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Association between early and late response in eyes with central or hemiretinal vein occlusion treated with anti-VEGF agents

SCORE2 report 12: secondary analysis of the SCORE2 clinical trial

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To assess whether early visual acuity letter score change from baseline (ΔVALS) and early spectral domain optical coherence tomography (SD-OCT) measures of center point thickness (CPT) are associated with later ΔVALS in eyes with macular edema due to central or hemiretinal vein occlusion treated with intravitreal aflibercept or bevacizumab.

Methods

Secondary analysis of a randomized clinical trial of 362 participants.

Results

Considered separately at month 3, CPT (categorized as ≤ 300 μm, > 300 μm) and ΔVALS (categorized as < 5, 5–9, ≥ 10) are predictive of ΔVALS at month 6 (aflibercept: P = 0.02 for CPT and P < 0.0001 for ΔVALS; bevacizumab: P = 0.007 for CPT and P < 0.0001 for ΔVALS) and, except for CPT in the bevacizumab arm, also predictive of ΔVALS at month 12 (aflibercept: P = 0.03 for CPT and P < 0.0001 for ΔVALS; bevacizumab: P = 0.18 for CPT and P < 0.0001 for ΔVALS). Month 3 predictors are also associated with average ΔVALS from months 4 to 12 (CPT P = 0.01 in the aflibercept arm, P = 0.02 in the bevacizumab arm; ΔVALS > 10 versus < 5; P < 0.001 for both aflibercept and bevacizumab). When month 3 measures are considered jointly, ΔVALS effect remains significant for average ΔVALS from months 4 to 12 (aflibercept: P = 0.002; bevacizumab: P < 0.0001) but not CPT (aflibercept: P = 0.18; bevacizumab: P = 0.22).

Conclusion

While both month 3 ΔVALS and CPT are predictive of ΔVALS after month 3 through month 12, early ΔVALS has a stronger relationship than CPT with later ΔVALS. SCORE2 registration number is NCT01969708.

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Data availability

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Notes

  1. Some of the month-pairs add no information about correlation. For example, VALS change from month 0 is identically 0 at month 0. Also, the autocorrelation of VALS change with itself in the same month must be 1. Thus, there are 66 informative autocorrelation coefficients and 90 informative cross-correlation coefficients.

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Acknowledgments

The Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) Investigator Group members are SCORE2 Executive Committee: Ingrid U. Scott, (Study Chair), Penn State College of Medicine; Michael S. Ip (Study Co-Chair), Doheny Eye Center UCLA; Barbara A. Blodi (Principal Investigator), Fundus Photograph Reading Center; Sangeeta Bhargava (Director, Clinical Trials), National Eye Institute, NIH; Paul VanVeldhuisen (DCC Principal Investigator), The Emmes Company, LLC; Neal L. Oden (DCC Statistician), The Emmes Company, LLC; Maria J. Figueroa (DCC Project Director), The Emmes Company, LLC. SCORE2 Data and Safety Monitoring Committee: David C. Musch (Chair), University of Michigan; Sangeeta Bhargava, National Eye Institute, NIH; Dennis P. Han, Medical College of Wisconsin; Srinivas R. Sadda, Doheny Eye Institute; George A. Williams, Beaumont Eye Institute; Stephen Wisniewski, University of Pittsburgh. Penn State University: Ingrid U. Scott (Study Chair), Janelle Gaston (Research Project Manager). SCORE2 Data Coordinating Center (DCC): Paul VanVeldhuisen (Principal Investigator), Maria Figueroa (Project Director), Lena Bradley, Jodi De Stefano, Eileen Guan, Anne Hoehn, Alexa Irazabal, Sue Isman, Jacquie King, Radhika Kondapaka, Hamsa Kumar, Matt Lahut, Robert Lindblad, Robin Lovett, Neal Oden, Michael Patschak, Ro Shauna Rothwell, Rosemary Smith, Janet Van Dyke, Valerie Watson, Lauren Yesko. SCORE2 Fundus Photograph Reading Center (FPRC): Barbara A. Blodi (Principal Investigator), Amitha Domalpally (Research Director), Susan Reed (Research Program Manager), Pam Vargo (Lead Imaging Specialist). Institute for Personalized Medicine: Cynthia Reed (Patient Enrollment Specialist).

