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1. Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration

Author

Jeannette J. Yu, Elvira Agrón, Traci E. Clemons, Amitha Domalpally, Freekje van Asten, Tiarnan D. Keenan, Catherine Cukras, Emily Y. Chew, Frederick L. Ferris, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Wai T. Wong, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, SriniVas Sadda, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert

Subjects
0303 health sciences, medicine.medical_specialty, Visual acuity, genetic structures, business.industry, Eye disease, Hazard ratio, Age-Related Eye Disease Study, Retrospective cohort study, Fundus (eye), Macular degeneration, medicine.disease, eye diseases, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030221 ophthalmology & optometry, medicine, sense organs, medicine.symptom, Prospective cohort study, business, 030304 developmental biology
Abstract

Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Published
2019
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2. DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes

Author

Thomas Donner, P. Rezaeian, John I. Malone, Sharon B. Schwartz, Xiaoyu Gao, Szilard Kiss, Matthew J. Budoff, David R. Sell, A. Dwoskin, Ronald J. Prineas, C. Pittman, M. Reid, C. McDonald, S. Caulder, M. Szpiech, Oscar B. Crofford, Rachel G. Miller, Louis A. Lobes, M. Patronas, C. Canny, M. E. Lackaye, Sandra R. Montezuma, Richard M. Bergenstal, Patricia Gatcomb, Julie A. Stoner, H. Pan, James L. Kinyoun, J. Mortenson, Osama Hamdy, Connie Fountain, David D. Moore, Kusiel Perlman, R. Trail, David A. Lee, J. Sheindlin, Samuel Dagogo-Jack, Jeffrey L. Mahon, Jill P. Crandall, L. Gill, T. Thompson, Lee M. Jampol, K. Koushan, David S. Schade, J. Brown-Friday, M. Basco, S. Dunnigan, J. Bylsma, R. Birk, L. H. Ketai, J. Hotaling, Stephen W. Scherer, W. Mestrezat, Stephan Villavicencio, R. Lyon, M. Carney, John Kramer, Sunder Mudaliar, David M. Nathan, M. Moran, F. Leandre, James W. Albers, L. Survant, Joseph F. Polak, Manjot K. Gill, Anton Orlin, M. Prince, Pamela A. Silver, Amy K. Saenger, John D. Brunzell, Kathleen E. Bainbridge, L. Babbione, Amisha Wallia, J. Vaccaro-Kish, Bradley D. Jones, M. Hebdon, L. McKenzie, Richard M. Hoffman, S. Chang, C. Siebert, George S. Sharuk, D. Counts, A. Lucas, P. Ramos, N. Burkhart, N. Bakshi, N. Flaherty, D. Kenny, M. Driscoll, Harjit Chahal, Ronald K. Mayfield, S. Hensley, E. Weimann, M. Franz, Martin J. Stevens, N. S. Gregory, Christopher J. O'Donnell, J. Laechelt, Pamela Ossorio, Jerry P. Palmer, Rama Natarajan, G. Ziegler, K. Martin, R. Beaser, C. Beck, L. Zhang, T. J. Declue, David M. Kendall, H. Solc, A. Vella, H. Martinez, Cormac T. Taylor, S. Neill, Douglas A. Greene, P. Lee, D. Norman, Andrew J. Barkmeier, Dean P. Hainsworth, Alka Jain, Sapna Gangaputra, N. Thangthaeng, Lorraine Thomas, Michael H. Brent, M. Bracey, Philip Raskin, Q. Clemens, Barbara H. Braffett, Mark S. Mandelcorn, Lloyd Paul Aiello, John E. Godine, T. Speigelberg, R. Chan, R. Hanna, Shelley B. Bull, William I. Sivitz, R. Sussman, C. Kwong, S. Cercone, P. Hollander, N. Leloudes, Joseph M. Terry, J. Wesche, E. A. Tanaka, D. Rosenberg, Wanjie Sun, L. Sun, Tom Clark, Deborah K. Schlossman, Louis M. Luttrell, R. Dunn, A. Farr, K. McVary, Gayle M. Lorenzi, A. Joseph, Catherine C. Cowie, M. Barr, D. Zimbler, S. Mendley, S. Schussler, N. Grove, Matthew D. Davis, Jong Mu Sun, Sophie Rogers, John P. Bantle, Brandy N. Rutledge, Senda Ajroud-Driss, Vincent M. Monnier, Cladd E. Stevens, Y. G. He, M. Phillips, C. Williams, J. MacIndoe, Kaleigh Farrell, Helen Lambeth, Ayad A. Jaffa, J. Quin, Morey W. Haymond, R. Kirby, D. Steinberg, William H. Herman, M. Mech, Arup Das, Robert Detrano, J. Brown, D. McMillan, Linda Snetselaar, Mark W. Johnson, R. Zeitler, T. Taylor, Peter R. Pavan, Michael H. Goldbaum, Bruce A. Perkins, R. G. Campbell, David A. Nicolle, R. J. van der Geest, Irene Hramiak, D. Freking, Lucy A. Levandoski, S. Colson, Charles Campbell, Victoria R. Trapani, Lawrence J. Singerman, D. Meyer, W. Tang, J. Soule, Anita Harrington, Julie A. Nelson, John A. Colwell, Naji Younes, P. Salemi, K. Hansen, Trevor J. Orchard, S. Huddleston, L. Steranchak, C. Sommer, G. Castle, J. Ginsberg, Paula McGee, V. Gama, John Dupre, Z. Strugula, M. Swenson, N. Wong, David A. Bluemke, M. Nutaitis, Anita Agarwal, M. Lin, K. Nickander, Elsayed Z. Soliman, Joao A. Lima, M. L. Schluter, Fred W. Whitehouse, Lisa