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Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic RetinopathyA Randomized Clinical Trial

Educational Objective
To learn about treatments for vitreous hemorrhage in patients with proliferative diabetic retinopathy.
1 Credit CME
Key Points

Question  Among patients with vitreous hemorrhage from proliferative diabetic retinopathy, what is the effect of initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation on vision?

Findings  In this randomized trial of 205 eyes among 205 participants, the mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) for the aflibercept group vs 63.0 (Snellen equivalent, 20/63) for the vitrectomy with panretinal photocoagulation group, a difference that was not statistically significant.

Meaning  In participants with vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in visual acuity over 24 weeks following initial treatment with aflibercept vs vitrectomy with panretinal photocoagulation, but the study may have been underpowered to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation.

Abstract

Importance  Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown.

Objective  To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy.

Design, Setting, and Participants  Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020.

Interventions  Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria.

Main Outcomes and Measures  The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years.

Results  Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, −5.0 [95% CI, −10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, −11.2 [95% CI, −18.5 to −3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, −3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept.

Conclusions and Relevance  Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation.

Trial Registration  ClinicalTrials.gov Identifier: NCT02858076

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Adam R. Glassman, MS, Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (drcrstat2@jaeb.org).

Accepted for Publication: November 4, 2020

Author Contributions: Dr Glassman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Antoszyk, Glassman, Jampol, Jhaveri, Punjabi, Wells, Stockdale, Sun.

Acquisition, analysis, or interpretation of data: Antoszyk, Glassman, Beaulieu, Jampol, Jhaveri, Punjabi, Salehi-Had, Wells, Maguire, Martin, Sun.

Drafting of the manuscript: Antoszyk, Glassman, Beaulieu, Jampol, Punjabi, Wells, Martin, Sun.

Critical revision of the manuscript for important intellectual content: Antoszyk, Beaulieu, Jampol, Jhaveri, Punjabi, Salehi-Had, Wells, Maguire, Stockdale, Martin, Sun.

Statistical analysis: Glassman, Beaulieu, Punjabi, Maguire.

Obtained funding: Glassman, Jampol, Martin, Sun.

Administrative, technical, or material support: Antoszyk, Glassman, Jampol, Punjabi, Salehi-Had, Stockdale.

Supervision: Antoszyk, Glassman, Punjabi, Wells, Martin, Sun.

Conflict of Interest Disclosures: Dr Antoszyk reported receiving grants from Roche Genentech; and serving as a consultant to the Jaeb Center for Health Research, Opthea, Clearside, Roche Genentech, Regeneron, and Novartis. Mr Glassman reported receiving grants and nonfinancial support from Genentech, Regeneron, and Allergan. Dr Beaulieu reported receiving grants and nonfinancial support from Genentech, Regeneron, and Allergan. Dr Jampol reported receiving personal fees from Sanofi. Dr Jhaveri reported receiving personal fees from Genentech, Allergan, and Novartis. Dr Wells reported receiving grants and personal fees from Genentech and Adverum; and participating in clinical research with Emmes, Genentech, Kodiak, Lpath Incorporated, Neurotech, Ophthotech, Opthea, Regeneron, and Thrombogenics. Dr Maguire reported receiving personal fees from Genentech; and receiving payment from the Jaeb Center for Health Research paid to her institution. Ms Stockdale reported receiving grants and nonfinancial support from Genentech, Regeneron, and Allergan. Dr Sun reported receiving grants from the Jaeb Center for Health Research, Roche Genentech, the Juvenile Diabetes Research Foundation, and Kalvista; receiving personal fees from Current Diabetes Reports, JAMA Ophthalmology, and Merck; receiving nonfinancial support from Optovue (equipment loaned for research), Boston Micromachines, Adaptive Sensory Technologies, Roche Genentech (food/beverage), Novartis, and Kalvista (travel support); and receiving grants and nonfinancial support from Novo Nordisk, Boehringer Ingelheim, and Roche. No other disclosures were reported.

Funding/Support: Supported through cooperative agreement EY14231 from the National Eye Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, and the US Department of Health and Human Services. Regeneron Pharmaceuticals Inc provided aflibercept for the study and funds to DRCR Retina Network to defray the study’s clinical site costs.

