront of governments’ agendas.

“If governments worldwide are interested in saving money over the long run and are aiming at social inclusion for all of their citizens, they should take a stronger lead in vision health policies. Awareness is part of the prevention agenda,” she said.

In addition, associations can provide expertise, partnering with governments to deliver programs. Initiatives should focus on personal health responsibility, a concept that needs more attention, she said.

“The population that we categorized as ‘high risk’ in another piece of research on level of awareness of risk behaviors were those who, even knowing they were at risk, did not have a sufficient level of concern about their behavior,” Ms. Hamilton said. “Just knowing that something is a problem doesn’t always mean that action is taken to change behaviors.”

Health care professionals also have an important role to play and should be among those included first in government awareness strategies, she said. The general practitioner, optometrist and ophthalmologist all must assist in bringing health awareness to patients. Without personalized services and care from both health care professionals and governments, patients who need to be reached might not be, and vision could be lost as a result, she said.

Governments and associations have done a great deal in recent years to address the need for awareness, but more must still be done.

“The need to implement effective vision health policies will grow in importance as the population ages and developing countries are increasingly adopting Westernized lifestyles,” Ms. Hamilton said. “In terms of modifiable risk factors, fighting health hazards such as smoking and obesity and investing on educating people to healthier lifestyles can indeed be cost-beneficial to societies, as well as advantageous for the individuals in terms of health and life quality.” – by Michela Cimberle

What recommendations do you make to your AMD patients regarding antioxidant vitamins and supplements specifically formulated to help prevent disease progression?

References:

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• Wanda Hamilton can be reached at Royal National Institute of Blind People, 105 Judd St., London, WC1H 9NE, U.K.; 44-20-7391-2339; e-mail: wanda.hamilton@rnib.org.uk.
• Sarah Parker Read, PhD, and Elias Reichel, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; e-mail: ereichel@tuftsmedicalcenter.org.
• Johanna M. Seddon, MD, ScM, can be reached at Department of Ophthalmology, Tufts Medical Center, 800 Washington St. #450, Boston, MA 02111; 617-636-9000; fax: 617-636-1124; e-mail: jseddon@tuftsmedicalcenter.org.
• Tien Y. Wong, MBBS, PhD, can be reached at Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Ave., Singapore 168751; 65-63224571; fax: 65-63231903; e-mail: tien_yin_wong@nuhs.edu.sg.