Sites are listed in alphabetical order. Personnel are listed by their primary role as PI (PI), subinvestigator (SI), clinic coordinator (CC), visual acuity technician (V), photographer (P), pharmacist (PH), and other (O). Black Hills Regional Eye Institute Prema Abraham (PI), Beth Bement-Stump (V), Leah Callahan (CC), Mindi Dockter (V), Kristi Livermont (CC), Robert Nixon (SI), Dan Parks (P), Nathan Steinle (SI), Alison Thompson (CC), Dylan Yu (SI); Casey Eye Institute-Oregon Health & Science University Steven Bailey (SI), Jordan Barth (P), J. Peter Campbell (SI), Christina Flaxel (SI), Christopher Howell (P), Jocelyn Hui (P), Thomas Hwang (SI), Shirley Ira (V), Andreas Lauer (PI), Phoebe Lin (SI), Ann Lundquist (CC), Susan Nolte (V), Scott Pickell (P), Dawn Ryan (P), Mitchell Schain (CC), Peter Steinkamp (P), Chiedozie Ukachukwu (P), Sara Blefgen (PH), Brad Fujisaki (PH), Jeanne Liming (PH), Frank Mistretta (PH), Jennifer Petrolati (PH); Center for Retina and Macular Disease Adam Berger (SI), Erika Darby (P), Vera Dilts (V), Richard Hamilton (SI), Laura Holm (V), Tammy McCarty (CC), Esmeralda Medina (CC), David Misch (SI), Suk Jin Moon (SI), Kari Owen (P), John Randolph (SI), Jason Strickland (P), Dawn Sutherland (CC), Michael Tolentino (PI), Nicole Varner (V); Charlotte Eye Ear Nose & Throat Andrew Antoszyk (PI), Uma Balasubramaniam (P), Swann Bojaj (P), David Browning (SI), Loraine Clark (P), Sarah Ennis (V), Christina Fleming (CC), Autumn Finch (P), Sherry Fredenberg (V), Angie Gentile (CC), Lisa Jackson (P), Donna McClain (P), Michael McOwen (P), Angela Price (CC), Omar Punjabi (SI), Beverly Rowland (P), Lynn Watson (P); Cumberland Valley Retina Consultants Ellis Bloom (P), Thomas Catapano (P), Mariia Chornobai (CC), Nicole Hollimon (P), Allen Hu (SI), Donna King (V), Christa McChancy (P), Wendy McCullough (V), Kristen Miller (CC), George Sanborn (SI), Ejiatu Sesay (P), Veronica Shetler (V), Paula Smith (CC), Becca Varner (P), Leslee Wallech (V), Shayla Ward (CC), David Warrow (SI), Cherie Wenger (P), Alison Wentz (CC), Kimberly Wood (P), John Wroblewski (PI); Dean McGee Eye Institute Shannon Almeida (CC), Vanessa Bergman (V), Joann Booth (P), Reagan Bradford (SI), Alisha Brewer (CC), Russ Burris (P), Mandi Butt (P), Vanessa Drummond (CC), Stephen Fransen (SI), Sonny Icks (V), Ronald Kingsley (PI), Robert Leonard (SI), Heather Miller (V), Vinay Shah (SI), Vicki Wolzen (P); Delaware Valley Retina Associates Krista Bayer (P), Lorraine Eggert (V), Susan Geraghty (P), Morgan Harper (V), Darmakusuma Ie (PI), Lauren Knezek (P), Jeffrey Lipkowitz (SI), Beverly Sannazzaro (CC), Kekul Shah (SI); East Bay Retina Consultants Inc. Renjini Balakrishnan (CC), Fazilla Bano (V), Daniel Brinton (SI), Denise Bustamante (V), Elyssa Casugay (CC), Roby Casupanan (V), Patty Chung (V), Heather Enyart (P), Caroline Frambach (V), Khaliah Jackson (V), Afsoon Jamali (P), Mae Kwan (V), Scott Lee (SI), Eugene Lit (PI), Joshua Machacon (V), Patty Madrigal (V), Scotty Renslow (CC), Helen Ricks (V), Soraya Rofagha (SI), Heidi Winje (CC); Elman Retina Group PA Jennifer Belz (CC), Theresa Cain (P), Teresa Coffey (V), Ashley Davis (V), Michael Elman (PI), Henry Leder (SI), Ashley Metzger (P), Peggy Orr (V), Dallas Sandler (V), Jennifer Simmons (V), Perel Simpson (V), Pamela Singletary (V), Peter Sotirakos (P), JoAnn Starr (CC), Amy Thompson (V); Emory University Eye Center Judy Brower (V), Blaine Cribbs (SI), Linda Curtis (CC), Jannah Dobbs (P), Deborah Gibbs (CC), Andrew Hendrick (PI), G. Baker Hubbard (SI), Debbie Jordan (P), Donna Leef (V), Darien Middleton (O), Ghazala O’Keefe (SI), Timothy Olson (SI), Samillya Pearson (P), Matthew Raeber (P), Joshua Robinson (SI), Susan Rogers (PH), Jiong Yan (SI); Florida Retina Consultants Jackie Andrews (V), Steve Carlton (P), Katrina Dawson (CC), Damanda Fagan (CC), Scott Friedman (PI), Tammi Marsh (CC), Allen McKinney (V), Nader Moinfar (SI), Karen Seyez (V), Paige Walters (V), Ceara Wendel (CC), Kimberly Williamson (CC); Georgia Retina Jini Jones (P), Leslie Jones (V), Scott Lampert (SI), Leslie Marcus (CC), Krishna Mukkamala (SI), Lindsey Neal (P), Lauren Nunn (CC), Maria Rogers (V), Atul Sharma (SI), Robert Stoltz (PI), Morgan West (P); Henry Ford Health System Megan Allis (P),Celia Benvenutti (CC), David Burley (P), Uday Desai (SI), Paul Edwards (PI), Hua Gao (SI), John Grybas (P), Melanie Gutkowski (V), Julianne Hall (CC), Thomas Hessburg (SI), Nitin Kumar (SI), Nicole Massu (P), Melina Mazurek (V), Mary Monk (CC), Janet Murphy (V), Jessica Nelson (P), Dinah Oude-Reimerink (V), Brian Rusinek (P), Jenny Shaheen (P), Jessica Staffne (P), Bradley Stern (P), Tracey Troszak (P), Katie Ventimiglia (V); Icahn School of Medicine at Mount Sinai Wanda Carrasquillo-Boyd (P), John Bo Soo Choi (V), Yuen Ping Chui (SI), Ronald Gentile (SI), Priya Mehta (V), Melissa Rivas (CC), Richard Rosen (PI), Katy Tai (CC), Jia Tan (V), Meliza Unson (V), Paul Whitten (P), Alex Yang (V); Illinois Eye and Ear Infirmary University of Illinois at Chicago Catherine Carroll (P), Felix Chau (SI), Mark Janowicz (P), Tametha Johnson (V), Yannek Leiderman (SI), Jennifer Lim (PI), Marcia Niec (CC), Yesenia Ovando (V), Kevin Reyes (P), Natasa Stankovic (V), Jie (Jessica) Sun (CC), Lauren Talasnik (CC), Lawrence Ulanski (SI); Loma Linda University Armand Assissini (P), Marvyn Cerdenio (CC), Joseph Fan (SI), Raquel Hernandez (CC), Lynn Huang (SI), William Kiernan (V), Jesse Knabb (P), Michael Rauser (PI), Gisela Santiago (CC), Mukesh Suthar (SI), Brandon Williams (P); Long Island Vitreoretinal Consultants Michael Chitjian (P), Kristen D’Amore (CC), Vincent Deramo (SI), David Fastenberg (SI), Philip Ferrone (PI), Barry Golub (SI), Kenneth Graham (SI), Sandra Jaya (V), Jonathan Jonisch (SI), David Rhee (SI), Juan Romero (SI), Brett Rosenblatt (SI), Marianne Schlameuss (CC), Jeffrey Shakin (SI), Eric Shakin (SI), Vasanti Sookhai (V), Jamie Szczepanski (V); Mayo Clinic Betsy Baker (CC), Sophie Bakri (PI), Andrew Barkmeier (SI), Jean Burrington (V), Gillian Currie (CC), Melissa Franzen (CC), Shannon Goddard (P), Denise Lewison (P), Jessica Morgan (V), Rebecca Nielsen (CC), Joan Overend (V), Heidi Rubin (CC), Wendy Smith (SI), Jamie Tesmer (P), Stephanie Thatcher (P), Diane Vogen (CC); Medical Center Ophthalmology Associates Rahen Ahmed (SI), Rene Andrade (P), Darren Bell (SI), Connie Bermea (V), Carrisa Bolado (CC), Jason Burns (SI), Melissa Dominguez (V), Catherine Ellis (CC), Rosa Escobar (P), Richard Evans (SI), Shelli Goel (P), Roxanne Gomez (V), Felicia Huron (V), Lita Kirschbaum (CC), Guillermo Montoya (CC), Cynthia Myrick (CC), Nellie Quiroga (P), Judy Rittimann (CC), Vincent Segovia (P), Michael Singer (PI); Medical College of Wisconsin Marriner Altmann (P), Vicki Barwick (V), Joe Beringer (P), Joseph Carroll (SI), Thomas Connor (SI), Eleanor Dorsey (CC), Mara Goldberg (P), Kristy Keller (P), Judy Kim (PI), Katie McKenney (CC), Stephanie Moebius (P), Krissa Packard (CC), Brittany Rego (V), Amber Roberts (V), Hannah Russell (P), Kimberly Stepien (SI), David Weinberg (SI), Vesper Williams (CC), Pat Winter (V), William Wirostko (SI); Mid Atlantic Retina Hannah Benfield (CC), Christina Centinaro (V), Allen Chiang (SI), Lauren Devine (V), Mitchell Fineman (SI), Michele Formoso (CC), Sunir Garg (SI), Cedric George (O), Elaine Gonzales (P), Lisa Grande (V), Omesh Gupta (SI), Allen Ho (SI), Samuel Houston (SI), Jason Hsu (SI), Maryann Jay (P), Richard Kaiser (SI), Brianna Kenney (CC), Lisa Lavetsky (P), Theresa Listner (CC), Joseph Maguire (SI), Sonia Mehta (SI), Jill Noble (O), Carl Park (SI), Ehsan Rahimy (SI), David Reed (SI), Carl Regillo (PI), Noga Senderowitsch (CC), Arunan Sivalingam (SI), Marc Spirn (SI), Jamilla Sudler (V); Midwest Eye Institute Erin Brown (CC), Thomas Ciulla (SI), Tammy Dale (V), Neil Finnen (PI), Charlotte Harris (P), Cindi Hood (P), Shyla Keesling (CC), Ingrid Kerr (CC), Raj Maturi (SI), Stephanie Morrow (P), Kristin Phillips (V), Ashley Radtke (V), Bethany Sink (CC), Tom Steele (P); National Ophthalmic Research Institute A. Thomas Ghuman (PI), Laura Greenhoe (CC), Cheryl Kiesel (CC), Ray Kiesel (P), Eileen Knips (P), Anita Leslie (V), Kristi Maro (CC), Crystal Peters (CC), Paul Raskauskas (SI), Cheryl Ryan (CC), Jessica Lynn Saez (CC), Ashish Sharma (SI), Natalie Torres (Crawford) (CC), Danielle Turnbo (V), Joseph Walker (SI), Glenn Wing (SI); New Jersey Medical School Tamara Berezina (P), Neelakshi Bhagat (PI), Kathryn Boschert (CC), Eileen Buroff (V), Janie Ellenberger (CC), Catherine Fay (CC), Marian Konop (P), Michael Lazar (P), Tatiana Mikheyeva (P), Monique Roy (SI), Marco Zarbin (SI); NJ Retina Howard Fine (SI), Laura Fox Gadless (CC), Eric Friedman (SI), Robyn Green (CC), Stuart Green (SI), Bruce Keyser (SI), Amy Leviton (V), Celeste Nelson (CC), Jennifer Pilato (CC), Jonathan Prenner (SI), Daniel Roth (SI), Alex Schlosser (P), Sumit Shah (PI), H. Matthew Wheatley (SI), David Yarian (SI); Northern California Retina Vitreous Assoc. Roxanne Arrivas (P), Alok Bansal (SI), Edwin Boldrey (SI), Jesus Borrillo (SI), Louis Chang (SI), Giovanna Corazzi (V), Amy Dennis (V), Sharon Depaz (CC), Andrea Gadda (V), Amy Goldstein (P), Rahul Khurana (PI), Diana Lam (CC), Celeste Obando (P), James Palmer (SI), Olga Sessions (P), Mark Wieland (SI); Orange County Retina Medical Group Trisha Ambrocio (CC), Marinel Casiano (CC), Eugene Chang (SI), Sanford Chen (PI), Millie Liu (V), Jessica Lowery (P), John Maggiano (SI), Rajiv Rathod (SI), Timothy You (SI); Paducah Retinal Center Carl Baker (PI), Tracey Caldwell (CC), Alecia Camp (P), Samantha Kettler (P), Lynnette Lambert (CC), Tracey Martin (V), Margaret Orr (V), Mary Jill Palmer (V), Ron Tilford (SI), Tana Williams (P); Palmetto Retina Center Ruth Bearden (O), Lloyd Clark (PI), Pamela Darlington (O), Rene Griggs (O), David Johnson (SI), Stephanie Karuza (CC), Peggy Miller (CC), Tiffany Ogbuewu (V), John Payne (SI), Robin Spivey (P), Ashley Studebaker (P), Tiffany Swinford (V), Mallie Taylor (CC), Deborah Watts (O), John Wells (SI), Amanda Wilson (O); Palmetto Retina Center, LLC Florence Krystal Canupp (CC), W. Lloyd Clark (SI), Ashley Floyd (V), Cassandra Garrison (CC), David Johnson (SI), Tyler Huggins (P), Crystal Parker (V), John Payne (PI), Erin Poston (P), Jessica Ross (P), Kristin Stokes (CC), John Wells (SI), Ashley Williams (P); Retina & Vitreous of Texas Diana Abdelgani (CC), Doug Blanchard (P), Colin Blank (P), Emmanuel Chang (SI), Deborah Fredrickson (V), Joseph Khawly (PI), Desiree Lopez (P), Donald Lowd (P), Lorena Martinez (V), Pam Miller (CC), Jason Muniz (P), Erica Pineda (V), Hassan Rahman (SI), Natalie Roncancio (P), Andrea Sales (P), Arthur Willis (SI); Retina Associates Lexie Ainley (CC), Ivan Batlle (PI), Karla Batlle (CC), Kiersten Bruce (V), Ryan Christensen (SI), Blake Cooper (SI), David Dyer (SI), Gregory Fox (SI), Amber Konrade (V), Samantha Perkins (P), Katherine Pippin (P), Ravi Singh (SI), Beatty Suiter (SI), Frank Yeager (P); Retina Associates of Cleveland Inc. Brett Amonett (CC), Cindy Boehm (P), Joseph Coney (SI), Jim Coyne (P), Tia Drugan (V), John DuBois (P), Gregg Greanoff (P), Mary Ilc (V), Aimee Kenska (P), Elizabeth McNamara (P), David Miller (SI), Michael Novak (SI), Llewelyn Rao (SI), Susan Rath (CC), Cecelia Rykena (V), Jerome Schartman (SI), Lawrence Singerman (PI), Veronica Smith (CC), Vivian Tanner (CC); Retina Associates of Kentucky Lisa Bicknell (V), Michelle Buck (P), Vernie Daniels (CC), Diana Holcomb (CC), Ricky Isernhagen (SI), John Kitchens (SI), Andrew Moshfeghi (PI), Bryan Noel (P), Ed Slade (P), Thomas Stone (SI), Jeanne Van Arsdall (V), Brenda VanHoose (V), William Wood (PI); Retina Associates of Western New York Mindy Burgess (V), Brian Connolly (SI), Mary Jo Doran (CC), Ernest Guillet (SI), Edward Hall (PI), Tiffany Heard (P), Anne Reynard (V), Steven Rose (SI), Joseph Territo (P), Margaret Whelehan (P), Meg Yagoda (CC); Retina Centers Dyonne Bachmann (V), Sally Brandon (CC), Kassandra Burdick (V), Jennifer Carreon (CC), Crystal Duncan (P), Susana Flores (V), Stacey Halper (P), Henry Hudson (SI), Amy Kan (CC), Shree Kurup (SI), Claudia Mendoza (P), Brianna Morris (V), George Novalis (SI), Patricia Wilkins (CC), Ryan Wong (SI), Martin Worrall (PI); Retina Consultants of Houston PA Belinda Almanza (V), Matthew Benz (SI), Meredith Berry (CC), David Brown (PI), JoLene Carranza (CC), Eric Chen (SI), Brenda Dives (V), Lauren Epp (CC), Richard Fish (SI), Nikki Franks (CC), Debbie Gillaspia (CC), Amy Hutson Hernandez (CC), Eric Kegley (P), Rosa