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Validation of the Children’s Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model

Educational Objective
To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model’s sensitivity for treatment-requiring ROP.
1 Credit CME
Key Points

Question  Can the CHOP ROP model be validated in a multicenter cohort large enough to obtain a precise estimate of the model’s sensitivity for treatment-requiring retinopathy of prematurity?

Findings  In this secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity Study of 7483 premature infants at risk for retinopathy of prematurity, the original CHOP ROP model correctly predicted 452 of 459 infants with type 1 retinopathy of prematurity, reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations.

Meaning  These results suggest that the CHOP ROP model has high but not 100% sensitivity and may be better used to reduce examination frequency.

Abstract

Importance  The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines.

Objective  To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model’s sensitivity for treatment-requiring ROP.

Design, Setting, and Participants  This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome.

Main Outcomes and Measures  Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations.

Results  Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations. Lowering the cut point to capture all type 1 ROP cases (sensitivity, 100%; 95% CI, 99.2%-100%) resulted in only 6.8% of infants not requiring examinations. However, if low-risk infants were examined at 37 weeks’ postmenstrual age and followed up only if ROP was present at that examination, all type 1 ROP cases would be captured, and the number of examinations performed among infants with GA exceeding 27 weeks would be reduced by 28.4%.

Conclusion and Relevance  The CHOP ROP model demonstrated high but not 100% sensitivity and may be better used to reduce examination frequency. The model might be used reliably to guide a modified ROP screening schedule and decrease the number of examinations performed.

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Article Information

Accepted for Publication: May 27, 2017.

Corresponding Author: Gil Binenbaum, MD, MSCE, Children’s Hospital of Philadelphia, Ophthalmology 9-MAIN, 3401 Civic Center Blvd, Philadelphia, PA 19104 (binenbaum@email.chop.edu).

Published Online: July 13, 2017. doi:10.1001/jamaophthalmol.2017.2295

Author Contributions: Dr Binenbaum had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Binenbaum, Ying.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Binenbaum, Tomlinson.

Critical revision of the manuscript for important intellectual content: Binenbaum, Ying.

Statistical analysis: Binenbaum, Ying.

Obtained funding: Binenbaum, Ying.

Administrative, technical, or material support: Ying, Tomlinson.

Study supervision: Binenbaum, Ying.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and none were reported.

Funding/Support: This work was supported by grant R01EY021137 from the National Institutes of Health.

Role of the Funder/Sponsor: The funding source 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 Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study Group investigators are as follows:

Office of Study Chair:Children’s Hospital of Philadelphia: Gil Binenbaum, MD, MSCE (principal investigator [PI]), Lauren A. Tomlinson, BS, and Trang B. Duros.

Data Coordinating Center:Perelman School of Medicine at the University of Pennsylvania: Gui-shuang Ying, PhD (PI), Maureen G. Maguire, PhD, Mary Brightwell-Arnold, BA, SCP, James Shaffer, MS, Maria Blanco, Trina Brown, and Christopher P. Helker, MSPH.

