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Review
. 2023 Sep 13;9(9):CD000254.
doi: 10.1002/14651858.CD000254.pub5.

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

Jennifer R Evans  1 , John G Lawrenson  2
Affiliations
Review

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

Jennifer R Evans et al. Cochrane Database Syst Rev. .

Abstract

Background: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review.

Objectives: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD.

Search methods: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022.

Selection criteria: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD.

Data collection and analysis: We used standard methods expected by Cochrane.

Main results: We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers.

Authors' conclusions: Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.

Trial registration: ClinicalTrials.gov NCT00345176 NCT00879671 NCT00763659 NCT01048476 NCT00893724 NCT02264938 NCT00006202 NCT00563979 NCT00306488 NCT00564902 NCT01694680 NCT02625376 NCT03845582.

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Conflict of interest statement

JE and JGL: none known

Figures

1
1
PRISMA study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: Antioxidant multivitamin and mineral supplement versus placebo or no treatment, Outcome 1: Progression to late AMD (neovascular AMD and/or geographic atrophy)
1.2
1.2. Analysis
Comparison 1: Antioxidant multivitamin and mineral supplement versus placebo or no treatment, Outcome 2: Progression to neovascular AMD
1.3
1.3. Analysis
Comparison 1: Antioxidant multivitamin and mineral supplement versus placebo or no treatment, Outcome 3: Progression to geographic atrophy
1.4
1.4. Analysis
Comparison 1: Antioxidant multivitamin and mineral supplement versus placebo or no treatment, Outcome 4: Progression to visual loss (loss of 3 or more lines on logMAR chart)
1.5
1.5. Analysis
Comparison 1: Antioxidant multivitamin and mineral supplement versus placebo or no treatment, Outcome 5: Mean visual acuity
1.6
1.6. Analysis
Comparison 1: Antioxidant multivitamin and mineral supplement versus placebo or no treatment, Outcome 6: Quality of life
2.1
2.1. Analysis
Comparison 2: Lutein with or without zeaxanthin versus placebo, Outcome 1: Progression to late AMD (neovascular AMD and/or geographic atrophy)
2.2
2.2. Analysis
Comparison 2: Lutein with or without zeaxanthin versus placebo, Outcome 2: Progression to neovascular AMD
2.3
2.3. Analysis
Comparison 2: Lutein with or without zeaxanthin versus placebo, Outcome 3: Progression to geographic atrophy
2.4
2.4. Analysis
Comparison 2: Lutein with or without zeaxanthin versus placebo, Outcome 4: Progression to visual loss (loss of 3 or more lines on logMAR chart)
2.5
2.5. Analysis
Comparison 2: Lutein with or without zeaxanthin versus placebo, Outcome 5: Distance visual acuity: mean
2.6
2.6. Analysis
Comparison 2: Lutein with or without zeaxanthin versus placebo, Outcome 6: Quality of life
3.1
3.1. Analysis
Comparison 3: Vitamin E versus placebo, Outcome 1: Progression to late AMD (neovascular AMD and/or geographic atrophy
3.2
3.2. Analysis
Comparison 3: Vitamin E versus placebo, Outcome 2: Progression to visual loss (loss of 3 or more lines on logMAR chart)
4.1
4.1. Analysis
Comparison 4: Zinc versus placebo, Outcome 1: Progression to late AMD (neovascular AMD and/or geographic atrophy)
4.2
4.2. Analysis
Comparison 4: Zinc versus placebo, Outcome 2: Progression to neovascular AMD
4.3
4.3. Analysis
Comparison 4: Zinc versus placebo, Outcome 3: Progression to geographic atrophy
4.4
4.4. Analysis
Comparison 4: Zinc versus placebo, Outcome 4: Progression to visual loss (loss of 3 or more lines on logMAR chart)
4.5
4.5. Analysis
Comparison 4: Zinc versus placebo, Outcome 5: Distance visual acuity: mean
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References

