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Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials
  1. Jason Q Core1,
  2. Peiying Hua2,
  3. Ebenezer Daniel2,
  4. Juan E Grunwald2,
  5. Glenn Jaffe3,
  6. Maureen G Maguire2,
  7. Gui-shuang Ying2
  8. for the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group
    1. 1Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    2. 2Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
    3. 3Ophthalmology, Duke Medicine, Durham, North Carolina, USA
    1. Correspondence to Dr Gui-shuang Ying, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA; gsying{at}pennmedicine.upenn.edu

    Abstract

    Background Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

    Methods Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models.

    Results Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference −6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference −75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference −41.9 um; p=0.001) and year 2 (difference −43.3 um; p=0.001).

    Conclusions In this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones.

    Trial registration number ClinicalTrials.gov NCT00593450.

    • Retina
    • Vision
    • Neovascularisation

    Data availability statement

    Data is available at the following website: https://hyperprod.cceb.med.upenn.edu/catt/catt_index.php

    Statistics from Altmetric.com

    Data availability statement

    Data is available at the following website: https://hyperprod.cceb.med.upenn.edu/catt/catt_index.php

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    Footnotes

    • Collaborators Credit Roster for the Comparison of AMD Treatments Trials: Clinical Centers (Ordered by Number of Patients Enrolled): Certified Roles at Clinical Centers: Clinic Coordinator (CC), Data Entry Staff (DE), Participating Ophthalmologist (O), Ophthalmic Photographer (OP); Optical Coherent Tomography Technician (OCT), Principal Investigator (PI), Refractionist (R), Visual Acuity Examiner (VA). VitreoRetinal Surgery, PA (Edina, MN): David F. Williams, MD (PI); Sara Beardsley, COA (VA/R); Steven Bennett, MD (O); Herbert Cantrill, MD (O); Carmen Chan-Tram, COA (VA/R); Holly Cheshier, CRA, COT, OCTC (OP); John Davies, MD (O); Sundeep Dev, MD (O); Julianne Enloe, CCRP, COA (CC); Gennaro Follano (OP/OCT); Peggy Gilbert, COA (VA/R); Jill Johnson, MD (O); Tori Jones, COA (OCT); Lisa Mayleben, COMT (CC/VA/R/OCT); Robert Mittra, MD (O); Martha Moos, COMT, OSA (VA/R); Ryan Neist, COMT (VA/R); Neal Oestreich, COT (CC); Polly Quiram, MD (O); Robert Ramsay, MD (O); Edwin Ryan, MD (O); Stephanie Schindeldecker, OA (VA/R); Trenise Steele, COA (VA); Jessica Tonsfeldt, AO (OP); Shelly Valardi, COT (VA/R). Texas Retina Associates (Dallas, TX): Gary Edd Fish, MD (PI); Hank A. Aguado, CRA (OP/OCT); Sally Arceneaux (CC/VA/R); Jean Arnwine (CC); Kim Bell, COA (VA/R); Tina Bell (CC/OCT); Bob Boleman (OP); Patricia Bradley, COT (CC); David Callanan, MD (O); Lori Coors, MD (O); Jodi Creighton, COA (VA/R); Kimberly Cummings (OP/OCT); Christopher Dock (OCT); Karen Duignan, COT (VA/R); Dwain Fuller, MD (O); Keith Gray (OP/OCT); Betsy Hendrix, COT, ROUB (OCT); Nicholas Hesse (OCT); Diana Jaramillo, COA (OCT); Bradley Jost, MD (O); Sandy Lash (VA/R); Laura Lonsdale, CCRP (DE); Michael Mackens (OP/OCT); Karin Mutz, COA (CC); Michael Potts (VA/R); Brenda Sanchez (VA/R); William Snyder, MD (O); Wayne Solley, MD (O); Carrie Tarter (VA/R); Robert Wang, MD (O); Patrick Williams, MD (O). Southeastern Retina Associates (Knoxville, TN): Stephen L. Perkins, MD (PI); Nicholas Anderson, MD (O); Ann Arnold, COT (VA/R); Paul Blais (OP/OCT); Joseph Googe, MD (O); Tina T. Higdon, (CC); Cecile Hunt (VA/R); Mary Johnson, COA (VA/R); James Miller, MD (O); Misty Moore (VA/R); Charity K. Morris, RN (CC); Christopher Morris (OCT); Sarah Oelrich, COT (OP/OCT); Kristina Oliver, COA (VA/R); Vicky Seitz, COT (VA/R); Jerry Whetstone (OP/OCT). Retina Vitreous Consultants (Pittsburgh, PA): Bernard H. Doft (PI); Jay Bedel, RN, (CC); Robert Bergren, MD (O); Ann Borthwick (VA/R); Paul Conrad, MD, PHD (O); Christina Fulwylie (VA/R); Willia Ingram (DE); Shawnique Latham (VA/R); Gina Lester (VA/R); Judy Liu, MD (O); Louis Lobes, MD (O); Nicole M. Lucko, (CC); Lori Merlotti, MS, CCRC (CC); Karl Olsen, MD (O); Danielle Puskas, COA (VA/R); Pamela Rath, MD (O); Lynn Schueckler (OCT); Christina Schultz (CC/VA/R); Heather Shultz (OP/OCT); David Steinberg, CRA (OP/OCT); Avni Vyas, MD (O); Kim Whale (VA/R); Kimberly Yeckel, COA, COT (VA/R). Ingalls Memorial Hospital/Illinois Retina Associates (Harvey, IL): David H. Orth, MD (PI); Linda S. Arredondo, RN (CC/VA); Susan Brown (VA/R); Barbara J. Ciscato (CC/VA); Joseph M. Civantos, MD (O); Celeste Figliulo (VA/R); Sohail Hasan, MD (O); Belinda Kosinski, COA (VA/R); Dan Muir (OP/OCT); Kiersten Nelson (OP/OCT); Kirk Packo, MD (O); John S. Pollack, MD (O); Kourous Rezaei, MD (O); Gina Shelton (VA); Shannya Townsend-Patrick (OP/OCT); Marian Walsh, CRA (OP/OCT). West Coast Retina Medical Group, Inc. (San Francisco, CA): H. Richard McDonald, MD (PI); Nina Ansari (VA/R/OCT); Amanda Bye, (OP/OCT); Arthur D. Fu, MD (O); Sean Grout (OP/OCT); Chad Indermill (OCT); Robert N. Johnson, MD (O); J. Michael Jumper, MD (O); Silvia Linares (VA/R); Brandon J. Lujan, MD (O); Ames Munden (OP/OCT); Rosa Rodriguez (CC); Jennifer M. Rose (CC); Brandi Teske, COA (VA/R); Yesmin Urias (OCT); Stephen Young (OP/OCT). Retina Northwest, P.C. (Portland, OR): Richard F. Dreyer, MD (PI); Howard Daniel (OP/OCT); Michele Connaughton, CRA (OP/OCT); Irvin Handelman, MD (O); Stephen Hobbs (VA/R/OCT); Christine Hoerner (OP/OCT); Dawn Hudson (VA/R/OCT); Marcia Kopfer, COT (CC/VA/R/OCT); Michael Lee, MD (O); Craig Lemley, MD (O); Joe Logan, COA (OP/OCT); Colin Ma, MD (O); Christophe Mallet (VA/R); Amanda Milliron (VA/R); Mark Peters, MD (O); Harry Wohlsein, COA (OP). Retinal Consultants Medical Group, Inc. (Sacramento, CA): Joel A. Pearlman, MD, PHD (PI); Margo Andrews (OP); Melissa Bartlett (OCT); Nanette Carlson (CC/OCT); Emily Cox (VA/R); Robert Equi, MD (O); Marta Gonzalez (VA/R); Sophia Griffin (OP/OCT); Fran Hogue (VA/R); Lance Kennedy (OP/OCT); Lana Kryuchkov (OCT); Carmen Lopez (VA/R); Danny Lopez (OP/OCT); Bertha Luevano (VA/R); Erin McKenna, (CC); Arun Patel, MD (O); Brian Reed, MD (O); Nyla Secor (CC/OCT); Iris R. Sison (CC); Tony Tsai, MD (O); Nina Varghis, (CC); Brooke Waller (OCT); Robert Wendel, MD (O); Reina Yebra (OCT). Retina Vitreous Center, PA (New Brunswick, NJ): Daniel B. Roth, MD (PI); Jane Deinzer, RN (VA/R); Howard Fine, MD MHSC (O); Flory Green (VA/R); Stuart Green, MD (O); Bruce Keyser, MD (O); Steven Leff, MD (O); Amy Leviton (VA/R); Amy Martir (OCT); Kristin Mosenthine (VA/R/OCT); Starr Muscle, RN (CC); Linda Okoren (VA/R); Sandy Parker (VA/R); Jonathan Prenner, MD (O); Nancy Price (CC); Deana Rogers (OP/OCT); Linda Rosas (OP/OCT); Alex Schlosser (OP/OCT); Loretta Studenko (DE); Thea Tantum (CC); Harold Wheatley, MD (O). Vision Research Foundation/Associated