Kellyn N Bellsmith1, James Brown2, Sang Jin Kim3, Isaac H Goldstein1, Aaron Coyner4, Susan Ostmo1, Kishan Gupta1, R V Paul Chan5, Jayashree Kalpathy-Cramer6, Michael F Chiang7, J Peter Campbell8. 1. Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon. 2. School of Computer Science, University of Lincoln, Lincoln, United Kingdom; Massachusetts General Hospital & Brigham and Women's Hospital Center for Clinical Data Science, Boston, Massachusetts. 3. Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4. Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon. 5. Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois. 6. Massachusetts General Hospital & Brigham and Women's Hospital Center for Clinical Data Science, Boston, Massachusetts. 7. Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon. 8. Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon. Electronic address: campbelp@ohsu.edu.
Abstract
PURPOSE: Aggressive posterior retinopathy of prematurity (AP-ROP) is a vision-threatening disease with a significant rate of progression to retinal detachment. The purpose of this study was to characterize AP-ROP quantitatively by demographics, rate of disease progression, and a deep learning-based vascular severity score. DESIGN: Retrospective analysis. PARTICIPANTS: The Imaging and Informatics in ROP cohort from 8 North American centers, consisting of 947 patients and 5945 clinical eye examinations with fundus images, was used. Pretreatment eyes were categorized by disease severity: none, mild, type 2 or pre-plus, treatment-requiring (TR) without AP-ROP, TR with AP-ROP. Analyses compared TR with AP-ROP and TR without AP-ROP to investigate differences between AP-ROP and other TR disease. METHODS: A reference standard diagnosis was generated for each eye examination using previously published methods combining 3 independent image-based gradings and 1 ophthalmoscopic grading. All fundus images were analyzed using a previously published deep learning system and were assigned a score from 1 through 9. MAIN OUTCOME MEASURES: Birth weight, gestational age, postmenstrual age, and vascular severity score. RESULTS: Infants who demonstrated AP-ROP were more premature by birth weight (617 g vs. 679 g; P = 0.01) and gestational age (24.3 weeks vs. 25.0 weeks; P < 0.01) and reached peak severity at an earlier postmenstrual age (34.7 weeks vs. 36.9 weeks; P < 0.001) compared with infants with TR without AP-ROP. The mean vascular severity score was greatest in TR with AP-ROP infants compared with TR without AP-ROP infants (8.79 vs. 7.19; P < 0.001). Analyzing the severity score over time, the rate of progression was fastest in infants with AP-ROP (P < 0.002 at 30-32 weeks). CONCLUSIONS: Premature infants in North America with AP-ROP are born younger and demonstrate disease earlier than infants with less severe ROP. Disease severity is quantifiable with a deep learning-based score, which correlates with clinically identified categories of disease, including AP-ROP. The rate of progression to peak disease is greatest in eyes that demonstrate AP-ROP compared with other treatment-requiring eyes. Analysis of quantitative characteristics of AP-ROP may help improve diagnosis and treatment of an aggressive, vision-threatening form of ROP.
PURPOSE:Aggressive posterior retinopathy of prematurity (AP-ROP) is a vision-threatening disease with a significant rate of progression to retinal detachment. The purpose of this study was to characterize AP-ROP quantitatively by demographics, rate of disease progression, and a deep learning-based vascular severity score. DESIGN: Retrospective analysis. PARTICIPANTS: The Imaging and Informatics in ROP cohort from 8 North American centers, consisting of 947 patients and 5945 clinical eye examinations with fundus images, was used. Pretreatment eyes were categorized by disease severity: none, mild, type 2 or pre-plus, treatment-requiring (TR) without AP-ROP, TR with AP-ROP. Analyses compared TR with AP-ROP and TR without AP-ROP to investigate differences between AP-ROP and other TR disease. METHODS: A reference standard diagnosis was generated for each eye examination using previously published methods combining 3 independent image-based gradings and 1 ophthalmoscopic grading. All fundus images were analyzed using a previously published deep learning system and were assigned a score from 1 through 9. MAIN OUTCOME MEASURES: Birth weight, gestational age, postmenstrual age, and vascular severity score. RESULTS:Infants who demonstrated AP-ROP were more premature by birth weight (617 g vs. 679 g; P = 0.01) and gestational age (24.3 weeks vs. 25.0 weeks; P < 0.01) and reached peak severity at an earlier postmenstrual age (34.7 weeks vs. 36.9 weeks; P < 0.001) compared with infants with TR without AP-ROP. The mean vascular severity score was greatest in TR with AP-ROPinfants compared with TR without AP-ROPinfants (8.79 vs. 7.19; P < 0.001). Analyzing the severity score over time, the rate of progression was fastest in infants with AP-ROP (P < 0.002 at 30-32 weeks). CONCLUSIONS: Premature infants in North America with AP-ROP are born younger and demonstrate disease earlier than infants with less severe ROP. Disease severity is quantifiable with a deep learning-based score, which correlates with clinically identified categories of disease, including AP-ROP. The rate of progression to peak disease is greatest in eyes that demonstrate AP-ROP compared with other treatment-requiring eyes. Analysis of quantitative characteristics of AP-ROP may help improve diagnosis and treatment of an aggressive, vision-threatening form of ROP.
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