The study requires recruitment of people with and without age-related macular disease. Recruitment methods employed include sending information to Birmingham optometrists, ophthalmologists, and a specialist centre for rehabilitation of people with sight loss, an editorial in the Birmingham Evening Mail, recruitment e-mails sent to the Royal National Institute for the Blind (RNIB) and all staff and students at Aston University and Aston Science Park. A project website has also been developed at http://www.aston.ac.uk/lhs/research/nri/opo/amd. Data collection takes place in a standard consulting room at Aston University. Enrolment, randomisation, and data collection are carried out by HB. HB and FE are masked to group assignment. HB is a research optometrist and FE is an optometrist and lecturer at Aston University, Birmingham, UK.
For inclusion participants a) have to provide written informed consent, b) have to be available for three visits to Aston University, c) have to present with no ocular pathology in one eye, or no ocular pathology other than dry AMD in one eye. A cataract grading system consisting of grades one, two and three for each of cortical, nuclear, and posterior subcapsular cataracts has been developed. Participants presenting with lens opacities precluding fundus photography are excluded. Throughout the trial period, progression of any type of cataract to the successive grade will require the participant to withdraw.
Exclusion criteria include type I and II diabetes because vitamin E has been shown to affect glucose tolerance [78–82] and diabetic retinopathy may confound the results. Those taking Warfarin medication are excluded as zinc may decrease its absorption and activity , as are those who use nutritional supplements that potentially raise vitamin and mineral intake above safe limits. The most recent guidelines for upper limits of nutritional supplementation are set out in the UK Food Standards Agency report . Neovascular AMD and other ocular disease that could potentially interfere with the results are excluded.
The study formulation and placebo tablets have been produced by Quest Vitamins Ltd, Aston Science Park, Birmingham, B7 4AP, and are identical in external and internal appearance, and taste. The manufacturer has allocated distinguishing symbols, μ and λ. The tablets are packaged in identical, sealed, white containers; the only difference being the symbol on the label. Investigators and participants do not know which symbol represents the placebo tablets, and which represents the active formulation.
The study formulation contains the following:
Lutein 6 mg
Vitamin A 750 μg
Vitamin C 250 mg
Vitamin E 34 mg
Zinc 10 mg
Copper 0.5 mg
Participants in both groups are instructed to take one tablet, at the same time every day, with food.
The random number generator function in Microsoft Excel is being used to allocate participants to μ and λ groups. Odd numbers allocate to the μ group.
On application, participants complete a health questionnaire, a food frequency questionnaire, and a food diary. The health questionnaire provides information about general health, medication, nutritional supplementation, smoking history, ocular health, and time spent living abroad. The food questionnaire and diary ask for information about diet for analysis using Foodbase 2000 software (The Institute of Brain Chemistry and Human Nutrition, London N7 8DB).
The investigation of several measures of visual function is required, as age-related macular disease can produce varying signs and symptoms.
Distance and near visual acuity (VA) measured using Bailey-Lovie logMAR charts. LogMAR charts have 5 letters and 0.1 log MAR progression per line. The advantage of using these charts is that they provide an equal-interval scale, and there are five letters per line. Standard Snellen charts do not provide a linear scale and have a decreasing number of letters per line as the letter size increases.
Contrast sensitivity (CS) is measured using a Pelli-Robson chart (Clement Clarke International, Edinburgh Way, Harlow, Essex, CM20 2TT, UK) and provides additional information about vision. The Pelli-Robson chart determines the contrast required to read large letters and is designed to test mid- to low-spatial frequencies. Some people may have normal visual acuity, but reduced contrast sensitivity at low spatial frequencies, particularly if they suffer from ocular pathologies such as age-related macular disease.
Colour vision measured using the PV-16 quantitative colour vision test (Precision Vision Inc, 944 First Street, La Salle, IL, 61301, USA). Macular disease can cause a deficiency in blue-yellow colour vision as the short-wavelength photoreceptors are concentrated around the fovea.
Macular Mapping Test
Macular Mapping (MM) test (The Smith-Kettlewell Research Institute, 2318 Fillmore Street, San Francisco, CA, 94115, USA) was developed to map visual defects caused by macular disease. It was developed by MacKeben and Colenbrander  and differs from conventional field analysis in that the stimuli are single letters rather than spots of light. This is a novel piece of equipment and each participant is given a practice run to eliminate learning effects. At the end of the test a single figure score is presented.
Eger Macular Stressometer (EMS) (Gulden Ophthalmics, Elkins Park, PA 19027) is used to assess glare recovery, also known as photostress recovery time (PSRT). This is the time taken for the regeneration of photopigments in bleached photoreceptors to a level that allows resolution of, for example, a letter at near. Resynthesis of the photopigments is dependent upon the integrity of the photoreceptors and RPE ; it follows that the PSRT may be extended in those with diseases affecting these structures. This is a novel piece of equipment and each participant is given a practice run to eliminate learning effects.
Fundus photographs of the macular will be assessed using colour and edge analysis software.
Data collection will take place at baseline, nine, and 18 months.
For each outcome measure the change between baseline, nine month, and 18 month values will be calculated. A Student's t test will be used to determine whether the means of these values differ at the 5% significance level between the placebo and active formulation results for age-related macular disease participants, and normal participants, after differences in age, gender and diet have been taken into account.
From initial data collection we have calculated the treatment group sizes required in order to have 80% power at the 5% significance level for VA, CS, MM test, and the EMS. These values suggest that a total of 63 normal, and 96 age-related macular disease participants are required.
The study has been approved by the Aston University Human Sciences Ethical Committee. The tenets of the Declaration of Helsinki are being followed .