Diet, Exercise & Socialising: The Impact on Macular Disease

GREEN LEAFY VEGETABLES, BEETROOT AND EARLY AMD

For many years, patients with signs of AMD have been told to eat plenty of leafy greens – but how much is enough and how do they help? A longitudinal cohort study led by Professor Bamini Gopinath found that dietary nitrate intake from vegetables and non-vegetable sources, had a potential influence on early AMD risk.¹ 

Dietary nitrate, predominantly found in green leafy vegetables and beetroot, is a precursor to nitric oxide, which is released in the body by cells that line blood vessels. In the eye, nitric oxide helps increase blood flow to the retina, which is believed to reduce the risk of AMD.

These findings underscore the importance of ongoing nutritional advice for nAMD patients presenting for treatment

Many processed meats and cheeses are also high in nitrates due to their ability to stabilise food and improve colour. These nitrates have a potential carcinogenic effect.

Prof Gopinath’s study examined 2,856 participants from the Blue Mountains Eye Study conducted from 1992-1994 and 2007-2009.

A semi-quantitative food-frequency questionnaire (FFQ) was used to capture participant’s complete dietary intake and retinal photographs were used to identify the incidence of AMD. Of the original 2,856 participants, 2,037 were re-examined 15 years later and included in incidence analysis.

Adjusting for age, sex, smoking, energy intake, fish consumption, and AMD risk alleles (complement factor H and age-related maculopathy susceptibility-2 single nucleotide polymorphisms), they found those participants who had consumed 120–162mg/day of total nitrate (i.e. in the third tertile of dietary intake) compared to the reference group (≤87mg/day) had a 39% reduced risk of incident early AMD 15 years later. Similarly, participants who consumed 100-142mg per day of total vegetable nitrate (third tertile of dietary intake) compared to the reference group (≤69mg/day) had a 35% reduced risk of developing early AMD at the 15-year follow-up.

No significant associations were observed between total nitrate and vegetable nitrate intake with 15-year incidence of late AMD.

They concluded, “These novel findings could have important implications, if the association between total nitrate intake and vegetable nitrate intake and 15-year incidence of early AMD is confirmed in other observational or intervention studies”.

EGGS AND LATE STAGE AMD

We know eggs are a naturally rich source of lutein and zeaxanthin – bioavailable carotenoids that are associated with reduced risk of advanced AMD.² But how many eggs should a person with AMD eat each week to reduce the risk of progression to an advanced state?

With this question top of mind, Prof Gopinath and her team set to work, finding that moderate consumption of eggs significantly reduced the risk of developing incident late-stage AMD over 15 years.³ 

Their research involved a cohort of 3,654 participants aged 49+, of whom 2,034 participants had complete information on baseline egg consumption. As in the nitrate study, they were assessed using a semi-quantitative FFQ, and AMD signs over 15 years were measured using retinal photographs.

The researchers summarised total egg consumption as follows:

• One or less eggs per week (reference group);
• Two to four eggs per week;
• Five to six eggs per week; and
• One or more eggs per day.

Results 

At baseline, participants who consumed two to four eggs per week had reduced risk of incident late-stage AMD after 15 years compared to the reference group, and a 62% reduced risk of developing neovascular AMD (nAMD).

Among those whose AMD onset was at or before the 10-year follow-up, consumption of two to four, and five to six eggs per week was associated with 54% and 65% reduced risk of incident late AMD, respectively.

When analysed as a dichotomised variable, participants who consumed more than one egg per week vs one or less eggs per week at baseline, had 46% reduced risk of developing late-stage AMD 15 years later. Non-significant associations were observed between egg consumption and incident early AMD.

BERRIES AND nAMD

While there has been plenty of research looking into the impact of dietary intervention on reducing the progression from early to late AMD, less research has been focussed on how dietary intervention can influence the disease state of patients diagnosed with nAMD.

One study looked at the influence of blueberries, known to be a rich source of antioxidant flavonoids, dietary fibre, trace elements, and vitamins. While blueberry supplementation has reportedly improved ocular health and offset macular degeneration, a study by Vihayan et al,⁴ added weight to their value, finding an association with better long-term treatment outcomes in nAMD patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy.

This longitudinal study recruited 547 participants with nAMD at baseline, 494 of whom were followed-up after receiving 12 months of anti-VEGF therapy.

Baseline dietary intake of flavonoids was determined using a validated FFQ and at follow-up the presence of intra-retinal and sub-retinal fluid (IRF and SRF), retinal pigment epithelium detachment and measurements for central macular thickness were recorded from optical coherence tomography scans. Visual acuity was also documented using LogMAR charts.

The researchers found that higher intakes of dietary flavonoids, specifically flavonols and flavan-3-ols, could be associated with better long-term treatment outcomes in nAMD patients receiving anti-VEGF therapy. While suggesting this could lead to new therapeutic approaches to the treatment of nAMD, they acknowledged the need for interventional studies.

ZINC AND nAMD

A cross-sectional study of 547 participants with nAMD by Detaram et al, published in European Journal of Nutrition,⁵ found low dietary zinc intake was associated with a greater likelihood of subretinal fluid presence, particularly in those treated for at least six months, as well as increased macular thickness in treated eyes with nAMD.

Another study by the same author6 aimed to determine whether dietary intake high in antioxidants and zinc – fruits, vegetables and fish – was associated with favourable clinical outcomes in patients with nAMD undergoing anti-VEGF therapy.

The author concluded a higher intake of dietary zinc was associated with a reduced likelihood of SRF at one year. Conversely, a higher intake of dietary β-carotene was associated with an increased risk of intraretinal fluid and pigment epithelium detachment.