Retinal Consultants, P.C. (Royal Oak, MI): Michael T. Trese, MD (PI); Thomas Aaberg, MD (O); Denis Bezaire, CRA (OP/OCT); Craig Bridges, CRA (OP/OCT); Doug Bryant, CRA (OP/OCT); Antonio Capone, MD (O); Michelle Coleman, RN (CC); Christina Consolo, CRA, COT (OP/OCT); Cindy Cook, RN (CC); Candice DuLong (VA/R); Bruce Garretson, MD (O); Tracy Grooten (VA/R); Julie Hammersley, RN (CC); Tarek Hassan, MD (O); Heather Jessick (OP/OCT); Nanette Jones (VA/R/OP/OCT); Crystal Kinsman (VA/R); Jennifer Krumlauf (VA/R); Sandy Lewis, COT (VA/R/OP/OCT); Heather Locke (VA/R); Alan Margherio, MD (O); Debra Markus, COT (CC/VA/R/OP/OCT); Tanya Marsh, COA (OP/OCT); Serena Neal (CC); Amy Noffke, MD (O); Kean Oh, MD (O); Clarence Pence (OP/OCT); Lisa Preston (VA/R); Paul Raphaelian, MD (O); Virginia R. Regan, RN, CCRP (VA/R); Peter Roberts (OP/OCT); Alan Ruby, MD (O); Ramin Sarrafizadeh, MD, PHD (O); Marissa Scherf (OP/OCT); Sarita Scott (VA/R); Scott Sneed, MD (O); Lisa Staples (CC); Brad Terry (VA/R/OP/OCT); Matthew T. Trese (OCT); Joan Videtich, RN (VA/R); George Williams, MD (O); Mary Zajechowski, COT, CCRC (CC/VA/R). Barnes Retina Institute (St. Louis, MO): Daniel P. Joseph, MD (PI); Kevin Blinder, MD (O); Lynda Boyd, COT (VA/R); Sarah Buckley (OP/OCT); Meaghan Crow (VA/R); Amanda Dinatale, (OCT); Nicholas Engelbrecht, MD (O); Bridget Forke (OP/OCT); Dana Gabel (OP/OCT); Gilbert Grand, MD (O); Jennifer Grillion-Cerone (VA/R); Nancy Holekamp, MD (O); Charlotte Kelly, COA (VA/R); Ginny Nobel, COT (CC); Kelly Pepple (VA/R); Matt Raeber, (OP/OCT); P. Kumar Rao, MD (O); Tammy Ressel, COT (VA/R); Steven Schremp (OCT); Merrilee Sgorlon (VA/R); Shantia Shears, MA (CC); Matthew Thomas, MD (O); Cathy Timma (VA/R); Annette Vaughn,(OP/OCT); Carolyn Walters, COT (CC/VA/R); Rhonda Weeks, CRC (CC/VA/R); Jarrod Wehmeier (OP/OCT); Tim Wright (OCT). The Retina Group of Washington (Chevy Chase, MD): Daniel M. Berinstein, MD (PI); Aida Ayyad (VA/R); Mohammed K. Barazi, MD (O); Erica Bickhart (VA/R); Lisa Byank, MA (CC); Alysia Cronise, COA (VA/R); Vanessa Denny (VA/R); Courtney Dunn (VA/R); Michael Flory (OP/OCT); Robert Frantz (OP/OCT); Richard A. Garfinkel, MD (O); William Gilbert, MD (O); Michael M. Lai, MD, PHD (O); Alexander Melamud, MD (O); Janine Newgen (VA/R); Shamekia Newton (CC); Debbie Oliver (CC); Michael Osman, MD (O); Reginald Sanders, MD (O); Manfred von Fricken, MD (O). Retinal Consultants of Arizona (Phoenix, AZ): Pravin Dugel, MD (PI); Sandra Arenas (CC); Gabe Balea (OCT); Dayna Bartoli (OP/OCT); John Bucci (OP/OCT); Jennifer A. Cornelius (CC); Scheleen Dickens, (CC); Don Doherty (OP/OCT); Heather Dunlap, COA (VA/R); David Goldenberg, MD (O); Karim Jamal, MD (O); Norma Jimenez (OP/OCT); Nicole Kavanagh (VA/R); Derek Kunimoto, MD (O); John Martin (OP/OCT); Jessica Miner, RN (VA/R); Sarah Mobley, CCRC (CC/VA/R); Donald Park, MD (O); Edward Quinlan, MD (O); Jack Sipperley, MD (O); Carol Slagle (R); Danielle Smith (OP/OCT); Rohana Yager, COA (OCT). Casey Eye Institute (Portland, OR): Christina J. Flaxel, MD (PI); Steven Bailey, MD (O); Peter Francis, MD, PHD (O); Chris Howell, (OCT); Thomas Hwang, MD (O); Shirley Ira, COT (VA/R); Michael Klein, MD (O); Andreas Lauer, MD (O); Teresa Liesegang, COT (CC/VA/R); Ann Lundquist, (CC/VA/R); Sarah Nolte (DE); Susan K. Nolte (VA/R); Scott Pickell (OP/OCT); Susan Pope, COT (VA/R); Joseph Rossi (OP/OCT); Mitchell Schain (VA/R); Peter Steinkamp, MS (OP/OCT); Maureen D. Toomey (CC/VA/R); Debora Vahrenwald, COT (VA/R); Kelly West (OP/OCT). Emory Eye Center (Atlanta, GA): Baker Hubbard, MD (PI); Stacey Andelman, MMSC, COMT (CC/VA/R); Chris Bergstrom, MD (O); Judy Brower, COMT (CC/VA/R); Blaine Cribbs, MD (O); Linda Curtis (VA/R); Jannah Dobbs (OP/OCT); Lindreth DuBois, MED, MMSC, CO, COMT (CC/VA/R); Jessica Gaultney (OCT); Deborah Gibbs, COMT, CCRC (VA/R); Debora Jordan, CRA (OP/OCT); Donna Leef, MMSC, COMT (VA/R); Daniel F. Martin, MD (O); Robert Myles, CRA (OP); Timothy Olsen, MD (O); Bryan Schwent, MD (O); Sunil Srivastava, MD (O); Rhonda Waldron, MMSC, COMT, CRA, RDMS (OCT). Charlotte Eye, Ear, Nose & Throat Associates/Southeast Clinical Research (Charlotte, NC): Andrew N. Antoszyk, MD (PI); Uma Balasubramaniam, COA (OCT); Danielle Brooks, CCRP (VA/R); Justin Brown, MD (O); David Browning, MD, PHD (O); Loraine Clark, COA (OP/OCT); Sarah Ennis, CCRC (VA/R); Jennifer V. Helms, CCRC,(CC); Jenna Herby, CCRC (CC); Angie Karow, CCRP (VA/R); Pearl Leotaud, CRA (OP/OCT); Caterina Massimino (OCT); Donna McClain, COA (OP/OCT); Michael McOwen, CRA (OP/OCT); Jennifer Mindel, CRA, COA (OP/OCT); Candace Pereira, CRC (CC); Rachel Pierce, COA (VA/R); Michele Powers (OP/OCT); Angela Price, MPH, CCRC (CC); Jason Rohrer (CC); Jason Sanders, MD (O). California Retina Consultants (Santa Barbara, CA): Robert L. Avery, MD (PI); Kelly Avery (VA/R); Jessica Basefsky (CC/OCT); Liz Beckner (OP); Alessandro Castellarin, MD (O); Stephen Couvillion, MD (O); Jack Giust (CC/OCT); Matthew Giust (OP); Maan Nasir, MD (O); Dante Pieramici, MD (O); Melvin Rabena (VA/R); Sarah Risard (VA/R/OCT/DE); Robert See, MD (O); Jerry Smith (VA/R). Mayo Clinic (Rochester, MN): Sophie J. Bakri, MD (PI); Nakhleh Abu-Yaghi, MD (O); Andrew Barkmeier, MD (O); Karin Berg, COA (VA); Jean Burrington, COA (VA/R); Albert Edwards, MD (O); Shannon Goddard, COA (OP/OCT); Shannon Howard (VA/R); Raymond Iezzi, MD (O); Denise Lewison, COA (OP/OCT); Thomas Link, CRA (OP/OCT); Colin A. McCannel, MD (O); Joan Overend (VA/R); John Pach, MD (O); Margaret Ruszczyk, CCRP (CC); Ryan Shultz, MD (O); Cindy Stephan, COT (VA/R); Diane Vogen (CC). Dean A. McGee Eye Institute (Oklahoma City, OK): Reagan H. Bradford Jr, MD (PI); Vanessa Bergman, COA, CCRC (CC); Russ Burris (OP/OCT); Amanda Butt, CRA (OP/OCT); Beth Daniels, COA (CC); Connie Dwiggins, CCRC (CC); Stephen Fransen, MD (O); Tiffany Guerrero (CC/DE); Darin Haivala, MD (O); Amy Harris (CC); Sonny Icks (CC/DE); Ronald Kingsley, MD (O); Rob Richmond (OP/OCT); Brittany Ross (VA/R); Kammerin White, CCRC (VA/R); Misty Youngberg, COA, CCRC (VA/R). Ophthalmic Consultants of Boston (Boston, MA): Trexler M. Topping, MD (PI); Steve Bennett (OCT); Sandy Chong (VA/R); Tina Cleary, MD (O); Emily Corey (VA/R); Dennis Donovan (OP/OCT); Albert Frederick, MD (O); Lesley Freese (CC/VA/R); Margaret Graham (OP/OCT); Natalya Gud, COA (VA/R); Taneika Howard (VA/R); Mike Jones (OP/OCT); Michael Morley, MD (O); Katie Moses (VA/R); Jen Stone (VA/R); Robin Ty, COA (VA/R); Torsten Wiegand, PHD, MD (O); Lindsey Williams (CC); Beth Winder (CC). Tennessee Retina, P.C. (Nashville, TN): Carl C. Awh, MD (PI); Everton Arrindell, MD (O); Dena Beck (OCT); Brandon Busbee, MD (O); Amy Dilback (OP/OCT); Sara Downs (VA/R); Allison Guidry, COA (VA/R); Gary Gutow, MD (O); Jackey Hardin (VA/R); Sarah Hines, COA (CC); Emily Hutchins (VA/R); Kim LaCivita, MA (OP/OCT); Ashley Lester (OCT); Larry Malott (OP/OCT); MaryAnn McCain, RN, CNOR (CC); Jayme Miracle (VA/R); Kenneth Moffat, MD (O); Lacy Palazzotta (VA/R); Kelly Robinson, COA (VA/R); Peter Sonkin, MD (O); Alecia Travis (OP/OCT); RoyTrent