2. Characteristics of included trials.
| Study | Type of AMD | Treatment (dose/day) | Treatment duration | Follow‐up | Data on eyes or people | Visual acuity | Progression AMD | Notes |
| AMDSG 1996 | Early AMD | Ocuguard: Beta‐carotene 20,000 IU Vitamin E 200 IU Vitamin C 750 mg Citrus bioflavonoid complex 125 mg Quercitin (bioflavonoid) 50 mg Bilberry extract (bioflavonoid) 5 mg Rutin (bioflavonoid) 50 mg Zinc picolinate 12.5 mg Selenium 50 µg Taurine 100 mg N‐acetyl cysteine 100 mg l‐glutathione 5 mg Vitamin B2 25 mg Chromium 100 µg |
18 months | 18 months | Right and left eyes reported separately | Measured using Snellen chart but reported in logMAR units | Based on Chesapeake Bay grading but using indirect ophthalmoscopy: expressed as an average grade | ‐ |
| AREDS 2001 | AMD and VA 20/32 or better in 1 eye 956/3640 had AMD |
Antioxidants: Vitamin C 500 mg Vitamin E 400 IU Beta‐carotene 15 mg Zinc (zinc oxide) 80 mg Cupric oxide 2 mg Factorial design Antioxidants x zinc |
Average duration 6.3 years | Average follow‐up 6.3 years; 2.4% lost to follow‐up | Person; outcome 'in at least one eye' | Loss of 3 or more lines VA (equivalent to doubling visual angle) measured using ETDRS chart | Progression to advanced AMD: photocoagulation or other treatment for CNV; GA involving centre of the macula, RPE detachment, haemorrhage under the retina, subretinal fibrosis. Colour fundus photography |
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| AREDS2 2013 | bilateral large drusen or non‐foveal geographic atrophy (no advanced AMD) or large drusen or non‐foveal geographic atrophy in one eye and advanced AMD in the fellow eye (AREDS Simple Scale Score of 2, 3 or 4) | lutein 10 mg and zeaxanthin 2 mg (1 tablet/day) Almost all participants in both intervention and comparator groups took AREDS supplement and multivitamin with the study medication. Other study arm: There was another study arm looking at docosahexaenoic acid (DHA) 350 mg and eicosapentaenoic acid (EPA) 650 mg (2 soft‐gel capsules/day); it was not included in this review |
5 years (median) | 5 years (median) | Eyes adjusted for within person correlation | Progression to moderate vision loss using ETDRS charts. | Progression to advanced AMD | ‐ |
| Bartlett 2007 | Soft or hard drusen, and areas of increased or decreased pigment associated with these drusen | Lutein esters 6 mg Retinol 750 mg Vitamin C 250 mg Vitamin E 34 mg Zinc 10 mg Copper 0.5 mg | 9 months | 9 months | Trial eye selected (initial visit only); If both eyes were eligible for inclusion, the right eye was used | Change in logMAR acuity measured using ETDRS chart | Fundus photographs graded using AREDS classification system (4 categories). Mean (SD) grade was reported | ‐ |
| Berrow 2013 | ARM | Ocuvite Duo (Bausch and Lomb) vitamin C 150 mg, cupric oxide 400 µg, vitamin E 15 mg, zinc oxide 20 mg, lutein 12 mg, zeaxanthin 0.6 mg, EPA 240 mg, DHA 840 mg | 40 weeks | 40 weeks and 60 weeks | One eye per participant | NA | NA | ‐ |
| CARMA 2013 | any severity of early AMD in one eye and late AMD (neovascular AMD or central geographic atrophy) in the fellow eye. The study eye was the eye free of late‐stage AMD. | Ocuvite (Bausch and Lomb, Berlin, Germany) lutein 12 mg, zeaxanthin 0.6 mg, vitamin E 15 mg, vitamin C 150 mg, zinc oxide 20 mg, copper 0.4 mg (daily dose) one tablet twice daily | 3 years | every 6 months for 3 years | Mixture of one and two eyes | ETDRS charts (logMAR) | Grading of colour fundus photographs | ‐ |
| CARMIS 2011 | AMD in at least 1 eye having extensive (as measured by drusen area) intermediate (≥ 63 mm, < 125 mm) drusen; and at least one large (≥ 125 mm) drusen or geographic atrophy not involving the centre of the macula | Vitamin C 180 mg Vitamin E 30 mg Zinc 22.5 mg Copper 1 mg Lutein 10 mg Zeaxanthin 1 mg Astaxanthin 4 mg |
24 months | 24 months | The eye with the best VA was selected; when both eyes had the same VA, the right eye was chosen for final analysis | Letters and lines reported as continuous variable (ETDRS chart) | Not reported | ‐ |