Diminick, C. Cornish, M. Spencer, Daniel T. Lackland, Ionut Bebu, Hunter Wessells, S. Yacoub-Wasef, A. Determan, L. Van Ottingham, Howard Wolpert, R. Ehrlich, A. Blevins, L. Jovanovic, D. Finegold, Davida F. Kruger, Jye-Yu C. Backlund, K. Chan, Timothy J. Murtha, R. K. Mayfield, Robert W. Cavicchi, Maria F. Lopes-Virella, Thomas A. Weingeist, K. Lee, Mary E. Larkin, B. Blodi, J. Gott, Timothy J. Lyons, J. Selby, Chris Ryan, J. Harth, P. Pugsley, L. Keasler, John D. Maynard, Paul G. Arrigg, Amy B. Karger, P. Colby, J. Farquhar, Mark H. Schutta, Murk-Hein Heinemann, Kathie L. Hermayer, B. Bosco, C. Lovell, A. Bhan, A. Galprin, M. Cayford, M. Schumer, John E. Chapin, D. Rubinstein, F. Miao, V. Asuquo, Catherine L. Martin, Rodney A. Lorenz, Samuel S. Engel, L. Funk, Cyndi F. Liu, Barbara J. Maschak-Carey, Stephen S. Feman, P. Lindsey, M. Giotta, Philip A. Low, S. Kwon, R. Fahlstrom, A. Iannacone, B. French, H. Remtema, L. Cimino, S. Barron, J. McConnell, Jane L. Lynch, L. Kim, T. Williams, A. Degillio, Blanche M. Chavers, M. Novak, Julio V. Santiago, Ronald P. Danis, P. Gaston, Tae Sup Lee, T. Woodfill, R. Cuddihy, Scott M. Steidl, Alanna C. Morrison, E. Ryan, D. Lawrence, D. Cros, T. Adkins, D. Adelman, L. Dews, Patricia A. Cleary, J. Parker, L. Olmos De Koo, C. Kim, Mark R. Palmert, P. Astelford, Stefan Fritz, B. Olson, Kelvin C. Fong, Alan M. Jacobson, Stanley L. Hazen, D. Hornbeck, K. Folino, M. L. Bernal, Gabriel Virella, William V. Tamborlane, Neil H. White, Daniel L. McGee, Denis Daneman, H. Shamoon, William Dahms, S. Elsing, S. Brink, J. Ahern, Delnaz Roshandel, John M. Pach, N. W. Rodger, E. Cupelli, Dara D. Koozekanani, Abbas E. Kitabchi, K. Stoessel, B. Petty, Jamie R. Wood, J. Seegmiller, T. Strand, Y. Li, Eva L. Feldman, Larry Rand, Robert C. Colligan, T. Smith, A. Carlson, David J. Brillon, Margaret L. Bayless, M. Ong, S. Darabian, W. Hsu, Janet E. Olson, B. Rogness, N. Silvers, M. Pfiefer, B. Schaefer, E. Mendelson, S. Braunstein, Maren Nowicki, R. Reed, James S. Floyd, Z. M. Zhang, T. Sandford, R. B. Avery, A. Pratt, Paolo S. Silva, H. Bode, Alexander J. Brucker, Nikhil D. Patel, Alexander R. Lyon, M. Jenner, N. Wimmergren, L. Tuason, J. Rosenzwieg, D. J. Becker, C. Gauthier-Kelly, M. Richardson, Richard S. Crow, Andrew D. Paterson, Mark E. Molitch, Suzanne M. Strowig, S. Pendegast, M. Burger, Ramzi K. Hemady, J. Dingledine, I. H. de Boer, L. Mayer, F. Perdikaris, Om P. Ganda, F. Thoma, Karen J. Cruickshanks, Abraham Thomas, K. Klumpp, Jerry D. Cavallerano, D. Zheng, Annette Barnie, J. L. Canady, C. Wigley, David G. Miller, Sheila Smith-Brewer, D. Ostrowski, P. Crawford, K. Kelly, Robert G. Devenyi, B. Zimmerman, Susan M. Hitt, C. Johnson, L. Gurry, R. Jarboe, E. Angus, David E. Goldstein, A. Killeen, H. Schrott, Orville G. Kolterman, Mark R. Burge, Michael Rubin, J. Lipps Hagan, Alicia J. Jenkins, Hugh D. Wabers, R. Warhol, Edward Chaum, Karen L. Jones, L. Spillers, C. Miao, J. K. Jones, Angelo J. Canty, Rickey E. Carter, Evrim B. Turkbey, B. Burzuk, R. Woodwick, Evica Simjanoski, Michael W. Steffes, S. Crowell, Suresh D. Shah, H. Ricks, J. D. Carey, Paul A. Edwards, S. Holt, W. F. Schwenk, Ronald J. Oudiz, E. Brown, J. Heier, R. L. Ufret-Vincenty, L. M. Aiello, Robert A. Rizza, Karen L. Anderson, Valerie L. Arends, J. Giangiacomo, R. Liss, Aruna V. Sarma, B. Levy, Ellen J. Anderson, S. Catton, P. Callahan, Rodica Pop-Busui, S. Debrabandere, S. Moser, Bernard H. Doft, A. Malayeri, C. Johannes, R. Ramker, J. Rich, M. Fox, Rukhsana G. Mirza, Katherine A. Morgan, Thomas J. Songer, C. Shah, H. Engel, Saul M. Genuth, S. Ferguson, Anushka Patel, C. Haggan, P. Lou, J. Gordon, M. B. Murphy, D. Sandstrom, Dawn M. Ryan, Daniel H. O'Leary, B. Gloeb, Lois E. Schmidt, H. Zegarra, D. Dalton, W. Brown, Tom G. Sheidow, Margaret E. Stockman, Shyam M. Thomas, Charles McKitrick, Jyotika K. Fernandes, P. A. Bourne, L. Baker, G. Friedenberg, Allan Gordon, Allan L. Drash, S. Yoser, D. Wood, S. Johnsonbaugh, A. De Manbey, L. Kaminski, M. May, L. Bestourous, A. Kowarski, M. Geckle, M. Hartmuller, Michael Bryer-Ash, S. List, F. Goetz, V. Reppucci, D. Etzwiler, Rose A. Gubitosi-Klug, M. Brabham, E. Golden, A. Nayate, J. Hu, M. McLellan, Ronald Klein, N. Rude, B. Vittetoe, John M. Lachin, M. Christofi, Zhuo Chen, Isaac Boniuk, C. Strauch, K. Gunyou, L. Delahanty, W. T. Garvey, Andrew P. Boright, Larry D. Hubbard, D. Weiss, Igor Grant, Jonathan Q. Purnell, Jean M. Bucksa, N. Olson, and B. Zinman