Role of the Funder/Sponsor: As per the DRCR Retina Network industry collaboration guidelines (https://public.jaeb.org/drcrnet/view/Investig_Info), the DRCR Retina Network had complete control over the design of the protocol, ownership of the data, all editorial content of presentation and publication related to the protocol, and the decision to submit the manuscript for publication. The National Institutes of Health participated in oversight of the conduct of the study and review of the manuscript but not directly in the design or conduct of the study, nor in the collection, management, analysis, or interpretation of the data, or in the preparation of the manuscript.

The DRCR Retina Network: Coordinating Center Staff at Jaeb Center for Health Research: Adam R. Glassman, MS (director and principal investigator), Roy W. Beck, MD, PhD (executive director), Alyssa Baptista, BS, Wesley T. Beaulieu, PhD, Claire T. Boyle, MS, Sharon R. Constantine, BS, Brian B. Dale, Simone S. Dupre, BS, Sandra Galusic, MSPH, Meagan Huggins, BA, Paula A. Johnson, MPH, Kristen Josic, PhD, Brittany Kelly, MS, Danni Liu, MSPH, Brenda L. Loggins, BS, Maureen G. Maguire, PhD, Michele Melia, ScM, Ilona Nemeth, MA, Carin M. Preston, MPH, Cynthia R. Stockdale, MSPH, and Katie Stutz, BS. Duke Reading Center Staff: Katrina Postell Winter, BS (lead reader), Garrett Thompson, MD (reader), Dee Busian, BA (reader), Glenn J. Jaffe, MD (director of grading), Adiel Mora, BA (project manager), Lucia Foster, MA (assistant project manager), and John Keifer McGugan, BS (assistant project manager). DRCR Retina Network Chairs: Jennifer K. Sun, MD, MPH (Joslin Diabetes Center, Beetham Eye Institute, Harvard Department of Ophthalmology; 2018-present), Daniel F. Martin, MD (Cole Eye Institute at Cleveland Clinic; 2018-present), Lee M. Jampol, MD (Feinberg School of Medicine, Northwestern University; 2013-2017), and Neil M. Bressler, MD (Department of Ophthalmology, Johns Hopkins University School of Medicine; 2006-2012). DRCR Retina Network Vice Chairs: Carl W. Baker, MD (Paducah Retinal Center; 2011-2013 and 2017-2019), Chirag Jhaveri, MD (Retina Consultants of Austin; 2016-2018), Mathew MacCumber, MD, PhD (Rush University Medical Center; 2018-present), Andrew Antoszyk, MD (Charlotte Eye, Ear, Nose & Throat Associates; 2013-2016 and 2020-present), Susan B. Bressler, MD (Wilmer Eye Institute; 2009-2011), Scott Friedman, MD (Florida Retina Consultants; 2009-2012), Judy Kim, MD (Medical College of Wisconsin; 2015-2017), Ingrid U. Scott, MD, MPH (Penn State College of Medicine; 2009-2010), Jennifer K. Sun, MD, MPH (Joslin Diabetes Center, Beetham Eye Institute, Harvard Department of Ophthalmology; 2012-2014), and John A. Wells III, MD (Palmetto Retina Center; 2013-2015). National Eye Institute: Sangeeta Bhargava, PhD (2016-current), and Eleanor Schron, PhD (2009-2015). Executive Committee: Andrew N. Antoszyk, MD (Charlotte Eye, Ear, Nose & Throat Associates; 2009 and 2013-present), Roy W. Beck, MD, PhD (Jaeb Center for Health Research; 2002-present), Sangeeta Bhargava, PhD (National Eye Institute, National Institutes of Health; 2016-present), Barbra Blodi, MD (University of Wisconsin, Madison; 2014-present), Frederick L. Ferris III, MD (Ophthalmic Research Consultants; 2002-present), Adam R. Glassman, MS (Jaeb Center for Health Research; 2005-present), Glenn J. Jaffe, MD (Duke Reading Center; 2012-present), Lee M. Jampol, MD (Feinberg School of Medicine, Northwestern