Can food supplements prevent blindness?

Age-related macular degeneration (AMD) is a common eye disease. It affects around 25% of people over the age of 75 in the UK to some extent, and presents with gradual deterioration and distortion of central vision. Although in the early stages most have no symptoms (when the condition is termed age-related maculopathy), late AMD that significantly impairs vision affects 2.4% of people over the age of 65 (Owen, Jarrar, Wormald et al, 2012).

Wet and dry AMD

A detailed review of AMD can be found in a previous issue of InnovAiT (Newsom and Simon, 2008). All patients start with dry (or ‘geographic’) AMD. It is caused by a reduction in blood flow to the macula and release of free radicals. The cells of the macula break down resulting in drusen formation (yellowish lipid deposits – Figure 1). As the number and size of the drusen increase, central vision deteriorates.

Retinal photographs of AMD

Figure 1: Retinal photographs of AMD

 

Wet AMD is much less common than dry AMD but is much more likely to cause blindness. In patients with dry AMD, drusen may lift the retinal pigment epithelium away from its blood supply. New blood vessels then grow from the choroid (choroidal neovascularisation) and these new vessels may bleed forming scars and leading to irreversible loss of central vision.

How can vitamin supplements help?

The Age-Related Eye Disease Study (AREDS) run by the US-based National Eye Institute reported in 2001 (Age Related Eye Disease Study Group, 2001). It involved 4,757 participants aged between 55-80 years, in 11 clinical centres across the US. Participants in the study were given food supplements containing different combinations of antioxidants (500 mg of vitamin C; 400 international units of vitamin E; 15 mg of beta-carotene) and zinc (80mg of zinc oxide and 2mg of copper as cupric oxide to prevent the copper deficiency associated with zinc supplementation). Participants were randomised to one of four treatments:

  • Zinc alone
  • Antioxidants alone
  • A combination of antioxidants and zinc, or
  • A placebo formulation

The trial was double-blinded with neither participants nor investigators knowing which preparation each individual was receiving. The study found that the combination of antioxidants and zinc reduced the risk of developing advanced dry AMD or wet AMD and its accompanying visual loss (odds ratio (OR) 0.72; 99% confidence interval (CI) 0.52-0.98). This equates to a risk reduction of around 20% overall. The risk reduction was most pronounced (up to 30%) for those with more advanced AMD with little or no visual loss, and those who already had advanced dry or wet AMD in one eye (with loss of vision in that eye) but preserved vision in the other eye. This reduction in risk was maintained after 10 years follow up (Chew, Clemons, Agral et al, 2013).

However, there were ongoing concerns that the beta-carotene component of the AREDS formula was associated with an increased risk of lung cancer in smokers and former smokers, and suggestions that other antioxidants might be at least as effective (or even more effective) than those used in the AREDS formula. In addition, the high doses of zinc used in the AREDS formula caused gastrointestinal upset and made the formula unpalatable for some.

In 2006, a new five-year study was started (AREDS2). It explored whether the AREDS formulation could be improved by adding omega-3 fatty acids and/or the carotenoids lutein and zeaxanthin, or by removing beta-carotene and/or reducing zinc content (Age Related Eye Disease Study  2 Research Group, 2013).

Participants were aged 50-85 years and were all at risk for progression to advanced AMD with bilateral large drusen, or large drusen in one eye and advanced AMD in the other eye. In total there were 4203 participants. The study used a double-blinded factorial randomised controlled trial design in which participants were randomised into groups taking:

  • The original AREDS formulation unchanged
  • The original AREDS formulation with no beta-carotene
  • The original AREDS formulation with reduced zinc (25mg), and
  • The original AREDS formulation with no beta-carotene and low zinc.

Within each of these four groups, participants were further randomised into groups taking additional supplements:

  • Lutein 10mg and zeaxanthin 2mg
  • Omega-3 fatty acids (1g)
  • Lutein, zeaxanthin and omega-3 fatty acids, or
  • Placebo.

