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Can a quantitative measurement of retinopathy of prematurity severity be used over time to monitor disease regression after treatment?
In this cohort study of at-risk infants using data collected for the Imaging and Informatics in Retinopathy of Prematurity study, the quantitative retinopathy of prematurity vascular severity score developed using an automated deep learning–based plus disease classifier consistently reflected clinical disease posttreatment regression in 46 included eyes with laser or bevacizumab treatment.
Tracking quantitative measurements of retinopathy of prematurity severity may be an effective method of following disease regression and identifying patients at risk for recurrence after retinopathy of prematurity treatment.
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, but treatment failure and disease recurrence are important causes of adverse outcomes in patients with treatment-requiring ROP (TR-ROP).
To apply an automated ROP vascular severity score obtained using a deep learning algorithm and to assess its utility for objectively monitoring ROP regression after treatment.
Design, Setting, and Participants
This retrospective cohort study used data from the Imaging and Informatics in ROP consortium, which comprises 9 tertiary referral centers in North America that screen high volumes of at-risk infants for ROP. Images of 5255 clinical eye examinations from 871 infants performed between July 2011 and December 2016 were assessed for eligibility in the present study. The disease course was assessed with time across the numerous examinations for patients with TR-ROP. Infants born prematurely meeting screening criteria for ROP who developed TR-ROP and who had images captured within 4 weeks before and after treatment as well as at the time of treatment were included.
Main Outcomes and Measures
The primary outcome was mean (SD) ROP vascular severity score before, at time of, and after treatment. A deep learning classifier was used to assign a continuous ROP vascular severity score, which ranged from 1 (normal) to 9 (most severe), at each examination. A secondary outcome was the difference in ROP vascular severity score among eyes treated with laser or the vascular endothelial growth factor antagonist bevacizumab. Differences between groups for both outcomes were assessed using unpaired 2-tailed t tests with Bonferroni correction.
Of 5255 examined eyes, 91 developed TR-ROP, of which 46 eyes met the inclusion criteria based on the available images. The mean (SD) birth weight of those patients was 653 (185) g, with a mean (SD) gestational age of 24.9 (1.3) weeks. The mean (SD) ROP vascular severity scores significantly increased 2 weeks prior to treatment (4.19 [1.75]), peaked at treatment (7.43 [1.89]), and decreased for at least 2 weeks after treatment (4.00 [1.88]) (all P < .001). Eyes requiring retreatment with laser had higher ROP vascular severity scores at the time of initial treatment compared with eyes receiving a single treatment (P < .001).
Conclusions and Relevance
This quantitative ROP vascular severity score appears to consistently reflect clinical disease progression and posttreatment regression in eyes with TR-ROP. These study results may have implications for the monitoring of patients with ROP for treatment failure and disease recurrence and for determining the appropriate level of disease severity for primary treatment in eyes with aggressive disease.
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Accepted for Publication: April 14, 2019.
Corresponding Author: Michael F. Chiang, MD, Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239 (email@example.com).
Published Online: July 3, 2019. doi:10.1001/jamaophthalmol.2019.2442
Author Contributions: Drs Gupta and Campbell contributed equally to this work and are considered co–first authors. Dr Chiang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Campbell, Taylor, Erdogmus, Ioannidis, Kalpathy-Cramer, Kim, Chiang.
Acquisition, analysis, or interpretation of data: Gupta, Campbell, Taylor, Brown, Ostmo, Chan, Dy, Kalpathy-Cramer, Kim, Chiang.
Drafting of the manuscript: Gupta, Campbell, Brown.
Critical revision of the manuscript for important intellectual content: Campbell, Taylor, Ostmo, Chan, Dy, Erdogmus, Ioannidis, Kalpathy-Cramer, Kim, Chiang.
Statistical analysis: Gupta, Campbell, Chiang.
Obtained funding: Erdogmus, Ioannidis, Kalpathy-Cramer, Chiang.
Administrative, technical, or material support: Gupta, Campbell, Brown, Ostmo, Kalpathy-Cramer, Chiang.
Supervision: Campbell, Chan, Dy, Erdogmus, Kalpathy-Cramer, Chiang.
Conflict of Interest Disclosures: Dr Campbell reported receiving grants from Genentech and personal fees from Allergan outside the submitted work. Dr Chan reported receiving personal fees from Alcon, Allergan, Visunex Medical Systems, Beyeonics, and Genentech outside the submitted work. Dr Dy reported receiving grants from the National Science Foundation. Dr Ioannidis reported receiving grants from National Science Foundation and from the National Institutes of Health during the conduct of the study. Dr Kalpathy-Cramer reported receiving grants from the National Eye Institute and the National Science Foundation during the conduct of the study and receiving personal fees from INFOTECHSoft outside the submitted work. Dr Chiang reported receiving grants from the National Institutes of Health, the National Science Foundation, and Genentech; receiving nonfinancial support from Clarity Medical Systems; receiving personal fees from Novartis during the conduct of the study; and being an equity owner in Initeleretina outside the submitted work. Drs Campbell and Brown, Ms Ostmo, and Drs Chan, Dy, Erdogmus, Ioannidis, Kalpathy-Cramer, and Chiang have a patent application pending on the described technology.
Funding/Support: This project was supported by grants R01EY19474, K12EY027720, and P30EY10572 from the National Institutes of Health; by grants SCH-1622679, SCH-1622542, and SCH-1622536 from the National Science Foundation; and by Research to Prevent Blindness in the form of unrestricted departmental funding to the Casey Institute and a Career Development Award (Dr Campbell).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: The members of the Imaging and Informatics in Retinopathy of Prematurity (i-ROP) Consortium follow. Oregon Health & Science University: Michael F. Chiang, MD, Susan Ostmo, MS, Sang Jin Kim, MD, PhD, Kemal Sonmez, PhD, and J. Peter Campbell, MD, MPH. University of Illinois at Chicago: R. V. Paul Chan, MD and Karyn Jonas, RN. Columbia University: Jason Horowitz, MD, Osode Coki, RN, Cheryl-Ann Eccles, RN, and Leora Sarna, RN. Weill Cornell Medical College: Anton Orlin, MD. Bascom Palmer Eye Institute: Audina Berrocal, MD, and Catherin Negron, BA. William Beaumont Hospital: Kimberly Denser, MD, Kristi Cumming, RN, Tammy Osentoski, RN, Tammy Check, RN, and Mary Zajechowski, RN. Children’s Hospital Los Angeles: Thomas Lee, MD, Evan Kruger, BA, and Kathryn McGovern, MPH. Cedars Sinai Hospital: Charles Simmons, MD, Raghu Murthy, MD, and Sharon Galvis, NNP. LA Biomedical Research Institute: Jerome Rotter, MD, Ida Chen, PhD, Xiaohui Li, MD, Kent Taylor, PhD, and Kaye Roll, RN. Massachusetts General Hospital: Jayashree Kalpathy-Cramer, PhD. Northeastern University: Deniz Erdogmus, PhD, and Stratis Ioannidis, PhD. Asociacion para Evitar la Ceguera en Mexico: Maria Ana Martinez-Castellanos, MD, Samantha Salinas-Longoria, MD, Rafael Romero, MD, Andrea Arriola, MD, Francisco Olguin-Manriquez, MD, Miroslava Meraz-Gutierrez, MD, Carlos M. Dulanto-Reinoso, MD, and Cristina Montero-Mendoza, MD.
Meeting Presentation: This paper was presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology; May 1, 2018; Honolulu, Hawaii.
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