Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time
Authors: Marcus Dennis M. , Silva Paolo S. , Liu Danni , Aiello Lloyd Paul , Antoszyk Andrew , Elman Michael , Friedman Scott , Glassman Adam R. , Googe Joseph M. , Jampol Lee Merrill , Martin Daniel F. , Melia Michele , Preston Carin M. , Wykoff Charles C. , Sun Jennifer K. ,   DRCR Retina Network, Harara Abla M , Palacios Angela N. , Berger Brian B. , Corak Boris , Luong Bianca , Jhaveri Chirag D. , Wilson Daniela Mariel , Jonna Gowtham , Gunderson Ivana , Hosein Kimberly , Reid Ryan M. , Chexal Saradha , Moore Tori , Seidu Tina A , Gatavaski Valerie , Ren Yong , Stern Bradley A. , Benvenutti Celia E , Oude-Reimerink Dinah S , Shaheen Jenny , Grybas John , Vitale-Kuhn Julianne , Staffne Jessica L. , Ventimiglia Katie M. , Allis Megan , Monk Mary K. , Thomas Marc E. , Massu Nicole M. , Edwards Paul Andrew , Troszak Tracy A. , Irons Amber N , Rego Brittany , Han Dennis P. , Dorsey Eleanor , Nelson Erika , Sheppard Hannah , Beringer Joseph R. , Kim Judy E. , Keller Kristy L. , Packard Krissa L. , Altmann Marriner L. , Goldberg Mara , Chen Nickolas , Winter Pat A. , Bourgeois Shay , Jacobo Samantha , Moebius Stephanie J , Connor Thomas B. , Barwick Vicki , Williams Vesper V. , Wirostko William J. , Ghuman A. Thomas , Leslie Anita H. , Sharma Ashish G. , Kiesel Cheryl , Dyshanowitz Danielle , Knips Eileen , Wing Glenn , Walker Joseph P. , Raskauskas Paul A. , Kiesel Raymond K. , Schlossman Deborah K. , Weimann Elizabeth S. , Sharuk George S. , Kwak Hanna , Cavallerano Jerry D. , Rhee Jae W , Sampani Konstantina , Tran Katie V , Bestourous Leila , Miranda Linette , Krigman Michael N. , Stockman Margaret E. , Arrigg Paul G. , Cavicchi Robert W. , Kirby Rita K. , Glynn Shireen , Papaconstantinou Steve L. , Shah Sabera T. , Murtha Timothy J. , Carli William , Finch Autumn K. , Gentile Angella K. , Price Angela K. , Murphy Brittany A , Rowland Beverly O , Fleming Christina J. , Mahr Courtney , Shore Carol A , Browning David , McClain Donna , Breglio Erica , Lester Gina M. , Herby Jenna T. , Bratcher Kayla A , Clark Loraine M. , Jackson Lisa A. , Watson Lynn , McOwen Michael D. , Punjabi Omar S. , Bojaj Swann J , Ennis Sarah A. , Fredenberg Sherry L. , Jones Taylor S. , Ragin Teneisha A. , Balasubramaniam Uma M. , Ornelas Blanca , Rodriquez Brenda , Edwards Carla , Carns Danielle R. , Tonner Eileen E. , Woo Kisung , Richine Len , MacCumber Mathew W. , Merrill Pauline Townsend , Kociborski Sarah , Harless Ashley M. , Harris Charlotte , White Lorraine , Maturi Raj K. , Asher Julie , Walsh Justin , Wheeler Jeff , Milstead Katie , Oliver Kristina , Lovelady Lisa , Anderson Nicholas G. , Coppola Patricia , Lince Raul E. , Shuler R. Keith , Morris Steve , Oelrich Sarah M. , Gardner Brandon S , Moore Bob , Cain Dennis , Donohue Deborah , Emmert David , Adeyemo Kemi , Levin Lisa K. , Frey Mary , Rhoton Nick , Bressler Susan , Solomon Sharon D. , Ford Amy L , Hughes Ashley , Brewer Alisha N , Booth JoAnn T , Lunsford Keven W , Ukleya Lauren D. , Burris Russ , Kingsley Ronald M. , Almeida Shannon R. , Icks Sonny , Shah Vinay A. , Bergman Vanessa A. , Castellarin Alessandro A. , Shook Aimee H. , Walker Aimee , Pieramici Dante J. , Hong Gina , Avery Kelly , McKee Kate M , Giust Matthew , Munoz Marco A , Fishbein Sarah , Camp Alecia B. , Baker Carl W. , Baker Jil D , Sedberry Kylie S. , Lambert Lynnette F. , Orr Margaret J. , Alcaraz Sonya L , Kettler Samantha , Caldwell Tracey M. , Miller Abigail , Dorr Christine M. , Hampton G. Robert , Brown Jamin S. , Barker Jeffrey P , Rosenberg Kevin I. , Kwasniewski Lynn M. , Sienkiewycz Laurie J. , Spuches Lisa , Manley Michelle L. , Robarge Nicole E. , DeSantis Stefanie