University; 2012-present), Chirag D. Jhaveri, MD (Retina Consultants of Austin; 2016-present), Judy E. Kim, MD (Medical College or Wisconsin; 2015-2017 and 2020-present), Brandon Lujan, MD (Casey Eye Center; 2017-present), Mathew MacCumber, MD, PhD (Rush University Medical Center; 2018-present), Dennis M. Marcus, MD (Southeast Retina Center, PC; 2011-2012 and 2018-present), Daniel F. Martin, MD (Cole Eye Institute at Cleveland Clinic; 2017-present), Raj K. Maturi, MD (private practice of Raj K. Maturi, MD; 2009-2011 and 2013-present), Jennifer K. Sun, MD, MPH (Joslin Diabetes Center, Beetham Eye Institute, Harvard Department of Ophthalmology; 2009-present). Previously on Executive Committee: Lloyd Paul Aiello, MD, PhD (Beetham Eye Institute, Joslin Diabetes Center, Harvard Medical School; 2002-2018 and chair for 2002-2005), Carl W. Baker, MD (Paducah Retinal Center; 2009-2019), Abdhish Bhavsar, MD (Retina Center of Minnesota; 2007-2008 and 2010-2012), Neil M. Bressler, MD (Department of Ophthalmology, Johns Hopkins University School of Medicine; 2006-2019 and chair for 2006-2008), Susan B. Bressler, MD (Wilmer Eye Institute; 2009-2019), Alexander J. Brucker, MD (Scheie Eye Institute; 2009-2011), Kakarla V. Chalam, MD, PhD, MBA (Loma Linda University Eye Institute; 2009-2011), Ronald P. Danis, MD (University of Wisconsin, Madison; 2004-2015), Matthew D. Davis, MD (Medical College of Wisconsin; 2002-2017), Michael J. Elman, MD (Elman Retina Group, PA; 2006-2018 and chair for 2009 and 2012), Donald F. Everett, MA (National Eye Institute, National Institutes of Health; 2002-2009), Joan Fish, RN (Wake Forest University Eye Center; 2008-2009), Scott Friedman, MD (Florida Retina Consultants; 2007-2013), Joseph Googe Jr, MD (Southeastern Retina Associates, PC; 2009-2011), Jeffrey G. Gross, MD (Carolina Retina Center, PA; 2012-2017), Diana M. Holcomb (Retina Associates of Kentucky; 2011-2012), Andreas K. Lauer, MD (Casey Eye Center; 2007-2008), Ashley A. McClain, BS (Charlotte Eye, Ear, Nose & Throat Associates; 2013), Brandi J. Perez (Loma Linda University Eye Institute; 2013), Eleanor Schron, PhD (National Eye Institute, National Institutes of Health; 2009-2015), Ingrid U. Scott, MD, MPH (Penn State College of Medicine; 2009-2010), JoAnn Starr, BS (Elman Retina Group, PA; 2009-2011), and John A. Wells III, MD (Palmetto Retina Center; 2012-2015). Clinical Sites: (ordered by No. of participants enrolled) Huntington Beach, CA (Atlantis Eye Care; n = 20): Hani Salehi-Had, MD (study investigator); Evelyn Ceja and Sara Ahmed, BS (coordinators); Stephanie Ramirez (coordinator, photographer, and visual acuity technician); Mailan Tran, OD, Mary Ma, OD, and Scott F. Lee, OD (visual acuity technicians); and Nikki Nguyen, BS, Lily Castillo, and Janet Reyes (photographers). Austin, TX (Retina Research Center; n = 19): Chirag D. Jhaveri, MD, Gowtham Jonna, MD, and Saradha Chexal, MD (study investigators); Daniela Mariel Wilson, Tina A. Seidu, and Cori Renfroe (coordinators); Ivana Gunderson, Valerie Gatavaski, and Abla M. Harara (visual acuity technicians); Ryan M. Reid (coordinator and photographer); Boris Corak, BS (photographer and visual acuity technician); and Yong Ren (photographer). Charlotte, NC (Charlotte Eye, Ear, Nose & Throat Associates; n = 19): Andrew N. Antoszyk, MD, Omar S. Punjabi, MD, and David Browning, MD, PhD (study investigators); Angela K. Price, MPH, Christina J. Fleming, BS, Taylor S. Jones, Sherry