title: Expert Diagnosis of Plus Disease in Retinopathy of Prematurity From Computer-Based Image Analysis.
abstract: OBJECTIVE
  Published definitions of plus disease in retinopathy of prematurity (ROP) reference arterial tortuosity and venous dilation within the posterior pole based on a standard published photograph. One possible explanation for limited interexpert reliability for a diagnosis of plus disease is that experts deviate from the published definitions.
  
  
  OBJECTIVE
  To identify vascular features used by experts for diagnosis of plus disease through quantitative image analysis.
  
  
  METHODS
  A computer-based image analysis system (Imaging and Informatics in ROP [i-ROP]) was developed using a set of 77 digital fundus images, and the system was designed to classify images compared with a reference standard diagnosis (RSD). System performance was analyzed as a function of the field of view (circular crops with a radius of 1-6 disc diameters) and vessel subtype (arteries only, veins only, or all vessels). Routine ROP screening was conducted from June 29, 2011, to October 14, 2014, in neonatal intensive care units at 8 academic institutions, with a subset of 73 images independently classified by 11 ROP experts for validation. The RSD was compared with the majority diagnosis of experts.
  
  
  METHODS
  The primary outcome measure was the percentage of accuracy of the i-ROP system classification of plus disease, with the RSD as a function of the field of view and vessel type. Secondary outcome measures included the accuracy of the 11 experts compared with the RSD.
  
  
  RESULTS
  Accuracy of plus disease diagnosis by the i-ROP computer-based system was highest (95%; 95% CI, 94%-95%) when it incorporated vascular tortuosity from both arteries and veins and with the widest field of view (6-disc diameter radius). Accuracy was 90% or less when using only arterial tortuosity and 85% or less using a 2- to 3-disc diameter view similar to the standard published photograph. Diagnostic accuracy of the i-ROP system (95%) was comparable to that of 11 expert physicians (mean 87%, range 79%-99%).
  
  
  CONCLUSIONS
  Experts in ROP appear to consider findings from beyond the posterior retina when diagnosing plus disease and consider tortuosity of both arteries and veins, in contrast with published definitions. It is feasible for a computer-based image analysis system to perform comparably with ROP experts, using manually segmented images.
authors.affiliation: Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Campbell
authors.affiliation: Cognitive Systems Laboratory, Northeastern University, Boston, Massachusetts.
authors.forename: Esra
authors.initials: E
authors.lastname: Ataer-Cansizoglu
authors.affiliation: Department of Computer Science, Universidade da Coruña, A Coruña, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bolon-Canedo
authors.affiliation: Cognitive Systems Laboratory, Northeastern University, Boston, Massachusetts.
authors.forename: Alican
authors.initials: A
authors.lastname: Bozkurt
authors.affiliation: Cognitive Systems Laboratory, Northeastern University, Boston, Massachusetts.
authors.forename: Deniz
authors.initials: D
authors.lastname: Erdogmus
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Kalpathy-Cramer
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology, Ross Eye Institute, State University of New York at Buffalo.
authors.forename: James D
authors.initials: JD
authors.lastname: Reynolds
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York.
authors.forename: Jason
authors.initials: J
authors.lastname: Horowitz
authors.affiliation: Department of Ophthalmology, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hutcheson
authors.affiliation: Retina Consultants, Chicago, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Shapiro
authors.affiliation: Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael X
authors.initials: MX
authors.lastname: Repka
authors.affiliation: Long Island Vitreoretinal Consultants, Great Neck, New York.
authors.forename: Phillip
authors.initials: P
authors.lastname: Ferrone
authors.affiliation: Associated Retinal Consultants, Oakland University, Royal Oak, Michigan.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Drenser
authors.affiliation: Asociacion para Evitar la Ceguera en Mexico, Mexico City, Mexico.
authors.forename: Maria Ana
authors.initials: MA
authors.lastname: Martinez-Castellanos
authors.affiliation: Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Susan
authors.initials: S
authors.lastname: Ostmo
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago.
authors.forename: Karyn
authors.initials: K
authors.lastname: Jonas
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago.
authors.forename: R V Paul
authors.initials: RV
authors.lastname: Chan
authors.affiliation: Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland15Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Chiang
mesh_terms: D001158:Arteries / Q000002:abnormalities*; D003936:Diagnosis, Computer-Assisted; D005103:Expert Systems; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D007593:Joint Instability / Q000145:classification / Q000175:diagnosis*; D015203:Reproducibility of Results; D012171:Retinal Vessels / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000145:classification / Q000175:diagnosis*; D012873:Skin Diseases, Genetic / Q000145:classification / Q000175:diagnosis*; D054079:Vascular Malformations / Q000145:classification / Q000175:diagnosis*