Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35
Emily Y Chew, Traci E Clemons, Elvira Agrón, Robert D Sperduto, John Paul Sangiovanni, Natalie Kurinij, Matthew D Davis, Age-Related Eye Disease Study Research Group, Aaron Kassoff, Jordan Kassoff, JoAnne Buehler, Mary Eglow, Susan Silverman, Michel Mehu, Shalom Kieval, Francine Kaufman, Michael Mairs, Barbara Graig, Andrea Quattrocchi, Denise Jones, Joan Locatelli, Alan Ruby, Antonio Capone Jr, Bruce Garretson, Tarek Hassan, Michael T Trese, George A Williams, Virginia Regan, Patricia Manatrey, Patricia Streasick, Lynette Szydlowski, Fran McIver, Craig Bridges, Cheryl Stanley, Kristi Cumming, Beth Mitchell, Joanne Holloway, Bobbie Lewis, Mary Zajechowski, Raymond R Margherio, Morton S Cox, Jane Camille Werner, Rachel Falk, Patricia Siedlak, Cheryl Neubert, Michael L Klein, J Timothy Stout, Andreas K Lauer, Carolyn Beardsley, Hiroko Anderson, Patrick Wallace, Garland Smith, Shannon Howard, Richard F Dreyer, Colin Ma, Richard G Chenoweth, John D Zilis, Adrian O'Malley, Joseph E Robertson, David J Wilson, Milton Johnson, Patrick Rice, Howard Daniel, Harold Crider, Sheryl Parker, Kathryn Sherman, Daniel F Martin, Thomas M Aaberg Sr, G Baker Hubbard, Enrique Garcia, Linda T Curtis, Alex DeLeon, Bob Myles, Hannah Yi, Antonio Capone Jr, Michael Lambert, Travis Meredith, Thomas M Aaberg Jr, Paul Sternberg Jr, David Saperstein, Jennifer I Lim, Barbara Stribling, Bora Ju, Denise Armiger, Jim Gilman, Debbie Jordan, Sandra Strittman, Ray Swords, David H Orth, Timothy P Flood, Joseph Civantos, Serge deBustros, Kirk H Packo, Pauline T Merrill, Jack A Cohen, David Chow, Celeste Figliulo, Chris Morrison, Douglas A Bryant, Don Doherty, Marian McVicker, Tana Drefcinski, Johanna M Seddon, Michael K Pinnolis, Mala Sachdeva, Tatyana Taytsel, Ilene Burton, David Walsh, Charlene Callahan, Claudia Evans, Kristin K Snow, Desiree A Jones-Devonish, Valerie D Crouse, N Jennifer Rosenberg, Nancy Davis, Jennifer Dubois-Moran, Emily Y Chew, Karl Csaky, Frederick L Ferris 3rd, Katherine Hall Shimel, Merria A Woods, Denise Cunningham, Ernest M Kuehl, Marilois Palmer, Gloria Babilonia-Ayukawa, Guy E Foster, Young Ja Kim, Iris J Kivitz, Dessie Koutsandreas, Antoinette LaReau, Richard F Mercer, Roula Nashwinter, John Rowan, Greg Short, Sally A McCarthy, Patrick F Ciatto, Leanne M Ayres, Linda Goodman, Patrick Lopez, Cheryl Perry, Anne Randalls, Thomas R Friberg, Andrew W Eller, Michael B Gorin, Barbara Mack, Diane Y Curtin, Phyllis P Ostroska, Edward Fijewski, Jane Alexander, Shannon Nixon, Melissa K Paine, Patricia S Corbin, Joseph Warnicki, Susan B Bressler, Neil M Bressler, Gary Cassel, Daniel Finkelstein, Morton Goldberg, Julia A Haller, Lois Ratner, Andrew P Schachat, Steven H Sherman, Janet S Sunness, Sherrie Schenning, Catherine Sackett, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, Rachel Falk, Stacy Wheeler, Mary Mcmillan, Terry George, Michael J Elman, Rex Ballinger, Arturo Betancourt, Michael Herr, Joyce Lammlein, Robert Z Raden, Ronald Seff, Martin Shuman, JoAnn Starr, Dena Firestone, Michelle Sloan, Peter Sotirakos, Theresa Cain, Terri Mathews, David Glasser, Dahlia Hirsch, Daniel Killingsworth, Paul Kohlhepp, Christine Ringrose, Anita Carrigan, Suresh R Chandra, Justin L Gottlieb, Michael S Ip, Ronald Klein, T Michael Nork, Thomas S Stevens, Barbara A Blodi, Michael Altaweel, Barbara E K Klein, Matthew D Davis, Michelle Olson, Alyson Skoldberg, Erika Christianson, Barbara Soderling, Jennie R Perry-Raymond, Kathryn Burke, Gene Knutson, John Peterson, Denise Krolnik, Robert Harrison, Guy Somers, Frank