Development of Deep Ensembles to Screen for Autism and Symptom Severity Using Retinal Photographs

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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 (32×4d) 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.

Exposures: Autism Diagnostic Observation Schedule-Second Edition calibrated severity scores (cutoff of 8) and Social Responsiveness Scale-Second Edition T scores (cutoff of 76) were used to assess symptom severity.

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Figure 1.. Density Plots of Predictive Uncertainty on the Test and Out-of-Distribution (OOD) Sets

A to C, Screening for autism spectrum disorder (ASD) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria only (A), for ASD with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and Autism Diagnostic Observation Schedule–Second Edition scores (B), and for symptom severity based on Autism Diagnostic Observation Schedule–Second Edition scores (C).

Figure 2.. Quantitative Validation of the Heat Map With the Progressive Erasing Technique for Autism Spectrum Disorder (ASD) Screening

A, Area under the receiver operating characteristic curve (AUROC) with shaded 95% CI obtained from masked images. B, Progressive erasing for ASD and typical development (TD). ADOS-2 indicates Autism Diagnostic Observation Schedule–Second Edition; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Figure 3.. Quantitative Validation of the Heat Map With the Progressive Erasing Technique for ADOS-2–Based Symptom Severity Screening

A, Area under the receiver operating characteristic curve (AUROC) with shaded 95% CI obtained from masked images. B, Progressive erasing for severe autism spectrum disorder (ASD) and mild to moderate ASD. ADOS-2 indicates Autism Diagnostic Observation Schedule–Second Edition.