Plus Disease in Retinopathy of Prematurity: Convolutional Neural Network Performance Using a Combined Neural Network and Feature Extraction Approach

Purpose Retinopathy of prematurity (ROP), a leading cause of childhood blindness, is diagnosed by clinical ophthalmoscopic examinations or reading retinal images. Plus disease, defined as abnormal tortuosity and dilation of the posterior retinal blood vessels, is the most important feature to determine treatment-requiring ROP. We aimed to create a complete, publicly available and feature-extraction-based pipeline, I-ROP ASSIST, that achieves convolutional neural network (CNN)-like performance when diagnosing plus disease from retinal images. Methods We developed two datasets containing 100 and 5512 posterior retinal images, respectively. After segmenting retinal vessels, we detected the vessel centerlines. Then, we extracted features relevant to ROP, including tortuosity and dilation measures, and used these features in the classifiers including logistic regression, support vector machine and neural networks to assess a severity score for the input. We tested our system with fivefold cross-validation and calculated the area under the curve (AUC) metric for each classifier and dataset. Results For predicting plus versus not-plus categories, we achieved 99% and 94% AUC on the first and second datasets, respectively. For predicting pre-plus or worse versus normal categories, we achieved 99% and 88% AUC on the first and second datasets, respectively. The CNN method achieved 98% and 94% for predicting two categories on the second dataset. Conclusions Our system combining automatic retinal vessel segmentation, tracing, feature extraction and classification is able to diagnose plus disease in ROP with CNN-like performance. Translational Relevance The high performance of I-ROP ASSIST suggests potential applications in automated and objective diagnosis of plus disease.

[1]  Gabriel J. Brostow,et al.  Automated Retinopathy of Prematurity Case Detection with Convolutional Neural Networks , 2016, LABELS/DLMIA@MICCAI.

[2]  Bram van Ginneken,et al.  A survey on deep learning in medical image analysis , 2017, Medical Image Anal..

[3]  James M. Brown,et al.  Automated Diagnosis of Plus Disease in Retinopathy of Prematurity Using Deep Convolutional Neural Networks , 2018, JAMA ophthalmology.

[4]  Michael F Chiang,et al.  Plus disease in retinopathy of prematurity: quantitative analysis of vascular change. , 2010, American journal of ophthalmology.

[5]  J. Català Mora,et al.  Computer-automated quantification of plus disease in retinopathy of prematurity , 2003 .

[6]  Alfredo Ruggeri,et al.  Computerized analysis of narrow-field ROP images for the assessment of vessel caliber and tortuosity , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[7]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[8]  Chia-Ling Tsai,et al.  Automated Retinal Image Analysis Over the Internet , 2008, IEEE Transactions on Information Technology in Biomedicine.

[9]  W. Fierson Screening Examination of Premature Infants for Retinopathy of Prematurity , 2013, Pediatrics.

[10]  A. Fulton,et al.  Diagnosis of plus disease in retinopathy of prematurity using Retinal Image multiScale Analysis. , 2005, Investigative ophthalmology & visual science.

[11]  Thomas Brox,et al.  U-Net: Convolutional Networks for Biomedical Image Segmentation , 2015, MICCAI.

[12]  Davide Castelvecchi,et al.  Can we open the black box of AI? , 2016, Nature.

[13]  Michael F. Chiang,et al.  Development and Evaluation of Reference Standards for Image-based Telemedicine Diagnosis and Clinical Research Studies in Ophthalmology , 2014, AMIA.

[14]  L. Peng,et al.  Deep learning in ophthalmology: The technical and clinical considerations , 2019, Progress in Retinal and Eye Research.

[15]  Esra Ataer-Cansizoglu,et al.  Retinal image analytics: a complete framework from segmentation to diagnosis. , 2015 .

[16]  W. Fierson,et al.  Screening Examination of Premature Infants for Retinopathy of Prematurity , 1997, Pediatrics.

[17]  Deniz Erdogmus,et al.  Locally Defined Principal Curves and Surfaces , 2011, J. Mach. Learn. Res..

[18]  Deniz Erdogmus,et al.  Computationally Efficient Exact Calculation of Kernel Density Derivatives , 2015, J. Signal Process. Syst..

[19]  C. Gilbert,et al.  Childhood blindness in the context of VISION 2020--the right to sight. , 2001, Bulletin of the World Health Organization.

[20]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[21]  Julien Jomier,et al.  Computer-automated quantification of plus disease in retinopathy of prematurity. , 2003, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[22]  S. T. Clay,et al.  Computerized analysis of retinal vessel width and tortuosity in premature infants. , 2008, Investigative ophthalmology & visual science.

[24]  E. Shortliffe,et al.  Clinical Decision Support in the Era of Artificial Intelligence. , 2018, JAMA.

[25]  Deniz Erdogmus,et al.  Plus Disease in Retinopathy of Prematurity: Improving Diagnosis by Ranking Disease Severity and Using Quantitative Image Analysis. , 2016, Ophthalmology.

[26]  Martin A Lindquist,et al.  PLUS DISEASE IN RETINOPATHY OF PREMATURITY: Diagnostic Impact of Field of View , 2011, Retina.

[27]  Christopher Ré,et al.  Machine learning and deep analytics for biocomputing: Call for better explainability , 2018, PSB.

[28]  Deniz Erdoğmuş,et al.  Computer-Based Image Analysis for Plus Disease Diagnosis in Retinopathy of Prematurity: Performance of the "i-ROP" System and Image Features Associated With Expert Diagnosis. , 2015, Translational vision science & technology.

[29]  Deniz Erdogmus,et al.  Plus Disease in Retinopathy of Prematurity: A Continuous Spectrum of Vascular Abnormality as a Basis of Diagnostic Variability. , 2016, Ophthalmology.

[30]  T. Hastie,et al.  Principal Curves , 2007 .

[31]  Isaac Ben-Sira,et al.  An international classification of retinopathy of prematurity. Clinical experience. , 1985, Ophthalmology.

[32]  Deniz Erdogmus,et al.  Self-Consistent Locally Defined Principal Surfaces , 2007, 2007 IEEE International Conference on Acoustics, Speech and Signal Processing - ICASSP '07.

[33]  Mohammad Riazi Esfahani,et al.  Retinopathy of Prematurity-assist: Novel Software for Detecting Plus Disease , 2017, Korean journal of ophthalmology : KJO.

[34]  Michael F Chiang,et al.  Agreement among pediatric ophthalmologists in diagnosing plus and pre-plus disease in retinopathy of prematurity. , 2008, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[35]  G. Quinn,et al.  Characteristics of Infants With Severe Retinopathy of Prematurity in Countries With Low, Moderate, and High Levels of Development: Implications for Screening Programs , 2005, Pediatrics.

[36]  Stratis Ioannidis,et al.  Fully automated disease severity assessment and treatment monitoring in retinopathy of prematurity using deep learning , 2018, Medical Imaging.

[37]  Michael F Chiang,et al.  Interexpert agreement of plus disease diagnosis in retinopathy of prematurity. , 2007, Archives of ophthalmology.

[38]  Anna L. Ells,et al.  The International Classification of Retinopathy of Prematurity revisited. , 2005, Archives of ophthalmology.