References to studies included in this review

AMDSG 1996 {published data only}
    1. Richer S. Multicenter ophthalmic and nutritional age-related macular degeneration study - part 1: design, subjects and procedures. Journal of the American Optometric Association 1996;67(1):12-29. - PubMed
    1. Richer S. Multicenter ophthalmic and nutritional age-related macular degeneration study - part 2: antioxidant intervention and conclusions. Journal of the American Optometry Association 1996;67(1):30-49. - PubMed
AREDS 2001 {published data only}
    1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of Ophthalmology 2001;119(10):1417-36. - PMC - PubMed
    1. Age-Related Eye Disease Study Research Group. The age-related eye disease study (AREDS) system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the age-related eye disease study report no. 6. American Journal of Ophthalmology 2001;132(5):668-81. - PubMed
    1. Chew EY, Clemons TE, Agron E, Sperduto RD, Sangiovanni JP, Davis MD, et al. Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report no. 36. JAMA Ophthalmology 2014;132(3):272-7. - PubMed
    1. Chew EY, Clemons TE, Agron E, Sperduto RD, Sangiovanni JP, Kurinij N, et al. Long-term effects of vitamins C and E, beta-carotene, and zinc on age-related macular degeneration: AREDS report no. 35. Ophthalmology 2013;120(8):1604-11. - PMC - PubMed
    1. Chew EY, Klein ML, Clemons TE, Agron E, Ratnapriya R, Edwards AO, et al. No clinically significant association between CFH and ARMS2 genotypes and response to nutritional supplements: AREDS report number 38. Ophthalmology 2014;121(11):2173-80. - PMC - PubMed
AREDS2 2013 {published data only}
    1. Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, Sangiovanni JP, Danis RP, Ferris FL 3rd, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmology 2014;132(2):142-9. - PMC - PubMed
    1. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013;309(19):2005-15. - PubMed
    1. Awh CC, Zanke B. Treatment response to AREDS components as a function of CFH and ARMS2 risk in patients with AMD. Investigative Ophthalmology and Visual Science 2014;55(13):ARVO E-abstract 2994.
    1. Chew EY, Chiu CY, Agron E, Clemons TE, Asten F, Fan R. Genetic interaction with response to oral micronutrient supplements in the Age-Related Eye Disease Study 2 (AREDS2). Investigative Ophthalmology and Visual Science 2017;58(8):ARVO E-abstract 2985.
    1. Chew EY, Clemons T, SanGiovanni JP, Danis R, Domalpally A, McBee W, AREDS2 Research Group. The age-related eye disease study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology 2012;119(11):2282-9. - PMC - PubMed
Azar 2017 {published data only}
    1. Azar G, Quaranta-El Maftouhi M, Masella JJ, Mauget-Faÿsse M. Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam® 200 pigment module: impact of age-related macular degeneration and lens status. Journal Français d'Ophtalmologie 2017;40(4):303-13. - PubMed
Bartlett 2007 {published data only}
    1. Bartlett H, Eperjesi F. A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology. Nutrition Journal 2003;2:12. - PMC - PubMed
    1. Bartlett HE, Eperjesi F. Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease: a randomized controlled trial. European Journal of Clinical Nutrition 2007;61(9):1121-7. - PubMed
Berrow 2013 {published data only}
    1. Berrow EJ, Bartlett HE, Eperjesi F, Gibson JM. The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy - a randomised controlled trial. British Journal of Nutrition 2013;109(11):2008-14. - PubMed
CARMA 2013 {published data only}
    1. Beatty S, Chakravarthy U, Nolan JM, Muldrew KA, Woodside JV, Denny F, et al. Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration. Ophthalmology 2013;120(3):600-6. - PubMed
    1. Beatty S, Nolan JM, Muldrew KA, Woodside J, Stevenson MR, Chakravarthy U. Visual outcome after antioxidant supplementation. Ophthalmology 2013;120(3):645. - PubMed
    1. Lai Y, Grattan J, Shi Y, Young G, Muldrew A, Chakravarthy U. Functional and morphologic benefits in early detection of neovascular age-related macular degeneration using the preferential hyperacuity perimeter. Retina 2011;31(8):1620-6. - PubMed
    1. Neelam K, Hogg RE, Stevenson MR, Johnston E, Anderson R, Beatty S, et al. Carotenoids and co-antioxidants in age-related maculopathy: design and methods. Ophthalmic Epidemiology 2008;15(6):389-401. - PubMed
CARMIS 2011 {published data only}
    1. Piermarocchi S, Saviano S, Parisi V, Tedeschi M, Panozzo G, Scarpa G, et al. Carotenoids in age-related maculopathy Italian study (CARMIS): two-year results of a randomized study. European Journal of Ophthalmology 2011;22(2):216-25. - PubMed
CLEAR 2013 {published data only}
    1. Murray IJ, Makridaki M, Van der Veen RL, Carden D, Parry NR, Berendschot TT. Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study. Investigative Ophthalmology and Visual Science 2013;54(3):1781-8. - PubMed
    1. Tian Y, Kijlstra A, Van der Veen RL, Makridaki M, Murray IJ, Berendschot TT. The effect of lutein supplementation on blood plasma levels of complement factor D, C5a and C3d. PLoS One 2013;8:e73387. - PMC - PubMed
France 1998 {unpublished data only}
    1. There is no publication for this study.
Garcia‐Layana 2021 {published data only}
    1. Abraldes MJ, Nascimento J, Hernández-Galilea E, Olmedilla-Alonso B, Escobar-Barranco JJ, Zapata MA, et al. A randomized study of nutritional supplementation in patients with unilateral wet age-related macular degeneration. Nutrients 2021;13(4):1253. - PMC - PubMed
Holz 1993 {published data only}
    1. Holz FG, Wolfensberger TJ, Piguet B, Gross-Jendroska M, Arden GB, Bird AC. Oral zinc-therapy in age-related macular degeneration: a double-blind study. German Journal of Ophthalmology 1993;2:391.
Kaiser 1995 {published and unpublished data}
    1. Kaiser HJ, Flammer J, Stumpfig D, Hendrickson P. Visaline in the treatment of age-related macular degeneration: a pilot study. Ophthalmologica 1995;209(6):302-5. - PubMed
LAST 2004 {published data only}
    1. Richer S, Devenport J, Lang JC. LAST II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. Optometry 2007;78(5):213-9. - PubMed