Wallace, MD (O); Kelly J. Winters, COA (CC); Julia Wray (OP/OCT). Retina Associates Southwest, P.C. (Tucson, AZ): April E. Harris, MD (PI); Mari Bunnell (OCT); Katrina Crooks (VA/R); Rebecca Fitzgerald, CCRC (CC); Cameron Javid, MD (O); Corin Kew (VA/R); Erica Kill, VAE (VA/R); Patricia Kline (VA/R); Janet Kreienkamp (VA/R); RoyAnn Moore, OMA (CC/OCT); Egbert Saavedra, MD (O); LuAnne Taylor, CSC (CC/OCT); Mark Walsh, MD (O); Larry Wilson (OP). Midwest Eye Institute (Indianapolis, IN): Thomas A. Ciulla, MD (PI); Ellen Coyle, COMT (VA/R); Tonya Harrington, COA (VA/R); Charlotte Harris, COA (VA); Raj Maturi, MD (O); Stephanie Morrow, COA (OP); Jennifer Savage, COA (VA); Bethany Sink, COA (VA/R); Tom Steele, CRA (OP); Neelam Thukral, CCRC (CC/OCT); Janet Wilburn, COA (CC). National Ophthalmic Research Institute (Fort Myers, FL): Joseph P. Walker, MD (PI); Jennifer Banks (VA/R); Debbie Ciampaglia (OP/OCT); Danielle Dyshanowitz (VA/R); Jennifer Frederick, CRC (CC); A. Tom Ghuman, MD (O); Richard Grodin, MD (O); Cheryl Kiesel, CCRC (CC); Eileen Knips, RN, CCRC, CRA (OP/OCT); Crystal Peters, CCRC (CC); Paul Raskauskas, MD (O); Etienne Schoeman (OP/OCT); Ashish Sharma, MD (O); Glenn Wing, MD (O). University of Wisconsin Madison (Madison, WI): Suresh R. Chandra, MD (PI); Michael Altaweel, MD (O); Barbara Blodi, MD (O); Kathryn Burke, BA (VA/R); Kristine A. Dietzman, (CC); Justin Gottlieb, MD (O); Gene Knutson (OP/OCT); Denise Krolnik (OP/OCT); T. Michael Nork, MD (O); Shelly Olson (VA/R); John Peterson, CRA (OP/OCT); Sandra Reed (OP/OCT); Barbara Soderling (VA/R); Guy Somers (VA/R); Thomas Stevens, MD (O); Angela Wealti, (CC). Duke University Eye Center (Durham, NC): Srilaxmi Bearelly, MD (PI); Brenda Branchaud (VA/R); Joyce W. Bryant, COT, CPT (CC/VA/R); Sara Crowell (CC/VA); Sharon Fekrat, MD (O); Merritt Gammage (OP/OCT); Cheala Harrison, COA (VA/R); Sarah Jones (VA); Noreen McClain, COT, CPT, CCRC (VA/R); Brooks McCuen, MD (O); Prithvi Mruthyunjaya, MD (O); Jeanne Queen, CPT (OP/OCT); Neeru Sarin, MBBS (VA/R); Cindy Skalak, RN, COT (VA/R); Marriner Skelly, CRA (OP/OCT); Ivan Suner, MD (O); Ronnie Tomany (OP/OCT); Lauren Welch (OP/OCT). University of California-Davis Medical Center (Sacramento, CA): Susanna S. Park, MD, PHD (PI); Allison Cassidy (VA/R); Karishma Chandra (OP/OCT); Idalew Good (VA/R); Katrina Imson (CC); Sashi Kaur (OP/OCT); Helen Metzler, COA, CCRP (CC/VA/R); Lawrence Morse, MD, PHD (O); Ellen Redenbo, ROUB (OP/OCT); Marisa Salvador (VA/R); David Telander, MD (O); Mark Thomas, CRA (OCT); Cindy Wallace, COA (CC). University of Louisville School of Medicine, KY (Louisville, KY): Charles C. Barr, MD (PI); Amanda Battcher (VA/R); Michelle Bottorff, COA (CC/OCT); Mary Chasteen (VA/R); Kelly Clark (VA/R); Diane Denning, COT (OCT); Amy Schultz (OP); Evie Tempel, CRA, COA (OP); Greg K. Whittington, MPS, PSY (CC). Retina Associates of Kentucky (Lexington, KY): Thomas W. Stone, MD (PI); Todd Blevins (OP/OCT); Michelle Buck, COT, (VA/R/OCT); Lynn Cruz, COT (CC); Wanda Heath (VA/R); Diana Holcomb (VA/R); Rick Isernhagen, MD (O); Terri Kidd, COA (OCT); John Kitchens, MD (O); Cathy Sears, CST, COA (VA/R); Ed Slade, CRA, COA (OP/OCT); Jeanne Van Arsdall, COA (VA/R); Brenda VanHoose, COA (VA/R); Jenny Wolfe, RN (CC); William Wood, MD (O). Colorado Retina Associates (Denver, CO): John Zilis, MD (PI); Carol Crooks, COA (VA/R); Larry Disney (VA/R); Mimi Liu, MD (O); Stephen Petty, MD (O); Sandra Sall, ROUB, COA (CC/VA/R/OP/OCT). University of Iowa Hospitals & Clinics (Iowa