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Diabetic neuropathy, Adolescent, 030209 endocrinology & metabolism, Gastroenterology, Nephropathy, Epigenesis, Genetic, Diabetic complications, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Diabetic Neuropathies, Internal medicine, Diabetes mellitus, Albumins, Genetics, Medicine, Humans, Molecular Biology, Genetics (clinical), Whole blood, Oligonucleotide Array Sequence Analysis, Type 1 diabetes, business.industry, Research, dNaM, DNA methylation age, DNA Methylation, medicine.disease, 030104 developmental biology, Blood pressure, Peripheral neuropathy, Diabetes Mellitus, Type 1, CpG Islands, Female, business, Developmental Biology, Genome-Wide Association Study
Abstract

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Published
2020

3. Progression of Geographic Atrophy in Age-related Macular Degeneration

Author

Tiarnan D. Keenan, Elvira Agrón, Amitha Domalpally, Traci E. Clemons, Freekje van Asten, Wai T. Wong, Ronald G. Danis, SriniVas Sadda, Philip J. Rosenfeld, Michael L. Klein, Rinki Ratnapriya, Anand Swaroop, Frederick L. Ferris, Emily Y. Chew, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Catherine Cukras, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert

Subjects
0301 basic medicine, medicine.medical_specialty, genetic structures, business.industry, Eye disease, Incidence (epidemiology), Fundus (eye), Macular degeneration, medicine.disease, eye diseases, Confidence interval, Geographic atrophy, 03 medical and health sciences, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, Age related, 030221 ophthalmology & optometry, medicine, sense organs, Prospective cohort study, business
Abstract

Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

Published
2018
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4. Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema

Author

Lee M. Jampol, Adam R. Glassman, Danni Liu, Lloyd Paul Aiello, Neil M. Bressler, Elia J. Duh, Susan Quaggin, John A. Wells, Charles C. Wykoff, David Browning, Andrew N. Antoszyk, Angela K. Price, Sherry L. Fredenberg, Jenna T. Herby, Christina J. Fleming, Ashley A. McClain, Sarah A. Ennis, Kelly R. Gallagher, Angella S. Karow, Autumn C. Grupp, Danielle Puskas, Lynn Watson, Swann J. Bojaj, Uma M. Balasubramaniam, Donna McClain, Donna R. Styles, Jeff A. Kuopus, Kathryn Kimrey, Loraine M. Clark, Lisa A. Jackson, Michael D. McOwen, Matt Dunlap, Susannah J. Held, Dante J. Pieramici, Ma'an A. Nasir, Alessandro A. Castellarin, Dilsher Dhoot, Sarah Fishbein, Jack Giust, Lisha Wan, Michelle S. Hanna, Melvin D. Rabena, Jerry Smith, Layne J. Bone, Kelly Avery, Matthew Giust, Aimee Walker, Aimee H. Shook, Sara Esau, Nitce L. Ruvalcaba, W. Lloyd Clark, David L. Johnson, John F. Payne, Tiffany R. Swinford, Mallie M. Taylor, Cassandra L. Garrison, Peggy D. Miller, Amber R. Houlahan, Charlotte A. O'Neill, Ashley Floyd, Crystal C. Parker, Courtney Sease, Tara Graham, Robin Spencer, Tiffany N. Ogbuewu, Ashley Studebaker, Tyler Huggins, Robbin Spivey, Brian Jones, Ashley Williams, Ron Petty, Erin L. Poston, G. Michael Ward, Carl W. Baker, Ron H. Tilford, Tracey M. Caldwell, Lynnette F. Lambert, Mary J. Palmer, Tracey R. Martin, Tana R. Williams, Samantha Kettler, Alecia B. Camp, Paolo S. Silva, Paul G. Arrigg, George S. Sharuk, Sabera T. Shah, Jennifer K. Sun, Corey Westerfeld, Christopher Michael Andreoli, Deborah Schlossman, Timothy Murtha, Hanna Kwak, Flor M. Flores, Margaret E. Stockman, Troy Kieser, Michael N. Krigman, Leila Bestourous, Elizabeth S. Weimann, Jerry D. Cavallerano, Kristen M. Hock, Mary Ann Robertson, Rita K. Kirby, Steve L. Papaconstantinou, Kylie M. Madigan, Robert W. Cavicchi, Kate A. Palitsch, Taygan Yilmaz, Brian B. Berger, Chirag D. Jhaveri, Tori Moore, Ginger J. Manhart, Rachel A. Walsh, Ivana Gunderson, Dietrich Riepen, Chelsey A. Bravenec, Ryan M. Reid, Yong Ren, Ben Ostrander, Christopher C. Stovall, Michael J. Elman, Robert A. Liss, Henry A. Leder, JoAnn Starr, Jennifer L. Belz, Charlene K. Putzulo, Dallas R. Sandler, Jennifer L. Simmons, Pamela V. Singletary, Ashley Davis, Perel M. Simpson, Teresa Coffey, Daniel J. Ketner, Terri Cain, Ashley M. Metzger, Peter Sotirakos, Dennis M. Marcus, Harinderjit Singh, Courtney N. Roberts, Geri L. Floyd, Siobhan O. Ortiz, Virginia Mims, L. Allison Foster, Christy Coursey, Jared C. Gardner, Ken Ivey, John Stewart O'Keefe, Juan A. Astruc, Bryan J. Schwent, Ali R. Tabassian, Suzette A. Rosen, David C. Vaughan, Jeffrey Michaels, Natalie J. Arndt, John J. Maziarz, Scott M. Friedman, Nader Moinfar, Kimberly A. Williamson, Damanda F. Fagan, Katrina L. Dawson, Paige N. Walters, Allen McKinney, Steve Carlton, Robert C. Kwun, Victoria L. Knudsen, Kirk E. Winward, Mano Swartz, James G. Howard, Michelle Riley, Gena Taylor, Michelle Holt, Jason G. Winward, Adam Walsh, Teresa Taylor, Daniel Walsh, G. Robert Hampton, Jamin S. Brown, Rajeev K. Seth, Laurie J. Sienkiewycz, Deborah A. Appleton, Cindy J. Grinnell, Charity A. Cowley, Lynn M. Kwasniewski, Michelle L. Manley, Nicole E. Robarge, Stefanie R. DeSantis, Peter B. Hay, Teresa M. DeForge, Tien P. Wong, Eric Chen, David M. Brown, Rosa Y. Kim, James C. Major, Amy C. Schefler, Richard H. Fish, Matthew S. Benz, Meredith Lipman, Amy Hutson, Nubia Landaverde, Ashley E. Chancey, Cassie Cone, Tressa Royse, Veronica A. Sneed, Belinda A. Almanza, Brenda Dives, Beau A. Richter, Eric N. Kegley, Andreas K. Lauer, Christina J. Flaxel, Steven T. Bailey, Mitchell Schain, Ann D. Lundquist, Shelley A. Hanel, Shirley D. Ira, Susan K. Nolte, Peter N. Steinkamp, Dawn M. Ryan, Scott R. Pickell, Jocelyn T. Hui, Michelle Brix, Jordan Barth, Chris S. Howell, Gregory M. Fox, Blake A. Cooper, Ivan R. Batlle, Lexie R. Manning, Karla A. Batlle, Holly Wyrick, Katherine Pippin, Samantha Perkins, Frank T. Yeager, Ryan B. Rush, Glenn R. Gardner, Christi Rush, Johnathan R. Hawkins, Brenda Dumas, Ben Ysasaga, Chirag P. Shah, Michael G. Morley, Torsten W. Wiegand, Tina S. Cleary, Trexler M. Topping, Lindsey Colegrove, Katharine Bechtel, Britta Johnson, Lisa Lebedew, Natacha Lorius, Sandy G. Chong, Jennifer L. Stone, Michael Cullen Jones, Dennis Donovan, Sherry Malone, Margie Graham, Audrey Santos, Steve A. Bennett, Kevin J. Blinder, Bradley T. Smith, Ginny S. Nobel, Rhonda F. Weeks, Erika A. Hoehn, Maria A. Stuart, Kelly E. Pepple, Lynda K. Boyd, Brook G. Pulliam, Steve A. Schremp, Stephanie L. Guevara, Jarrod Wehmeier, Timothy L. Wright, Dana L. Gabel, David G. Miller, Jerome P. Schartman, Lawrence J. Singerman, Joseph M. Coney, Michael A. Novak, Llewelyn J. Rao, Susan C. Rath, Elizabeth McNamara, Larraine Stone, Veronica A. Smith, Cecelia Rykena, Kimberly A. DuBois, Mary A. Ilc, Vivian Tanner, Kim Drury, Trina M. Nitzsche, Gregg A. Greanoff, John C. DuBois, Stuart K. Burgess, Tirso M. Lara, Noel H. Pereda, Cindy V. Fernandez, Deborah Davis, Evelyn Quinchia, Karen Workman, Jared S. Nielsen, Jeong-Hyeon Sohn, Kyle J. Alliman, David D. Saggau, Marianne Parker, Bethany George, Carrie L. Eastvold, Kristin Sells, Tami Jo Woehl, Marilyn A. Johnson, Holly Keenan, Jennifer L. Coleman, Jamie Spillman, Shannon Freeman, Leigh S. Schmidt, Lisa M. Boender, Jill L. Partin, Bailey R. Bennett, Jay Rostvold, Cameron McLure Stone, Lea R. Raymer, Andrea K. Menzel, Leslie D. Rickman, Barbara Campbell, Lorraine P. Sherlin, Lisa H. Hawkins, Melissa L. Buckner, Olesya N. Matsipura, Paula A. Price, A. Thomas Ghuman, Paul A. Raskauskas, Ashish G. Sharma, Glenn Wing, Joseph P. Walker, Eileen Knips, Cheryl Kiesel, Crystal Y. Peters, Cheryl