Detection of anaemia from retinal fundus images via deep learning

Owing to the invasiveness of diagnostic tests for anaemia and the costs associated with screening for it, the condition is often undetected. Here, we show that anaemia can be detected via machine-learning algorithms trained using retinal fundus images, study participant metadata (including race or ethnicity, age, sex and blood pressure) or the combination of both data types (images and study participant metadata). In a validation dataset of 11,388 study participants from the UK Biobank, the metadata-only, fundus-image-only and combined models predicted haemoglobin concentration (in g dl –1 ) with mean absolute error values of 0.73 (95% confidence interval: 0.72–0.74), 0.67 (0.66–0.68) and 0.63 (0.62–0.64), respectively, and with areas under the receiver operating characteristic curve (AUC) values of 0.74 (0.71–0.76), 0.87 (0.85–0.89) and 0.88 (0.86–0.89), respectively. For 539 study participants with self-reported diabetes, the combined model predicted haemoglobin concentration with a mean absolute error of 0.73 (0.68–0.78) and anaemia an AUC of 0.89 (0.85–0.93). Automated anaemia screening on the basis of fundus images could particularly aid patients with diabetes undergoing regular retinal imaging and for whom anaemia can increase morbidity and mortality risks. Machine-learning algorithms trained with retinal fundus images, with subject metadata or with both data types, predict haemoglobin concentration with mean absolute errors lower than 0.75 g dl –1 and anaemia with areas under the curve in the range of 0.74–0.89.

[1]  W. C. Posey THE OCULAR MANIFESTATIONS OF ANEMIA. , 1897 .

[2]  A. Beckett,et al.  AKUFO AND IBARAPA. , 1965, Lancet.

[3]  M. Aisen,et al.  Retinal abnormalities associated with anemia. , 1983, Archives of ophthalmology.

[4]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[5]  J. Bigby Harrison's Principles of Internal Medicine , 1988 .

[6]  F. Ferris,et al.  Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18. , 1998, Investigative ophthalmology & visual science.

[7]  Martin Prince,et al.  The cross-sectional survey , 1998 .

[8]  D. Opitz,et al.  Popular Ensemble Methods: An Empirical Study , 1999, J. Artif. Intell. Res..

[9]  D. Altman,et al.  Measuring agreement in method comparison studies , 1999, Statistical methods in medical research.

[10]  Rich Caruana,et al.  Overfitting in Neural Nets: Backpropagation, Conjugate Gradient, and Early Stopping , 2000, NIPS.

[11]  R. Stoltzfus Iron-deficiency anemia: reexamining the nature and magnitude of the public health problem. Summary: implications for research and programs. , 2001, The Journal of nutrition.

[12]  C. Hornberger,et al.  Accuracy of point‐of‐care‐testing (POCT) for determining hemoglobin concentrations , 2002, Acta anaesthesiologica Scandinavica.

[13]  Merlin C. Thomas,et al.  Unrecognized anemia in patients with diabetes: a cross-sectional survey. , 2003, Diabetes care.

[14]  Walter F. Stenning,et al.  AN EMPIRICAL STUDY , 2003 .

[15]  A. Cavallerano,et al.  Nonmydriatic teleretinal imaging improves adherence to annual eye examinations in patients with diabetes. , 2006, Journal of rehabilitation research and development.

[16]  S. Barker,et al.  The measurement of dyshemoglobins and total hemoglobin by pulse oximetry , 2008, Current opinion in anaesthesiology.

[17]  P. Elliott,et al.  The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine. , 2008, International journal of epidemiology.

[18]  E. McLean,et al.  Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005 , 2009, Public Health Nutrition.

[19]  Uzma F Mehdi,et al.  Anemia, Diabetes, and Chronic Kidney Disease , 2009, Diabetes Care.

[20]  Robert E. Smith The clinical and economic burden of anemia. , 2010, The American journal of managed care.

[21]  S. Jones,et al.  Prevalence and nature of anaemia in a prospective, population‐based sample of people with diabetes: Teesside anaemia in diabetes (TAD) study , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[22]  N. Milman Anemia—still a major health problem in many parts of the world! , 2011, Annals of Hematology.

[23]  A. Kalantri,et al.  Accuracy and Reliability of Pallor for Detecting Anaemia: A Hospital-Based Diagnostic Accuracy Study , 2010, PloS one.

[24]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[25]  E. Chaum,et al.  Telemedicine and retinal imaging for improving diabetic retinopathy evaluation. , 2012, Archives of internal medicine.

[26]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[27]  Kenneth Tran,et al.  Construction of an inexpensive, hand-held fundus camera through modification of a consumer "point-and-shoot" camera. , 2012, Investigative ophthalmology & visual science.

[28]  Gretchen A. Stevens,et al.  Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data , 2013, The Lancet. Global health.

[29]  Márcio Pinto,et al.  The new noninvasive occlusion spectroscopy hemoglobin measurement method: a reliable and easy anemia screening test for blood donors , 2013, Transfusion.

[30]  Geoffrey E. Hinton,et al.  On the importance of initialization and momentum in deep learning , 2013, ICML.