    1. Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (lutein antioxidant supplementation trial). Optometry 2004;75(4):216-30. - PubMed
Li 2017 {published data only}
    1. Li C, Ren W, Sui YJ. Effect of lutein intervention on visual function in patients with early age-related macular degeneration. International Eye Science 2017;17(11):2109-11.
Li 2018 {published data only}
    1. Li S, Liu N, Lin L, Sun ED, Li JD, Li PK. Macular pigment and serum zeaxanthin levels with Goji berry supplement in early age-related macular degeneration. International Journal of Ophthalmology 2018;11(6):970-5. - PMC - PubMed
LISA 2011 {published data only}
    1. Schmetterer L, Weigert G, Kaya S, Werkmeister R, Gahofer G. Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. European Journal of Ophthalmology 2013;23(4):605. - PubMed
    1. Schmidl D, Weigert G, Kaya S, Pemp B, Sacu S, Lasta M, et al. How lutein supplementation affects macular pigment optical density and visual acuity in patients with age related macular degeneration. In: Joint Annual Meeting of the German, Swiss, and Austrian Societies for Clinical Pharmacology and Toxicology; 2011 Oct 20-22; Zurich, Switzerland. British Journal of Clinical Pharmacology, 2011.
    1. Weigert G, Kaya S, Pemp B, Sacu S, Lasta M, Werkmeister RM, et al. Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. Investigative Ophthalmology and Visual Science 2011;52(11):8174-8. - PubMed
LUTEGA 2013 {published data only}
    1. Arnold C, Winter L, Frohlich K, Jentsch S, Dawczynski J, Jahreis G, et al. Macular xanthophylls and omega-3 long-chain polyunsaturated fatty acids in age-related macular degeneration: a randomized trial. JAMA Ophthalmology 2013;131(5):564-72. - PubMed
    1. Dawczynski J, Jentsch S, Schweitzer D, Hammer M, Lang GE, Strobel J. Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study. Graefes Archive for Clinical and Experimental Ophthalmology 2013;251(12):2711-23. - PubMed
    1. Dawczynski J, Jentsch S, Schweitzer D, Hammer M, Strobel J. Changes of macular pigment and drusen morphology in patients with lutein supplementation [Anderung von makulapigment und drusenmorphologie unter luteinsupplementation]. Klinische Monatsblatter fur Augenheilkunde 2012;229(1):69-71. - PubMed
Ma 2012 {published data only}
    1. Huang YM, Dou HL, Huang FF, Xu XR, Zou ZY, Lin XM. Effect of supplemental lutein and zeaxanthin on serum, macular pigmentation, and visual performance in patients with early age-related macular degeneration. Biomed Research International 2015;2015:564738. - PMC - PubMed
    1. Huang YM, Dou HL, Huang FF, Xu XR, Zou ZY, Lu XR, et al. Changes following supplementation with lutein and zeaxanthin in retinal function in eyes with early age-related macular degeneration: a randomised, double-blind, placebo-controlled trial. British Journal of Ophthalmology 2015;99(3):371-5. - PubMed
    1. Huang YM, Yan SF, Ma L, Zou ZY, Xu XR, Dou HL, et al. Serum and macular responses to multiple xanthophyll supplements in patients with early age-related macular degeneration. Nutrition 2013;29(2):387-92. - PubMed
    1. Ma L, Dou HL, Huang YM, Lu XR, Xu XR, Qian F, et al. Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. American Journal of Ophthalmology 2012;154(4):625-34. - PubMed
    1. Ma L, Yan SF, Huang YM, Lu XR, Qian F, Pang HL, et al. Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration. Ophthalmology 2012;119(11):2290-7. - PubMed
Newsome 1988 {published data only}
    1. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral zinc in macular degeneration. Archives of Ophthalmology 1988;106(2):192-8. - PubMed
Newsome 2008 {published data only}
    1. Newsome DA. A randomized, prospective, placebo-controlled clinical trial of a novel zinc-monocysteine compound in age-related macular degeneration. Current Eye Research 2008;33(7):591-8. - PubMed
Parravano 2019 {published data only}
    1. Parravano M, Tedeschi M, Manca D, Costanzo E, Di Renzo A, Giorno P, et al. Effects of Macuprev® supplementation in age-related macular degeneration: a double-blind randomized morpho-functional study along 6 months of follow-up. Advances in Therapy 2019;36(9):2493-505. - PMC - PubMed
Piatti 2020 {published data only}
    1. Piatti A, Croce A, Mazzacane D, Traina G, Ambrosino L, Boni L, et al. Effect of 2-year nutritional supplementation on progression of age-related macular degeneration. European Journal of Ophthalmology 2020;30(2):376-81. - PubMed
Stur 1996 {published data only}
    1. Stur M, Tittl M, Reitner A, Meisinger V. Oral zinc and the second eye in age-related macular degeneration. Investigative Ophthalmology and Visual Science 1996;37(7):1225-35. - PubMed
VECAT 2002 {published data only}
    1. Garrett SK, McNeil JJ, Silagy C, Sinclair M, Thomas AP, Robman LD, et al. Methodology of the VECAT study: vitamin E intervention in cataract and age-related maculopathy. Ophthalmic Epidemiology 1999;6(3):195-208. - PubMed
    1. Garrett SK, Thomas AP, Cicuttini F, Silagy C, Taylor HR, McNeil JJ. Community-based recruitment strategies for a longitudinal interventional study: the VECAT experience. Journal of Clinical Epidemiology 2000;53(5):541-8. - PubMed
    1. Robman LD, Tikellis G, Garrett SK, Harper CA, McNeil JJ, Taylor HR, et al. Baseline ophthalmic findings in the vitamin E, cataract and age-related maculopathy (VECAT) study. Australian and New Zealand Journal of Ophthalmology 1999;27(6):410-6. - PubMed
    1. Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ. Vitamin E supplementation and age-related maculopathy. Investigative Ophthalmology and Visual Science 2001;42:S311.
    1. Tikellis G, Robman LD, Harper CA, Garrett SK, McNeil JJ, Taylor HR, et al. The VECAT study: methodology and statistical power for measurement of age-related macular features. Vitamin E, cataract, and age-related maculopathy study. Ophthalmic Epidemiology 1999;6(3):181-94. - PubMed
Wang 2004 {published data only}
    1. Wang H, Li RX, Wang MF. Effects of zinc and antioxidant on visual function of patients with age-related macular degeneration. Zhongguo Linchuant Kangfu 2004;8:1290-1.