Clinical Centers:Albany Medical College: Gerard P. Barry, MD (PI), Marilyn Fisher, MD, MS, Maria V. Battaglia, and Alex M. Drach. The Johns Hopkins University: Pamela Donohue, ScD (PI), Michael X. Repka, MD, Megan Doherty, Dorothy Dow, and Jennifer A. Shepard, CRNP. University at Buffalo (Women & Children’s Hospital of Buffalo): James D. Reynolds, MD (PI) and Erin Connelly. Medical University of South Carolina: Edward Cheeseman, MD, MBA (PI), Carol Bradham, COA, CCRC, Allison McAlpine, Sudeep Sunthankar, and Kinsey Shirer, RN. University of Illinois at Chicago: Javaneh Abbasian, MD (PI) and Janet Lim, MD. Cincinnati Children’s Hospital Medical Center (Cincinnati Children’s Hospital Medical Center, Good Samaritan Hospital, and University of Cincinnati Medical Center): Michael Yang, MD (PI), Elizabeth L. Alfano, and Patricia Cobb. Nationwide Children’s Hospital: David Rogers, MD (PI), Rae R. Fellows, MEd, CCRC, Kaitlyn Loh, Madeline A. McGregor, Thabit Mustafa, Rachel E. Reem, MD, Tess Russell, Rebecca Stattler, and Sara Oravec. Kapiolani Medical Center for Women and Children: David Young (PI), Andrea Siu, MPH, RAC, and Michele Kanemori. Indiana University (Riley Hospital for Children at Indiana University Health): Jingyun Wang (PI), Kathryn Haider, MD, and Elizabeth Hynes, RNC-NIC. University of Iowa Children’s Hospital: Edward F. Bell, MD (PI), Alina V. Dumitrescu, MD, Jonathan M. Klein, MD, Avanthi S. Ajjarapu, Gretchen A. Cress, RN, MPH, Bethany M. Funk, Claire L. Johnson, and Angela C. Platt. Loma Linda University (Loma Linda University Children’s Hospital): Leila Khazaeni, MD (PI), Jennifer Dunbar, MD, Kelley Hawkins, Sharon Lee, RN, and Lily Sung. University of Louisville (Norton Kosair Children’s Hospital): Rahul Bhola, MD (PI), Michelle Bottorff, COA, Neviana Dimova, MD, MS, Rachel Keith, PhD, MSN, NP-C, and Laura Thomas, RN, BSN, CCRN. University of Minnesota (Masonic Children’s Hospital, formerly University of Minnesota–Amplatz Children’s Hospital): Jill Anderson, MD (PI), Jordan Gross, Ann Marie Holleschau, CCRP, and Andrea Kramer. Vanderbilt Eye Institute and Vanderbilt University Medical Center (Monroe Carell Jr Children’s Hospital at Vanderbilt): David Morrison, MD (PI), Sean Donahue, MD, PhD, Neva Fukuda, CO, Sandy Owings, COA, CCRP, and Scott Ruark. University of Oklahoma (Children’s Hospital at Oklahoma University Medical Center): R. Michael Siatkowski, MD (PI), Faizah Bhatti, MD, Vanessa Bergman, COT, CCRC, Karen Corff, APRN, NNP, Kari Harkey, RNC-NIC, Amy Manfredo, APRN-CNP, Shrenik Talsania, MBBS, MPH, CPH, and Terri Whisenhunt, MS, RN. Children’s Hospital of Philadelphia (Children’s Hospital of Philadelphia and Hospital of the University of Pennsylvania): Gil Binenbaum, MD, MSCE (PI), Haresh Kirpalani, MD, MSc, Graham E. Quinn, MD, MSCE, Lindsay Dawson, MD, and Lauren A. Tomlinson, BS. Rhode Island Hospital (Women and Infants Hospital of Rhode Island): Wendy S. Chen, MD, PhD (PI) and Deidrya Jackson. Saint Louis University (Cardinal Glennon Children’s Hospital): Bradley Davitt, MD (PI), Dawn Govreau, COT, Linda Breuer, LPN, and September Noonan, RN. University of Utah (University of Utah Hospital and Primary Children’s Hospital): Robert Hoffman, MD (PI), Joanna Beachy, MD, PhD, Deborah Harrison, MS, Ashlie Bernhisel, Bonnie Carlstrom, and Katie Jo Farnsworth, CRC. University of California San Francisco (UCSF Benioff Children’s Hospital and Zuckerberg San Francisco General Hospital, formerly San Francisco General Hospital): Alejandra G. de Alba Campomanes, MD, MPH (PI), Jacquelyn Kemmer, Alexandra Neiman, and Sarah Sitati-Ng’Anda, MD. Seattle Children’s Hospital (University of Washington Medical Center): Francine Baran, MD (PI), Kristina Tarczy-Hornoch, MD, DPhil (PI), and Lauren Eaton. The Hospital for Sick Children (Sick Kids), Toronto: Nasrin Najm-Tehrani, MD, MSc (PI), Maram Isaac, and Robin Knighton. Los Angeles Biomedical Research Institute (Harbor–UCLA Medical Center): Monica Ralli Khitri, MD (PI) and Madeline Del Signore, RN. Crozer-Chester Medical Center: Cynthia Dembofsky, MD (PI), Andrew Meyer, MD (PI), Karen Flaherty, Tracey Harris, and Jamie Heeneke. Nemours/Alfred I. duPont Hospital for Children: Christopher M. Fecarotta, MD (PI), Dorothy Hendricks, MD (PI), Alicia Olivant Fisher, MS, and Mark Paullin, MS.

Cost-effectiveness Component:Beth Israel Deaconess Medical Center: John Zupancic, MD, MS, ScD (PI).

Editorial Committee: Edward F. Bell, MD, Gil Binenbaum, MD, MSCE, Pamela Donohue, ScD, Graham E. Quinn, MD, MSCE, Lauren A. Tomlinson, BS, and Gui-shuang Ying, PhD.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Meeting Presentation: This study was presented in part at the 2016 Annual Meeting of the American Association for Pediatric Ophthalmology and Strabismus; April 7, 2016; Vancouver, British Columbia, Canada.

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