Retinal Structures in Autism Spectrum Disorder: Results from a Case-Control Study.

Objective: To assess retinal structures in patients with autism spectrum disorder (ASD) and its correlation with cognitive impairments and brain volumes.

Design: A retrospective case-control study.

Subjects: Adults with ASD and matched neurotypical controls were identified from the UK Biobank (UKBB). The exclusion criteria included a history of neurodegenerative diseases, optic nerve pathology, retinal disorders, glaucoma surgery, high refractive error, or intraocular pressure outside the range of 6 to 21 mmHg.

Methods: Using OCT images, 9 distinct retinal layers were segmented: the retinal nerve fiber layer (RNFL), ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), combined outer plexiform layer and outer nuclear layer, photoreceptor inner segment, photoreceptor outer segment, retinal pigment epithelium, and choroidoscleral interface. Cognitive function was evaluated using 4 standardized tests: pairs matching, prospective memory, numerical or verbal reasoning, and reaction time. Additionally, brain imaging-derived phenotypes from the UKBB were included in the analysis. Generalized linear models were used to evaluate associations.

Main Outcome Measures: Differences in retinal layer thickness between autistic individuals and controls, and the association with cognitive impairment and brain volumes.

Results: We examined 240 eyes, including 80 from autistic participants and 160 from matched neurotypical controls. Autistic participants showed significantly higher thickness in the inner retina (adjusted mean differences: 5.71 μm, 95% confidence interval [2.49-8.93], = 0.001), as well as RNFL (2.52 μm [0.97-4.06], = 0.001), inner plexiform layer (1.18 [0.28-2.07], = 0.010), and INL (0.93 [0.22-1.66], = 0.010). No significant correlation was found between inner retinal thickness and cognitive impairment. However, brain magnetic resonance imaging data indicated associations between inner retinal thickness and volumes of the total brain, corpus collosum, hippocampus, and temporal gyrus.

Conclusions: The inner retina may offer valuable insights into neurodevelopmental features in ASD, with observed associations with specific brain volumetric measurements. These findings could inform future research on ASD diagnostics and treatment.

Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.