AREDS (Age-related Eye Disease Study) was a prospective, multicentric, randomised clinical trial conducted between 1992 and 2006, mainly sponsored by the National Eye Institute (NEI) of the National Institutes of Health (NIH).

This study was designed to evaluate the clinical aspects, natural course and risk factors associated with age-related cataract and AMD, as well as the effects of antioxidant vitamins and minerals on these two ocular conditions.

Eligible patients were aged 55-80 by occasion of enrolment 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 photographs 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 intermediate drusen (63 to 124 microns in diameter) or RPE abnormalities.

AREDS category 3 – (Intermediate AMD) – characterised by extensive intermediate drusen, at least one large drusen (>125 microns in diameter) or geographic atrophy not involving the centre of the fovea.

AREDS category 4 – (Advanced/Late AMD) – characterised 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⁾.

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 intermediate 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 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⁾

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 progression of intermediate or advanced AMD to advanced AMD in the fellow eye, corresponding to 25%.

Therefore, a formulation has been proposed⁽¹²⁾:

The Age-related Eye Disease Study 2 (AREDS2), initiated 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 polyunsaturated 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 assess whether forms of the AREDS nutritional supplement with reduced zinc and/or no beta-carotene works as well as the original supplement in reducing the risk of progression to advanced AMD.