{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:26:15Z","timestamp":1793172375128,"version":"4.5.0"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Screening for autism spectrum disorder (ASD) is constrained by limited resources, particularly trained professionals to conduct evaluations. Individuals with ASD have structural retinal changes that potentially reflect brain alterations, including visual pathway abnormalities through embryonic and anatomic connections. Whether deep learning algorithms can aid in objective screening for ASD and symptom severity using retinal photographs is unknown.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To develop deep ensemble models to differentiate between retinal photographs of individuals with ASD vs typical development (TD) and between individuals with severe ASD vs mild to moderate ASD.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This diagnostic study was conducted at a single tertiary-care hospital (Severance Hospital, Yonsei University College of Medicine) in Seoul, Republic of Korea. Retinal photographs of individuals with ASD were prospectively collected between April and October 2022, and those of age- and sex-matched individuals with TD were retrospectively collected between December 2007 and February 2023. Deep ensembles of 5 models were built with 10-fold cross-validation using the pretrained ResNeXt-50 (32\u00d74d) network. Score-weighted visual explanations for convolutional neural networks, with a progressive erasing technique, were used for model visualization and quantitative validation. Data analysis was performed between December 2022 and October 2023.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Autism Diagnostic Observation Schedule\u2013Second Edition calibrated severity scores (cutoff of 8) and Social Responsiveness Scale\u2013Second Edition T scores (cutoff of 76) were used to assess symptom severity.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The main outcomes were participant-level area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. The 95% CI was estimated through the bootstrapping method with 1000 resamples.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n This study included 1890 eyes of 958 participants. The ASD and TD groups each included 479 participants (945 eyes), had a mean (SD) age of 7.8 (3.2) years, and comprised mostly boys (392 [81.8%]). For ASD screening, the models had a mean AUROC, sensitivity, and specificity of 1.00 (95% CI, 1.00-1.00) on the test set. These models retained a mean AUROC of 1.00 using only 10% of the image containing the optic disc. For symptom severity screening, the models had a mean AUROC of 0.74 (95% CI, 0.67-0.80), sensitivity of 0.58 (95% CI, 0.49-0.66), and specificity of 0.74 (95% CI, 0.67-0.82) on the test set.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n These findings suggest that retinal photographs may be a viable objective screening tool for ASD and possibly for symptom severity. Retinal photograph use may speed the ASD screening process, which may help improve accessibility to specialized child psychiatry assessments currently strained by limited resources.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.47692","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:30:56Z","timestamp":1702639856000},"page":"e2347692","source":"Crossref","is-referenced-by-count":25,"title":["Development of Deep Ensembles to Screen for Autism and Symptom Severity Using Retinal Photographs"],"prefix":"10.1001","volume":"6","author":[{"given":"Jae Han","family":"Kim","sequence":"first","affiliation":[{"name":"Yonsei University College of Medicine, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JaeSeong","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangnyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Goo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Severance Eye Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangchul","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Medical Humanities and Social Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Yeon","family":"Hwang","sequence":"additional","affiliation":[{"name":"Yonsei University College of Medicine, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Rang","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keun-Ah","family":"Cheon","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"issue":"2","key":"zoi231394r2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss7202a1","article-title":"Prevalence and characteristics of autism spectrum disorder among children aged 8 years\u2014Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020.","volume":"72","author":"Maenner","year":"2023","journal-title":"MMWR