Fundus Peripapillary Vascular Changes in Autism Spectrum Disorder: A Cross-Sectional Study.

Researchers studied blood vessels in the eyes of children with autism compared to typical children using special eye scans. They found that children with autism had different patterns in their eye blood vessels - some vessels were denser or wider in certain areas. These eye vessel differences were linked to brain activity and could help predict social skills and thinking abilities. The findings suggest eye scans might one day help with autism screening, though more research is needed.

This cross-sectional study examined retinal blood vessel characteristics in 53 children with autism spectrum disorder (ASD) aged 7-13 years compared to matched neurotypical controls using advanced eye imaging techniques. Researchers found significant differences in blood vessel patterns around the optic nerve, including increased vessel density and diameter in specific regions, altered blood flow patterns, and abnormal vessel complexity measures. A machine learning model based on these retinal features showed promising ability to distinguish ASD from neurotypical children (AUC = 0.785). Retinal vessel characteristics correlated with brain activity in key regions like the amygdala and could partially predict social functioning and cognitive abilities in children with ASD.

Findings suggest retinal imaging could potentially complement existing ASD assessment tools, though current discriminative ability is moderate. Correlations with brain activity and clinical features indicate promise for objective biomarker development. However, validation studies are essential before considering clinical implementation. This research opens new avenues for understanding ASD neurobiology through eye-brain connections.

Single-site cross-sectional design limits generalizability. Convenience sampling may introduce selection bias. Machine learning model performance (AUC = 0.785) indicates moderate discriminative ability. Predictive models explained limited variance in clinical outcomes (R² = 0.091-0.279). Requires validation in larger, more diverse populations before clinical application.

In this cross-sectional study, participants were recruited through convenience sampling from the Children's Mental Health Research Center at The Affiliated Brain Hospital of Nanjing Medical University and the Department of Ophthalmology at The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, between December 2019 and October 2024. A total of 200 eyes were ultimately enrolled in this study, sourced from 53 individuals with ASD, aged between 7 and 13 years, and an equal number of age- and sex-matched neurotypical (NT) controls. The aim of this research is to explore the changes in retinal and choroidal vasculature in children with ASD, evaluated through optical coherence tomography and its angiography, and to further investigate the potential value of retinal vascular characteristics in the auxiliary screening and diagnosis of ASD. We analyzed intergroup differences in perfusion density (PD), vessel density, flux index (FI), fractal dimension (FD), and vessel diameter (Dm) in the peripapillary region, further stratified by subquadrants and vessel types.

The results show that ASD children exhibited significant differences compared to neurotypical controls, including increased PD and Dm in the supero-nasal quadrant (p < 0.01), changes in capillary FI in the nasal quadrant (p = 0.008), increased venous FD (p = 0.009), and abnormal choroidal FI in the temporal quadrant (p = 0.008). A random forest classification model constructed based on these key features demonstrated promising performance (AUC = 0.7853) in distinguishing ASD from NT individuals, highlighting the potential of retinal vascular characteristics for auxiliary ASD screening. Moreover, retinal vascular parameters were significantly correlated (p < 0.01) with blood oxygen level-dependent signals from functional magnetic resonance imaging in several brain regions, such as the amygdala (p = 0.004-0.009) and temporal lobe (p = 0.000-0.009). Further stepwise regression analysis indicates that key retinal vascular characteristics could partially predict core clinical features of ASD, such as social functioning (adjusted R = 0.091-0.104, quantified by total and subscale scores of Social Responsiveness Scale) and cognitive ability (adjusted R = 0.2785, quantified by total intelligence quotient scores).

This study underscores the potential of retinal vascular features as biomarkers for ASD and provides a basis for future research on non-invasive retinal imaging-based approaches for ASD screening and diagnosis, while offering new perspectives for understanding the pathological mechanisms and clinical applications of ASD.