L. Fredenberg, and Brittany A. Murphy, BA (coordinators and visual acuity technicians); Sarah A. Ennis, Kayla A. Bratcher, Christina Mutch, Angella K. Gentile, and Erica Breglio (visual acuity technicians); and Lisa A. Jackson, Loraine M. Clark, Lynn Watson, Donna McClain, Carol A. Shore, Uma M. Balasubramaniam, and Shannon Stobbe (photographers). Indianapolis, IN (private practice of Raj K. Maturi, MD; n = 15): Raj K. Maturi, MD, David A. Lightman, MD, and Stephen J. Saxe (study investigators); Ashley M. Harless and Lorraine White (coordinators, photographers, and visual acuity technicians); Myra K. Retrum and Carolee K. Novak (visual acuity technicians); and Yesenia Sarmiento (photographer). McAllen, TX (Valley Retina Institute; n = 12): Victor Hugo Gonzalez, MD, and Nehal R. Patel, MD (study investigators); Elyssa Navarro, Nancy L. Salinas, Angelina Garza, BS, Amber B. Ibarra, BS, and Ana L. Pina, BA (coordinators); Monica R. Cantu, Brenda Velasquez, Christina Villegas, Enrique Chavez, Isaac Cabrera, Yvonne Diaz, Jennifer Moreno, Rebecca R. Flores, and Janette Arredondo (visual acuity technicians); and Monique Montemayor, Georgia L. Villarreal, Stephanie Tamez, Samuel Alonso, and Santos Garza (photographers). West Columbia, SC (Palmetto Retina Center; n = 12): John A. Wells III, MD, and John F. Payne, MD (study investigators); Cassandra L. Garrison, BS, and Kristin R. Stokes (coordinators); Tiffany R. Swinford (coordinator and visual acuity technician); Ashley Floyd and Tiffany N. Ogbuewu (visual acuity technicians); and Robbin Spivey and Ashley Studebaker (photographers). Campbell, CA (Retinal Diagnostic Center; n = 11): Clement Chow, MD, Amr Dessouki, MD, and Lingmin He, MD (study investigators); Joel M. Barra, BSBM, Thanh T. Nguyen, and Carla Trujillo (coordinators); Whitney Kuang, Danielle Dinh, and Lynise Cummins (coordinators and visual acuity technicians); Kelly To, Hienmy Dang, and Dao Tran (visual acuity technicians); and Pete Donovan Fernandez, Kenny Trang, Tim Kelley, and Juan Hernandez (photographers). Baltimore, MD (Elman Retina Group, PA; n = 9): Michael J. Elman, MD (study investigator); JoAnn Starr, Jennifer L. Belz, and Twyla J. Robinson (coordinators); Pamela V. Singletary, Christine Ringrose, Alesia K. McCalla, Amy Thompson, Katherine L. Wentz, Peggy R. Orr, MPH, BSN, RN, and Teresa Coffey (visual acuity technicians); and Peter Sotirakos, Terri Cain, and Ashley M. Metzger (photographers). Edmond, OK (Retina Vitreous Center; n = 8): Sandeep N. Shah, MD, and Brian S. Phelps, MD (study investigators); Amy L. West, BS (coordinator and photographer); Romesh Babaria, MS (coordinator, visual acuity technician, and photographer); and Jeannette Rodriguez, Mayra Viruet-Nieves, Kellie Meiwes, and Lisa Holley (photographers). San Antonio, TX (Retinal Consultants of San Antonio; n = 8): Calvin E. Mein, MD, Richard Gary Lane, MD, Darrell E. Baskin, MD, and Moises A. Chica, MD (study investigators); Lydia Adams, Lita Kirschbaum, Sara L. Cloudt, Stacy Rodriguez, Vanessa D. Martinez, and Jenny M. Bermea (coordinators); Victoria Lopez (visual acuity technician); and Samantha Bankston, Christopher Sean Wienecke, Jorge Castellanos, and Brenda Nakoski (photographers). Paducah, KY (Paducah Retinal Center; n = 7): Carl W. Baker, MD, and Ron H. Tilford, MD (study investigators); Tracey M. Caldwell and Jil D. Baker (coordinators); Lynnette F. Lambert, Mary J. Sharp, and Margaret J. Orr (visual acuity technicians); and