Surveill Summ"},{"key":"zoi231394r3","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1071181","article-title":"The global prevalence of autism spectrum disorder: a three-level meta-analysis.","volume":"14","author":"Talantseva","year":"2023","journal-title":"Front Psychiatry"},{"issue":"10","key":"zoi231394r4","doi-asserted-by":"publisher","first-page":"4172","DOI":"10.1038\/s41380-022-01630-7","article-title":"Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.","volume":"27","author":"Solmi","year":"2022","journal-title":"Mol Psychiatry"},{"key":"zoi231394r5","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.1542\/peds.2019-1895H","article-title":"Screening tools for autism spectrum disorder in primary care: a systematic evidence review.","volume":"145","author":"Levy","year":"2020","journal-title":"Pediatrics"},{"issue":"2","key":"zoi231394r6","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1002\/aur.2019.12.issue-2","article-title":"A review of screening tools for the identification of autism spectrum disorders and developmental delay in infants and young children: recommendations for use in low- and middle-income countries.","volume":"12","author":"Marlow","year":"2019","journal-title":"Autism Res"},{"issue":"4","key":"zoi231394r7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1001\/jamapediatrics.2022.5975","article-title":"Sensitivity and specificity of the Modified Checklist for Autism in Toddlers (Original and Revised): a systematic review and meta-analysis.","volume":"177","author":"Wieckowski","year":"2023","journal-title":"JAMA Pediatr"},{"issue":"6","key":"zoi231394r8","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1007\/s10803-011-1343-5","article-title":"Screening young children for autism spectrum disorders in primary practice.","volume":"42","author":"Barton","year":"2012","journal-title":"J Autism Dev Disord"},{"issue":"3","key":"zoi231394r9","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.46415","article-title":"Diagnostic accuracy of the Social Attention and Communication Surveillance\u2014Revised With Preschool Tool for early autism detection in very young children.","volume":"5","author":"Barbaro","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"2","key":"zoi231394r10","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/jcpp.v62.2","article-title":"The autism waitlist crisis and remembering what families need.","volume":"62","author":"Kanne","year":"2021","journal-title":"J Child Psychol Psychiatry"},{"key":"zoi231394r11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13229-018-0201-0","article-title":"Practice patterns and determinants of wait time for autism spectrum disorder diagnosis in Canada.","volume":"9","author":"Penner","year":"2018","journal-title":"Mol Autism"},{"issue":"1","key":"zoi231394r12","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrneurol.2012.227","article-title":"The retina as a window to the brain-from eye research to CNS disorders.","volume":"9","author":"London","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"zoi231394r13","doi-asserted-by":"publisher","DOI":"10.1177\/2040622320905215","article-title":"Retinal correlates of psychiatric disorders.","volume":"11","author":"Almonte","year":"2020","journal-title":"Ther Adv Chronic Dis"},{"issue":"4","key":"zoi231394r14","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1007\/s10803-013-1939-z","article-title":"Reduction in retinal nerve fiber layer thickness in young adults with autism spectrum disorders.","volume":"44","author":"Emberti Gialloreti","year":"2014","journal-title":"J Autism Dev Disord"},{"key":"zoi231394r15","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-022-05882-8","article-title":"Retinal thinning in adults with autism spectrum disorder.","author":"Friedel","year":"2022","journal-title":"J Autism Dev Disord"},{"key":"zoi231394r16","doi-asserted-by":"publisher","DOI":"10.1016\/j.rasd.2022.102050","article-title":"Evaluation of retinal nerve fiber layer thickness in children with autism spectrum disorders.","volume":"98","author":"Bozkurt","year":"2022","journal-title":"Res Autism Spectr Disord"},{"issue":"13","key":"zoi231394r17","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1167\/iovs.17-22238","article-title":"Comparison of foveal, macular, and peripapillary intraretinal thicknesses between autism spectrum disorder and neurotypical subjects.","volume":"58","author":"Garc\u00eda-Medina","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"zoi231394r18","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02143-7","article-title":"Association between autism