Ryan, Laura Greenhoe, Natalie N. Torres, Rebecca J. Youngblood, Danielle Turnbo, Anita H. Leslie, Etienne C. Schoeman, Raymond K. Kiesel, Ronald M. Kingsley, Vinay A. Shah, Robert E. Leonard, Heather R. Miller, Sonny Icks, Vanessa A. Bergman, Vanessa K. Drummond, Brittany L. Ross, Reshial D. Ellis, Tina R. Whittington, Shannon R. Almeida, Amanda M. Butt, Russ Burris, Mark A. Peters, Michael S. Lee, Paul S. Tlucek, Colin Ma, Stephen Hobbs, Amanda C. Milliron, Stephanie L. Ho, Marcia Kopfer, Joe Logan, Christine Hoerner, Joseph A. Khawly, Hassan T. Rahman, Diana Abdelgani, Pam S. Miller, Debbie Fredrickson, Erica Pineda, Desiree Lopez, Donald K. Lowd, Colin Blank, Lorena R. Martinez, Jason E. Muniz, Justin Gottlieb, Michael S. Ip, Barbara A. Blodi, Kristine A. Dietzman, Kathryn F. Burke, Christopher M. Smith, Shelly R. Olson, Angela M. Wealti, Sandie L. Reed, Denise A. Krolnik, John C. Peterson, Victor Hugo Gonzalez, Roberto Diaz-Rohena, Juan G. Santiago, Rohit Adyanthaya, Nehal R. Patel, Deyla Anaya, Dina Garcia, Edna E. Cruz, Crystal A. Alvarez, Ruth Iracheta, Jessica Rodriguez, Monica R. Cantu, Rebecca R. Flores, Hector Jasso, Rachel Rodriguez, Karina Miranda, Krystle R. Lozano, Maricela Garza, Lazaro Aguero, Amanda L. Sandoval, Monique Montemayor, Samuel Alonso, Santos Garza, David Allen DiLoreto, Rajeev S. Ramchandran, David M. Kleinman, George W. O'Gara, Andrea M. Czubinski, Peter MacDowell, Kari M. Steinmetz, Dan A. Castillo, Yvonne F. Yu, Salina M. Tongue, Melissa S. Keim, Rachel Hollar, Brandi N. Deats, Brittany S. Richardson, Lynn Singer, Taylor A. Pannell, Stewart A. Daniels, Tushar M. Ranchod, Craig J. Leong, Stacey Touson, Shannon R. Earl, Melissa C. Bartlett, Christine Fernando, Djorella Factor, Jessica Garcia, Anna K. Nguyen, Betty Hom, Cathy Walker, Grace M. Marudo, Jose Carlos Suazo, Leah M. McNeil, Fred Hanamoto, Matthew D. Hughes, Robin D. Ross, Susan M. Sanford, Nicole Martini Markiewicz, Tracy M. Utley, Shannon Henderson, Joanie H. Lippincott, Patricia Streasick, Louis C. Glazer, Frank W. Garber, Jeffrey D. Zheutlin, Angela D. Listerman, Christine E. Feehan, Heather L. Cruz, Donald E. Kuitula, Olivia P. Rainey, Sue Weatherbee, Joseph M. Googe, R. Keith Shuler, Nicholas G. Anderson, Stephen L. Perkins, Kristina Oliver, Nicole Grindall, Ann Arnold, Jennifer Beerbower, Cecile Hunt, Kathy L. Schulz, Sarah M. Oelrich, Jerry K. Whetstone, Justin Walsh, Chris Morris, Robert W. Wong, Peter A. Nixon, Jeni L. Leon, Chris A. Montesclaros, Carrie E. Leung, Phill Le, Codey L. Harborth, Margaret A. Rodriguez, Cory Mangham, Thomas M. Aaberg, Scott J. Westhouse, Holly L. Vincent, Rebecca Malone, Kathy L. Karsten, Raj K. Maturi, Ashley M. Harless, Carolee K. Novak, Laura A. Bleau, Thomas Steele, Charlotte Harris, Alisha Bildner, Abby Maple, Thomas W. Stone, Rick D. Isernhagen, John W. Kitchens, Diana M. Holcomb, Jeanne Van Arsdall, Michelle Buck, Edward A. Slade, Mark T. Chiu, Ashok K. Reddy, Frank W. Wyant, Mary M. Montano-Niles, Lorraine J. Carter, Shirley Maerki, Laura Tartaglia, Paul P. Gomez, Stephen A. Maestas, Camille Shanta, Lisbrenda M. Jimenez, Robert A. Stoltz, Stephanie L. Vanderveldt, Scott I. Lampert, Leslie G. Marcus, Shelly Fulbright, James P. Martin, Roger L. Novack, David S. Liao, Tammy Eileen Lo, Janet Kurokouchi, Richard Ngo, Connie V. Hoang, Julio Sierra, Adam Zamboni, Eric G. Protacio, Jeff Kessinger, Seema Garg, Odette M. Houghton, Jan Niklas Ulrich, Sai H. Chavala, Elizabeth L. DuBose, Cassandra J. Barnhart, Megha Karmalkar, Pooja D. Jani, Justin Goble, Debra Cantrell, Rona Lyn Esquejo, Sandeep N. Shah, Natasha Harmon, Mandeep S. Dhalla, Mario R. del Cid, Lawrence S. Halperin, Jaclyn A. Brady, Monica Hamlin, Monica L. Lopez, Jamie Mariano, Candace M. Neale, Rita R. Veksler, Angelica Mannarelli, Robert E. Coffee, Petros Euthymiou Carvounis, Pejman Hemati, Cindy J. Dorenbach, Annika S. Joshi, April Leger, Dana B. Barnett, Joseph F. Morales, Sam E. Mansour, Cathy Choyce, Aissa L. Dirawatun, Emma A. Nagy, Jamie C. Kerkstra, Joseph T. Fan, Mukesh Bhogilal Suthar, Michael E. Rauser, Gisela Santiago, Liel Marvyn Cerdenio, Brandi J. Perez, Kara E. Halsey, William H. Kiernan, Jesse Knabb, Rachel Catren, Michel Shami, Brenda K. Arrington, Keri S. Neuling, Ashaki Meeks, Natalie R. Garcia, Kayla Blair, Ginger K. Rhymes, Janet Medrano, Judy E. Kim, David V. Weinberg, Kimberly E. Stepien, Thomas B. Connor, Vesper V. Williams, Tracy L. Kaczanowski, Krissa L. Packard, Judy Flanders, Vicki Barwick, Pat A. Winter, Joseph R. Beringer, Kathy J. Selchert, John T. Lehr, Elaine Rodriguez-Roman, Teri Jones, Martha Eileen Haddox, Mark Pena, Brenda Hernandez, Clement K. Chan, Maziar Lalezary, Steven G. Lin, Kimberly S. Walther, Tiana Gonzales, Lenise E. Myers, Kenneth M. Huff, Richard Chace, Sunny Kallay, Kirsten Stevens, Nicole Dolbec, Ronda Baker-Hill, Janea Surette, Steven J. Rose, Brian P. Connolly, Ernest G. Guillet, Edward F. Hall, Margaret M. Yagoda, Mary Jo Doran, Mindy Burgess, Ann Reynard, Margaret Powers, Joe Territo, Calvin E. Mein, Moises A. Chica, R. Gary Lane, Sarah Elizabeth Holy, Lita Kirschbaum, Vanessa D. Martinez, Jaynee Baker, Christa G. Kincaid, Elaine Castillo, Christopher Sean Wienecke, Sara L. Schlichting, Brenda Nakoski, Kenneth R. Diddie, Deborah M. Cadwell, Louise Van Arsdale, Taryn F. Boisvert, Joyce Galonsky, Susie O'Hayer, Melissa L. Johnson, Frank J. McCabe, Brad J. Baker, Melvyn H. Defrin, Marie V. Lampson, Heather Pratte, Selena A. Baron, Aundrea S. Borelli, Frederick H. Davidorf, Michael B. Wells, Susie Chang, John Byron Christoforidis, Alan D. Letson, Jill A. Salerno, Jerilyn G. Perry, Stephen E. Shelley, Patrick J. Fish, Michael