References to studies excluded from this review

Akuffo 2015 {published data only}
    1. Akuffo KO, Nolan JM, Howard AN, Moran R, Stack J, Klein R, et al. Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration. Eye 2015;29(7):902-12. - PMC - PubMed
Anonymous 2015 {published data only}
    1. Anonymous. Eye health: the role of nutritional supplements in reducing the risk and progression of age-related macular degeneration. Australian Journal of Pharmacy 2015;96(1139):60-2.
Bahrami 2006 {published data only}
    1. Bahrami H, Melia M, Dagnelie G. Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial. BMC Ophthalmology 2006;6:23. - PMC - PubMed
Barakat 2006 {published data only}
    1. Barakat MR, Metelitsina TI, DuPont JC, Grunwald JE. Effect of niacin on retinal vascular diameter in patients with age-related macular degeneration. Current Eye Research 2006;31(7-8):629-34. - PubMed
Benzie 2006 {published data only}
    1. Benzie IF, Chung WY, Wang J, Richelle M, Bucheli P. Enhanced bioavailability of zeaxanthin in a milk-based formulation of wolfberry (Gou Qi Zi; Fructus barbarum L). British Journal of Nutrition 2006;96(1):154-60. - PubMed
Berendschot 2015 {published data only}
    1. Berendschot TT, Van Der Made S, Kelly ER, Plat J, Kijlstra A. Consuming a buttermilk drink containing lutein-enriched egg-yolk daily for 1 year improves macular pigment optical density and visual acuity in subjects with early signs of age-related macular degeneration. Investigative Ophthalmology and Visual Science 2015;56(7):ARVO E-abstract 5135.
Bone 2007 {published data only}
    1. Bone RA, Landrum JT, Cao Y, Howard AN, Alvarez-Calderon F. Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin. Nutrition and Metabolism 2007;4:12. - PMC - PubMed
Broadhead 2019 {published data only}
    1. Broadhead GK, Grigg JR, McCluskey P, Hong T, Schlub TE, Chang AA. Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial. Graefe's Archive for Clinical and Experimental Ophthalmology 2019;257(1):31-40. - PubMed
Cangemi 2007 {published data only}57556290
    1. Cangemi FE. TOZAL Study: an open case control study of an oral antioxidant and omega-3 supplement for dry AMD. BMC Ophthalmology 2007;7:3. - PMC - PubMed
Christen 2007 {published data only}
    1. Christen WG, Manson JE, Glynn RJ, Gaziano JM, Chew EY, Buring JE, et al. Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians. Archives of Ophthalmology 2007;125(3):333-9. - PMC - PubMed
Connolly 2011 {published data only}ISRCTN60816411
    1. Connolly EE, Beatty S, Loughman J, Howard AN, Louw MS, Nolan JM. Supplementation with all three macular carotenoids: response, stability, and safety. Investigative Ophthalmology and Visual Science 2011;52(12):9207-17. - PubMed
CREST 2014 {published data only}
    1. Akuffo KO, Beatty S, Stack J, Dennison J, O'Regan S, Meagher KA, et al. Central retinal enrichment supplementation trials (CREST): design and methodology of the CREST randomized controlled trials. Ophthalmic Epidemiology 2014;21(2):111-23. - PMC - PubMed
Cumurcu 2006 {published data only}
    1. Cumurcu T, Mendil D, Etikan I. Serum zinc and copper level in age-related macular degeneration. Trace Elements and Electrolytes 2006;23(2):103-7.
EXIT 2017 {published data only}25867083
    1. Kelly D, Nolan JM, Howard AN, Stack J, Akuffo KO, Moran R, et al. Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT). British Journal of Nutrition 2017;117(1):108-23. - PMC - PubMed
Falsini 2010 {published data only}
    1. Falsini B, Piccardi M, Minnella A, Savastano C, Capoluonga E, Fadda A, et al. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Investigative Ophthalmology and Visual Science 2010;51(12):6118-24. - PubMed
Franciose 2006 {published data only}
    1. Franciose JL, Askew EW, Lang JC, Bernstein PS. Serum and macular responses to antioxidant supplementation versus a carotenoid-rich dietary intervention in the elderly. Current Topics in Nutraceuticals Research 2006;4(1):69-78.
Goodrow 2006 {published data only}
    1. Goodrow EF, Wilson TA, Houde SC, Vishwanathan R, Scollin PA, Handelman G, et al. Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. Journal of Nutrition 2006;136(10):2519-24. - PubMed
ISRCTN35481392 {published data only}35481392
    1. ISRCTN35481392. Macular pigment and its contribution to visual performance and comfort. controlled-trials.com/ISRCTN35481392 (first received 24 July 2008).
ISRCTN81595685 {published data only}81595685
    1. ISRCTN81595685. Comparison of macular and serum responses after supplementation with two different macular carotenoid formulations. controlled-trials.com/ISRCTN81595685 (first received 27 August 2009).
JPRN‐UMIN000027962 {published data only}
    1. JPRN-UMIN000027962. Randomized parallel-group trial of lutein supplementation for macular pigment optical density and visual function in the patients with unilateral age-related macular degeneration. www.who.int/trialsearch/Trial2.aspx?TrialID=JPRN-UMIN000027962 (first posted 28 June 2017).
Kamburoglu 2006 {published data only}
    1. Kamburoglu G, Gumus K, Kadayifcilar S, Eldem B. Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration. Graefe's Archive for Clinical and Experimental Ophthalmology 2006;244(5):565-9. - PubMed
Kolber 2013 {published data only}
    1. Kolber MR, Tennant M, Nickonchuk T. Vitamins for age-related macular degeneration demonstrate minimal differences. Canadian Family Physician 2013;59(5):503. - PMC - PubMed
Kopsell 2006 {published data only}
    1. Kopsell DA, Lefsrud MG, Kopsell DE, Wenzel AJ, Gerweck C, Curran-Celentano J. Spinach cultigen variation for tissue carotenoid concentrations influences human serum carotenoid levels and macular pigment optical density following a 12-week dietary intervention. Journal of Agricultural and Food Chemistry 2006;54(21):7998-8005. - PubMed
Landrum 2012 {published data only}
    1. Landrum J, Bone R, Mendez V, Valenciaga A, Babino D. Comparison of dietary supplementation with lutein diacetate and lutein: a pilot study of the effects on serum and macular pigment. Acta Biochimica Polonica 2012;59(1):167-9. - PubMed
Lim 2006 {published data only}
    1. Lim JI, Walonker AF, Levin L, Mahmoud M, Sadda S, Flaxel CJ, et al. One-year results of a pilot study using oral 13-cis retinoic acid as a treatment for subfoveal predominantly occult choroidal neovascularization in patients with age-related macular degeneration. Retina 2006;26(3):314-21. - PubMed
LIMPIA 2013 {published data only}
    1. Korobelnik JF, Rougier MB, Delyfer MN, Bron A, Merle BM, Savel H, et al. Effect of dietary supplementation with lutein, zeaxanthin, and ω-3 on macular pigment: a randomized clinical trial. JAMA Ophthalmology 2017 ;135(11):1259-66. - PMC - PubMed
    1. Korobelnik JF, Delyfer MN, Rougier M, Savel H, Chine G, Delcourt C, et al. A randomized trial of supplementation with lutein, zeaxanthin, omega 3 fatty acids and antioxidants for increasing macular pigment optical density in high-risk subjects: the LIMPIA Study. Investigative Ophthalmology and Visual Science 2013;54(15):ARVO E-abstract 3780.
LUNA 2007 {published data only}
    1. Trieschmann M, Beatty S, Nolan JM, Hense HW, Heimes B, Austermann U, et al. Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: the LUNA study. Experimental Eye Research 2007;84(4):718-28. - PubMed
    1. Zeimer M, Dietzel M, Hense HW, Heimes B, Austermann U, Pauleikhoff D. Profiles of macular pigment optical density and their changes following supplemental lutein and zeaxanthin: new results from the LUNA study. Investigative Ophthalmology and Visual Science 2012;53(8):4852-9. - PubMed
LUXEA 2006 {published data only}
    1. Kvansakul J, Rodriguez-Carmona M, Edgar DF, Barker FM, Kopcke W, Schalch W, et al. Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic and Physiological Optics 2006;26(4):362-71. - PubMed
    1. Rodriguez-Carmona M, Kvansakul J, Harlow JA, Köpcke W, Schalch W, Barbur JL. The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision. Ophthalmic and Physiological Optics 2006;26(2):137-47. - PubMed
    1. Schalch W, Cohn W, Barker FM, Köpcke W, Mellerio J, Bird AC, et al. Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (lutein xanthophyll eye accumulation) study. Archives of Biochemistry and Biophysics 2007;458(2):128-35. - PubMed
Meagher 2013 {published data only}
    1. Meagher K, Nolan JM, Thurnham DI, Howard AN, Beatty S. Macular response to supplementation with differing carotenoid formulations in subjects with and without age-related macular degeneration. European Journal of Ophthalmology 2013;23(4):604-13.
