Ultra-Widefield Fluorescein Angiographic Quantitative Leakage Parameters and Clinical Outcomes in Nonproliferative Diabetic Retinopathy
Year: 2026
Type: article
Abstract: Importance: This study could facilitate the generation of automated quantitative assessments, providing clinicians and clinical trials with a continuous severity scale of retinal leakage to improve the prediction of future diabetic retinopathy (DR) worsening. Objective: To examine ultra-widefield fluorescein angiography (UWF-FA) retinal leakage associated with DR progression and complications. Design, Setting, and Participants: This cohort study was a post hoc analysis of the DRCR Retina Network Protocol AA clinical trial. Participants were adults with nonproliferative diabetic retinopathy (NPDR). Data was collected from February 2015 to March 2020. Analysis was performed June 2023 to April 2024. Interventions: Treatment of DR or diabetic macular edema was at the investigator's discretion. Main Outcomes and Measures: Time to Diabetic Retinopathy Severity Scale (DRSS) worsening of 2 or more steps, vitreous hemorrhage (VH), and proliferative diabetic retinopathy (PDR) over 4 years. Baseline and 1-year leakage index, calculated as the area with leakage divided by the total area in the analyzable retina on UWF-FA, were evaluated as risk factors. Results: Among 537 eyes (363 participants; mean [SD] age, 61 [12] years; 183 [50%] male, 180 [50%] female), the baseline leakage index (mean [SD], 3.5% [3.9%]) was associated with DRSS worsening over 4 years (hazard ratio [HR] for 1% increase, 1.09; 95% CI, 1.05-1.13; P < .001). At 1 year, 114 of 453 eyes (25%) had an absolute leakage increase 1% or greater from baseline, which was associated with a higher risk of DRSS worsening over 4 years (61% vs 33%; HR, 2.63; 95% CI, 1.90-3.64; P < .001). Baseline leakage and a 1% or greater increase at 1 year were also associated with development of VH and PDR. Conclusions and Relevance: In eyes with NPDR, higher leakage at baseline and an increase from baseline to 1 year were associated with greater risk of DRSS worsening and vision-threatening complications, including VH and PDR. These findings support quantitative leakage assessment at baseline and over time as a promising biomarker for predicting the severity and progression of diabetic retinopathy.
Source: JAMA Ophthalmology
Authors: Justis P. Ehlers, Kristin Josic, Lloyd P. Aiello, Reem Amine, Asmita Indurkar, Alison A. Martin, Karen Matar, Paolo S. Silva, Jennifer K. Sun, DRCR Retina Network, Abla M Harara, Angela N. Palacios, Brian B. Berger, Boris Corak, Bianca Luong, Chirag D. Jhaveri, Daniela Mariel Wilson, Gowtham Jonna, Ivana Gunderson, Kimberly Hosein, Ryan M. Reid, Saradha Chexal, Tori Moore, Tina A Seidu, Valerie Gatavaski, Yong Ren, Bradley A. Stern, Celia E Benvenutti, Dinah S Oude-Reimerink, Jenny Shaheen, John Grybas, Julianne Vitale-Kuhn, Jessica L. Staffne, Katie M. Ventimiglia, Megan Allis, Mary K. Monk, Marc E. Thomas, Nicole M. Massu, Paul Andrew Edwards, Tracy A. Troszak, Amber N Irons, Brittany Rego, Dennis P. Han, Eleanor Dorsey, Erika Nelson, Hannah Sheppard, Joseph R. Beringer, Judy E. Kim, Kristy L. Keller, Krissa L. Packard, Marriner L. Altmann, Mara Goldberg, Nickolas Chen, Pat A. Winter, Shay Bourgeois, Samantha Jacobo, Stephanie J Moebius, Thomas B. Connor, Vicki Barwick, Vesper V. Williams, William J. Wirostko, A. Thomas Ghuman, Anita H. Leslie, Ashish G. Sharma, Cheryl Kiesel, Danielle