Kim (SI), Nubia Landaverde (CC), James Major (SI), Elizabeth Quellar (V), Mary Reagan (CC), Beau Richter (P), Tressa Royse (V), Amy Schefler (SI), Robert Smith (O), Veronica Sneed (V), Cary Stoever (P), Sushma Vance (SI), Tien Wong (SI), Charles Wykoff (SI); Retina Consultants of Nevada Kelly Anderson (CC), Thomas Arambula (P), Linda Cortes (CC), Jennie Fabro (V), Joe Galura (P), Nikki Garcia (V), Leide Gomes (V), Marcy Henry (P), Rodney Hollifield (SI), Roy Loo (SI), Janet Marchese (CC), Ifeyinwa Okeke (V), Matthew Pezda (SI), Javier Rendorio (P), Treseelyn Spencer (P), Allen Thach (PI), Irene Voo (SI), Jason Wickens (SI), Meher Yepremyan (SI); Retina Group of Florida Scott Anagnoste (SI), Jaclyn Brady-Pyka (CC), Mario del Cid (PI), Mandeep Dhalla (SI), Lawrence Halperin (SI), Monica Hamlin (CC), Ann Marie Lamb (V), Angelia Mannarelli (P), Jamie Mariano (V), Linda O’Koren (V), Krista Rosenberg (SI), Barry Taney (SI), W. Scott Thompson (SI), Eduardo Uchiyama (SI), Rita Veksler (P); Retina Group of New England Heather Casey (V), Nauman Chaudhry (PI), Justin Cocilo (P), Alison Fontecchio (V), Emma German (CC) Samantha Gunter (V); Retina Northwest Ashley Adamo (CC), Peggy Charpentier (V), Josh Cohen (P), Michele Connaughton (P), Richard Dreyer (SI), Inessa Flato (V), Stephanie Ho (V), Stephen Hobbs (CC), Christine Hoerner (P), Marcia Kopfer (CC), Michael Lee (SI), Joseph Logan (P), Colin Ma (SI), Amanda Milliron (V), Apurva Patel (SI), Mark Peters (PI), Paul Tlucek (SI); Retina Research Institute of Texas Leah Adams (V), Cecilia Escamilla (O), Geneva Espinoza (P), Kristen Garcia (CC), Grant Janzen (SI), Seong Lee (SI), Priscilla Moreno (V), Sunil Patel (PI), Cindy Petty (CC), Gary Rickert (P), Deisy Villarreal (CC), Eric Zavaleta (SI); Retina Vitreous Consultants Robert Bergren (PI), Jennifer Chamberlin (CC), Paul Conrad (SI), Dawn DiPerna (P), Bernard Doft (SI), James Eadie (SI), Amanda Fec (P), Moryssa Grossman (P), Keith McBroom (P), Lori Merlotti (CC), Karl Olsen (SI), Pamela Rath (SI), Christina Schultz (V), David Steinberg (P), Lois Stepansky (V), Avni Vyas (SI), Julie Walter (V); Retina Vitreous Surgeons of Central New York PC Jeffrey Barker (P), Brandi Bellows (V), Jamin Brown (SI), Teresa Deforge (P), Stefanie DeSantis (P), Christine Dorr (CC), Viki Gabris (CC), Cindy Grinnell (CC), Christy Hall (CC), G. Robert Hampton (PI), Peter Hay (P), Lynn Kwasniewski (V), Michelle Manley (V), Abigail Miller (P), Nicole Robarge (P), Kevin Rosenberg (SI), Rajeev Seth (SI), Laurie Sienkiewycz (CC), Lisa Spuches (V); Retinal and Ophthalmic Consultants P.C. Kim Clark (P), Brett Foxman (SI), Scott Foxman (SI), Natalie Mahan (CC), Thomas Margolis (PI), Chastity Mendez (V), Felisha Morales (P), Suzie Post (P), Julie Rosenthal (SI), Qahdirah Torres (V); Retinal Consultants Medical Group Margaret Chang (SI), Robert Equi (SI), Danny Lopez (P), Erin Nickerman (CC), Arun Patel (SI), Joel Pearlman (PI), Nanette Podesta (CC), J. Brian Reed (SI), David Telander (SI), Tony Tsai (SI), Brooke Waller (V), Robert Wendel (SI), Kimberlee Wong (V); Retinal Consultants of AZ Sandra Arenas (V), Mark Barakat (SI), Dayna Bartoli (P), Jermain Byers (CC), Deedra Caraveo (P), Pravin Dugel (SI), David Goldenberg (SI), L. Milad Haak (SI), Ronald Hawkins (CC), Valerie Hoback (CC), Sujit Itty (SI), Karim Jamal (SI), Norma Jimenez (P), Peter Khoury (V), Derek Kunimoto (PI), Ashleigh Levison (SI), Georgina Lopez-Wood (CC), Elena Marcos (V), John Martin (P), Sachin Mehta (SI), Neal Palejwala (SI), Edward Quinlan (SI), Nohemi Ramirez (V), Ignacio Torres (P), Diania Joy Wilson (CC), Heather Yoshimura (CC); Retinal Consultants of San Antonio Lydia Adams (CC), Jaynee Baker (CC), Elaine Castillo (V), Moises Chica (SI), Sarah Holy (SI), Lita Kirschbaum (CC), Richard Gary Lane (SI), Calvin Mein (PI), Tori Moore (V), Brenda Nakoski (P), C. Sean Wienecke (P); Sabates Eye Centers Kelli Burge (V), Michael Cassell (PI), Yin Chen (CC), Heather Elliott (P), Gary Gallimore (P), Kristen Kietzman (CC), Nancy Kunjukunju (SI), Jeanne Niblock (V), Abraham Poulose (SI), Felix Sabates (PI), Nelson Sabates (SI), April Snider (V); Sarasota Retina Institute Melvin Chen (PI), Evelyn