Moeller 2006 {published data only}
    1. Moeller SM, Parekh N, Tinker L, Ritenbaugh C, Blodi B, Wallace RB, et al. Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the carotenoids in age-related eye disease study (CAREDS): ancillary study of the women's health initiative. Archives of Ophthalmology 2006;124(8):1151-62. - PubMed
NCT00121589 {published data only}
    1. NCT00121589. Lutein/zeaxanthin and omega-3 supplementation in persons over age 60. clinicaltrials.gov/ct2/show/NCT00121589 (first received 20 July 2005).
NCT00718653 {published data only}
    1. NCT00718653. Effects of antioxidants on human macular pigments. clinicaltrials.gov/ct2/show/NCT00718653 (first received 17 July 2008).
NCT00800995 {published data only}
    1. NCT00800995. Superoxide Dismutase (SOD) as antioxidant treatment of age related macular degeneration (ARMD) [SOD as antioxidant treatment of ARMD]. clinicaltrials.gov/ct2/show/NCT00800995 (first received 2 December 2008).
NCT00893724 {published data only}
    1. NCT00893724. Supplemental adjuvants for intracellular nutrition and treatment (SAINTS) [The effect of supplemental adjuvants for intracellular nutrition and treatment on diabetic macular edema and neovascular age-related macular degeneration]. clinicaltrials.gov/ct2/show/NCT00893724 (first received 4 May 2009).
NCT02264938 {published data only}
    1. NCT02264938. Drusen morphology changes in nonexudative age-related degeneration after oral antioxidants supplementation [Drusen morphology changes in nonexudative age-related degeneration using spectral domain optical coherence tomography after oral antioxidants supplementation: one-year results]. clinicaltrials.gov/ct2/show/NCT02264938 (first received 9 October 2014).
NCT03205202 {published data only}
    1. NCT03205202. Cataract and AMD in a trial of a multivitamin and cocoa extract (COSMOS-Eye). clinicaltrials.gov/ct2/show/NCT03205202 (first received 2 July 2017).
NCT03478865 {published data only}
    1. NCT03478865. Vitamin A palmitate supplementation in people with age-related macular degeneration (and without reticular pPseudodrusen) and delayed dark adaptation. clinicaltrials.gov/ct2/show/NCT03478865 (first received 27 March 2018).
Nolan 2006 {published data only}
    1. Nolan J, Stack J, Mellerio J, Godhinio M, O'Donovan O, Neelam K, et al. Monthly consistency of macular pigment optical density and serum concentrations of lutein and zeaxanthin. Current Eye Research 2006;31(2):199-213. - PubMed
Nolan 2007 {published data only}
    1. Nolan JM, Stack J, O'Donovan O, Loane E, Beatty S. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment. Experimental Eye Research 2007;84(1):61-74. - PubMed
Nolan 2012 {published data only}
    1. Nolan JM, Akkali MC, Loughman J, Howard AN, Beatty S. Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment. Experimental Eye Research 2012;101:9-15. - PubMed
Nussenblatt 2006 {published data only}
    1. Nussenblatt RB, Kim J, Thompson DJ, Davis MD, Chew E, Ferris FL, et al. Vitamin E in the treatment of uveitis-associated macular edema. American Journal of Ophthalmology 2006;141(1):193-4. - PubMed
Owsley 2006 {published data only}
    1. Owsley C, McGwin G, Jackson GR, Heimburger DC, Piyathilake CJ, Klein R, et al. Effect of short-term, high-dose retinol on dark adaptation in aging and early age-related maculopathy. Investigative Ophthalmology and Visual Science 2006;47(4):1310-8. - PubMed
PHS II 2012 {published data only}
    1. Christen WG, Glynn RJ, Manson JE, MacFadyen J, Bubes V, Schvartz M, et al. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 2014;121(2):525-34. - PMC - PubMed
    1. Christen WG, Glynn RJ, Sesso HD, Kurth T, Macfadyen J, Bubes V, et al. Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 2012;119(8):1642-9. - PMC - PubMed
Rosenthal 2006 {published data only}
    1. Khachik F, Moura FF, Chew EY, Douglass LW, Ferris FL 3rd, Kim J, et al. The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older. Investigative Ophthalmology and Visual Science 2006;47(12):5234-42. - PubMed
    1. Rosenthal JM, Kim J, Monasterio F, Monastario F, Thompson DJ, Bone RA, et al. Dose-ranging study of lutein supplementation in persons aged 60 years or older. Investigative Ophthalmology and Visual Science 2006;47(12):5227-33. - PubMed
Sabour‐Pickett 2014 {published data only}
    1. Sabour-Pickett S, Beatty S, Connolly E, Loughman J, Stack J, Howard A, et al. Supplementation with three different macular carotenoid formulations in patients with early age-related macular degeneration. Retina 2014;34(9):1757-66. - PubMed
Saperstein 2015 {published data only}
    1. Saperstein DA, Pieramici DJ, Sall KN, Heier JS, Brown DM, Birch DG, et al. Clinical proof-of-concept study of oral synthetic cis-retinoid (QLT091001) in adult subjects with impaired dark adaptation and/or impaired low luminance vision. Investigative Ophthalmology and Visual Science 2015;56(7):ARVO E-abstract 3791.
Sasamoto 2011 {published data only}
    1. Sasamoto Y, Gomi F, Sawa M, Tsujikawa M, Nishida K. Effect of 1-year lutein supplementation on macular pigment optical density and visual function. Graefe's Archive for Clinical and Experimental Ophthalmology 2011;249(12):1847-54. - PubMed
Scorolli 2002 {published data only}
    1. Scorolli L, Scalinci SZ, Limoli PG, Morara M, Vismara S, Scorolli L, et al. Photodynamic therapy for age related macular degeneration with and without antioxidants. Canadian Journal of Ophthalmology 2002;37(7):399-404. - PubMed
Souied 2013 {published data only}
    1. Souied EH, Delcourt C, Querques G, Bassols A, Merle B, Zourdani A, et al. Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the nutritional AMD treatment 2 study. Ophthalmology 2013;120(8):1619-31. - PubMed
Told 2014 {published data only}
    1. Told R, Palkovits S, Schmidl D, Boltz A, Gouya G, Wolzt M, et al. Retinal hemodynamic effects of antioxidant supplementation in an endotoxin-induced model of oxidative stress in humans. Investigative Ophthalmology and Vision Science 2014;55(4):2220-7. - PubMed
Told 2015 {published data only}
    1. Told R, Schmidl D, Palkovits S, Boltz A, Gouya G, Wolzt M, et al. Antioxidative capacity of a dietary supplement on retinal hemodynamic function in a human lipopolysaccharide (LPS) model. Investigative Ophthalmology and Visual Science 2015;56(1):403-11. - PubMed
Vannas 1958 {published data only}
    1. Vannas S, Orma H. On the treatment of arteriosclerotic chorioretinopathy. Acta Ophthalmologica 1958;36:601-12. - PubMed
Vidal 2011 {published data only}
    1. Vidal K, Bucheli P, Gao QT, Moulin J, Shen LS, Blum S, et al. Effect of a milk-based wolfberry preparation on immune function and physical status of elderly. Clinical Nutrition Supplements 2011;6(1):133. [DOI: 10.1016/S1744-1161(11)70341-6] - DOI
Wang 2007 {published data only}
    1. Wang W, Connor SL, Johnson EJ, Klein ML, Hughes S, Connor WE. Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration. American Journal of Clinical Nutrition 2007;85(3):762-9. - PubMed
Wenzel 2006 {published data only}
    1. Wenzel AJ, Gerweck C, Barbato D, Nicolosi RJ, Handelman GJ, Curran-Celentano J. A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women. Journal of Nutrition 2006;136(10):2568-73. - PubMed
Wolf‐Schnurrbusch 2015 {published data only}
    1. Wolf-Schnurrbusch UE, Zinkernagel MS, Munk MR, Ebneter A, Wolf S. Oral lutein supplementation enhances macular pigment density and contrast sensitivity but not in combination with polyunsaturated fatty acids. Investigative Ophthalmology and Visual Science 2015;56(13):8069-74. - PubMed
Wong 2010 {published data only}
    1. Wong WT, Kam W, Cunningham D, Harrington M, Hammel K, Meyerle CB, et al. Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial. Investigative Ophthalmology and Visual Science 2010;51(12):6131-9. - PMC - PubMed
Zhao 2006 {published data only}
    1. Zhao DY, Bhosale P, Bernstein PS. Carotenoids and ocular health. Current Topics in Nutraceuticals Research 2006;4(1):53-68.
ZVF 2011 {published data only}
    1. NCT00564902. The zeaxanthin and visual function study (ZVF) [Randomized, double blind, lutein controlled study of zeaxanthin and visual function in atrophic age related macular degeneration patients]. clinicaltrials.gov/ct2/show/NCT00564902 (first received 27 November 2007).
    1. Richer SP, Stiles W, Graham-Hoffman K, Levin M, Ruskin D, Wrobel J, et al. Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973. Optometry 2011;82(11):667-80. - PubMed