Dyshanowitz, Eileen Knips, Glenn Wing, Joseph P. Walker, Paul A. Raskauskas, Raymond K. Kiesel, Deborah K. Schlossman, Elizabeth S. Weimann, George S. Sharuk, Hanna Kwak, Jerry D. Cavallerano, Jae W Rhee, Konstantina Sampani, Katie V Tran, Leila Bestourous, Linette Miranda, Michael N. Krigman, Margaret E. Stockman, Paul G. Arrigg, Robert W. Cavicchi, Rita K. Kirby, Shireen Glynn, Steve L. Papaconstantinou, Sabera T. Shah, Timothy J. Murtha, William Carli, Autumn K. Finch, Angella K. Gentile, Angela K. Price, Brittany A Murphy, Beverly O Rowland, Christina J. Fleming, Courtney Mahr, Carol A Shore, David Browning, Donna McClain, Erica Breglio, Gina M. Lester, Jenna T. Herby, Kayla A Bratcher, Loraine M. Clark, Lisa A. Jackson, Lynn Watson, Michael D. McOwen, Omar S. Punjabi, Swann J Bojaj, Sarah A. Ennis, Sherry L. Fredenberg, Taylor S. Jones, Teneisha A. Ragin, Uma M. Balasubramaniam, Blanca Ornelas, Brenda Rodriquez, Carla Edwards, Danielle R. Carns, Eileen E. Tonner, Kisung Woo, Len Richine, Mathew W. MacCumber, Pauline Townsend Merrill, Sarah Kociborski, Ashley M. Harless, Charlotte Harris, Lorraine White, Raj K. Maturi, Julie Asher, Justin Walsh, Jeff Wheeler, Katie Milstead, Kristina Oliver, Lisa Lovelady, Nicholas G. Anderson, Patricia Coppola, Raul E. Lince, R. Keith Shuler, Steve Morris, Sarah M. Oelrich, Brandon S Gardner, Bob Moore, Dennis Cain, Deborah Donohue, David Emmert, Kemi Adeyemo, Lisa K. Levin, Mary Frey, Nick Rhoton, Susan Bressler, Sharon D. Solomon, Amy L Ford, Ashley Hughes, Alisha N Brewer, JoAnn T Booth, Keven W Lunsford, Lauren D. Ukleya, Russ Burris, Ronald M. Kingsley, Shannon R. Almeida, Sonny Icks, Vinay A. Shah, Vanessa A. Bergman, Alessandro A. Castellarin, Aimee H. Shook, Aimee Walker, Dante J. Pieramici, Gina Hong, Kelly Avery, Kate M McKee, Matthew Giust, Marco A Munoz, Sarah Fishbein, Alecia B. Camp, Carl W. Baker, Jil D Baker, Kylie S. Sedberry, Lynnette F. Lambert, Margaret J. Orr, Sonya L Alcaraz, Samantha Kettler, Tracey M. Caldwell, Abigail Miller, Christine M. Dorr, G. Robert Hampton, Jamin S. Brown, Jeffrey P Barker, Kevin I. Rosenberg, Lynn M. Kwasniewski, Laurie J. Sienkiewycz, Lisa Spuches, Michelle L. Manley, Nicole E. Robarge, Stefanie R. DeSantis, Teresa M. DeForge, Alexander J. Brucker, Benjamin J. Kim, Jim M. Berger, Joan C. DuPont, Sheri Drossner, Sara Freeman, Ashley Studebaker, John F. Payne, John A. Wells, Robbin Spivey, Tiffany N. Ogbuewu, Tiffany R. Swinford, Adrienne Guillory, Amy Hutson, Amy C. Schefler, Ankoor R. Shah, Belinda A. Almanza, Brenda Dives, Beau A Richter, Cary A. Stoever, David M. Brown, Danee Foerster, David Garcia, Diana Rodriguez, Daniel Park, Eric Chen, Eric N. Kegley, Elizabeth Quellar, Garret L Twining, Heather Koger-Grifaldo, Ilsa Ortega, Jolene Carranza, James C. Major, Kimberly Williamson, Lindsay Burt, Luis R. Salinas, Lisa M Wolff, Matthew S. Benz, Maura A Estes, Miranda F James, Meredith Berry, Melina Vela, Nubia Landaverde, Nina A. Webb, Richard H. Fish, Rosa Y. Kim, Rebecca Yee, Sadia Y Karani, Stacy M. Supapo, Tamara L Dodel, Tyneisha McCoy, Tien P. Wong, Veronica A. Sneed, Cassandra J. Barnhart, Debra Cantrell, Elizabeth L. DuBose, Houston P Sharpe, Jan Niklas Ulrich, Kanika A Bhansali, Rona Lyn Esquejo, Seema Garg, Sean Grout, Allen McKinney, Brenda J. Bobbitt, Ceara L Wendel, Damanda F. Fagan, Jacqueline Andrews, Krystal Nikki Holmes, Karen L Seyez, Kimberly A. Williamson, Nader Moinfar, Paige N. Walters, Steve