L Myers, Ingolf Wallow, Timothy W Olsen, George Bresnik, G De Venecia, Tracy Perkins, Wendy Walker, Jennifer L Miller, Margo Blatz, Michael Neider, Hugh D Wabers, Greg Weber, Beth Amspaugh, Jennifer Buechner, Helen E Lyngaas Myers, Matthew D Davis, Barbara E K Klein, Ronald Klein, Barbara Blodi, Ronald Danis, Larry Hubbard, Michael Neider, Pamela Vargo, Hugh D Wabers, Jane Armstrong, Wendy Benz, Kristi L Dohm, Christina Fink, Trina Harding, Cynthia Hurtenbach, Kristine Lang, Susan Reed, Marian R Fisher, Ronald Gangnon, Li-Yin Lee, Alistair Carr, James Baliker, Linda Kastorff, Nancy Robinson, Kathleen E Glander, Jean Surfus, Sarah Ansay, Yvonne L Magli, Darlene Badal, Shirley Craanen, Julee Elledge, Barbara Esser, Patricia L Geithman, Kathleen D Miner, James Reimers, Mary Webster, Chunyang Gai, William King, Kurt Osterby, James Onofrey, Judith Brickbauer, Rosemary L Schleicher, Dayton T Miller, Anne L Sowell, Elaine W Gunter, Barbara A Bowman, Anne S Lindblad, Roy C Milton, Traci E Clemons, Gary Gensler, Molly Rankin, Alice Henning, Candice Davis, Gary Entler, Wendy McBee, Elaine Stine, Valerie Watson, Stuart H Berlin, Kumar Thotapally, Michelle Jackson, Kate Tomlin, Sophia Pallas, Phyllis R Scholl, Susan A Mengers, Fred Ederer, Ravinder Anand, Kiana Roberts, Frederick L Ferris III, Robert D Sperduto, Natalie Kurinij, Emily Y Chew, John Paul SanGiovanni, Emily Y Chew, Traci E Clemons, Elvira Agrón, Robert D Sperduto, John Paul Sangiovanni, Natalie Kurinij, Matthew D Davis, Age-Related Eye Disease Study Research Group, Aaron Kassoff, Jordan Kassoff, JoAnne Buehler, Mary Eglow, Susan Silverman, Michel Mehu, Shalom Kieval, Francine Kaufman, Michael Mairs, Barbara Graig, Andrea Quattrocchi, Denise Jones, Joan Locatelli, Alan Ruby, Antonio Capone Jr, Bruce Garretson, Tarek Hassan, Michael T Trese, George A Williams, Virginia Regan, Patricia Manatrey, Patricia Streasick, Lynette Szydlowski, Fran McIver, Craig Bridges, Cheryl Stanley, Kristi Cumming, Beth Mitchell, Joanne Holloway, Bobbie Lewis, Mary Zajechowski, Raymond R Margherio, Morton S Cox, Jane Camille Werner, Rachel Falk, Patricia Siedlak, Cheryl Neubert, Michael L Klein, J Timothy Stout, Andreas K Lauer, Carolyn Beardsley, Hiroko Anderson, Patrick Wallace, Garland Smith, Shannon Howard, Richard F Dreyer, Colin Ma, Richard G Chenoweth, John D Zilis, Adrian O'Malley, Joseph E Robertson, David J Wilson, Milton Johnson, Patrick Rice, Howard Daniel, Harold Crider, Sheryl Parker, Kathryn Sherman, Daniel F Martin, Thomas M Aaberg Sr, G Baker Hubbard, Enrique Garcia, Linda T Curtis, Alex DeLeon, Bob Myles, Hannah Yi, Antonio Capone Jr, Michael Lambert, Travis Meredith, Thomas M Aaberg Jr, Paul Sternberg Jr, David Saperstein, Jennifer I Lim, Barbara Stribling, Bora Ju, Denise Armiger, Jim Gilman, Debbie Jordan, Sandra Strittman, Ray Swords, David H Orth, Timothy P Flood, Joseph Civantos, Serge deBustros, Kirk H Packo, Pauline T Merrill, Jack A Cohen, David Chow, Celeste Figliulo, Chris Morrison, Douglas A Bryant, Don Doherty, Marian McVicker, Tana Drefcinski, Johanna M Seddon, Michael K Pinnolis, Mala Sachdeva, Tatyana Taytsel, Ilene Burton, David Walsh, Charlene Callahan, Claudia Evans, Kristin K Snow, Desiree A Jones-Devonish, Valerie D Crouse, N Jennifer Rosenberg, Nancy Davis, Jennifer Dubois-Moran, Emily Y Chew, Karl Csaky, Frederick L Ferris 3rd, Katherine Hall Shimel, Merria A Woods, Denise Cunningham, Ernest M Kuehl, Marilois Palmer, Gloria Babilonia-Ayukawa, Guy E Foster, Young Ja Kim, Iris J Kivitz, Dessie Koutsandreas, Antoinette LaReau, Richard F Mercer, Roula Nashwinter, John Rowan, Greg Short, Sally A McCarthy, Patrick F Ciatto, Leanne M Ayres, Linda Goodman, Patrick Lopez, Cheryl Perry, Anne Randalls, Thomas R Friberg, Andrew W Eller, Michael B Gorin, Barbara Mack, Diane Y Curtin, Phyllis P Ostroska, Edward Fijewski, Jane Alexander, Shannon Nixon, Melissa K Paine, Patricia S Corbin, Joseph Warnicki, Susan B Bressler, Neil M Bressler, Gary Cassel, Daniel Finkelstein, Morton Goldberg, Julia A Haller, Lois Ratner, Andrew P Schachat, Steven H Sherman, Janet S Sunness, Sherrie Schenning, Catherine Sackett, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, Rachel Falk, Stacy Wheeler, Mary Mcmillan, Terry George, Michael J Elman, Rex Ballinger, Arturo Betancourt, Michael Herr, Joyce Lammlein, Robert Z Raden, Ronald Seff, Martin Shuman, JoAnn Starr, Dena Firestone, Michelle Sloan, Peter Sotirakos, Theresa Cain, Terri Mathews, David Glasser, Dahlia Hirsch, Daniel Killingsworth, Paul Kohlhepp, Christine Ringrose, Anita Carrigan, Suresh R Chandra, Justin L Gottlieb, Michael S Ip, Ronald Klein, T Michael Nork, Thomas S Stevens, Barbara A Blodi, Michael Altaweel, Barbara E K Klein, Matthew D Davis, Michelle Olson, Alyson Skoldberg, Erika Christianson, Barbara Soderling, Jennie R Perry-Raymond, Kathryn Burke, Gene Knutson, John Peterson, Denise Krolnik, Robert Harrison, Guy Somers, Frank L Myers, Ingolf Wallow, Timothy W Olsen, George Bresnik, G De Venecia, Tracy Perkins, Wendy Walker, Jennifer L Miller, Margo Blatz, Michael Neider, Hugh D Wabers, Greg Weber, Beth Amspaugh, Jennifer Buechner, Helen E Lyngaas Myers, Matthew D Davis, Barbara E K Klein, Ronald Klein, Barbara Blodi, Ronald Danis, Larry Hubbard, Michael Neider, Pamela Vargo, Hugh D Wabers, Jane Armstrong, Wendy Benz, Kristi L Dohm, Christina Fink, Trina Harding, Cynthia Hurtenbach, Kristine Lang, Susan Reed, Marian R Fisher, Ronald Gangnon, Li-Yin Lee, Alistair Carr, James Baliker, Linda Kastorff, Nancy Robinson, Kathleen E Glander, Jean Surfus, Sarah Ansay, Yvonne L Magli, Darlene Badal, Shirley Craanen, Julee Elledge, Barbara Esser, Patricia L Geithman, Kathleen D Miner, James Reimers, Mary Webster, Chunyang Gai, William King, Kurt Osterby, James Onofrey, Judith Brickbauer, Rosemary L Schleicher, Dayton T Miller, Anne L Sowell, Elaine W Gunter, Barbara A Bowman, Anne S Lindblad, Roy C Milton, Traci E Clemons, Gary Gensler, Molly Rankin, Alice Henning, Candice Davis, Gary Entler, Wendy McBee, Elaine Stine, Valerie Watson, Stuart H Berlin, Kumar Thotapally, Michelle Jackson, Kate Tomlin, Sophia Pallas, Phyllis R Scholl, Susan A Mengers, Fred Ederer, Ravinder Anand, Kiana Roberts, Frederick L Ferris III, Robert D Sperduto, Natalie Kurinij, Emily Y Chew, John Paul SanGiovanni
Abstract
Objective: To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD).
Design: Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study.
Participants: We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study.
Methods: Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses.
Main outcome measures: Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (≥15 letters).
Results: Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio [OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0. 78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases.
Conclusions: Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation.
Financial disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Conflict of interest statement
No authors have any financial/conflicting interests to disclose.
Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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Source: PubMed