spectrum disorder (ASD) and vision problems: a systematic review and meta-analysis.","author":"Perna","year":"2023","journal-title":"Mol Psychiatry"},{"key":"zoi231394r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100588","article-title":"A machine learning approach for retinal images analysis as an objective screening method for children with autism spectrum disorder.","volume":"28","author":"Lai","year":"2020","journal-title":"EClinicalMedicine"},{"key":"zoi231394r20","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.inffus.2021.05.008","article-title":"A review of uncertainty quantification in deep learning: techniques, applications and challenges.","volume":"76","author":"Abdar","year":"2021","journal-title":"Inf Fusion"},{"key":"zoi231394r21","article-title":"Simple and scalable predictive uncertainty estimation using deep ensembles.","author":"Lakshminarayanan","year":"2017","journal-title":"arXiv"},{"issue":"4","key":"zoi231394r22","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1177\/0734282913517525","article-title":"Test review: Social Responsiveness Scale\u2013Second Edition (SRS-2).","volume":"32","author":"Bruni","year":"2014","journal-title":"J Psychoed Assess"},{"issue":"1","key":"zoi231394r25","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1038\/s41467-021-25138-w","article-title":"Automatic detection of 39 fundus diseases and conditions in retinal photographs using deep neural networks.","volume":"12","author":"Cen","year":"2021","journal-title":"Nat Commun"},{"key":"zoi231394r28","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/s42256-022-00566-5","article-title":"Detecting multiple retinal diseases in ultra-widefield fundus imaging and data-driven identification of informative regions with deep learning.","volume":"4","author":"Engelmann","year":"2022","journal-title":"Nat Mach Intell"},{"issue":"1","key":"zoi231394r29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1148\/radiology.143.1.7063747","article-title":"The meaning and use of the area under a receiver operating characteristic (ROC) curve.","volume":"143","author":"Hanley","year":"1982","journal-title":"Radiology"},{"issue":"1","key":"zoi231394r30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1175\/1520-0493(1950)078<0001:VOFEIT>2.0.CO;2","article-title":"Verification of forecasts expressed in terms of probability.","volume":"78","author":"Brier","year":"1950","journal-title":"Mon Weather Rev"},{"issue":"12","key":"zoi231394r32","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/eye.2012.216","article-title":"Retinal nerve fiber layer and optic disc measurements by spectral domain OCT: normative values and associations in young adults.","volume":"26","author":"Tariq","year":"2012","journal-title":"Eye (Lond)"},{"issue":"4","key":"zoi231394r33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1136\/bjo.2004.052498","article-title":"Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study.","volume":"89","author":"Savini","year":"2005","journal-title":"Br J Ophthalmol"},{"issue":"4","key":"zoi231394r34","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1176\/appi.ajp.2017.17010100","article-title":"Cortical and subcortical brain morphometry differences between patients with autism spectrum disorder and healthy individuals across the lifespan: results from the ENIGMA ASD Working Group.","volume":"175","author":"van Rooij","year":"2018","journal-title":"Am J Psychiatry"},{"issue":"5","key":"zoi231394r35","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.biopsych.2020.10.013","article-title":"A longitudinal study of white matter development in relation to changes in autism severity across early childhood.","volume":"89","author":"Andrews","year":"2021","journal-title":"Biol Psychiatry"},{"issue":"1","key":"zoi231394r36","doi-asserted-by":"crossref","first-page":"12390","DOI":"10.1038\/s41598-020-68589-9","article-title":"Atypical visual processing in a mouse model of autism.","volume":"10","author":"Cheng","year":"2020","journal-title":"Sci Rep"},{"issue":"1","key":"zoi231394r37","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/mp.2014.98","article-title":"Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.","volume":"20","author":"Ellegood","year":"2015","journal-title":"Mol Psychiatry"},{"key":"zoi231394r38","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.neuroscience.2019.03.061","article-title":"Retinal defects in mice lacking the autism-associated gene Engrailed-2.","volume":"408","author":"Zhang","year":"2019","journal-title":"Neuroscience"},{"issue":"1","key":"zoi231394r39","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41398-023-02374-w","article-title":"Comorbidities in autism spectrum disorder and their etiologies.","volume":"13","author":"Khachadourian","year":"2023","journal-title":"Transl Psychiatry"},{"issue":"10","key":"zoi231394r40","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S2215-0366(19)30289-5","article-title":"Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis.","volume":"6","author":"Lai","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"zoi231394r41","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2020.112922","article-title":"Prevalence of comorbid psychiatric disorders among people with autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses.","volume":"287","author":"Hossain","year":"2020","journal-title":"Psychiatry Res"},{"issue":"3","key":"zoi231394r42","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1017\/S0954579408000370","article-title":"Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder.","volume":"20","author":"Dawson","year":"2008","journal-title":"Dev Psychopathol"},{"issue":"5","key":"zoi231394r43","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/DBP.0b013e3181ba0f9f","article-title":"Autism spectrum disorders in infancy and toddlerhood: a review of the evidence on early signs, early identification tools, and early diagnosis.","volume":"30","author":"Barbaro","year":"2009","journal-title":"J Dev Behav Pediatr"},{"issue":"5","key":"zoi231394r44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1444-0938.2005.tb06711.x","article-title":"Anatomy and development of the macula: specialisation and the vulnerability to macular degeneration.","volume":"88","author":"Provis","year":"2005","journal-title":"Clin Exp Optom"},{"issue":"5","key":"zoi231394r45","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.ajo.2012.05.007","article-title":"Histologic development of the human fovea from midgestation to maturity.","volume":"154","author":"Hendrickson","year":"2012","journal-title":"Am J Ophthalmol"},{"issue":"4","key":"zoi231394r46","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1177\/1362361320971107","article-title":"Age at autism spectrum disorder diagnosis: a systematic review and meta-analysis from 2012 to 2019.","volume":"25","author":"van \u2019t Hof","year":"2021","journal-title":"Autism"},{"issue":"4","key":"zoi231394r47","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/IJG.0b013e318181545e","article-title":"Variance owing to observer, repeat imaging, and fundus camera type on cup-to-disc ratio estimates by stereo planimetry.","volume":"18","author":"Kwon","year":"2009","journal-title":"J Glaucoma"},{"issue":"1","key":"zoi231394r48","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10633-015-9494-x","article-title":"Aripiprazole-induced chorioretinopathy: multimodal imaging and electrophysiological features.","volume":"131","author":"Faure","year":"2015","journal-title":"Doc Ophthalmol"},{"issue":"1","key":"zoi231394r49","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13256-019-1978-y","article-title":"Risperidone-related bilateral cystoid macular edema: a case report.","volume":"13","author":"Kozlova","year":"2019","journal-title":"J Med Case Rep"},{"key":"zoi231394r1","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"2013","edition":"5th ed"},{"key":"zoi231394r23","first-page":"284","volume-title":"Autism Diagnostic Observation Schedule","author":"Lord","year":"2012","edition":"2nd ed"},{"key":"zoi231394r31","first-page":"1","volume-title":"Machine Learning Challenges Workshop","author":"Qui\u00f1onero-Candela","year":"2006"},{"key":"zoi231394r24","doi-asserted-by":"crossref","unstructured":"Xie? S, Girshick? R, Doll\u00e1r? P, Tu? Z, He? K. Aggregated residual transformations for deep neural networks.? arXiv. Preprint posted online April 11, 2017. doi:10.1109\/CVPR.2017.634?","DOI":"10.1109\/CVPR.2017.634"},{"key":"zoi231394r26","doi-asserted-by":"crossref","unstructured":"Wang? H, Wang? Z, Du? M, . Score-CAM: score-weighted visual explanations for convolutional neural networks.? arXiv. Preprint posted online April 13, 2020. doi:10.1109\/CVPRW50498.2020.00020?","DOI":"10.1109\/CVPRW50498.2020.00020"},{"key":"zoi231394r27","unstructured":"Engelmann? J, Storkey? A, Bernabeu? MO. Global explainability in aligned image modalities.? arXiv. Preprint posted online December 17, 2021."}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2812964\/kim_2023_oi_231394_1702050499.36439.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:31:12Z","timestamp":1702639872000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2812964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.47692","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]}}}