City, IA): James C. Folk, MD (PI); Tracy Aly, CRA (OP/OCT); Abby Brotherton (VA); Douglas Critser, CRA (OP/OCT); Connie J. Hinz, COT, CCRC (CC/VA/R); Stefani Karakas, CRA (OP/OCT); Cheyanne Lester (VA/R); Cindy Montague, CRA (OP/OCT); Stephen Russell, MD (O); Heather Stockman (VA/R); Barbara Taylor, CCRC (VA/R); Randy Verdick, FOPS (OP/OCT). Retina Specialists (Towson, MD): John T. Thompson, MD (PI) ; Barbara Connell (VA/R); Maryanth Constantine (CC); John L. Davis Jr (VA/R); Gwen Holsapple (VA/R); Lisa Hunter (OP/OCT); C. Nicki Lenane (CC/VA/R/OCT); Robin Mitchell (CC); Leslie Russel, CRA (OP/OCT); Raymond Sjaarda, MD (O). Retina Consultants of Houston (Houston, TX): David M. Brown, MD (PI); Matthew Benz, MD (O); Llewellyn Burns (OCT); JoLene G. Carranza, COA, CCRC (CC); Richard Fish, MD (O); Debra Goates (VA/R); Shayla Hay (VA/R); Theresa Jeffers, COT (VA/R); Eric Kegley, CRA, COA (OP/OCT); Dallas Kubecka (VA/R); Stacy McGilvra (VA/R); Beau Richter (OCT); Veronica Sneed, COA (VA/R); Cary Stoever (OCT); Isabell Tellez (VA/R); Tien Wong, MD (O). Massachusetts Eye & Ear Infirmary/Harvard Vanguard Medical Associates (Boston, MA): Ivana Kim, MD (PI); Christopher Andreoli, MD (O); Leslie Barresi, CRA, COA, OCT-C (VA/OP/OCT); Sarah Brett (OP); Charlene Callahan (OP); Karen Capaccioli (OCT); William Carli, COA (VA/R/OCT); Matthew Coppola, COA (VA); Nicholas Emmanuel (CC); Claudia Evans, OD (VA/R); Anna Fagan, COA (VA/R); Marcia Grillo (OCT); John Head, CRA, OCT-C (OP/OCT); Troy Kieser, COA, OCT-C (CC/VA/R); Ursula Lord, OD (VA/R); Edward Miretsky (CC); Kate Palitsch (OCT); Todd Petrin, RN (OCT); Liz Reader (CC); Svetlana Reznichenko, COA (VA); Mary Robertson, COA (VA); Demetrios Vavvas, MD, PHD (O). Palmetto Retina Center (West Columbia, SC): John Wells, MD (PI); Cassie Cahill (VA/R); W. Lloyd Clark, MD (O); Kayla Henry (VA/R); David Johnson, MD (O); Peggy Miller (CC/VA/R); LaDetrick Oliver, COT (OP/OCT); Robbin Spivey (OP/OCT); Mallie Taylor (CC). Retina and Vitreous of Texas (Houston, TX): Michael Lambert, MD (PI); Kris Chase (OP/OCT); Debbie Fredrickson, COA (VA/R); Joseph Khawly, MD, FACS (O); Valerie Lazarte (VA/R); Donald Lowd (OP/OCT); Pam Miller (CC); Arthur Willis, MD (O). Long Island Vitreoretinal Consultants (Great Neck, NY): Philip J. Ferrone, MD (PI); Miguel Almonte (OCT); Rachel Arnott, (CC); Ingrid Aviles (VA/R/OCT); Sheri Carbon (VA/R); Michael Chitjian (OP/OCT); Kristen DAmore (CC); Christin Elliott (VA/R); David Fastenberg, MD (O); Barry Golub, MD (O); Kenneth Graham, MD (O); AnnMarie Lavorna (CC); Laura Murphy (VA/R); Amanda Palomo (VA/R); Christina Puglisi (VA/R); David Rhee, MD (O); Juan Romero, MD (O); Brett Rosenblatt, MD (O); Glenda Salcedo (OP/OCT); Marianne Schlameuss, RN (CC); Eric Shakin, MD (O); Vasanti Sookhai (VA/R). Wills Eye Institute (Philadelphia, PA): Richard Kaiser, MD (PI); Elizabeth Affel, MS, OCT-C (OCT); Gary Brown, MD (O); Christina Centinaro (CC); Deborah Fine, COA (OCT); Mitchell Fineman, MD (O); Michele Formoso (CC); Sunir Garg, MD (O); Lisa Grande (VA/R); Carolyn Herbert (VA/R); Allen Ho, MD (O); Jason Hsu, MD (O); Maryann Jay (OCT); Lisa Lavetsky (OCT); Elaine Liebenbaum (OP); Joseph Maguire, MD (O); Julia Monsonego (OP); Lucia O’Connor (OCT); Carl Regillo, MD (O); Maria Rosario (DE); Marc Spirn, MD (O); James Vander, MD (O); Jennifer Walsh (VA/R). Ohio State University Eye Physicians & Surgeons-Retina Division (Dublin, OH): Frederick H. Davidorf, MD (PI); Amanda Barnett (OP/OCT); Susie Chang, MD (O); John Christoforidis, MD (O); Joy Elliott (CC); Heather Justice (VA/R); Alan Letson, MD (O); Kathryne McKinney, COMT (CC); Jeri Perry, COT (VA/R); Jill A. Salerno, COA (CC); Scott Savage (OP); Stephen Shelley (OCT). Retina Associates of Cleveland (Beachwood, OH): Lawrence J. Singerman, MD (PI);Joseph Coney, MD (O); John DuBois (OP/OCT); Kimberly DuBois, LPN, CCRP, COA (VA/R); Gregg Greanoff, CRA (OP/OCT); Dianne Himmelman, RN, CCRC (CC); Mary Ilc, COT (VA/R); Elizabeth Mcnamara (VA/R/OP); Michael Novak, MD (O); Scott Pendergast, MD (O); Susan Rath, PA-C (CC); Sheila Smith- Brewer, CRA (OP/OCT); Vivian Tanner, COT, CCRP (VA/R); Diane E. Weiss, RN, (CC); Hernando Zegarra, MD (O). Retina Group of Florida (Fort Lauderdale, FL): Lawrence Halperin, MD (PI); Patricia Aramayo (OCT); Mandeep Dhalla, MD (O); Brian Fernandez, MD (OP/OCT); Cindy Fernandez, MD (CC); Jaclyn Lopez (CC); Monica Lopez (OCT); Jamie Mariano, COA (VA/R); Kellie Murphy, COA (OCT); Clifford Sherley, COA (VA/R); Rita Veksler, COA (OP/OCT). Retina-Vitreous Associates Medical Group (Beverly Hills, CA): Firas Rahhal, MD (PI); Razmig Babikian (DE); David Boyer, MD (O); Sepideh Hami (DE); Jeff Kessinger (OP/OCT); Janet Kurokouchi (CC); Saba Mukarram (VA/R); Sarah Pachman (VA/R); Eric Protacio (OCT); Julio Sierra (VA/R); Homayoun Tabandeh, MD, MS, FRCP (O); Adam Zamboni (VA/R). Elman Retina Group, P.A. (Baltimore, MD): Michael Elman, MD (PI); Tammy Butcher (CC); Theresa Cain (OP/OCT); Teresa Coffey, COA (VA/R); Dena Firestone (VA/R); Nancy Gore (VA/R); Pamela Singletary (VA/R); Peter Sotirakos (OP/OCT); JoAnn Starr (CC). University of North Carolina at Chapel Hill (Chapel Hill, NC): Travis A. Meredith, MD (PI); Cassandra J. Barnhart, MPH (CC/VA/R); Debra Cantrell, COA (VA/R/OP/OCT); RonaLyn Esquejo- Leon (OP/OCT); Odette Houghton, MD (O); Harpreet Kaur (VA/R); Fatoumatta NDure, COA (CC). Ophthalmologists Enrolling Patients but No Longer Affiliated with a CATT Center: Ronald Glatzer, MD (O); Leonard Joffe, MD (O); Reid Schindler, MD (O). Resource Centers: Chairman’s Office (Cleveland Clinic, Cleveland, OH): Daniel F. Martin, MD (Chair); Stuart L. Fine, MD (Vice-Chair; University of Colorado, Denver CO); Marilyn Katz (Executive Assistant). Coordinating Center (University of Pennsylvania, Philadelphia, PA): Maureen G. Maguire, PhD (PI); Mary Brightwell-Arnold, SCP (Systems Analyst); Ruchira Glaser, MD (Medical Monitor); Judith Hall (Protocol Monitor); Sandra Harkins (Staff Assistant); Jiayan Huang, MS (Biostatistician); Alexander Khvatov, MS (Systems Analyst); Kathy McWilliams, CCRP (Protocol Monitor); Susan K. Nolte (Protocol Monitor); Ellen Peskin, MA, CCRP (Project Director); Maxwell Pistilli, MS, MEd (Biostatistician); Susan Ryan (Financial Administrator); Allison Schnader (Administrative Coordinator); Gui-shuang Ying, PhD (Senior Biostatistician). OCT Reading Center (Duke University, Durham, NC): Glenn Jaffe, MD (PI); Jennifer Afrani-Sakyi (CATT PowerPoint Presentations); Brannon Balsley (OCT Technician Certifications); Linda S. Bennett (Project Manager); Adam Brooks (Reader/SD-Reader); Adrienne Brower-Lingsch (Reader); Lori Bruce (Data Verification); Russell Burns (Senior Technical Analyst/Senior Reader/SD Reader/OCT Technician Certifications); Dee Busian (Reader); John Choong (Reader); Lindsey Cloaninger (Reader Reliability Studies/ Document Creation/CATT PPT Files); Francis Char DeCroos (Research Associate); Emily DuBois (Data Entry); Mays El-Dairi (Reader/SD-Reader); Sarah Gach (Reader); Katelyn Hall (Reader Reliability Studies/ Data Verification/Document