Inlow (CC), Peggy Jelemensky (CC), Marc Levy (SI), Rosa Miller (V), Tara Raphael (V), Mark Sneath (P); Scheie Eye Institute Jim Berger (P), Alexander Brucker (PI), Dominique Caggiano (CC), Judy Chen (CC), Sheri Drossner (V), Joan DuPont (CC), Armin Farazdaghi (V), Benjamin Kim (SI), Sara Morales (P), Jessica Morgan (SI), Beth Serpentine (P), Brian VanderBeek (SI); Southeast Retina Center Thomas Bailey (V), Amina Farooq (CC), Allison Foster (CC), Ken Ivey (P), Robert Lalane (SI), Dennis Marcus (PI), Siobhan Ortiz (CC), Bryan Rivera (V), Harinderjit Singh (SI), Kim Tuey (CC), Michele Woodward (CC); Southeastern Retina Associates PC Julie Asher (V), Patricia Coppola (V), Joseph Googe (SI), Raul Lince (P), Lisa Lovelady (CC), Tod McMillan (SI), Steve Morris (CC), Sarah Oelrich (P), Kristina Oliver (CC), R. Keith Shuler (PI), Justin Walsh (V), Jerry Whetstone (P); Southern California Desert Retina Isela Aldana (V), Clement Chan (PI), Tonya Gieser (CC), Tiana Gonzales (CC), Kenneth Huff (P), Maziar Lalezary (SI), Steven Lin (SI), Lenise Myers (V), Kim Walther (CC); Tennessee Retina Everton Arrindell (SI), Carl Awh (PI), Michelle Bowers (P), Amanda Briley (V), Brandon Busbee (SI), Talisha Campbell (V), Narey Cooper (CC), John Delaney (CC), Dezirae Elkins (P), Tara Farmer (P), Amanda Ferrell (CC), Casi Fleischman (P), Paul (Dustin) Freeman (P), Courtney Harris (V), Sarah Hines (CC), Kenneth Moffat (SI), Stephanie Morrow (P), Sue Rataski (CC), Franco Recchia (SI), David Reichstein (SI), Kris Rose (V), Eric Schneider (SI), Natalie Schwebel (V), Shari Scott (V), Gina Smith (CC), Peter Sonkin (SI), Cora Sonnier (CC), Kyra Stepney (V), Katlyne Thompson (V), Caleb Walker (P), R. Trent Wallace (SI), Susan Wiser (CC), Julia Wray (P); Texas Retina Associates-Arlington Melissa Alva (CC), Bob Boleman (P), David Callanan (SI), Jodi Creighton (V), Michelle Curry (CC), Chris Dock (P), Sandy Lash (V), Wayne Solley (SI), Patrick Williams (PI); Texas Retina Associates-Dallas Rajiv Anand (SI), Sally Arceneaux (V),Erik Arredondo-Perez (P), Daniel Carpintero (P), Deborah Chong (SI), Lori Coors (SI), Karl Csaky (SI), Karen Duignan (CC), Gary Fish (PI), Dwain Fuller (SI), Nick Hesse (P), Diana Jaramillo (CC), Tiffany Keaton (P), Michael Mackens (P), Amy Madrid (P), Gary Maines (P), Samantha Marin (P), James Nguyen (P), Brenda Sanchez (V), Kimberly Stanfel (P), Tina Stanley (P), Robert Wang (SI); The Ohio State University William Bloom (CC), PJ Fish (P), Alan Letson (PI), Barbara Mihalik (V), Matthew Ohr (SI), Jerilyn Perry (V), Jill Salerno (CC); The Retina Group of Washington Tanya Alexander-Snowden (CC), Sekou Alou (P), Daniel Berinstein (PI), Thomas Blondo (V), Jennifer Camia (V), Maggie Cashion (CC), Ashley Chancey (CC), Clete Clark (O), Justin Davis (P), William Deegan (SI), Vanessa Denny (V), Irene Fanous (CC), Richard Garfinkel (SI), Bryan Gallerson (V), Smitha Gopakumar (CC), Sarah Hanselman (V), Jessica Iglesias (O), Yury Iraheta (V), Thomas Johnson (SI), Molly Kalisch (V), Andrew King (V), Michael Lai (SI), Myradis Marin-Quinones (O), Alexander Melamud (SI), Howard Morris (O), Bryan Murphy (P), Robert Murphy (SI), Stacie Orencia (P), Michael Osman (SI), Jennifer Phosaksee (V), Steve Rauch (P), Gayatri Reilly (SI), Pamela Renteria (V), Michael Rivers (SI), James Russell (V), Reginald Sanders (SI), Nicole Schorer (V), Mona Shah (V), Manali Shah (CC), Maya Talatory (CC), Tiffany Tam (V), Manfred von Fricken (SI), Danielle Walker (V); The Retina Institute Kevin Blinder (PI), Lynda Boyd (V), Dana Gabel (P), Erika Hoehn (CC), Stephanie Guevara (V), Ginny Nobel (CC), Kelly Pepple (V), Brooke Pulliam (V), Diana Reardon (V), Steve Schremp (P), Gaurav Shah (SI), Bradley Smith (SI), Maria Stuart (V), Rhonda Weeks (CC), Jarrod Wehmeier (P), Tim Wright (P); The Retina Research Center Brian Berger (PI), Chelsey Bravenec (V), Saradha Chexal (SI), Boris Corak (V), Ivana Gunderson (V), Kimberly Hosein (CC), Chirag Jhaveri (SI), Ginger Manhart (CC), Brandon Nguyen (V), Ryan Reid (V), Yong Ren (P), Tina Seidu (CC), Chandler Stovall (P); TLC Eyecare & Laser Centers Kristi Ballard (P), Ashley Blaisdell (P), April Clay (CC), Shellie Fuentes (CC), Stephanie