Pupillary reflex and retinal imaging as potential early biomarkers of Autism Spectrum Disorder – a narrative review

Introduction: Autism spectrum disorder is a neurodevelopmental condition characterized by multilevel alterations in brain organization and function, leading to deficits in social communication and repetitive behaviors. Current diagnosis relies primarily on behavioral phenotype assessment, which usually enables diagnosis no earlier than the second year of life. Objective ophthalmological methods, such as optical coherence tomography and pupillary light reflex assessment, do not require verbal or motor responses and may therefore be applicable in infants. This review summarizes recent clinical studies evaluating ophthalmic biomarkers of autism spectrum disorder and their clinical utility. Materials and methods: A structured review of English-language publications from 2020–2025 was conducted using PubMed and Scopus databases. Following the removal of duplicates and screening based on titles and abstracts, study design and publication type, 68 records were included in the qualitative analysis. Results: Children with autism spectrum disorder showed significant differences in pupillary reflex parameters (including a larger baseline pupil diameter and altered latency of the response) and changes in retinal layer thickness on optical coherence tomography, particularly in the ganglion cell layer, inner nuclear layer and inner plexiform layer, indicating their potential as biomarkers of the disorder. Discussion and conclusions: Pupillary light reflex and optical coherence tomography findings may reflect autonomic dysregulation and atypical neural network development in autism spectrum disorder. However, limited specificity, heterogenity of results and small sample sizes indicate that these techniques should currently be considered supportive rather than independent diagnostic tools.