Corneal structural alterations in autism spectrum disorder: An in vivo confocal microscopy study
Abstract
Individuals with autism spectrum disorder (ASD) often exhibit joint hypermobility and connective tissue disorders. However, it remains unclear if ASD individuals also have structural alterations in the connective tissue of the cornea. This study aims to determine whether the Kobayashi structure (K-structure) characteristics differ between adults with ASD and typically developing controls (TDC) and explore the clinical correlates of the K-structure abnormality. We recruited 30 ASD adults and 35 TDC. Corneal structures, particularly the K-structure in the Bowman's layer, of the participants were examined using in vivo confocal microscopy (IVCM), and a K-grading ranging from 1 to 4 was given to each eye based on the level of morphological mosaicism. The ASD participants' eyes received a significantly higher single-eye K-grading than that of the TDC eyes (p 6 and >3, respectively. Additionally, a higher K-grading was associated with fewer visual sensation seeking in ASD (Spearman's correlation coefficient ρ = -0.518, p = 0.008) and low visual registration (i.e., higher sensory threshold) in TDC (ρ = 0.446, p = 0.023). This study provided novel evidence of corneal structural alterations in ASD by IVCM. Our findings may not only support the prior hypothesis of the association between ASD and connective tissue abnormalities but also shed light on the relationship between connective tissue disorder and neurodevelopmental disorders.
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Chien et al. (2023) found significant differences in corneal K-structure between adults with ASD and typically developing controls, suggesting alterations in the connective tissue of the cornea in people with ASD.
“The results showed significant differences between the groups in the K-structure, suggesting alterations in the connective tissue of the cornea in people with ASD, thus reinforcing the hypothesis of an association between ASD and connective tissue abnormalities.”
From Autism in the context of joint hypermobility, hypermobility spectrum disorders, and Ehlers–Danlos syndromes: A systematic review and prevalence meta-analyses (2025) · cites this paper as Chien et al. (2023)
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“However, other studies have drawn different conclusions (Glans et al., 2017; Hakim & Grahame, 2003).”
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Baeza-Velasco, C., Vergne, J., Poli, M., Kalisch, L., & Calati, R. (2025) · Autism · doi:10.1177/13623613251328059 · Cited by 10 · see citing works
“Interesting, these results are supported by recent data such as those of Chien et al. (2023), who conducted a study to determine whether corneal structure characteristics (K-structure which is rich in connective tissue) differ between adults with ASD ( n = 30) and typically developing controls ( n…”
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“A recent study utilising in vivo confocal microscopy revealed significant changes in the corneal connective tissue structure of adults with ASD compared to typically developing controls [20].”
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Zukerman, G., & Ben‐Itzchak, E. (2026) · Autism Research · doi:10.1002/aur.70215 · Cited by 1 · see citing works
- Authors
- Chien, Y., Wu, P., Wu, J., Huang, W., Hsiao, C., Hsieh, Y., Cheng, T., Gau, S. S., & Chen, W.
- Affiliations
- National Taiwan University (TW)
- Kaohsiung Medical University (TW)
- University of California San Diego (US)
- National Taiwan University Hospital (TW)
- Corresponding author
- Gau, Susan Shur‐Fen
- Chen, Wei‐Li
- ORCID
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2023-12
- Volume
- 16
- Issue
- 12
- Pages
- 2316-2325
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- OpenAlex
- W4389346333
- Cited by
- 4
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health Research Institutes (NHRI‐EX110‐11008PC, NHRI‐EX111‐11008PC, NHRI‐EX112‐11008PC)
- National Taiwan University Hospital (NTUH110‐S4826, NTUH108‐A144)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- autism spectrum disorder, corneal structure, Bowman's layer, connective tissue abnormalities, in vivo confocal microscopy, visual registration, sensory threshold, neurodevelopmental disorders
- MeSH terms
- Autism Spectrum Disorder, Adult, Cornea, Humans, Research Design, Microscopy, Confocal, Neurodevelopmental Disorders
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