Gillispie (CC), Carmelina Gordon (PI), Heather Hill (V), Hailey Litzer (P), Elaine Lok (P), Bonnie Minier (CC), Susan Partridge (V), Surendar Purohit (SI), Tiffany Westgate (P), Jennifer Wireman (CC), Celia Wohlscheid (CC); University of California-Davis Marie Andrada (PH), Ashley Bryant (PH), Dominique Cargill (PH), Karishma Chandra (P), Sashi Deo (P), Katrina Imson (CC), Lawrence Morse (SI), Ala Moshiri (SI), Susanna Park (PI), Ellen Redenbo (P), Marisa Salvador (V), Nadir Sarwary (PH), Igor Slabosnitskiy (P), Peter Trovitch (PH), Jessica Turner (PH), Cindy Wallace (CC); University of California-San Francisco Jacque Duncan (PI), Don Eubank (CC), Scott Fields (PH), Betty Hom (P), Mary Lew (V), Andrew Light (P), Arshia Mian (CC), John Peterson (P), Jay Stewart (SI); University of Florida Kakarla Chalam (PI), Ashley Cowart (V), Sandeep Grover (SI), Shailesh Gupta (SI), Shamim Haji (V), Ghulam Hamdani (CC), Sherri Hart (P), Kumar Sambhav (CC), Jazzmin Smith (P); University of Kentucky Miroslava Aprelkov (V), Peter Blackburn (SI), Claire Fraser (SI), Mike Hanson (P), Eric Higgins (SI), Mark Kleinman (SI), Deborah McDonald (P), P. Andrew Pearson (PI), Susan Phillips (O), Lyudmila Pigulko (V), Michele Reg (CC), Stephen Sitzlar (PH), Lakisha Smith (V); University of Rochester Flaum Eye Institute Rachel Aleese (V), Mina Chung (PI), Arielle Conrad (V), Andrea Czubinski (V), David DiLoreto (PI), Tanya Forbes (CC), Gary Gagarinas (V), Rachel Hollar (P), Lisa Latchney (CC), Katherine Nedrow (CC), Taylor Pannell (P), Brittany Richardson (P); University of Wisconsin Angie Adler (CC), Michael Altaweel (PI), Barbara Blodi (SI), Shirley Craanen (P), Kristine Dietzman (V), Justin Gottlieb (SI), Michael Ip (SI), Denise Krolnik (P), Jennie Perry-Raymond (CC), Sandie Reed (P), Christopher Smith (V), John Peterson (P); University of Nebraska Medical Center Truhlsen Eye Institute Bryan Angle (PI), Lola Berg (P), Maria Blaiotta (V), Christopher Blodi (PI), Kunal Dansingani (PI), Diana Do (SI), Lisa Greer (CC), Fayez Jawed (V), Kristi Miller (CC), Donna Neely (P), Quan Nguyen (PI), Julie Sigmund (CC); University of Washington Medicine Eye Institute Brad Clifton (P), Patricia Ernst (V), Ron Jones (P), James Kinyoun (PI), Soojin Kyle (P), Jim Leslie (P), Juli Pettingill (V), Jeffrey Purcell (PH), Sue Rath (CC), Kasra Rezaei (SI), Gurunadh Vemulakonda (SI), Bao-Chau Vo (O); Valley Retina Institute Rohit Adyanthaya (SI), Lazaro Aguero (P), Samuel Alonso (P), Deyla Anaya (CC), Isaac Cabrera (V), Monica Cantu (V), Tabatha Deluna (V), Roberto Diaz-Rohena (SI), Santos Garza (P), Victor Gonzalez (PI), Hector Jasso (P), Karina Miranda (V), Jessica Muniz (P), Nehal Patel (SI), Jessica Rodriguez (CC), Rachel Rodriguez (V), Kethsaly Salinas (CC), Nancy Salinas (CC), Yesenia Salinas (CC), Juan Santiago (SI), Lissete Villanueva (CC); Vanderbilt Eye Institute Tony Adkins (P), Anita Agarwal (SI), Milam Brantley (PI), Joshua Carlson (SI), Edward Cherney (SI), Anthony Daniels (SI), Gowtham Jonna (SI), Stephen Kim (SI), Janice Law (SI), Rocky Munn (P), Sandy Owings (CC), Shriji Patel (SI), Scott Ruark (CC), Richard Skellie (P), Paul Sternberg (SI), Maryann Taylor-Ward (V); Virginia Eye Institute Lea Anderlini (V), Mark Bartlett (P), James Combs (SI), Eleanore Ebert (SI), Michael Hughes (P), Byron Ladd (PI), Kristin McKeever (V), Lynn Roderick (P), George Sanborn (SI), Karen Sullivan (CC), Melissa Vaughan (CC); Vitreoretinal Associates of Washington A. Samuel Barloon (SI), Charles Birnbach (SI), Andrea Blustein (V), Robert Francis (SI), Renee Gagnon (CC), Pamela Goldman (P), Ray Hunt (V), Frances Kipp (V), Todd Klesert (SI), DeShawn Minnis (P), Robert Nash (SI), Tetyana Nazarchuk (CC), David Saperstein (PI), Craig Wells (SI); Vitreoretinal Surgery Steven Bennett (SI), Tamra Bogolin (V), Carmen Chan-Tram (CC), Holly Cheshier (P), John Davies (SI), Sundeep Dev (PI), Julianne Enloe (CC), Peggy Gilbert (V), Timothy Gromov (V), Jill Johnson (SI), Tori Jones (P), Robert Mittra (SI), Neal Oestreich (CC), D. Wilkin Parke (SI), Polly Quiram (SI), Robert Ramsay (SI), Carol Rogers (V), Joy Royle (V), Trenise Steele (P), Jessica Tonsfeldt (P), David Williams (SI).

