TY - JOUR
T1 - Association of Ultra-Widefield Fluorescein Angiography-Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening over Time
AU - Silva, Paolo S.
AU - Marcus, Dennis M.
AU - Liu, Danni
AU - Aiello, Lloyd Paul
AU - Antoszyk, Andrew
AU - Elman, Michael
AU - Friedman, Scott
AU - Glassman, Adam R.
AU - Googe, Joseph M.
AU - Jampol, Lee Merrill
AU - Martin, Daniel F.
AU - Melia, Michele
AU - Preston, Carin M.
AU - Wykoff, Charles C.
AU - Sun, Jennifer K.
N1 - Funding Information:
serving on an advisory board for Allergan. Dr Elman reported grants from the Jaeb Center for Health Research during the conduct of the study. Dr Friedman reported research support from Amgen, Boehringer Ingelheim, Chengdu Kang Hong, Opthea, and Regeneron. Mr Glassman reported grants from the NIH and JDRF; loaner ophthalmic cameras to clinical sites from Optos, Zeiss, and Optovue; and additional funding or devices outside of the submitted work from Regeneron, Helmsley Charitable Trust, PhotoOptx, and Roche. Dr Jampol reported professional fees from Alkahest. Ms Melia reported grants from the NIH and JDRF; loaner ophthalmic cameras to clinical sites from Optos, Zeiss, and Optovue; and additional funding or devices outside of the submitted work from Regeneron, Helmsley Charitable Trust, PhotoOptx, and Roche. Ms Preston reported grants from the NIH and JDRF; loaner ophthalmic cameras to clinical sites from Optos, Zeiss, and Optovue; and additional funding or devices outside of the submitted work from Regeneron, Helmsley Charitable Trust, PhotoOptx, and Roche. Dr Wykoff reported grants and other research or professional fees from AbbVie, Adverum, Aerie, AGTC, Aldeyra, Alexion, Alimera Sciences, Alkahest, Allergan, Amgen, Allgenesis, Alnylam, Annexon Biosciences, Apellis, Arrowhead, Asclepix, Bausch and Lomb, Bayer, Boehringer Ingelheim, Bionic Vision, Chengdu Kang Hong, Cholgene Therapeutics, Clearside Biomedical, Curacle, EyePoint, Frontera, Gemini Therapeutics, Genentech, Graybug, Gyroscope Therapeutics, IACTA, Ionis Pharmaceuticals, Irenix, Iveric Bio, Janssen Pharmaceuticals, Kato Pharmaceuticals, Kiora, Kodiak, Kriya, Lowy Medical Research Institute, Nanoscope Technologies, Neurotech, NGM Biopharmaceuticals, Novartis, Ocular Therapeutix, Ocuphire Phara, OccuRx, OliX, ONL Therapeutics, Opthea, Oxurion, Palatin, Perfuse, Polyphotonix, Ray, Recens Medical, Regeneron, RegenXBio, Roche, SamChunDang Pharm, Sandoz, Stealth, Surrozen, THEA, Taiwan Liposome Company, Tissue Gen, Unity Biotechnology, Unity Valo Health, Vitranu, and Xbrane Biopharma and equity or stock in ONL Therapeutics, Polyphotonix Tissue, Gen Visgenx, and Vitranu. Dr Sun reported grants from Jaeb Center for Health Research during the conduct of the study; grants from Optovue, JDRF, Kalvista, Novartis, Novo Nordisk, Boerhinger Ingelheim, Genentech/Roche, Physical Sciences, Janssen, and the Massachusetts Lions Eye Research Foundation outside the submitted work; nonfinancial support from Optovue, Merck, Novartis, Novo Nordisk, Genentech/Roche, Boston Micromachines, and Adaptive Sensory Technologies outside the submitted work; and professional fees from the American Medical Association and American Diabetes Association outside the submitted work. No other disclosures were reported.
Funding Information:
was supported by the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award UG1EY014231, grants from the Juvenile Diabetes Research Foundation, and supplies from Optos.
Funding Information:
grants from Optos, the Massachusetts Lions Eye Research Foundation, the Medical Research Council (United Kingdom), and the Philippine Council of Health Research and Development; personal fees and nonfinancial research support from Optos during the conduct of the study; personal fees and nonfinancial support from Optomed outside the submitted work; and professional fees from the American Diabetes Association outside the submitted work. Dr Marcus reported fees from Jaeb Center for Health Research for serving as protocol chair during the conduct of the study; grants from Allergan, Amgen, Boehringer Ingelheim, Alcon, Kalvista, Ionis, Xplore, Mylan, Samsung, Novartis, Opthea, Chenghdu, Clearside, Ophthotech/Iveric, Outlook, Gemini, Genentech, Graybug, Topcon, Optos, Gyroscope, Stealth Spiam, Apellis, Roche, Novartis, Xplore, Regenxbio, Kodiak, Zeiss, Annexon, Oculis, Alexion, and Regeneron Pharmaceuticals; and serving as a consultant for Regenxbio, Genentech/Roche, Regeneron, Clearside, and Vial outside the submitted work. Ms Liu reported grants from the National Institutes of Health (NIH) and JDRF; loaner ophthalmic cameras to clinical sites from Optos, Zeiss, and Optovue; and additional funding or devices outside of the submitted work from Regeneron, Helmsley Charitable Trust, PhotoOptx, and Roche. Dr Aiello reported professional fees from Guidepoint Global, Japan Society of Ophthalmology and Diabetes, Johns Hopkins, Novo Nordisk, Perfuse Therapeutics, Samsung, System Analytic, and Valo Health and equity stock and professional fees from Kalvista. Dr Antoszyk reported research support from Apellis, Gemini Therapeutics, Genentech, Kodiak, NGM Biopharmaceutical, Novartis, Novo Nordisk, Amgen, Regeneron, Roche, and Notal and
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - Importance: Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. Objective: To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. Design, Setting, and Participants: This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200° ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200° UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Interventions: Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures: Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. Results: After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95% CI, 1.02-1.21; P =.02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95% CI, 1.17-1.56; P <.001) and midperiphery (HR for 0.1-unit increase, 1.08; 95% CI, 1.00-1.16; P =.04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02-1.22; P =.02) and presence of FA PPL (HR, 1.89; 95% CI, 1.35-2.65; P <.001) remained associated with disease worsening. Conclusions and Relevance: This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.
AB - Importance: Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. Objective: To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. Design, Setting, and Participants: This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200° ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200° UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Interventions: Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures: Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. Results: After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95% CI, 1.02-1.21; P =.02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95% CI, 1.17-1.56; P <.001) and midperiphery (HR for 0.1-unit increase, 1.08; 95% CI, 1.00-1.16; P =.04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02-1.22; P =.02) and presence of FA PPL (HR, 1.89; 95% CI, 1.35-2.65; P <.001) remained associated with disease worsening. Conclusions and Relevance: This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.
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U2 - 10.1001/jamaophthalmol.2022.3130
DO - 10.1001/jamaophthalmol.2022.3130
M3 - Article
C2 - 35980610
AN - SCOPUS:85137106843
VL - 140
SP - 936
EP - 945
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
SN - 2168-6165
IS - 10
ER -