AMD: it's inflammation, not age

Failing eyesight has become so closely associated with old age that the
condition has become known as AMD, or 'age-related macular degeneration'.
Around 15 million Americans and four million Britons suffer from the
problem-where the sharpness of our central vision deteriorates-and health
experts now fear that AMD will take on epi-demic proportions once the
baby-boomers reach their 60s and 70s.
AMD comes in two forms-'wet' and 'dry'. The dry type is by far the more
common. This type occurs when photoreceptors in the central part of the eye,
or 'macula', deteriorate and die. In contrast, the wet variety is caused by
abnormal blood-vessel growth, which can lead to blood and protein leakages,
irreversible and rapid vision loss, and even blindness. Also, the dry form
can worsen and become wet.
Because medicine has associated AMD with the ageing process, it hasn't
looked much beyond that for other causes of the condition. This view has
also influenced its treatment. Medicine contends that it has nothing to
offer the sufferer who has dry AMD, and has only recently begun to offer
regular injections of anti-angiogenic drugs designed to reverse blood-vessel
growth in those with the wet form. However, it's a controversial-and
painful-treatment, and only one of the drugs-Lucentis (ranibizumab)-is
approved in the US for wet AMD treatment.
However, doctors are now starting to recommend something called
'photo-dynamic therapy' (PDT), using the light-activated drug Visudyne
(verte-porfin), for some forms of wet AMD. The drug is injected into the
patient's arm and, after a short wait, a laser beam is shone into the
patient's eyes to activate the drug, which is supposed to seal up abnormal
blood vessels and destroy any that are leaking. However, PDT has proved to
be less effective than Lucentis injections in a study of 423 AMD patients
over a two-year period (Ophthalmology, 2009; 116: 57-65.e5).

Possible causes of AMD
While macular degeneration primarily affects older people, there's little
evidence to suggest that ageing is, on its own, the major cause of such
failing eyesight. AMD affects 10 per cent of people aged up to 74 years and,
despite its name, increases to only around a third of those between 75 and
85 years  of age (www.agingeye.net/maculardegen/
maculardegeninformation.php).
Medicine believes that one of its causes could be exposure over the years to
direct sunlight and, especially, to blue-spectrum light. Doctors often
advise older people to wear sunglasses in direct sunlight to lessen their
risk of developing AMD. This advice, however, may have been based on a
series of animal studies that did not properly replicate the human
experience. In a series of laboratory tests, researchers shone intense
ultraviolet light into animals' eyes, which were held open mechanically.
Aside from the fact that these studies amounted to extreme animal cruelty,
the tests also failed to take account of the blinking reflex and the way
that we humans have of avoiding looking directly at the sun.
This idea has also been supported by a Cambridge, UK, study of 446 AMD
sufferers that found that direct sunlight is not a cause (Br J
Ophthal-mology, 2006; 90: 29-32), whereas other studies suggest that, in
fact, sunlight is important for good health. Blue light, in particular,
helps the body to release melatonin, which protects the heart and the eyes
by keeping blood pressure levels low (J Clin Endocrinol Metab, 2003; 88:
4502-5).
Another commonly held belief-that alcohol can cause AMD-may also be
mistaken. A major study involving 4439 people living in Beijing and in rural
areas of China could find no connection between wine- and beer-drinking, and
AMD (Ophthalamology, 2009; August 25, published online ahead of print).
Instead, there's growing evidence to suggest that AMD is more likely to be
the result of a mineral imbalance that is cumulative and so becomes more
apparent as we get older. Low levels of zinc and copper are commonly found
in people with AMD, as one study discovered when it analyzed the health
profiles of 44 subjects with the condition. On average, the subjects' zinc
and copper levels were 24-per-
cent lower than those of the healthy controls. The researchers, from the
Mayo Clinic in Rochester, Minnesota, also pointed out that, as shown by
other studies where supplements were able to slow the progress of AMD, there
appears to be a direct causal link between zinc and copper levels, and
failing eyesight (Am J Ophthalmol, 2009; 147: 276-82.e1).
On the other hand, iron tends to cluster in the retina, and may also play a
role in a broad range of ocular diseases, including AMD (along with
glaucoma, cataract and conditions causing intraocular haemorrhage) because
of iron-induced ocular oxidative damage (Prog Retin Eye Res, 2007; 26:
649-73).
Furthermore, too much lead can cause AMD. One study of 25 AMD patients
discovered that they all had retinal lead levels that were up to 75 per cent
higher than those found in people with healthy eyes (Am J Ophthalmol, 2009;
September 4, published online ahead of print).
A diet that's high in processed foods can also lead to AMD. A survey of more
than 4000 people, carried out by researchers at Tufts University in Boston,
MA, concluded that up to 20 per cent of all cases of AMD could have been
avoided by a diet lower in processed foods such as white bread, cakes and
biscuits (Am J Clin Nutr, 2007; 86: 180-8).
What's more, new breakthrough research suggests that AMD could be an
inflammatory disease brought about by a polymorphism (variation) in the
complement factor H (CFH) gene. Researchers from the US National Eye
Institute (NEI) and the National Cancer Institute (NCI) reckon that the gene
variation could be responsible for half of all cases of AMD. Indeed, people
who carry the polymorphism are nearly six times more likely to develop the
condition (Science, 2005; 308: 385-9).