Analysis of the results from the 16 different treatment groups showed that reducing the dose of zinc did not change the effectiveness of the preparation but did reduce side effects. Addition of omega-3 fatty acids also made no difference to outcomes. Substitution of lutein and zeaxanthin for beta-carotene into the formulation was at least as effective (and up to 18% more effective amongst those with low dietary intake of green.leafy vegetables) without increasing the risk of lung cancer.

What do these studies mean for GPs?

In the GP surgery, patients with AMD usually present with slowly progressive loss of vision. This causes problems with reading and face recognition first and is worse with changes in lighting. A dark patch that rapidly fades may be noticed on waking. This can be interpreted as ‘seeing a shadowy figure’ and be very frightening. With severe visual loss patients may see visual hallucinations, usually of faces or stars. These can also be very frightening and patients may need considerable reassurance.

With the equipment available in the GP surgery, it is often difficult to visualise any changes at the back of the eye in patients with AMD, even if the pupil is dilated. Further slit-lamp assessment (with or without retinal photography if available) may be helpful from a community-based optician.

An Amsler grid (Figure 2) can be a useful test for AMD in the GP surgery. Each eye should be tested separately with the other eye covered. Patients with AMD affecting their vision may find that when fixing their gaze on the dot in the middle of the chart (with reading glasses on if worn), the straight lines appear wavy or missing. The defect can be marked on the chart. Once a diagnosis is established any change in the area of the defect may represent a progression and warrants further assessment by an eye specialist. It is worth finding out what your local referral pathways are.

Amsler Grid

Figure 1: Amsler Grid

Refer any patient with progressive loss of vision with either no obvious cause, or a suspicion of AMD, to ophthalmology for confirmation of diagnosis. Refer urgently if the loss of vision is of recent onset or there is rapid reduction in vision.

Once AMD is confirmed, patients are usually followed up at least annually according to local protocols. However, there is an ongoing role for GPs in their care. Risk factors for development and progression of AMD include age, family history, smoking, hypertension and diet. Whilst age and family history are not modifiable, GPs have a role in:

  • promoting smoking cessation for all patients with AMD
  • helping to control blood pressure to within current national targets
  • promoting a healthy diet rich in green, leafy vegetables and
  • recommending AREDS2 formula antioxidant and zinc supplementation

Of note, it is impossible to obtain the required levels of antixidants and zinc to reduce progression of AMD with diet alone.

Referral for treatment of other coexisting conditions that affect vision (e.g. cataract) can also help. Finally, provision of visual aids, registration of blindness and social support are important for those with significant visual loss.

Conclusion

The AREDS and AREDS2 trials show that dietary factors are important to prevent progression of AMD both in the short and longer term. Several companies are now producing AREDS2 food supplements for patients with AMD to purchase. In addition to control of blood pressure and promotion of smoking cessation, GPs should include dietary advice for patients with AMD whenever they are seen in primary care to eat more green, leafy vegetables, and recommend that they take AREDS2 formulation food supplements, check their vision regularly on the Amsler grid, and report any changes in vision.

References and further information

Age Related Eye Disease Study  2 Research Group (2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. Journal of the American Medical Association 309(19):2005-15.

Age Related Eye Disease Study Group. (2001). 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(10), 1417-36.

Chew EY, Clemons TE, Agron E, Sperduto RD, Sangiovanni JP, Kurinii N, Davis MD; Age Related Eye Disease Study Research Group (2013) Long-Term Effects of Vitamins C, E, Beta-Carotene and Zinc on Age-Related Macular Degeneration. Ophthalmology. DoI: 10.1016/j.ophtha.2013.01.021 (ePub ahead of print)

Newsom R, Simon C (2008) Age-related macular degeneration. InnovAiT (10): 710-713

Owen CG, Jarrar Z, Wormmald R, Cook DG, Fletcher AE, Rudnicka AR (2012). The estimated prevalence and incidence of late stage age related macular degeneration in the UK. British Journal of Ophthalmology 96 (5): 752-6

Simon C, Everett H, van Dorp F, Burkes M (2013). Oxford Handbook of General Practice (4th Edition): Chapter 26: Ophthalmology. Oxford University Press.