Detaram observed, “These findings underscore the importance of ongoing nutritional advice for nAMD patients presenting for treatment”.

HOW CAN WE MAKE A DIFFERENCE?

Studies show that people with AMD have worse diets, are less physically active, and suffer higher rates of depression than those without the disease. The importance of understanding the diet of patients with AMD, and offering them advice on nutrition as well as exercise and social interaction, has been highlighted by Diana Tang, a Postdoctoral Research Fellow at Macquarie University (Sydney).

Dr Tang and colleagues undertook a study⁷ to evaluate the clinical use of a novel, short dietary questionnaire (SDQAMD) to screen for inadequate food intake in AMD patients by comparing it against a validated FFQ.

One hundred and fifty five participants, (57% female, aged 78 Å} 8 years; control: 78, intervention: 77), recruited from Sydney-based private eye clinics and research databases completed the questionnaires which had a scoring criteria based on the Australian Dietary Guidelines and published dietary recommendations for AMD. The researchers found potential for the SDQAMD as a diet screening tool for clinical use, but acknowledged further studies were required for its validation.

Additionally, Dr Tang reported on telephone-delivered counselling to improve dietary behaviours. The same AMD patients were randomised with one group receiving four monthly calls with a dietitian and access to an evidence-based nutrition resource. The intervention group repeated the SDQ-AMD and completed a feedback form immediately following the dietary intervention.

Dr Tang reported statistical analyses included t-tests and McNemar’s test. Intervention participants reported satisfaction with the tailored phone calls, nutrition resource and education provided. While there was no statistically significant difference between study arms in the proportion of participants meeting the dietary goals, nor in mean intake of total vegetables (primary outcome) and other key food groups; there was a significantly higher intake of nuts (secondary outcome) (3.96 Å} 0.51 vs. 2.71 Å} 0.32; p = 0.04) among participants in the intervention versus control group.

The intervention arm had also increased consumption of dark green leafy vegetables and legumes and decreased consumption of sweets and processed/prepared foods.

Participants found the intervention “acceptable”, leading Dr Tang to conclude that, “This type of intervention… has the potential to provide people with AMD the needed support for improving their nutrition knowledge and dietary practices, especially if continued over a longer period”.

With support of AU$45,466 from a Macular Disease Foundation Australia research grant, Dr Tang is now undertaking a one-year project to assess the effectiveness of a program that encourages people with AMD to socialise, practise home-based exercises to prevent injuries, and access nutrition advice.⁸

Known as MINGLE – Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly; the participants will be involved in a 10-week interventional program delivered via Zoom (due to COVID-19).

Recruitment to participate in MINGLE is currently ongoing. To express interest in participating in the study or for more information, Dr Tang can be contacted via email at [email protected]. The results for the MINGLE study are expected in 2023.

References 

1. Gopinath, B., Liew, G., Kifley, A., Lewis, J. R., Bondonno, C., Joachim, N., Hodgson, J. M., & Mitchell, P. (2018). Association of dietary nitrate intake with the 15-year incidence of age-related macular degeneration. Journal of the Academy of Nutrition and Dietetics, 118(12), 2311- 2314. https://doi.org/10.1016/j.jand.2018.07.012
2. Juan Wu, MS, Eunyoung Cho, ScD, Walter C. Willett, MD, MPH, DrPH, Srinivas M. Sastry, MD, MPH, and Debra A. Schaumberg, ScD, OD, MPH. Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up. JAMA Ophthalmol. 2015 Dec; 133(12): 1415–1424. doi: 10.1001/jamaophthalmol.2015.3590) 
3. Bamini Gopinath*, Gerald Liew, Diana Tang, George Burlutsky, Victoria M. Flood, Paul Mitchell. Consumption of eggs and the 15-year incidence of age-related macular degeneration. 
4. Vijayan, R. K., Essa, M. M., Al-Rawahi, A. S., Guillemin, G. J., Selvaraju, S., & Memon, M. A. (2013). Blueberries and health benefits. In M. M. Essa, & M. A. Memon (Eds.), Food as medicine (pp. 17-35). (Food science and technology). Nova Science Publishers. 
5. Detaram, H. D., Liew, G., Lewis, J. R., Bondonno, N. P., Bondonno, C. P., Van Vu, K., Burlutsky, G., Hodgson, J. M., Mitchell, P., & Gopinath, B. (2021). Dietary flavonoids are associated with longitudinal treatment outcomes in neovascular age-related macular degeneration. European Journal of Nutrition, 60(8), 4243-4250. doi.org/10.1007/ s00394-021-02582-4 
6. Detaram, H. D., Mitchell, P., Russell, J., Burlutsky, G., Liew, G., & Gopinath, B. (2020). Dietary zinc intake is associated with macular fluid in neovascular age-related macular degeneration. Clinical and Experimental Ophthalmology, 48(1), 61-68. https://doi.org/10.1111/ceo.13644
7. Tang, D., Mitchell, P., Liew, G., Burlutsky, G., Flood, V., & Gopinath, B. (2019). Evaluation of a novel tool for screening inadequate food intake in age-related macular degeneration patients. Nutrients, 11(12), [3031]. doi. org/10.3390/nu11123031 
8. Tang, D., Mitchell, P., Liew, G., Burlutsky, G., Flood, V. M., & Gopinath, B. (2020). Telephone-delivered dietary intervention in patients with age-related macular degeneration: 3-month post-intervention findings of a randomised controlled trial. Nutrients, 12(10), [3083]. doi. org/10.3390/nu12103083