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scale (0-4) according to which the approximate 5-year
risk of developing advanced AMD in at least one eye
increases as follows
(11)
:
Stage 0 (zero factors) – 0.5% in five years
Stage 1 (one factor) – 3% in five years
Stage 2 (two factors) – 12% in five years
Stage 3 (three factors) – 25% in five years
Stage 4 (four factors) – 50% in five years
(11)
2.1.3 Results
AREDS results show an overall beneficial effect for high
doses of antioxidant vitamin (vitamins C, E and beta-
carotene) and zinc supplements in reducing the progres-
sion of intermediate or advanced AMD to advanced
AMD in the fellow eye, corresponding to 25%.
Therefore, a formulation has been proposed
(12)
:
2.1.3.1 AREDS 1 formulation:
Antioxidant vitamins – 500 mg of vitamin C;
400 IU of vitamin E
15 mg of beta-carotene
80 mg of zinc oxide and 2 mg of cupric oxide
This formulation has been shown to reduce the risk of
developing advanced AMD and the associated visual loss
by as much as 25%, over 5 years, in individuals with
moderate to high risk of age-related macular degenera-
tion (AREDS categories 3 and 4).
These findings were accompanied by a 19% reduction
in the risk of moderate vision loss (loss of three or more
lines on the visual acuity chart), at 5 years
(13)
.
However, this formulation is not recommended for
smokers, since beta-carotene has been shown to increase
the risk of lung cancer
(14,15)
.
2.2 AREDS 2
The Age-related Eye Disease Study 2 (AREDS2), initi-
ated in 2006 and still in course, enrolled 4000 patients
with non-neovascular AMD consisting of large drusen
in both eyes or advanced AMD in one eye and large
drusen in the fellow eye (AREDS categories 3 and 4).
The aim of this study is to evaluate the effect of dietary
supplements – xanthophylls (10 mg of lutein and 2 mg
of zeaxanthin) and/or long-chain omega-3 polyunsatu-
rated fatty acids (1 g of docosahexaenoic acid [DHA]
and eicosapentaenoic acid [EPA]) – on the progression
to advanced AMD. An additional goal of the study is to
of antioxidant vitamins and minerals on these two ocular
conditions.
Eligible patients were aged 55-80 by occasion of enrol-
ment and required to be free of any illness or condition that
would make long-term follow-up or compliance with study
medications unlikely or difficult. Participants were placed in
one of several
AMD categories
according to fundus pho-
tographs graded by a central reading centre, best corrected
visual acuity and ophthalmic examination
(10)
:
AREDS category 1
– (No AMD) – this was the AREDS
control group, consisting of patients with no or a few
small drusen (<63 microns in diameter).
AREDS category 2
– (Early AMD) – characterised by
a combination of multiple small drusen, a few interme-
diate drusen (63 to 124 microns in diameter) or RPE
abnormalities.
AREDS category 3
– (Intermediate AMD) – character-
ised by extensive intermediate drusen, at least one large
drusen (>125 microns in diameter) or geographic atro-
phy not involving the centre of the fovea.
AREDS category 4
– (Advanced/Late AMD) – charac-
terised by one or more of the following (in the absence of
other causes), in one eye:
Geographic atrophy of the RPE and choriocapillaris,
including the centre of the fovea
Neovascular maculopathies, such as the following:
Choroidal neovascularization (CNV)
Serous and/or haemorrhagic detachment of the sensory
retina or the RPE
Hard exudates in the retina
Subretinal and sub-RPE fibrovascular proliferation
Disciform scar
(10)
.
2.1.2 Risk factors and categories
AREDS Report no. 18 described a simplified clinical
scale that defines risk categories for the development of
advanced AMD.
The grading system described assigns one risk factor to
each eye for the presence of one or more large drusen
(125 microns) and one risk factor for the presence of any
pigment abnormality.
If no large drusen are present, the presence of interme-
diate drusen in both eyes is counted as one risk factor.
Advanced AMD in one eye is counted as two risk factors;
if this is observed together with large drusen and hypo/
hyperpigmentary changes in the RPE, four risk factors
are considered, which corresponds to the highest risk
level for patients with AMD.
Risk factors are added for both eyes, leading to a 5-stage