H. Scott, James A. Dixon, Shannon R. Walsh, Philomina M. Ozpirincci, Brenda L. Tebon, Marcia J. Moyle, Michael R. Pavlica, Noelle S. Matta, Cristina M. Brubaker, Alyson B. Backer, Neelakshi Bhagat, Catherine Fay, Tatiana Mikheyeva, Michael Lazar, Janie D. Ellenberger, Beth Malpica, Alexander J. Brucker, Benjamin J. Kim, Brian L. VanderBeek, Sheri Drossner, Joan C. DuPont, Rebecca Salvo, Stephanie B. Engelhard, Jim M. Berger, Sara Morales, Beth Serpentine, Paul L. Kaufman, Jessica D. McCluskey, Kathy T. Wynne, Julian Jordan, Brandun Watson, Robert S. Wirthlin, Eric S. Guglielmo, Eileen A. Dittman, Dylan C. Waidelich, Cristofer J. Garza, Adeline M. Stone, Ashley Nicole Oakes, Ivan J. Suner, Mark E. Hammer, Marc C. Peden, Janet R. Traynom, Rochelle DenBoer, Heidi Vargo, Susan Ramsey, Anita Kim Malzahn, Debra Jeffres, Nauman A. Chaudhry, Sumit P. Shah, Gregory M. Haffner, Emiliya German, Shannan Moreau, Laura A. Fox, Jennifer M. Matteson, JoAnna L. Pelletier, Alison Fontecchio, Emily Morse, Greg McNamara, Marie Grace Laglivia, Marissa L. Scherf, Angela LaPre, Justin A. Cocilo, Arup Das, Linda Friesen, Michele Franco, Johnny Lucero, Melissa Frazier, Robert Laviolette, Umar Khalil Mian, Rebecca L. Riemer, Evelyn Koestenblatt, Louise V. Wolf, Christine Kim, Irina Katkovskaya, Erica Otoo, Kevin A. Ellerbe, Kenneth Boyd, Caroline Costa, Paul Andrew Edwards, Hua Gao, Thomas Hessburg, Uday Desai, Janet Murphy, Mary K. Monk, Julianne Hall, Melina Mazurek, Katie M. Ventimiglia, Brian A. Rusinek, Bradley A. Stern, Kris Brouhard, Katie M. Weier, Megan Allis, Jenny Shaken, Nicole M. Massu, Tracy A. Troszak, David Burley, Abdhish R. Bhavsar, Geoffrey G. Emerson, Jacob M. Jones, Tracy A. Anderson, Andrea Gilchrist, Matt D. Peloquin, Gaid Gaid, Yang Vang, Samantha Ryan, Denise Vang, Alanna C. Evans, Tonja Scherer, Howard S. Lazarus, Debra Paige Bunch, Liana C. Davis, Kelly Booth, Margaret Trimble, Mary A. Bledsaw, Jay Moore, Daniel F. Rosberger, Sandra Groeschel, Miriam A. Madry, Nikoletta DiGirolamo, Dustin Pressley, Robert Santora, Yenelda M. Gomez, Karl R. Olsen, Robert L. Bergren, P. William Conrad, Pamela P. Rath, Avni Patel Vyas, Judy C. Liu, Lori A. Merlotti, Jennifer L. Chamberlin, Holly M. Mechling, Mary E. Kelly, Kellianne Marfisi, Kimberly A. Yeckel, Veronica L. Bennett, Christina M. Schultz, Grace A. Rigoni, Julie Walter, Missy A. Forish, Amanda Fec, Courtney L. Foreman, David Steinberg, Keith D. McBroom, Melvin C. Chen, Marc H. Levy, Waldemar Torres, Peggy Jelemensky, Tara L. Raphael, Joann Rich, Mark Sneath, James L. Kinyoun, Gurunadh Atmaram Vemulakonda, Susan A. Rath, Patricia K. Ernst, Juli A. Pettingill, Ronald C. Jones, Brad C. Clifton, James D. Leslie, Sharon D. Solomon, Lisa K. Levin, Deborah Donohue, Mary Frey, Lorena Larez, Keisha Murray, Rita L. Denbow, Janis Graul, David Emmert, Charles Herring, Nick Rhoton, Joe Belz, Alice T. Lyon, Rukhsana G. Mirza, Amanda M. Krug, Carmen Ramirez, Lori Kaminski, Anna Liza M. Castro-Malek, Amber N. Mills, Zuzanna Rozenbajgier, Marriner L. Skelly, Evica Simjanoski, Andrea R. Degillio, Jennifer I. Lim, Felix Y. Chau, Marcia Niec, Tametha Johnson, Yesenia Ovando, Mark Janowicz, Catherine Carroll, Jeffrey G. Gross, Barron C. Fishburne, Amy M. Flowers, Riley Stroman, Christen Ochieng, Angelique S.A. McDowell, Ally M. Paul, Randall L. Price, John H. Drouilhet, Erica N. Lacaden, Deborah J. Nobler, Howard L. Cummings, Deanna Jo Long, Ben McCord, Jason Robinson, Jamie Swift, Julie P. Maynard, Patricia J. Pahk, Hannah Palmer-Dwore, Dipali H. Dave, Mariebelle Pacheco, Barbara A. Galati, Eneil Simpson, Andrew J. Barkmeier, Diane L. Vogen, Karin A. Berg, Shannon L. Howard, Jean M. Burrington, Jessica Ann Morgan, Joan T. Overend, Shannon Goddard, Denise M. Lewison, Jaime L. Tesmer, Craig Michael Greven, Joan Fish, Cara Everhart, Mark D. Clark, David T. Miller, George Baker Hubbard, Jiong Yan, Blaine E. Cribbs, Linda T. Curtis, Judy L. Brower, Jannah L. Dobbs, Debora J. Jordan, Baseer U. Ahmad, Suber S. Huang, Hillary M. Sedlacek, Cherie L. Hornsby, Lisa P. Ferguson, Kathy Carlton, Kelly A. Sholtis, Peggy Allchin, Claudia Clow, Mark A. Harrod, Geoffrey Pankhurst, Irit Baum-Rawraway, Stacie A. Hrvatin, Ronald C. Gentile, Alex Yang, Wanda Carrasquillo-Boyd, Robert Masini, Chander N. Samy, Robert J. Kraut, Kathy Shirley, Linsey Corso, Karen Ely, Elizabeth Scala, Stewart Gross, Vanessa Alava, Eyal Margalit, Donna G. Neely, Maria Blaiotta, Lori Hagensen, April E. Harris, Rita L. Lennon, Denice R. Cota, Larry Wilson, Lloyd P. Aiello, Roy W. Beck, Susan B. Bressler, Kakarla V. Chalam, Ronald P. Danis, Bambi J. Arnold-Bush, Frederick Ferris, Talat Almukhtar, Brian B. Dale, Alyssa Baptista, Crystal Connor, Jasmine Conner, Sharon R. Constantine, Kimberly Dowling, Simone S. Dupre, Allison R. Ayala, Meagan L. Huggins, Seidu Inusah, Paula A. Johnson, Brenda L. Loggins, Shannon L. McClellan, Michele Melia, Eureca Battle, Cynthia R. Stockdale, Danielle Stanley, Glenn Jaffe, Brannon Balsley, Michael Barbas, Russell Burns, Dee Busian, Ryan Ebersohl, Cynthia Heydary, Sasha McEwan, Justin Myers, Amanda Robertson, Kelly Shields, Garrett Thompson, Katrina Winter, Ellen Young, Matthew D. Davis, Yijun Huang, Barbara Blodi, Amitha Domalpally, James Reimers, Pamela Vargo, Hugh Wabers, Dawn Myers, Daniel Lawrence, James Allan, Andrew Antoszyk, Scott Friedman, Ingrid U. Scott, Eleanor Schron, Donald F. Everett, Päivi H. Miskala, John Connett, Gary Abrams, Deborah R. Barnbaum, Harry Flynn, Ruth S. Weinstock, Charles P. Wilkinson, Stephen Wisniewski, Saul Genuth, Robert Frank, Frederick L. Ferris, Glenn J. Jaffe, Abdhish Bhavsar, Joseph Googe, Andreas Lauer, and Ashley McClain