R. , DeForge Teresa M. , Brucker Alexander J. , Kim Benjamin J. , Berger Jim M. , DuPont Joan C. , Drossner Sheri , Freeman Sara , Studebaker Ashley , Payne John F. , Wells John A. , Spivey Robbin , Ogbuewu Tiffany N. , Swinford Tiffany R. , Guillory Adrienne , Hutson Amy , Schefler Amy C. , Shah Ankoor R. , Almanza Belinda A. , Dives Brenda , Richter Beau A , Stoever Cary A. , Brown David M. , Foerster Danee , Garcia David , Rodriguez Diana , Park Daniel , Chen Eric , Kegley Eric N. , Quellar Elizabeth , Twining Garret L , Koger-Grifaldo Heather , Ortega Ilsa , Carranza Jolene , Major James C. , Williamson Kimberly , Burt Lindsay , Salinas Luis R. , Wolff Lisa M , Benz Matthew S. , Estes Maura A , James Miranda F , Berry Meredith , Vela Melina , Landaverde Nubia , Webb Nina A. , Fish Richard H. , Kim Rosa Y. , Yee Rebecca , Karani Sadia Y , Supapo Stacy M. , Dodel Tamara L , McCoy Tyneisha , Wong Tien P. , Sneed Veronica A. , Barnhart Cassandra J. , Cantrell Debra , DuBose Elizabeth L. , Sharpe Houston P , Ulrich Jan Niklas , Bhansali Kanika A , Esquejo Rona Lyn , Garg Seema , Grout Sean , McKinney Allen , Bobbitt Brenda J. , Wendel Ceara L , Fagan Damanda F. , Andrews Jacqueline , Holmes Krystal Nikki , Seyez Karen L , Williamson Kimberly A. , Moinfar Nader , Walters Paige N. , Carlton Steve , Rehling Shannon M , Williams Shana E , Reed Tiara L. , VandeVelde Amber R , Yeager Frank T. , Fox Gregory M. , Batlle Ivan R. , Bruce Kiersten , Pippin Katherine , Ainley Lexie R. , Singh Ravi S. J. , Adamo Ashley M , Guardado Adrian , Patel Apurva K. , Puckett Brian S , Hoerner Christine , Ma Colin , Clark David J , Flato Inessa M , Cohen Joshua , Charpentier Margaret E , Kopfer Marcia , Peters Mark A. , Smith Pualani , Tlucek Paul S. , Hobbs Stephen , Ho Stephanie L. , Metzger Ashley M. , McCalla Alesia K , Thompson Amy , Ringrose Christine , Sandler Dallas R. , Leder Henry A. , Belz Jennifer L. , Starr JoAnn , Simmons Jennifer L. , Orr Peggy R , Sotirakos Peter , Singletary Pamela V. , Cain Terri , Coffey Teresa , Carter Tiffany M , Robinson Twyla J , Shah Chirag P. , Cammarata Dominique , Kruger Jennifer L. , Colegrove Lindsey , Graham Margie , Gleason Shane T. , Noel Bryan , Damron Catherine , Holcomb Diana M. , Slade Edward A , Van Arsdall Jeanne , Bicknell Lisa , Buck Michelle , Stone Thomas W. , Farooq Amina , Parsons Brook , Singh Harinderjit , Ivey Ken , Foster Lindsay Allison , Woodward Michele , Ortiz Siobhan O. , Bailey Thomas , Mynampati A Bharani Krishna , White Cheryl L , Hamdani Ghulam Shabbir , Smith Jazzmin N , Chalam Kakarla V. , Sambhav Kumar , Babaria Romesh , Grover Sandeep , Carroll Catherine , Chau Felix Y. , Lim Jennifer I. , Talasnik Lauren A , Janowicz Mark , Stankovic Natasa , Berlatsky Sarah L , Niec Marcia , Sun Jie , Johnson Tametha , Ovando Yesenia , Nakoski Brenda , Mein Calvin E. , Wienecke Christopher Sean , Castillo Elaine , Baker Jaynee , San Roman Jonathan , Adams Lydia , Kirschbaum Lita , Chica Moises A. , Cloudt Sara L , Moore Tori R. , Sabates Felix N. , Gallimore Gary S. , Chen Yin C. , Swann Adrienne C , Cadwell Deborah M. , Diddie Kenneth R. , Boisvert Taryn F. , Tessau Carrie D , Bowers Jack , Nielsen Jared S. , Rostvold Jay , Spillman Jamie , Alliman Kyle J. , Boender Lisa M. , Johnson Marilyn A. , Parker Marianne , Bix Paula L , Ridgway Spencer D , Woehl Tami Jo , Stonewall Whitney , Brown Christopher M. , Lema Gareth M.C. , Wiechelt Luann , Yoganathan Pradeepa , Boglione Sandra L. , Montesclaros Chris A. , Mangham Cory , Karsaliya Gopal , Le Phillip V. , Wong Robert W. , Godfrey Anne Marie , Kuzmanovic Aleksandra , Kirker Andrew William , Harrison Bryan , Forooghian Farzin , Elvena Garnet Louise , Hall Laura