References to studies awaiting assessment

Chiosi 2020 {published data only}
    1. Chiosi F, Minutillo E, Rinaldi M, Gallo O, Manzi G. The anti-oxidant effect of vitamin D and homotaurine on progression of early-intermediate age-related macular degeneration. Investigative Ophthalmology and Visual Science 2020;61(7):ARVO E-abstract 1789.

References to ongoing studies

NCT01694680 {published data only}
    1. NCT01694680. Intervention trial in early age-related macular degeneration (I-TEAM) [Intervention study to assess the effect of daily consumption of a lutein-enriched-egg beverage on maintenance of visual function in subjects with early signs of age-related macular degeneration]. clinicaltrials.gov/ct2/show/NCT01694680 (first received 25 September 2012).
NCT02625376 {published data only}
    1. NCT02625376. Resveratrol for exudative age-related macular degeneration (AGED) [Influence of resveratrol and resvega versus placebo on incidence of bilateralisation of exudative AMD: a double masked prospective study]. clinicaltrials.gov/ct2/show/NCT02625376 (first received 6 August 2015).
NCT03845582 {published data only}
    1. NCT03845582. Phase 3 study of ALK-001 in geographic atrophy (SAGA). clinicaltrials.gov/ct2/show/NCT03845582 (first received 19 February 2019).