Possible treatments
If AMD is an inflammatory disease, then high-dose supplements could be an
effective therapy. Vitamin B12 supplements have been successfully used to
reduce the symptoms of other inflammatory conditions such as  bursitis
(Lininger SW Jr et al., The Natural Pharmacy: Complete Home Reference to
Natural Medicine. New York, NY: Three Rivers Press, 1999), and vitamin C, at
high doses, has been proven to have anti-inflammatory properties (Exp Eye
Res, 1986; 42: 211-18). Vitamin E may be especially useful as it is able to
suppress the symptoms of inflammation in specific parts of the body (J
Vitaminol, 1972; 18: 204-9).
Copper and zinc are both strong anti-inflammatories, and AMD sufferers are
usually deficient in both. Inflam-mation requires a higher copper intake to
maintain levels of enzymes that are vital to the body's anti-inflammatory
processes, at least in animal studies (Agents Actions, 1985; 16: 504-13). In
addition, findings in animal (rat) studies showed that zinc is an important
healing agent during inflam-mation (Int J Tissue React, 1981; 3: 73-6). In
clinical studies, zinc was able to help 70 per cent of men suffering from
prostate problems (Bush IM et al., 'Zinc and the Prostate', presentation at
the annual meeting of the American Medical Association, Chicago, 1974).
Supplemental zinc, copper and manganese also reduced the risk of rheumatoid
arthritis in more than 29,000 women aged 55-69 years and followed for 18
years (Am J Epidemiol, 2003; 157: 345-54).
High-dose supplements of zinc and copper, and of vitamins A, C and E-the
usual antioxidants-prevented the progression of AMD in one study. The
researchers, from the Age-Related Eye Disease Study Group in New Zealand,
also found that most people are taking levels of vitamins that are too low
to be effective. Yet, at the correct dosages, any combination of
multivitamins and individual supplements can prevent AMD from worsening (N Z
Med J, 2009; 122: 32-8).
Lutein/zeaxanthin, the carotenoid antioxidants found in dark-green leafy
vegetables such as spinach and kale, are both highly effective in slowing
the progress of AMD. This finding was made when these vegetables were added
to the diets of 4519 study participants, aged 60-80 years (Arch Ophthalmol,
2007; 125: 1225-32).
Bryan Hubbard

Preventing AMD

Age-related macular degeneration (AMD) has features in common with heart
disease, and the many ways of maintaining a healthy cardiovascular system
appear to also apply to eye health.
-    Eat an organic, unprocessed diet that's low in fats, and high in
fruit and vegetables-especially lutein-rich varieties such as kale and
spinach
-    Supplement with zinc and copper every day, and take amounts that are
higher than the recommended daily allowance (RDA)
-    Drink a glass of red wine a day (Am J Ophthalmol, 1995; 120: 190-6)
as, in one study, those who drank one glass a day reduced their risk of AMD
by 20 per cent compared with those who either drank beer or spirits, or were
teetotalers (Lancet, 1995; 351: 117)
-    Don't smoke
-    Supplement with antioxidants A, C and E
-    Eat plenty of tomatoes, as they are rich in lycopene, which helps
ward off AMD (Arch Ophthalmol, 1995; 113: 1518-23)
-    Take vitamins B6 and B12 together with folic acid, as they can
reduce your AMD risk (Arch Intern Med, 2009; 169: 335-41)
-    Taking the antioxidant zeaxanthin can reduce your chances of
developing AMD. Besides supplements, it's also found in foods such as
mangoes, papaya, oranges, peaches, green beans, broccoli, sweet potatoes and
honeydew melon (Am J Clin Nutr, 1995; 62 [6 Suppl]: 1448S-61S). In addition,
the density of the macular pigment can be improved just by adding corn and
spinach to the diet (Invest Ophthalmol Vis Sci, 1997; 38: 1795-801).

Vol. 20 08 November 2009