[31]  A. Kliger,et al.  KDOQI US commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD. , 2013, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[32]  Sang-Hyun Kim,et al.  Accuracy of Continuous Noninvasive Hemoglobin Monitoring: A Systematic Review and Meta-Analysis , 2014, Anesthesia and analgesia.

[33]  J. A. Wright,et al.  Presence and Characterisation of Anaemia in Diabetic Foot Ulceration , 2014, Anemia.

[34]  N. Shah,et al.  Accuracy of noninvasive hemoglobin and invasive point-of-care hemoglobin testing compared with a laboratory analyzer , 2013, International journal of laboratory hematology.

[35]  Thomas Brox,et al.  Striving for Simplicity: The All Convolutional Net , 2014, ICLR.

[36]  Emily W. Gower,et al.  Diabetes eye screening in urban settings serving minority populations: detection of diabetic retinopathy and other ocular findings using telemedicine. , 2015, JAMA ophthalmology.

[37]  E. Wittenmeier,et al.  Comparison of the gold standard of hemoglobin measurement with the clinical standard (BGA) and noninvasive hemoglobin measurement (SpHb) in small children: a prospective diagnostic observational study , 2015, Paediatric anaesthesia.

[38]  Geoffrey E. Hinton,et al.  Deep Learning , 2015, Nature.

[39]  P. Elliott,et al.  UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age , 2015, PLoS medicine.

[40]  R. Hiscock,et al.  Systematic Review and Meta-Analysis of Method Comparison Studies of Masimo Pulse Co-Oximeters (Radical-7™ or Pronto-7™) and HemoCue® Absorption Spectrometers (B-Hemoglobin or 201+) with Laboratory Haemoglobin Estimation , 2015, Anaesthesia and intensive care.

[41]  S. Taylor-Phillips,et al.  Extending the diabetic retinopathy screening interval beyond 1 year: systematic review , 2015, British Journal of Ophthalmology.

[42]  Grace L Tsan,et al.  Assessment of diabetic teleretinal imaging program at the Portland Department of Veterans Affairs Medical Center. , 2015, Journal of rehabilitation research and development.

[43]  T. Das,et al.  Telemedicine in diabetic retinopathy: Access to rural India , 2016, Indian journal of ophthalmology.

[44]  Yuan Yu,et al.  TensorFlow: A system for large-scale machine learning , 2016, OSDI.

[45]  Subhashini Venugopalan,et al.  Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs. , 2016, JAMA.

[46]  S. Barker,et al.  Continuous Noninvasive Hemoglobin Monitoring: A Measured Response to a Critical Review , 2015, Anesthesia and analgesia.

[47]  Kaiming He,et al.  Accurate, Large Minibatch SGD: Training ImageNet in 1 Hour , 2017, ArXiv.

[48]  David A. Patterson,et al.  In-datacenter performance analysis of a tensor processing unit , 2017, 2017 ACM/IEEE 44th Annual International Symposium on Computer Architecture (ISCA).

[49]  P. Scanlon The English National Screening Programme for diabetic retinopathy 2003–2016 , 2017, Acta Diabetologica.

[50]  Sergey Ioffe,et al.  Inception-v4, Inception-ResNet and the Impact of Residual Connections on Learning , 2016, AAAI.

[51]  E. Finkelstein,et al.  Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes , 2017, JAMA.

[52]  Ankur Taly,et al.  Axiomatic Attribution for Deep Networks , 2017, ICML.

[53]  David R. Myers,et al.  Smartphone app for non-invasive detection of anemia using only patient-sourced photos , 2018, Nature Communications.

[54]  Michael V. McConnell,et al.  Prediction of cardiovascular risk factors from retinal fundus photographs via deep learning , 2017, Nature Biomedical Engineering.

[55]  Gregory S. Corrado,et al.  Deep learning for predicting refractive error from retinal fundus images , 2017, Investigative ophthalmology & visual science.

[56]  Weidong (Tom) Cai,et al.  A Deep Learning-Based Algorithm Identifies Glaucomatous Discs Using Monoscopic Fundus Photographs. , 2018, Ophthalmology. Glaucoma.

[57]  Christopher Bowd,et al.  Performance of Deep Learning Architectures and Transfer Learning for Detecting Glaucomatous Optic Neuropathy in Fundus Photographs , 2018, Scientific Reports.

[58]  W. Cefalu,et al.  Standards of Medical Care in Diabetes—2018 Abridged for Primary Care Providers , 2018, Clinical Diabetes.

[59]  M. Delgado-Rodríguez,et al.  Systematic review and meta-analysis. , 2017, Medicina intensiva.

[60]  M. Abràmoff,et al.  Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices , 2018, npj Digital Medicine.

[61]  Salma M. AlDallal,et al.  Prevalence of Anemia in Type 2 Diabetic Patients , 2018, Journal of hematology.

[62]  Jonathan Krause,et al.  Grader variability and the importance of reference standards for evaluating machine learning models for diabetic retinopathy , 2017, Ophthalmology.

[63]  P. Firat,et al.  Evaluation of Iron Deficiency Anemia Frequency as a Risk Factor in Glaucoma , 2018, Anemia.

[64]  M. He,et al.  Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs. , 2018, Ophthalmology.

[65]  Abhishek Das,et al.  Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization , 2016, 2017 IEEE International Conference on Computer Vision (ICCV).