Subjects
Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Visual acuity, genetic structures, Bevacizumab, Recombinant Fusion Proteins, Visual Acuity, 030232 urology & nephrology, Angiogenesis Inhibitors, Enzyme-Linked Immunosorbent Assay, Gastroenterology, Macular Edema, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Ranibizumab, Internal medicine, medicine, Humans, Stroke, Aflibercept, Diabetic Retinopathy, business.industry, Middle Aged, medicine.disease, Confidence interval, Vascular endothelial growth factor, Ophthalmology, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, chemistry, Intravitreal Injections, Retreatment, 030221 ophthalmology & optometry, Female, medicine.symptom, business, Tomography, Optical Coherence, Follow-Up Studies, medicine.drug
Abstract

PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P

Published
2018
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5. Quality Control Measures over 30 Years in a Multicenter Clinical Study: Results from the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Author

M. Bracey, B. French, Brandy N. Rutledge, Sharon B. Schwartz, D. Steinberg, Peter R. Pavan, Xiaoyu Gao, Alan M. Jacobson, David A. Nicolle, C. Canny, Maria F. Lopes-Virella, A. Kitabchi, K. Hansen, M. E. Lackaye, Denis Daneman, Kandace A. Klumpp, David A. Lee, H. Engel, L. Survant, C. Haggan, K. Lee, G. Ziegler, Dawn M. Ryan, Lloyd Paul Aiello, Tom G. Sheidow, Allan Gordon, Allan L. Drash, S. Johnsonbaugh, L. Kaminski, S. Yoser, David J. Brillon, Osama Hamdy, Connie Fountain, N. Silvers, Kusiel Perlman, S. Caulder, M. Szpiech, D. Freking, Paula McGee, George S. Sharuk, D. Counts, H. Solc, David E. Goldstein, L. Bestourous, W. F. Schwenk, E. Brown, S. Cercone, M. Patronas, James L. Kinyoun, G. Castle, Mark H. Schutta, M. L. Schluter, Anton Orlin, E. Chaum, Daniel P. Joseph, F. Goetz, V. Reppucci, D. Etzwiler, E. Golden, A. Iannacone, R. Kirby, Lucy A. Levandoski, Lawrence J. Singerman, P. Salemi, A. Morrison, G. Vagstad, J. Laechelt, Pamela Ossorio, Tae Sup Lee, R. Cuddihy, S. Hitt, Fred W. Whitehouse, Michael H. Brent, Gayle M. Lorenzi, Anthony D. Morrison, B. Zinman, Szilard Kiss, D. Norman, N. Olson, Thomas Donner, John Dupre, M. Swenson, M. Spencer, Jerry P. Palmer, Scott M. Steidl, M. Franz, R. Beaser, H. Martinez, Samuel S. Engel, L. Diminick, J. Mortenson, David S. Schade, S. Yacoub-Wasef, Misty Good, John E. Chapin, Paolo S. Silva, J. Ginsberg, A. Dwoskin, John P. Bantle, J. D. Carey, D. McMillan, R. G. Campbell, Lisa Diminick, C. Cornish, Ramzi K. Hemady, P. Hollander, A. Farr, D. Zimbler, M. Mech, A. Lucas, Jye-Yu C. Backlund, K. Chan, Timothy J. Murtha, V. Asuquo, A. Bhan, A. Galprin, F. Perdikaris, Michael D. Larsen, L. Gill, Pamela A. Silver, S. Brink, Louis M. Luttrell, Sheila Smith-Brewer, D. Ostrowski, M. Bratkowksi, P. Crawford, M. Bryer-Ash, E. Angus, S. Braunstein, John I. Malone, R. Conwit, C. Pittman, Louis A. Lobes, Rodney A. Lorenz, J. Rosenzwieg, Neil H. White, William I. Sivitz, D. J. Becker, Stephen S. Feman, M. Zaucha, M. Reid, M. Jenner, L. Tuason, C. Gauthier-Kelly, C. McDonald, William H. Herman, John Kramer, Jeffrey L. Mahon, A. Campbell, J. L. Canady, A. Degillio, T. Adkins, P. W. Conrad, Senda Ajroud-Driss, L. Dews, Stephan Villavicencio, David G. Miller, Manjot K. Gill, D. Curtin, J. Brown-Friday, M. Basco, Elsayed Z. Soliman, J. Selby, Bradley D. Jones, M. Hebdon, B. Olson, John M. Pach, N. W. Rodger, K. Stoessel, N. Leloudes, J. Floyd, H. Lambeth, G. Lorenzi, Richard M. Hoffman, S. Chang, M. Guiliani, H. Zegarra, N. Bakshi, Dean P. Hainsworth, Murk-Hein Heinemann, S. Dagogo-Jack, Wanjie Sun, J. Warnicki, Dean B. Burgess, D. Kenny, L. McKenzie, B. Rogness, Martin J. Stevens, M. Nutaitis, William V. Tamborlane, L. Schmidt, Deborah K. Schlossman, J. Giangiacomo, C. Williams, R. Liss, Barbara J. Maschak-Carey, Barbara H. Braffett, Stefan Fritz, J. MacIndoe, Tom Clark, M. Novak, Michael H. Goldbaum, A. DeManbey, J. Ahern, L. Jovanovic, D. Finegold, Davida F. Kruger, Mary E. Larkin, M. Johnson, S. Shah, M. Ong, Catherine L. Martin, M. Giotta, R. Reed, B. Levy, Evica Simjanoski, L. Cimino, P. Callahan, S. Crowell, Rodica Pop-Busui, Howard Wolpert, Bernard H. Doft, J. Arch, C. Shipe, Mark R. Palmert, Philip Raskin, B. Schaefer, P. Astelford, Dara D. Koozekanani, R. B. Avery, Michael W. Steffes, Robert A. Rizza, Karen L. Anderson, Charles McKitrick, P. A. Bourne, L. Baker, G. Friedenberg, D. Wood, J. Wesche, M. Phillips, Gaurav K. Shah, John M. Lachin, M. Christofi, Kevin J. Blinder, R. Ehrlich, J. Rinkoff, Morey W. Haymond, Irene Hramiak, Z. Strugula, A. Blevins, R. Hyre, M. Richardson, Mark E. Molitch, I. H. de Boer, Annette Barnie, Mark R. Burge, M. Prince, P. Ramos, R. Chan, R. Hanna, Jong Mu Sun, Suzanne M. Strowig, C. Wigley, Om P. Ganda, R. Harris, Abraham Thomas, K. Klumpp, K. Kelly, David D. Moore, J. Sheindlin, T. J. Declue, Cormac T. Taylor, C. Kwong, Rose Gubitosi-Klug, T. Sandford, Isaac Boniuk, B. Zimmerman, R. Zeitler, S. Rogers, Joseph M. Terry, C. Johnson, Linda Snetselaar, Naji Younes, Ionut Bebu, N. Wimmergren, Rukhsana G. Mirza, K. Gunyou, Karl R. Olsen, H. Bode, J. Fruit, Michael Rubin, G. Grand, Trevor J. Orchard, Douglas A. Greene, J. Quin, R. Birk, W. Mestrezat, P. Pugsley, Anupam Agarwal, L. Mayer, C. Palmer, Timothy J. Lyons, C. Johannes, A. Determan, L. Van Ottingham, J. Gott, Jerry D. Cavallerano, D. Cros, J. Parker, M. May, Robert Bergren, A. Kowarski, L. Delahanty, Katherine A. Morgan, E. A. Tanaka, Robert W. Cavicchi, Thomas J. Songer, Robert G. Devenyi, J. Harth, Jill P. Crandall, T. Thompson, Lee M. Jampol, H. Schrott, Paul G. Arrigg, Orville G. Kolterman, R. Warhol, L. Thomas, S. Kwon, Jane L. Lynch, Arup Das, Theresa M. Williams, Thomas A. Weingeist, Patricia A. Cleary, Matthew A. Thomas, L. Babbione, Amisha Wallia, J. Lipps Hagan, D. Meyer, D. Rubinstein, P. Lindsey, Mark S. Mandelcorn, R. Fahlstrom, John E. Godine, Kathie L. Hermayer, B. Bosco, J. Rich, K. Folino, M. L. Bernal, S. Yalamanchi, S. Barron, J. McConnell, J. K. Jones, J. Vaccaro-Kish, R. Woodwick, P. Colby, Kelvin C. Fong, Ronald K. Mayfield, L. H. Ketai, Julio V. Santiago, M. B. Murphy, S. Schussler, N. Grove, Larry Rand, Robert C. Colligan, Ronald P. Danis, Valerie L. Arends, S. Ferguson, B. Petty, Christine Stevens, P. Ostrosaka, Margaret L. Bayless, S. Moser, Paul A. Edwards, R. Lyon, M. Carney, Katrina Jones, T. Strand, W. Hsu, Alexander J. Brucker, H. Shamoon, Alice T. Lyon, T. Smith, David M. Nathan, P. Lou, Bruce A. Perkins, Janet E. Olson, D. Rosenberg, H. Ricks, J. Gordon, D. Hornbeck, Nikhil D. Patel, Shelly Olson, Ellen J. Anderson, William Dahms, P. Paczan Rath, S. Elsing, L. Steranchak, L. M. Aiello, Saul Genuth, S. Catton, Sandra R. Montezuma, S. Pendegast, Richard M. Bergenstal, Patricia Gatcomb, Igor Grant, B. Braffett, W. Brown, Margaret E. Stockman, N. Burkhart, David M. Kendall, Jyotika K. Fernandes, S. List, J. Soule, Julie A. Nelson, John A. Colwell, M. McLellan, Silva A. Arslanian, N. Rude, B. Vittetoe, M. Driscoll, and E. Weimann