Creation); Terry Hawks (Reader); ChengChenh Huang (Reader); Cindy Heydary (Senior Reader/Quality Assurance Coordinator/SD Reader/Data Verification); Alexander Ho (Reader, Transcription); Shashi Kini (Data Entry/Transcription); Michelle McCall (Data Verification); Daaimah Muhammad (Reader Feedback); Jayne Nicholson (Data Verification); Jeanne Queen (Reader/SD-Reader); Pamela Rieves (Transcription); Kelly Shields (Senior Reader); Cindy Skalak (Reader); Adam Specker (Reader); Sandra Stinnett (Biostatistician); Sujatha Subramaniam (Reader); Patrick Tenbrink (Reader); Cynthia Toth, MD (Director of Grading); Aaron Towe (Reader); Kimberly Welch (Data Verification); Natasha Williams (Data Verification); Katrina Winter (Senior Reader); Ellen Young (Senior Project Manager). Fundus Photograph Reading Center (University of Pennsylvania, Philadelphia, PA): Juan E. Grunwald, MD (PI); Judith Alexander (Director); Ebenezer Daniel, MBBS, MS, MPH, PhD (Director); Elisabeth Flannagan (Administrative Coordinator); E. Revell Martin (Reader); Candace Parker (Reader); Krista Sepielli (Reader); Tom Shannon (Systems Analyst); Claressa Whearry (Data Coordinator). National Eye Institute, National Institutes of Health: Maryann Redford, DDS, MPH (Program Officer). Committees: Executive Committee: Daniel F. Martin, MD (chair); Robert L. Avery, MD; Sophie J. Bakri, MD; Ebenezer Daniel, MBBS, MS, MPH; Stuart L. Fine, MD; Juan E. Grunwald, MD; Glenn Jaffe, MD, Marcia R. Kopfer, BS, COT; Maureen G. Maguire, PhD; Travis A. Meredith, MD; Ellen Peskin, MA, CCRP; Maryann Redford, DDS, MPH; David F. Williams, MD. Operations Committee: Daniel F. Martin, MD (chair); Linda S. Bennett; Ebenezer Daniel, MBBS, MS, MPH; Frederick L. Ferris III, MD; Stuart L. Fine, MD; Juan E. Grunwald, MD; Glenn Jaffe, MD; Maureen G. Maguire, PhD; Ellen Peskin, MA, CCRP; Maryann Redford, DDS, MPH; Cynthia Toth, MD. Clinic Monitoring Committee: Ellen Peskin, MA, CCRP (chair); Mary Brightwell-Arnold, SCP; Joan DuPont; Maureen G. Maguire, PhD; Kathy McWilliams, CCRP; Susan K. Nolte. Data and Safety Monitoring Committee: Lawrence M. Friedman, MD (chair); Susan B. Bressler, MD; David L. DeMets, PhD; Martin Friedlander, MD, PhD; Mark W. Johnson, MD; Anne Lindblad, PhD; Douglas W. Losordo, MD, FACC; Franklin G. Miller, PhD.

    • Contributors G-SY and MGM take responsibility for the integrity of the data and Jason Core takes responsibility for the accuracy of the data analysis. GJ and JEG take responsibility for the integrity of image acquisition and readings. Analysis design: all authors. Statistical Analysis: PH. Drafting of the manuscript: JQC. Critical revision of the manuscript: all authors. Supervision: G-SY, MGM and ED. Administrative support for clinical trial: MGM. G-SY is guarantor.

    • Funding This study was supported by cooperative agreements U10 EY017823, U10 EY017825, U10 EY017826, U10 EY017828 and R21EY023689 from the National Eye Institute, National Institutes of Health, and Department of Health and Human Services. ClinicalTrials.gov number: NCT00593450.

    • Competing interests ED is a consultant to Novartis International AG. MGM serves on a data and safety monitoring committee for Genentech/Roche. GJ has a consultancy relationship with Alcon/Novartis, Genentech/Roche, Neurotech, EyePoint Pharmaceuticals and Adverum. G-SY is a consultant to Chengdu Kanghong Biotech, Ziemer Ophthalmic Systems AG and Synergy Research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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