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HomemieyecareManaging Diet and the Risks of AMD

Managing Diet and the Risks of AMD

Strong evidence suggests that interventions to achieve dietary behaviour change in patients with age-related macular degeneration could help prevent disease progression. Co-management between eyecare practitioners and dietitians could provide an effective solution.

Age-related macular degeneration (AMD) is the leading cause of blindness in Australia, accounting for 50 per cent of cases among people aged over 50 years.1 Dietary modifications represent one of the only ways to prevent the development of AMD as well as slow its progression.2,3 Current evidence indicates that all AMD patients, regardless of their disease severity, should be given dietary advice to increase consumption of dark green leafy vegetables and fish, and to consume low glycemic index (GI) diets.3-8 The Age-Related Eye Disease Study (AREDS) demonstrated that taking a supplement containing high doses of vitamin C, vitamin E, beta-carotene, zinc, and copper could reduce AMD progression by 25 per cent.9-14 The follow up (AREDS 2), found adding lutein and zeaxanthin (naturally occurring carotenoids) or omega-3 fatty acids to the original AREDS formulation had no overall effect on the risk of late AMD. However, the trial found that replacing beta-carotene with a five to one mixture of lutein and zeaxanthin could help to further reduce late AMD risk.7,8

Currently, we aim to move the research forward in AMD by using the landmark Blue Mountains Eye Study (BMES) to investigate links between relatively unexplored or novel dietary parameters and risk of AMD. For instance, the epidemiological data available on the association between vitamin B12 and folate with AMD are largely equivocal. Using BMES data we were able to show that participants with vitamin B12 deficiency had around 58 per cent higher risk of developing early AMD, and just over two-fold increased risk of late AMD over a 10-year follow up. Similarly, folate deficiency was associated with 75 per cent and 89 per cent increased risk of early and any AMD, respectively. Conversely, participants who reported vitamin B12 supplement usage had 47 per cent reduced risk of developing any AMD 10 years later.5 These associations were independent of the potential confounding effects of factors such as smoking, fish consumption and antioxidant intake.5 It has been posited that the direct antioxidant effect of vitamin B12 and folate could explain its beneficial influence on AMD risk. However, the evidence is currently insufficient to recommend B12 and folate supplementation to prevent the development of AMD.

Intake of Dairy

Another dietary factor, that has not been well explored in relation to AMD risk and progression, are the intake of dairy foods. In the BMES, lower consumption of reduced-fat dairy foods was associated with three-fold increased risk of late AMD over a 15-year follow up.4 Reduced total dietary calcium intake over the 15 years was also associated with an increased risk of developing late AMD among BMES participants.4 Our findings are in agreement with existing studies that showed a protective effect of habitual dairy food consumption on various systemic conditions including metabolic syndrome, hypertension and cardiovascular disease.15-18 Nevertheless, we caution that any dietary recommendations from these data, such as an increase in the consumption of dairy products to prevent AMD, require further validation before they are incorporated into public health advice.19 Specifically, randomised clinical trials that more accurately determine the potential value of dairy food intake as a means of reducing the risk of developing AMD would be valuable.4

there exists a critical need to identify an effective intervention for dietary behaviour change in AMD patients that could be routinely implemented in clinical practice

Multiple healthy or unhealthy lifestyle factors considered jointly, may have a greater influence on AMD risk reduction than the effect of individual healthy or unhealthy lifestyle factors.20 In this context, we recently published BMES research examining the combined influence of poor health behaviours on AMD risk.21 At the baseline examination, BMES participants who engaged in all four poor health behaviours (smoking, low fruit and/or vegetable consumption, high intake of alcohol and low levels of physical activity) had five and 29.5-fold greater odds of any, and late, AMD respectively, compared to those exhibiting none of these unhealthy behaviours. Findings from the BMES and two other US studies20,22 therefore, suggest that broadly, a combination of lifestyle practices might have a more important effect on the likelihood of AMD than focusing on certain isolated components of an individual’s lifestyle.21

Micronutrient Usage and Other Modifiable Lifestyle Behaviours

Currently, there is a paucity of studies that have compared the micronutrient usage and other modifiable lifestyle behaviour patterns in the longer term among those with and without a diagnosis of AMD. Therefore, one of our aims was to document temporal changes in lifestyle behaviours and antioxidant supplement use among people presenting with AMD at the initial BMES exams. In the BMES, only ~46 per cent of participants who developed late AMD reported uptake of AREDS-type supplements over 10 years.23 A lower uptake of AREDS-type supplements was also observed in participants who developed early AMD, which is cause for concern given that this sub group is likely to be at greatest risk of progression to advanced AMD, and irreversible vision loss.24 Less than half of participants who had AMD were adhering to recommended daily intakes for fruit, vegetable and fish in the BMES.23 An extension of this report involved comparing dietary intakes in a large clinic based cohort of late AMD patients presenting for treatment with age-sex matched healthy controls from the BMES.25 This recent study showed that late stage AMD patients, compared to healthy controls, had lower intakes of vitamins C and E, beta-carotene and folate. A significantly lower proportion of late stage AMD cases were also meeting the recommended daily intake of vegetables compared to controls.25 These findings are of concern as vegetables are a rich source of lutein and zeaxanthein.7,8 Moreover, less than half of AMD patients were meeting the recommended fish intake, despite the known protective benefits of fish.6

Intervention Required

In summary, there is strong evidence from studies such as AREDS and BMES showing the benefits of micro and macronutrients, and food groups with respect to AMD with few, if any, adverse effects.3 Hence, dietary modifications for AMD are important as no other preventative treatments are available.3 Despite this, our research and the research of others have identified an evidence practice gap of dietary recommendations made by eye care professionals and the recommendations actually practiced by AMD patients.23,26,27 Therefore, there exists a critical need to identify an effective intervention for dietary behaviour change in AMD patients that could be routinely implemented in clinical practice.

Eye care professionals are extremely busy and do not always have the time to provide the support patients need to understand dietary recommendations and to achieve compliance. To address this evidence practice gap we are now conducting a NHMRC funded, randomised, controlled trial of a telephone intervention delivered by an accredited practicing dietitian, aimed at promoting a diet that is regularly rich in dark green, leafy vegetables, fruits and fish, as well as appropriate use of AREDS-type supplements in AMD patients. The basis of this study is that nutrition focused healthcare to positively change behaviours could be best achieved through appropriate comanagement between eye care practitioners and dietitians.28 It is anticipated that this intervention will quickly and efficiently provide tailored advice on nutrition and recommended support to AMD patients, thereby facilitating positive dietary behaviour changes. These types of intervention studies that expand the scope of translation efforts in AMD beyond screening, and drug or laser treatments,3 will become increasingly important due to ageing demographics and substantial increase in the estimated number of Australians with AMD in the coming years.

Associate Professor Bamini Gopinath is an epidemiologist with the University of Sydney. She currently holds a NHMRC TRIP Fellowship, which aims to implement a dietary behaviour intervention for AMD patients. Her ongoing public health research aims to translate key epidemiological findings into health policy and practice, with the intention of targeting current gaps that exist in Australian healthcare.

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2. Lim,L.S., Mitchell,P., Seddon,J.M., Holz,F.G. & Wong,T.Y. Age-related macular degeneration. Lancet 379, 1728-1738 (2012).

3. Broadhead,G.K., Grigg,J.R., Chang,A.A. & McCluskey,P. Dietary modification and supplementation for the treatment of age-related macular degeneration. Nutr Rev 73, 448-462 (2015).

4. Gopinath,B. et al. Consumption of dairy products and the 15-year incidence of age-related macular degeneration. Br J Nutr 111, 1673-1679 (2014).

5. Gopinath,B., Flood,V.M., Rochtchina,E., Wang,J.J. & Mitchell,P. Homocysteine, folate, vitamin B-12, and 10-y incidence of age-related macular degeneration. Am J Clin Nutr 98, 129-135 (2013).

6. Wang,J.J. et al. Combined Effects of Complement Factor H Genotypes, Fish Consumption, and Inflammatory Markers on Long-Term Risk for Age-related Macular Degeneration in a Cohort. Am J Epidemiol 169, 633-641 (2009).

7. Chew,E.Y. et al. Secondary Analyses of the Effects
of Lutein/Zeaxanthin on Age-Related Macular
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8. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 309, 2005-2015 (2013).

9. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 119, 1417-1436 (2001).

10. Bressler,N.M. et al. Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11. Arch Ophthalmol 121, 1621-1624 (2003).

11. Clemons,T.E., Milton,R.C., Klein,R., Seddon,J.M. & Ferris,F.L., III. Risk factors for the incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19. Ophthalmology 112, 533-539 (2005).

12. The Age-Related Eye Disease Study severity scale for Age-Related Macular Degeneration: AREDS report number 17. Arch Ophthalmol 123, 1484-1498 (2005).

13. A simplified severity scale for Age-Related Macular Degeneration: AREDS report number 18. Arch Ophthalmol 123, 1570-1574 (2005).

14. Age-related Eye Disease Study. About AREDS2. 2011. 5-7-2010.

15. Louie,J.C. et al. Higher regular fat dairy consumption is associated with lower incidence of metabolic syndrome but not type 2 diabetes. Nutr Metab Cardiovasc Dis (2012).

16. Malik,V.S. et al. Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women. Am J Clin Nutr 94, 854-861 (2011).

17. Lamarche,B. Review of the effect of dairy products on non-lipid risk factors for cardiovascular disease. J Am Coll Nutr 27, 741S-746S (2008).

18. van Meijl,L.E. & Mensink,R.P. Low-fat dairy consumption reduces systolic blood pressure, but does not improve other metabolic risk parameters in overweight and obese subjects. Nutr Metab Cardiovasc Dis 21, 355-361 (2011).

19. Guymer,R.H. & Chong,E.W. Modifiable risk factors for age-related macular degeneration. Med J Aust 184, 455-458 (2006).

20. Meyers,K.J. et al. Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration. Ophthalmology 122, 2286-2294 (2015).

21. Gopinath,B. et al. Combined influence of poor health behaviours on the prevalence and 15-year incidence of age-related macular degeneration. Sci Rep 7, 4359 (2017).

22. Mares,J.A. et al. Healthy lifestyles related to subsequent prevalence of age-related macular degeneration. Arch Ophthalmol 129, 470-480 (2011).

23. Gopinath,B., Flood,V.M., Kifley,A., Liew,G. & Mitchell,P. Smoking, Antioxidant Supplementation and Dietary Intakes among Older Adults with Age-Related Macular Degeneration over 10 Years. PLoS ONE 10, e0122548 (2015).

24. Christen,W.G., Glynn,R.J., Chew,E.Y., Albert,C.M. & Manson,J.E. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 169, 335-341 (2009).

25. Gopinath,B. et al. Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls. Br J Ophthalmol (2016).

26. Shah,S.U., Pilli,S., Telander,D.G., Morse,L.S. & Park,S.S. Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations. Can J Ophthalmol 48, 204-209 (2013).

27. Stevens,R., Bartlett,H., Walsh,R. & Cooke,R. Age-related macular degeneration patients’ awareness of nutritional factors. British Journal of Visual Impairment 32, 77-93 (2014).

28. Downie,L.E. & Keller,P.R. The self-reported clinical practice behaviors of Australian optometrists as related to smoking, diet and nutritional supplementation. PLoS ONE 10, e0124533 (2015).