Additional references

Andreatta 2014
    1. Andreatta W, El-Sherbiny S. Evidence-based nutritional advice for patients affected by age-related macular degeneration. Ophthalmologica 2014;231(4):185-90. - PubMed
Angelo 2015
    1. Angelo G, Drake VJ, Frei B. Efficacy of multivitamin/mineral supplementation to reduce chronic disease risk: a critical review of the evidence from observational studies and randomized controlled trials. Critical Reviews in Food Science and Nutrition 2015;55(14):1968-91. - PubMed
AREDS2 2014
    1. The Age-Related Eye Disease Study 2 (AREDS2) Research Group. Secondary analyses of the effects of lutein/zeaxanthinon age-related macular degeneration progression AREDS2 Report No. 3. JAMA Ophthalmology 2014;132(2):142-9. - PMC - PubMed
Assell 2018
    1. Assel MJ, Li F, Wang Y, Allen AS, Baggerly KA, Vickers AJ. Genetic polymorphisms of CFH and ARMS2 do not predict response to antioxidants and zinc in patients with age-related macular degeneration: independent statistical evaluations of data from the Age-Related Eye Disease Study. Ophthalmology 2018;125(3):391-7. - PMC - PubMed
ATBC 1994
    1. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England Journal of Medicine 1994;330(15):1029-35. - PubMed
Awh 2013
    1. Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology 2013;120(11):2317-23. - PubMed
Awh 2015
    1. Awh CC, Hawken S, Zanke BW. Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the Age-Related Eye Disease Study. Ophthalmology 2015;122(1):162-9. - PubMed
Azzi 2018
    1. Azzi A. Many tocopherols, one vitamin E. Molecular Aspects of Medicine 2018 ;61:92-103. - PubMed
Bjelakovic 2012
    1. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No: CD007176. [DOI: 10.1002/14651858.CD007176.pub2] - DOI - PubMed
Broadhead 2015
    1. Broadhead GK, Grigg JR, Chang AA, McCluskey P. Dietary modification and supplementation for the treatment of age-related macular degeneration. Nutrition Reviews 2015;73(7):448-62. - PubMed
Bunce 2010
    1. Bunce C, Xing W, Wormald R. Causes of blind and partial sight certifications in England and Wales: April 2007-March 2008. Eye 2010;24(11):1692-9. - PubMed
Buschini 2015
    1. Buschini E, Fea AM, Lavia CA, Nassisi M, Pignata G, Zola M, et al. Recent developments in the management of dry age-related macular degeneration. Clinical Ophthalmology 2015;9:563-74. - PMC - PubMed
Cai 2000
    1. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Progress in Retinal and Eye Research 2000;19(2):205-21. - PubMed
Carneiro 2017
    1. Carneiro A, Andrade JP. Nutritional and lifestyle interventions for age-related macular degeneration: a review. Oxidative Medicine and Cellular Longevity 2017;2017:Article ID 6469138. [DOI: 10.1155/2017/6469138] - DOI - PMC - PubMed
Chew 2014a
    1. Chew EY. Vitamins and minerals, for eyes only? JAMA Ophthalmology 2014;132(6):665-6. - PubMed
Chew 2014b
    1. Chew EY, Klein ML, Clemons TE, Agrón E, Ratnapriya R, Edwards AO, et al, Age-Related Eye Disease Study Research Group. No clinically significant association between CFH and ARMS2 genotypes and response to nutritional supplements: AREDS report number 38. Ophthalmology 2014;121(11):2173-80. [DOI: 10.1016/j.ophtha.2014.05.008] - DOI - PMC - PubMed
Chew 2015
    1. Chew EY, Klein ML, Clemons TE, Agrón E, Abecasis GR. Genetic testing in persons with age-related macular degeneration and the use of the AREDS supplements: to test or not to test? Ophthalmology 2015;122(1):212-5. - PMC - PubMed
Chong 2007
    1. Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH. Dietary antioxidants and primary prevention of age-related macular degeneration: systematic review and meta-analysis. BMJ 2007;335(7623):755. - PMC - PubMed
Christen 1996
    1. Christen WG, Glynn RJ, Hennekens CH. Antioxidants and age-related eye disease. Current and future perspectives. Annals of Epidemiology 1996;6(1):60-6. - PubMed
Covidence [Computer program]
    1. Covidence. Version accessed 30 November 2022. Melbourne, Australia: Veritas Health Innovation. Available at www.covidence.org.
Csader 2022
    1. Csader S, Korhonen S, Kaarniranta K, Schwab U. The effect of dietary supplementations on delaying the progression of age-related macular degeneration: a sytematic review and meta-analysis. Nutrients 2022;14(20):13. - PMC - PubMed
Deeks 2017
    1. Deeks JJ, Higgins JP, Altman DG (editors), on behalf of the Cochrane Statistical Methods Group. Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JP, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.
Downie 2014
    1. Downie LE, Keller PR. Nutrition and age-related macular degeneration: research evidence in practice. Optometry and Vision Science 2014;91(8):821-31. - PubMed
ETDRS 1980
    1. Early Treatment Diabetic Retinopathy Study Research Group. Early Treatment Diabetic Retinopathy Study Manual of Operations. Baltimore (MD): ETDRS Co-ordinating Center, 1980.
European Food Safety Authority 2023
    1. European Food Safety Authority. Dietary reference values. www.efsa.europa.eu/en/topics/topic/dietary-reference-values (accessed 31 January 2023).
Ferris 2013
    1. Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, et al, Beckman Initiative for Macular Research Classification Committee. Clinical classification of age-related macular degeneration. Ophthalmology 2013;120(4):844-51. - PubMed
Fitzpatrick 2022
    1. Fitzpatrick N, Chachay V, Bowtell J, Jackman S, Capra S, Shore A et al. An appraisal of trials investigating the effects on macular pigment optical density of lutein and zeaxanthin dietary interventions: a narrative review. Nutrition Reviews 2022;80(3):513-24. - PubMed
Fletcher 2010
    1. Fletcher AE. Free radicals, antioxidants and eye diseases: evidence from epidemiological studies on cataract and age-related macular degeneration. Ophthalmic Research 2010;44(3):191-8. - PubMed
Food and Agriculture Organization 2001
    1. Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) expert consultation. Human Vitamin and Mineral Requirements: Report of a Joint FAO/WHO Expert Consultation; Bangkok, Thailand; 2001. Available at: www.fao.org/3/y2809e/y2809e00.pdf (accessed 30 January 2023).
Glanville 2006
    1. Glanville JM, Lefebvre C, Miles JN, Camosso-Stefinovic J. How to identify randomized controlled trials in MEDLINE: ten years on. Journal of the Medical Library Association 2006;94(2):130-6. - PMC - PubMed
GRADEpro [Computer program]
    1. GRADEpro. Version accessed 31 January 2023. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at gradepro.org.
Grover 2014
    1. Grover AK, Samson SE. Antioxidants and vision health: facts and fiction. Molecular and Cellular Biochemistry 2014;388(1-2):173-83. - PubMed
Hanus 2016
    1. Hanus J, Zhao F, Wang S. Current therapeutic developments in atrophic age-related macular degeneration. British Journal of Ophthalmology 2016;100(1):122-7. - PMC - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. [DOI: 10.1136/bmj.327.7414.557] - DOI - PMC - PubMed
Higgins 2019
    1. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JA. Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from training.cochrane.org/handbook/archive/v6.
Huang 2006
    1. Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR, et al. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Annals of Internal Medicine 2006;145(5):372-85. - PubMed
Institute of Medicine 2000
    1. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Available at nap.nationalacademies.org/9810. Washington, DC: The National Academies Press, 2000. - PubMed
Institute of Medicine 2001
    1. Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,Nickel, Silicon, Vanadium, and Zinc. Available at nap.nationalacademies.org/10026. Washington, DC: The National Academies Press, 2001. - PubMed
Klein 1992
    1. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The beaver dam eye study. Ophthalmology 1992;99(6):933-43. - PubMed
Klein 2008
    1. Klein ML, Francis PJ, Rosner B, Reynolds R, Hamon SC, Schultz DW, et al. CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmology 2008;115(6):1019-25. [DOI: 10.1016/j.ophtha.2008.01.036.] - DOI - PubMed
Krezel 2019
    1. Krezel AK, Hogg R, Lohfeld L, Chakravarthy U, Azuara-Blanco A. Core outcomes for geographic atrophy trials. BritishJournal of Ophthalmology 2020;104(9):1196-1202. - PubMed
Lawrenson 2015
    1. Lawrenson JG, Evans JR. Omega 3 fatty acids for preventing or slowing the progression of age‐related macular degeneration. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No: CD010015. [DOI: 10.1002/14651858.CD010015.pub3] - DOI - PMC - PubMed
Liu 2015
    1. Liu R, Wang T, Zhang B, Qin L, Wu C, Li Q, et al. Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration. Investigative Ophthalmology and Visual Science 2016;56(1):252-8. - PubMed
Liu 2022
    1. Liu Y, Ni M, Wu R, Yang Z, Zhu X, Chen J. The level and efficacy of lutein in patients with age-related macular degeneration: a comprehensive systematic review and meta-analysis. Annals of Translational Medicine 2022;10(6):299. - PMC - PubMed
Lonn 2005
    1. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM. Effects of long term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293(11):1338-47. - PubMed
Manikandan 2016
    1. Manikandan R, Thiagarajan R, Goutham G, Arumugam M, Beulaja M, Rastrelli L, et al. Zeaxanthin and ocular health, from bench to bedside. Fitoterapia 2016;109:58-66. - PubMed
National Eye Institute 2023
    1. National Eye Institute. AREDS 2 supplements for age-related macular degeneration (AMD). www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-r... (accessed prior to 2 May 2023).
NICE 2018
    1. National Institute for Health and Care Excellence (NICE). Age-related macular degeneration. NICE guideline NG82; January 2018. www.nice.org.uk/guidance/ng82 (accessed 23 March 2021).
Omenn 1996
    1. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 1996;334(18):1189-90. - PubMed
Pameijer 2022
    1. Pameijer EM, Heus P, Damen JA, Spijker R, Hooft L, Ringens PJ, et al. What did we learn in 35 years of research on nutrition and supplements for age-related macular degeneration: a systematic review. Acta Ophthalmologica 2022;100(8):e1541-52. - PMC - PubMed
Prasad 2014
    1. Prasad AS. Zinc: an antioxidant and anti-inflammatory agent: role of zinc in degenerative disorders of aging. Journal of Trace Elements in Medicine and Biology 2014;28(4):364-71. - PubMed
Review Manager Web 2023 [Computer program]
    1. Review Manager Web (RevMan Web). Version 4.24.0. The Cochrane Collaboration, 2023. Available at revman.cochrane.org.
Rodrigues 2016
    1. Rodrigues IA, Sprinkhuizen SM, Barthelmes D, Blumenkranz M, Cheung G, Haller J, et al. Defining a minimum set of standardized patient-centered outcome measures for macular degeneration. American Journal of Ophthalmology 2016;168:1-12. - PubMed
Rudnicka 2012
    1. Rudnicka AR, Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology 2012;119(3):571-80. - PubMed
Sacconi 2017
    1. Sacconi R, Corbelli E, Querques L, Bandello F, Querques G. A review of current and future management of geographic atrophy. Ophthalmology and Therapy 2017;6(1):69-77. - PMC - PubMed
Schmidl 2015
    1. Schmidl D, Garhofer G, Schmetterer L. Nutritional supplements in age-related macular degeneration. Acta Ophthalmologica 2015;93(2):105-21. - PubMed
Schünemann 2019
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from handbook.cochrane.org.
Seddon 2016
    1. Seddon JM, Silver RE, Rosner B. Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis. British Journal of Ophthalmology 2016;100(12):1731-7. - PMC - PubMed
Vavvas 2018
    1. Vavvas DG, Small KW, Awh CC, Zanke BW, Tibshirani RJ, Kustra R. CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation. Proceedings of the National Academy of Sciences 2018;115(4):E696-704. - PMC - PubMed
Warwick 2018
    1. Warwick A, Lotery A. Genetics and genetic testing for age-related macular degeneration. Eye 2018;32:849–57. - PMC - PubMed
Waugh 2018
    1. Waugh N, Loveman E, Colquitt J, Royle P, Yeong JL, Hoad G, et al. Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review. Health Technology Assessment 2018;22(27):1-168. - PMC - PubMed
Young 1998
    1. Young VR, Erdman JW, King JC. Dietary reference intakes. Proposed definition and plan for review of dietary antioxidant and related compounds. Washington, DC: National Academy Press, 1998. - PubMed
Zampatti 2014
    1. Zampatti S, Ricci F, Cusumano A, Marsella LT, Novelli G, Giardina E. Review of nutrient actions on age-related macular degeneration. Nutrition Research 2014;34(2):95-105. - PubMed

References to other published versions of this review

Evans 2006
    1. Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No: CD000254. [DOI: 10.1002/14651858.CD000254.pub2] - DOI - PubMed
Evans 2012
    1. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No: CD000254. [DOI: 10.1002/14651858.CD000254.pub3] - DOI - PubMed
Evans 2017
    1. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age‐related macular degeneration. Cochrane Database of Systematic Reviews 2017, Issue 7. Art. No: CD000254. [DOI: 10.1002/14651858.CD000254.pub4] - DOI - PMC - PubMed

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