| CLEAR 2013 | AMD grade 0 to 4 in one eye (Rotterdam grading) and visual acuity 0.5 or better | Lutein 10 mg | 12 months | 12 months | One eye per participant | Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart at 4 m | Not reported | ‐ |
| Holz 1993 | People with drusen | Zinc sulfate 200 mg | Not stated but assume same as follow‐up duration | 12 to 24 months | Unclear but assumed to be people | Not reported | 'Incidence of new exudative or dry macula lesions' | ‐ |
| Kaiser 1995 | Nonserous AMD | Visaline: Buphenine HCL 1.5 mg Beta‐carotene 10 mg Tocopherol acetate 10 mg Vitamin C 50 mg |
6 months | 6 months | Study eye identified | Decimal acuity measured using a Snellen chart | Not reported | ‐ |
| LISA 2011 | AREDS categories 2, 3, or 4 | Lutein 20 mg a day for 3 months and then lutein 10 mg a day for 3 months | 6 months | 6 months | Study eye identified; if both eyes were eligible, one eye was selected randomly | Reported in graph form, not possible to extract data. Measured using ETDRS chart | Not reported | ‐ |
| Ma 2012 | Early AMD (drusen, pigmentary abnormalities) | Lutein 10mg Lutein 20mg Lutein 10mg and zeaxanthin 10mg |
12 months | 12 months | Unclear how many eyes included | Unclear how measured but reported in logMAR | Not reported | ‐ |
| Newsome 1988 | Drusen or pigmentary change (or both), VA 20/80 or better | Zinc sulfate 200 mg | 12 to 24 months | 12 to 24 months | Reported by eye; also data from 2 eyes averaged | Number of letters lost on EDTRS chart | Difficult to extract data on this. Reported number with increased pigment, drusen and atrophy for 2 observers. In general, found results favouring the zinc‐treated group | ‐ |
| Newsome 2008 | Presence of macular drusen with or without pigment changes | Zinc‐monocysteine 25 mg | 6 months | 6 months | Right and left eyes reported separately | Number of letters read on EDTRS chart | Not reported | ‐ |
| Stur 1996 | Neovascular AMD in 1 eye, VA better than 20/40 in other eye | Zinc sulfate 200 mg | 24 months | 24 months | Study eye, which was fellow eye; other eye had neovascular AMD | Mean logMAR score measured using Bailey‐Lovie chart Note: participants with neovascular event excluded from this outcome |
Incidence of neovascular lesion in study eye | Original trial of N = 500 terminated by sponsor (Astra) because statistical evaluation of first 40 participants at 24 months follow‐up "did not show any treatment benefit" |
| VECAT 2002 | Early AMD (18%) Late AMD (0.5%) Rest presumably had no signs of AMD |
Vitamin E 500 IU | 48 months | 48 months | Worse eye | Loss of more than 9 letters (2 or more lines) on (Bailey‐Lovie chart | Investigators defined 6 stages of AMD progression and defined progression as movement from a lower stage to a higher stage in their worst eye | ‐ |
| Veterans LAST study 2004 | Atrophic AMD and reduced vision | Lutein 10 mg Ocupower: Natural beta‐carotene (Betatenem) 15,000 IU Vitamin C 1500 mg (as calcium ascorbate‐Ester CB) Vitamin D3 400 IU Vitamin E 500 IU (d‐alpha tocopherol succinate) Vitamin B1 50 mg Vitamin B2 10 mg Vitamin B3 70 mg Vitamin B5 50 mg Vitamin B6 50 mg Vitamin B12 500 µg Folic acid 800 µg Biotin 300 µg Calcium 500 mg Magnesium 300 mg Iodine 75 µg Zinc 25 mg (as zinc L‐methionine‐L‐OptiZincB) Copper 1 mg Manganese 2 mg Selenium 200 µg Chromium 200 µg Molybdenum 75 µg Lycopene 600 µg Bilberry extract 160 mg (standardised to 25% anthocyanosides) Alpha lipoic acid 150 mg N‐acetyl cysteine 200 mg Quercetin 100 mg Rutin 100 mg Citrus bioflavonoids 250 mg Plant enzymes 50 mg Black pepper extract 5 mg (BioperineB) Malic acid 325 mg Taurine 900 mg L‐glycine 100 mg L‐glutathione 10 mg Boron 2 mg |
12 months | 12 months | Right and left eyes reported separately | Change in logMAR score. Measured using Snellen chart but reported in logMAR: units | Data not reported | ‐ |
AMD: age‐related macular degeneration CNV: choroidal neovascularisation ETDRS: Early Treatment Diabetic Retinopathy Study GA: geographic atrophy RPE: retinal pigment epithelium VA: visual acuity