Funding

Supported by the National Eye Institute (National Institutes of Health, Department of Health and Human Services) grants U10EY023529, U10EY023533, and U10EY023521. Support also provided in part by Regeneron, Inc. and Allergan, Inc. through donation of investigational drug. This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. to the University of Wisconsin Madison Department of Ophthalmology and Visual Sciences and to the Jules Stein Eye Institute and Doheny Eye Institute, Department of Ophthalmology at the University of California Los Angeles, CA.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Neal Oden and Paul VanVeldhuisen and staff at the SCORE2 Data Coordinating Center. The first draft of the manuscript was written by Rahul Khurana, MD and Neal Oden and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Paul C. VanVeldhuisen.

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Conflict of interest

Rahul N. Khurana, M.D.: serves as a consultant for Allergan (Irvine, CA), Apellis (Waltham, MA), Bausch + Lomb (Rochester, NY), Genentech (South San Francisco, CA), Merck & Co (Kenilworth, NJ), and Regeneron (Tarrytown, NJ); and has grant support from Allergan (Irvine, CA), Chengdu Kanghong (Shanghai, China), Clearside Biomedical (Alpharetta, GA), Roche (Basil, Switzerland), and Santen (Tokyo, Japan).

Neal L. Oden, Ph.D.: work supported by grant 1U10EY023529 from the National Eye Institute of the National Institutes of Health.

Paul C. VanVeldhuisen, Ph.D.: work supported by grant 1U10EY023529 from the National Eye Institute of the National Institutes of Health.

Ingrid U. Scott, M.D., M.P.H.: serves as Principal Investigator and Chair of SCORE2, which is funded by the National Eye Institute, and has served on the Data and Safety Monitoring Committee of clinical trials sponsored by Novartis (Basel, Switzerland).

Barbara A. Blodi, M.D.: No financial disclosures.

Michael S. Ip, M.D.: Dr. Ip is a consultant for the following: Novartis (Basel, Switzerland), Genentech (South San Francisco, CA), Allergan (Irvine, CA), Regeneron (Tarrytown, NJ), RegenxBio (Rockville, MD), Apellis (Waltham, MA), Aerie Pharmaceuticals (Durham, NC), Alimera Sciences (Alpharetta, GA), Amgen (Thousand Oaks, CA), Cell Lineage Therapeutics (Carlsbad, CA), Clearside Biomedical (Alpharetta, GA).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Khurana, R.N., Oden, N.L., VanVeldhuisen, P.C. et al. Association between early and late response in eyes with central or hemiretinal vein occlusion treated with anti-VEGF agents. Graefes Arch Clin Exp Ophthalmol 259, 1839–1851 (2021). https://doi.org/10.1007/s00417-020-05018-7

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