Sonya L. Alcaraz, Samantha Kettler, Alecia B. Camp, and Kylie S. Sedberry (photographers). Loma Linda, CA (Loma Linda University Health Care, Department of Ophthalmology; n = 6): Joseph T. Fan, MD, Samuel C. Kim, MD, David Isaiah Sierpina, MD, Michael E. Rauser, MD, and Kakarla V. Chalam, MD (study investigators); Raquel Hernandez, Vivian L. Garcia, Jayson S. Paw, and Tina L. Ramirez (coordinators); Anthoni Tampubolon (coordinator, visual acuity technician, and photographer); and Moises Tellez, Adel E. Alset, and Marcia Easterly (photographers). Amarillo, TX (Southwest Retina Specialists; n = 5): J. Edward Ysasaga, MD (study investigator); Kasey L. Dalrymple (coordinator); Johnathan R. Hawkins (visual acuity technician); and Ben Ysasaga (photographer). Augusta, GA (Southeast Retina Center PC; n = 5): Dennis M. Marcus, MD (study investigator); Siobhan O. Ortiz (coordinator); Thomas Bailey and Michele Woodward (visual acuity technicians); and Ken Ivey (photographer). Lubbock, TX (Texas Retina Associates; n = 4): Michel Shami, MD (study investigator); Yolanda Saldivar (coordinator); Ashaki Meeks (visual acuity technician); and Glenn R. Gardner and Ginger K. Rhymes (photographers). Oklahoma City, OK (Dean A. McGee Eye Institute; n = 4): Ronald M. Kingsley, MD, Robert E. Leonard, MD, and Vinay A. Shah, MD (study investigators); Alisha N. Brewer, BA, and Shannon R. Almeida (coordinators); Sonny Icks (coordinator and visual acuity technician); Amy L. Ford and Ashley Hughes (visual acuity technicians); and Markeisha Cheadle, Rachel Sohl, Russ Burris, and JoAnn T. Booth (photographers). San Antonio, TX (Medical Center Ophthalmology Associates; n = 4): Michael A. Singer, MD, and Darren J. Bell, MD (study investigators); Catherine Ellis, BS, and Rafael L. Wong (coordinators); Connie Bermea and Roxanne Gomez (visual acuity technicians); and Felicia Huron and Rosa Escobar (photographers). Marietta, GA (Marietta Eye Clinic; n = 3): Annal Dhanu Meleth, MD, MS, and Lakshmana Murthy Kooragayala, MD (study investigators); Chigozie Nkemka and Shakirah J. Sewell (coordinators); Minuette S. Jackson, BA (coordinator and visual acuity technician); Chenavia Lewis, MS (coordinator and photographer); and Adam Goff and Kenneth Thompson (photographers). Overland Park, KS (Mid-America Retina Consultants PA; n = 3): William N. Rosenthal, MD (study investigator); Sarah N. Lamaster, RN, BSN (coordinator and visual acuity technician); and R. Scott Varner and Mary C. Stewart, RN (photographers). Shawnee Mission, KS (Retina Associates PA; n = 3): Gregory M. Fox, MD, Ravi S. J. Singh, MD, Blake A. Cooper, MD, and Ivan R. Batlle, MD (study investigators); Lexie R. Ainley and Karla A. Batlle, BS (coordinators); Amber R VandeVelde, RN, and Holly Wyrick (visual acuity technicians); and Katherine Pippin and Frank T. Yeager (photographers). St Louis, MO (The Retina Institute; n = 3): Kevin J. Blinder, MD, and Sabin Dang, MD (study investigators); Rhonda F. Weeks, Ginny S. Nobel, and Erika A. Hoehn, BS (coordinators); Kelly E. Pepple, Diana Reardon, Maria A. Stuart, Brook G. Pulliam, and Lynda K. Boyd (visual acuity technicians); and Steve A. Schremp, Timothy L. Wright, Dana L. Gabel, and Jarrod Wehmeier (photographers). Sarasota, FL (Retina Associates of Sarasota; n = 3): Elizabeth R. Richter, MD, PhD, and John H. Niffenegger, MD (study investigators); Arysol Niffenegger, MD (coordinator); Marianne Cottrill (coordinator and photographer); Donna