Carlton, Shannon M Rehling, Shana E Williams, Tiara L. Reed, Amber R VandeVelde, Frank T. Yeager, Gregory M. Fox, Ivan R. Batlle, Kiersten Bruce, Katherine Pippin, Lexie R. Ainley, Ravi S. J. Singh, Ashley M Adamo, Adrian Guardado, Apurva K. Patel, Brian S Puckett, Christine Hoerner, Colin Ma, David J Clark, Inessa M Flato, Joshua Cohen, Margaret E Charpentier, Marcia Kopfer, Mark A. Peters, Pualani Smith, Paul S. Tlucek, Stephen Hobbs, Stephanie L. Ho, Ashley M. Metzger, Alesia K McCalla, Amy Thompson, Christine Ringrose, Dallas R. Sandler, Henry A. Leder, Jennifer L. Belz, JoAnn Starr, Jennifer L. Simmons, Peggy R Orr, Peter Sotirakos, Pamela V. Singletary, Terri Cain, Teresa Coffey, Tiffany M Carter, Twyla J Robinson, Chirag P. Shah, Dominique Cammarata, Jennifer L. Kruger, Lindsey Colegrove, Margie Graham, Shane T. Gleason, Bryan Noel, Catherine Damron, Diana M. Holcomb, Edward A Slade, Jeanne Van Arsdall, Lisa Bicknell, Michelle Buck, Thomas W. Stone, Amina Farooq, Brook Parsons, Harinderjit Singh, Ken Ivey, Lindsay Allison Foster, Michele Woodward, Siobhan O. Ortiz, Thomas Bailey, Bharani Krishna Mynampati A, Cheryl L White, Ghulam Shabbir Hamdani, Jazzmin N Smith, Kakarla V. Chalam, Kumar Sambhav, Romesh Babaria, Sandeep Grover, Catherine Carroll, Felix Y. Chau, Jennifer I. Lim, Lauren A Talasnik, Mark Janowicz, Natasa Stankovic, Sarah L Berlatsky, Marcia Niec, Jie Sun, Tametha Johnson, Yesenia Ovando, Brenda Nakoski, Calvin E. Mein, Christopher Sean Wienecke, Elaine Castillo, Jaynee Baker, Jonathan San Roman, Lydia Adams, Lita Kirschbaum, Moises A. Chica, Sara L Cloudt, Tori R. Moore, Felix N. Sabates, Gary S. Gallimore, Yin C. Chen, Adrienne C Swann, Deborah M. Cadwell, Kenneth R. Diddie, Taryn F. Boisvert, Carrie D Tessau, Jack Bowers, Jared S. Nielsen, Jay Rostvold, Jamie Spillman, Kyle J. Alliman, Lisa M. Boender, Marilyn A. Johnson, Marianne Parker, Paula L Bix, Spencer D Ridgway, Tami Jo Woehl, Whitney Stonewall, Christopher M. Brown, Gareth M.C. Lema, Luann Wiechelt, Pradeepa Yoganathan, Sandra L. Boglione, Chris A. Montesclaros, Cory Mangham, Gopal Karsaliya, Phillip V. Le, Robert W. Wong, Anne Marie Godfrey, Aleksandra Kuzmanovic, Andrew William Kirker, Bryan Harrison, Farzin Forooghian, Garnet Louise Elvena, Laura J. Hall, Bilgin Turhal, Ian Brown, Isaac A Kotei, Lina Chen, Michael Henry Brent, Michelle Moon, Olivera Sutakovic, Angela Chang, Anne-Marie Godfrey, David Albiani, David A.L. Maberley, Eduardo Vitor Navajas, Kelly Grant, Khoi A Tran, Mira Jovanovic, Sijia Cao, Theresa Wiens, Andrzej Kozbial, Anton Orlin, Courtney Nichole Lenane, Susan P. Herder, Szilard Kiss, Tom Reeves, Alan F. Cruess, Andrea Dean, Ann Hoskin-Mott, Christine Morrison, Meggie D Caldwell, Mitzi Hynes, R. Rishi Gupta, Stacey Durling, Trina MacDonnell, Alyssa Baptista, Lauren Brandt, Claire T. Calhoun, Sharon R. Constantine, Brian B. Dale, Dara Dombrowski, Simone S. Dupre, Crystal A. Franklin, Sandra Galusic, Adam R. Glassman, Meagan Huggins, Brenda L. Hunter, Paula A. Johnson, Brittany Kelly, Danni Liu, Britney Meadows, James Miller, Carin M. Preston, Cynthia R. Stockdale, Wei Tian, Carmen M. Valenzuela-Silva, Thu P. Vu, Daniel F. Martin, Lee M. Jampol, Frederick L. Ferris, III, Emily Y. Chew, Darrell Baskin, Negin Atri, Glenn J. Jaffe, Barbara A. Blodi, Andrew J. Barkmeier, Christina Y. Weng, Mohamed A. Elmasry, Leanne T. Labriola, Thomas W. Gardner, Roy W. Beck
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7126093486