J. , Turhal Bilgin , Brown Ian , Kotei Isaac A , Chen Lina , Brent Michael Henry , Moon Michelle , Sutakovic Olivera , Chang Angela , Godfrey Anne-Marie , Albiani David , Maberley David A.L. , Navajas Eduardo Vitor , Grant Kelly , Tran Khoi A , Jovanovic Mira , Cao Sijia , Wiens Theresa , Kozbial Andrzej , Orlin Anton , Lenane Courtney Nichole , Herder Susan P. , Kiss Szilard , Reeves Tom , Cruess Alan F. , Dean Andrea , Hoskin-Mott Ann , Morrison Christine , Caldwell Meggie D , Hynes Mitzi , Gupta R. Rishi , Durling Stacey , MacDonnell Trina , Beck Roy W. , Baptista Alyssa , Beaulieu Wesley T. , Calhoun Claire T. , Constantine Sharon R. , Correia Isabella , Dale Brian B. , Dupre Simone S. , Franklin Crystal A. , Galusic Sandra , Huggins Meagan , Hunter Brenda L. , Johnson Paula A. , Josic Kristin , Kelly Brittany , Maguire Maureen G. , Meadows Britney , Stockdale Cynthia R. , Zokruah Alice , Bhargava Sangeeta , Barkmeier Andrew J. , Baskin Darrell , Blodi Barbra , Chew Emily , Ferris Frederick L. , Jaffe Glenn J. , Bressler Neil M. , Lujan Brandon , Tolls Dorothy , Sheridan Daniel , Pitoc Cloyd M , Aquino Lizzie Anne C , Salva Claude Michael G. , Lewis Drew , Stainback Jeffery , Makkena Vijaya , Winter Katrina , Mora Adiel , Harrington Chris , Vinh Doc-Lap 
Published: August 2022

ImportanceUltra-widefield (UWF) imaging improves the ability to identify peripheral diabetic retinopathy (DR) lesions compared with standard imaging. Whether detection of predominantly peripheral lesions (PPLs) better predicts rates of disease worsening over time is unknown.ObjectiveTo determine whether PPLs identified on UWF imaging are associated with increased disease worsening beyond the risk associated with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score.Design, Setting, and ParticipantsThis cohort study was a prospective, multicenter, longitudinal observational study conducted at 37 US and Canadian sites with 388 participants enrolled between February and December 2015. At baseline and annually through 4 years, 200° UWF-color images were obtained and graded for DRSS at a reading center. Baseline UWF-color and UWF-fluorescein angiography (FA) images were evaluated for the presence of PPL. Data were analyzed from May 2020 to June 2022.InterventionsTreatment of DR or diabetic macular edema was at investigator discretion.Main Outcomes and MeasuresPredominantly peripheral lesions were defined as DR lesions with a greater extent outside vs inside the 7 standard ETDRS fields. Primary outcome was disease worsening defined as worsening 2 steps or more on the DRSS or receipt of DR treatment. Analyses were adjusted for baseline DRSS score and correlation between 2 study eyes of the same participant.ResultsData for 544 study eyes with nonproliferative DR (NPDR) were analyzed (182 [50%] female participants; median age, 62 years; 68% White). The 4-year disease worsening rates were 45% for eyes with baseline mild NPDR, 40% for moderate NPDR, 26% for moderately severe NPDR, and 43% for severe NPDR. Disease worsening was not associated with color PPL at baseline (present vs absent: 38% vs 43%; HR, 0.78; 95% CI, 0.57-1.08; P = .13) but was associated with FA PPL at baseline (present vs absent: 50% vs 31%; HR, 1.72; 95% CI, 1.25-2.36; P &amp;lt; .001).Conclusions and RelevanceAlthough no association was identified with color PPL, presence of FA PPL was associated with greater risk of disease worsening over 4 years, independent of baseline DRSS score. These results suggest that use of UWF-FA to evaluate retinas peripheral to standard ETDRS fields may improve the ability to predict disease worsening in NPDR eyes. These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes.