title: Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3.
abstract: OBJECTIVE
  The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina.
  
  
  OBJECTIVE
  To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD.
  
  
  METHODS
  The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye.
  
  
  METHODS
  In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination.
  
  
  METHODS
  S Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy.
  
  
  CONCLUSIONS
  The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00345176.
authors: Division of Epidemiology and Clinical Research, National Institutes of Health, Bethesda, Maryland.
authors: Emily Y
authors: EY
authors: Chew
authors: EMMES Corp, Rockville, Maryland.
authors: Traci E
authors: TE
authors: Clemons
authors: National Eye Institute, Clinical Trials Branch, Bethesda, Maryland.
authors: John Paul
authors: JP
authors: Sangiovanni
authors: Department of Ophthalmology, University of Wisconsin-Madison.
authors: Ronald P
authors: RP
authors: Danis
authors: National Eye Institute, Bethesda, Maryland.
authors: Frederick L
authors: FL
authors: Ferris
authors: Elman Retina Group, Baltimore, Maryland.
authors: Michael J
authors: MJ
authors: Elman
authors: Charlotte Eye Ear Nose and Throat, Charlotte, North Carolina.
authors: Andrew N
authors: AN
authors: Antoszyk
authors: Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, Michigan.
authors: Alan J
authors: AJ
authors: Ruby
authors: Ingalls Memorial Hospital, Harvey, Illinois.
authors: David
authors: D
authors: Orth
authors: Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland.
authors: Susan B
authors: SB
authors: Bressler
authors: Texas Retina Associates, Dallas, Texas.
authors: Gary E
authors: GE
authors: Fish
authors: Emory University, Atlanta, Georgia.
authors: George Baker
authors: GB
authors: Hubbard
authors: Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland.
authors: Michael L
authors: ML
authors: Klein
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health.
authors: Suresh R
authors: SR
authors: Chandra
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health15Fundus Photograph Reading Center, University of Wisconsin-Madison.
authors: Barbara A
authors: BA
authors: Blodi
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health.
authors: Amitha
authors: A
authors: Domalpally
authors: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Thomas
authors: T
authors: Friberg
authors: Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors: Wai T
authors: WT
authors: Wong
authors: Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida.
authors: Philip J
authors: PJ
authors: Rosenfeld
authors: National Eye Institute, Bethesda, Maryland.
authors: Elvira
authors: E
authors: Agrón
authors: Duke University Medical Center, Durham, North Carolina.
authors: Cynthia A
authors: CA
authors: Toth
authors: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah Health Sciences Center, University of Utah, Salt Lake City.
authors: Paul S
authors: PS
authors: Bernstein
authors: EMMES Corp, Rockville, Maryland.
authors: Robert D
authors: RD
authors: Sperduto
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D004032:Diet; D019587:Dietary Supplements; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D057092:Geographic Atrophy / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D014975:Lutein / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015593:Retinal Drusen / Q000175:diagnosis / Q000188:drug therapy; D014131:Trace Elements / Q000008:administration & dosage; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology; D014815:Vitamins / Q000008:administration & dosage; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy*; D024341:Xanthophylls / Q000009:adverse effects / Q000627:therapeutic use*; D065146:Zeaxanthins; D019207:beta Carotene / Q000008:administration & dosage
chemical_list: D015525:Fatty Acids, Omega-3; D014131:Trace Elements; D014815:Vitamins; D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene; D014975:Lutein