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

Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanley, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Camille, J Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Dubois-Moran, J Callahan, C Evans, C Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, NJ Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY
A. Kassoff et al., 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, ARCH OPHTH, 119(10), 2001, pp. 1417-1436
Citations number
Categorie Soggetti
Optalmology,"da verificare
Journal title
ISSN journal
0003-9950 → ACNP
Year of publication
1417 - 1436
SICI code
Background: Observational and experimental data suggest that antioxidant an d/or zinc supplements may delay progression of age-related macular degenera tion (AMD) and vision loss. Objective: To evaluate the effect of high-dose vitamins C and E, beta carot ene, and zinc supplements on AMD progression and visual acuity. Design: The Age-Related Eye Disease Study, an 11-center double-masked clini cal trial, enrolled participants in an AMD trial if they had extensive smal l drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20 /32 or better. Participants were randomly assigned to receive daily oral ta blets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; a nd beta carotene, 15 mg) (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, a s cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Me asures: (1)Photographic assessment of progression to or treatment for advan ced AMD and (2) at least moderate visual acuity loss from baseline ( : 15 l etters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurem ents, medical histories, and mortality rates were used for safety monitorin g. Results: Average follow-up of the 3640 enrolled study participants, aged 55 -80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with plac ebo demonstrated a statistically significant odds reduction for the develop ment of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99 % confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxid ants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respe ctively. Participants with extensive small drusen, nonextensive intermediat e size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when the se 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% C I, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99 % CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduce d the odds of developing advanced AMD in this higher-risk group. The only s tatistically significant reduction in rates of at least moderate visual acu ity loss occurred in persons assigned to receive antioxidants plus zinc (OR , 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse ef fect was associated with any of the formulations. Conclusions: Persons older than 55 years should have dilated eye examinatio ns to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic at rophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye , and without contraindications such as smoking, should consider taking a s upplement of antioxidants plus zinc such as that used in this study.