Subjects
Adult, Male, 030213 general clinical medicine, medicine.medical_specialty, Adolescent, Quality Assurance, Health Care, Psychological intervention, lcsh:Medicine, law.invention, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Health care, medicine, Humans, Medical physics, lcsh:Science, Multidisciplinary, Data collection, business.industry, lcsh:R, Quality control, 3. Good health, Surgery, Data quality, Cohort, 030221 ophthalmology & optometry, Female, lcsh:Q, business, Quality assurance, Follow-Up Studies, Research Article
Abstract

Implementation of multicenter and/or longitudinal studies requires an effective quality assurance program to identify trends, data inconsistencies and process variability of results over time. The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study represent over 30 years of data collection among a cohort of participants across 27 clinical centers. The quality assurance plan is overseen by the Data Coordinating Center and is implemented across the clinical centers and central reading units. Each central unit incorporates specific DCCT/EDIC quality monitoring activities into their routine quality assurance plan. The results are reviewed by a data quality assurance committee whose function is to identify variances in quality that may impact study results from the central units as well as within and across clinical centers, and to recommend implementation of corrective procedures when necessary. Over the 30-year period, changes to the methods, equipment, or clinical procedures have been required to keep procedures current and ensure continued collection of scientifically valid and clinically relevant results. Pilot testing to compare historic processes with contemporary alternatives is performed and comparability is validated prior to incorporation of new procedures into the study. Details of the quality assurance plan across and within the clinical and central reading units are described, and quality outcomes for core measures analyzed by the central reading units (e.g. biochemical samples, fundus photographs, ECGs) are presented.

Published
2015

6. Enhanced depth imaging optical coherence tomography of congenital cavitary optic disc anomaly (CODA)

Author

Lee M. Jampol, Evica Simjanoski, Marion R. Munk, and John H. Fingert

Subjects
Adult, Male, Retinal Ganglion Cells, genetic structures, Optic Disk, Visual Acuity, Retinal Pigment Epithelium, Fundus (eye), Coda, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Young Adult, Nerve Fibers, Optical coherence tomography, Medicine, Humans, 610 Medicine & health, Intraocular Pressure, Aged, Retinal pigment epithelium, medicine.diagnostic_test, business.industry, Retinal, Eye Diseases, Hereditary, Anatomy, Middle Aged, Sensory Systems, eye diseases, Ophthalmology, medicine.anatomical_structure, chemistry, Optic nerve, Female, Choroid, sense organs, business, Tomography, Optical Coherence, Optic disc
Abstract

Aim To report the finding of extension of the 4th hyper-reflective band and retinal tissue into the optic disc in patients with cavitary optic disc anomalies (CODAs). Methods In this observational study, 10 patients (18 eyes) with sporadic or autosomal dominant CODA were evaluated with enhanced depth imaging optical coherence tomography (EDI-OCT) and colour fundus images for the presence of 4th hyper-reflective band extension into the optic disc. Results Of 10 CODA patients (18 eyes), five patients (8 eyes) showed a definite 4th hyper-reflective band (presumed retinal pigment epithelium (RPE)) extension into the optic disc. In these five patients (seven eyes), the inner retinal layers also extended with the 4th hyper-reflective band into the optic disc. Best corrected visual acuity ranged from 20/20 to 20/200. In three patients (four eyes), retinal splitting/schisis was present and in two patients (two eyes), the macula was involved. In all cases, the 4th hyper-reflective band extended far beyond the termination of the choroid into the optic disc. The RPE extension was found either temporally or nasally in areas of optic nerve head excavation, most often adjacent to peripapillary pigment. Compared with eyes without RPE extension, eyes with RPE extension were more myopic (mean dioptres −0.9±2.6 vs −8.8±5, p=0.043). Conclusions The RPE usually stops near the optic nerve border separated by a border tissue. With CODA, extension of this hyper-reflective band and retinal tissue into the disc is possible and best evaluable using EDI-OCT or analogous image modalities. Whether this is a finding specific for CODA, linked to specific gene loci or is also seen in patients with other optic disc abnormalities needs further evaluation.

Published
2014

7. Retinal Macroaneurysm in Long-Standing Hypertension

Author

Peter L. Nesper, Rukhsana G. Mirza, and Evica Simjanoski

Subjects
0301 basic medicine, medicine.medical_specialty, Retinal Artery, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Retinal Diseases, Ophthalmology, medicine, Retinal macroaneurysm, Humans, Fluorescein Angiography, Aged, medicine.diagnostic_test, business.industry, Subretinal Fluid, Retinal Hemorrhage, medicine.disease, Fluorescein angiography, Arterioles, 030104 developmental biology, Hypertension complications, Hypertension, 030221 ophthalmology & optometry, Female, Subretinal fluid, business, Tomography, Optical Coherence
Published
2016
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