Scully (visual acuity technician); and Marisol Lopez (photographer). Chattanooga, TN (Southeastern Retina Associates; n = 2): Richard I. Breazeale, MD, Rohan J. Shah, MD, Francis C. DeCroos, MD, and Devon Ghodasra, MD (study investigators); Steve W. McBee Jr (coordinator); Elizabeth Lisa McDonald (coordinator and photographer); Kate Menefee and Courtney Duncan (visual acuity technicians); and David Woods and Roger P. Melendrez (photographers). Lakeland, FL (Florida Retina Consultants; n = 2): Nader Moinfar, MD, MPH, and Scott M. Friedman, MD (study investigators); Shannon M Rehling (coordinator and visual acuity technician); Ceara L. Wendel and Damanda F. Fagan (coordinators); Karen Seyez and Jacqueline Andrews (visual acuity technicians); and Brenda J. Bobbitt, Allen McKinney, and Shana E. Williams (photographers). Monroeville, PA (Retina Vitreous Consultants; n = 2): Karl R. Olsen, MD, Jared E. Knickelbein, MD, PhD, and P. William Conrad, MD, PhD (study investigators); Lori A. Merlotti (coordinator); Lois Stepansky and Julie Walter (visual acuity technicians); and Dawn Diperna and Phyllis P. Ostroska (photographers). Spokane, WA (Spokane Eye Clinic; n = 2): Robert S. Wirthlin, MD, Andrew G. Cheek, MD, and Loren S. Jack, MD (study investigators); Eileen A. Dittman, RN (coordinator and visual acuity technician); and Jillian N. Erstad, Brian G. Skea, and Dylan C. Waidelich (coordinators, photographers, and visual acuity technicians). Tampa, FL (Retina Associates of Florida LLC; n = 2): Ivan J. Suner, MD, and Marc C. Peden, MD (study investigators); Stephanie Munoz and Rochelle DenBoer, LPN (coordinators); Janet R. Traynom (coordinator and photographer); Susan Ramsey and Heidi Vargo (visual acuity technicians); and Anita Kim Malzahn and Lonie Bree Noel, LPN (photographers). Ann Arbor, MI (Kellogg Eye Center, University of Michigan; n = 1): Anjali R. Shah, MD, Thomas W. Gardner, MD, MS, and Grant M. Comer, MD, MS (study investigators); Pamela S. Campbell and Lindsay M. Godsey, MS (coordinators); and Laura A. Rozek, Laura B. Trebesh, and Timothy Sean Costello, BA (photographers). Ayer, MA (Valley Eye Physicians and Surgeons; n = 1): Gisela Velez, MD, MPH, MA (study investigator); Oksana Mykhaylyk, Elizabeth I. Johnson, MS, and Maa Ahema Parry, OD, MEd (coordinators); and Jhan Carlos Caro and Chandapilla C. Pallipeedikayil (photographers). Baltimore, MD (Wilmer Eye Institute at Johns Hopkins; n = 1): Sharon D. Solomon, MD (study investigator); Lisa K. Levin and Kemi Adeyemo (coordinators); Deborah Donohue (coordinator and visual acuity technician); Mary Frey, BSc, and Brandon S. Gardner (visual acuity technicians); and Dennis Cain, David Emmert, BA, Jacquelyn McDonald, Russ Distle, and Nick Rhoton, AA (photographers). Boston, MA (Joslin Diabetes Center; n = 1): Jennifer K. Sun, MD, MPH (study investigator); Tor Ekstrom (coordinator); Margaret E. Stockman and Emily Degan (coordinators and visual acuity technicians); Mina Sehizadeh, OD, and Jerry D. Cavallerano, OD, PhD (visual acuity technicians); and Kylie M. Madigan (photographer). Chicago, IL (Northwestern Medical Faculty Foundation; n = 1): Alice T. Lyon, MD, and Rukhsana G. Mirza (study investigators); Evan C. Davies, Priya M. Thakkar, BS, and Nicole M. Seddon (coordinators); Carmen Ramirez (coordinator and visual acuity technician); Julie Pecht and Anson Moore (visual acuity technicians); and Cason Moore, Maritza Barragan, and Evica Simjanoski, BFA (photographers). Cleveland, OH (University Hospitals Cleveland Medical Center; n = 1): Shree K. Kurup, MD, Georgios Trichonas, MD, and Yu Hyon Kim, MD (study investigators); Tatiana M. Riedel, BA, Jasmeen K. Randhawa, and Sangeetha P. Raghupathy, BS (coordinators); Peggy Allchin, Margaret N. Petrosky, and Claudia Clow (visual acuity technicians); and Ahmad Al Moshmosh, Geraldo R. Miranda, Ashley Y. Howard, and Irit Baum-Rawraway (photographers). Knoxville, TN (Southeastern Retina Associates PC; n = 1): Joseph M. Googe, MD, R. Keith Shuler, MD, and Nicholas G. Anderson, MD (study investigators); Kristina Oliver and Steve Morris (coordinators); Julie Asher (coordinator and visual acuity technician); Jeff Wheeler (visual acuity technician); and Justin Walsh, Sarah M. Oelrich, Raul E. Lince, and Hodge A. Griffone (photographers). Milwaukee, WI (Medical College of Wisconsin; n = 1): Judy E. Kim, MD, and Thomas B. Connor, MD (study investigators); Eleanor Dorsey, BS (coordinator); Shay Bourgeois (coordinator and visual acuity technician); Amber N. Roberts and Vicki Barwick, BS (visual acuity technicians); and Brittany Rego and Hannah Sheppard (photographers). Minneapolis, MN (Retina Center PA; n = 1): Abdhish R. Bhavsar, MD (study investigator); Andrea Gilchrist (coordinator); Celeste Moreno (coordinator and photographer); Matt D. Peloquin, AA, and Jason R. Sweet (visual acuity technicians); and Alanna C. Evans and Erin C. Kinney (photographers). New York, NY (New York Eye and Ear Infirmary/Faculty Eye Practice; n = 1): Meenakashi Gupta, MD, and Ronald C. Gentile, MD (study investigators); and Melissa Rivas and John Bo Soo Choi (coordinators and visual acuity technicians). Sandy Springs, GA (Thomas Eye Group; n = 1): Paul L. Kaufman, MD (study investigator); Kathy T. Wynne, BS (coordinator and visual acuity technician); Cynthia Weaver (visual acuity technician); and Sarah Matloff (photographer). Urbana, IL (Carle Foundation Hospital; n = 1): Michael S. Tsipursky, MD (study investigator); Sarah Berlatsky and Elida Iniguez (coordinators); Alexandra Y. Almasov (coordinator and visual acuity technician); Daniel A. Nielsen, OD, and Tina M. Gore (visual acuity technicians); and Zach Dupureur (photographer).

Data Sharing Statement: See Supplement 4.

Additional Contributions: We thank the DRCR Retina Network chairs, vice chairs, coordinating center staff, executive committee members, and the reading center staff. All individuals appearing in the DRCR Retina Network list above were compensated for their work as members of the DRCR Retina Network. We also thank the following members of the data and safety monitoring committee: Gary Abrams, MD (Kresge Eye Institute), Deborah R. Barnbaum, PhD (Kent State University), Harry Flynn, MD (Bascom Palmer Eye Institute), Kyle D. Rudser, PhD (University of Minnesota), Paul Sternberg Jr, MD (Vanderbilt Eye Institute), Sangeeta Bhargava, PhD (National Eye Institute, National Institutes of Health), Ruth S. Weinstock, MD, PhD (State University of New York Upstate Medical University), Stephen Wisniewski, PhD (University of Pittsburgh), John Connett, PhD (University of Minnesota; chair for 2003-2015), and Charles P. Wilkinson, MD (Greater Baltimore Medical Center; 2012-2018). The members of the data and safety monitoring committee received a small stipend for participating in semiannual meetings.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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