Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder

by Adnan Khan, Madeeha Kamal, Abdula Alhothi, Hoda Gad, Marian A. Adan, Georgios Ponirakis, Ioannis N. Petropoulos, Rayaz A. Malik

Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulty in communication and interaction with others. Postmortem studies have shown cerebral neuronal loss and neuroimaging studies show neuronal loss in the amygdala, cerebellum and inter-hemispheric regions of the brain. Recent studies have shown altered tactile discrimination and allodynia on the face, mouth, hands and feet and intraepidermal nerve fiber loss in the legs of subjects with ASD. Fifteen children with ASD (age: 12.00 ± 3.55 years) and twenty age-matched healthy controls (age: 12.83 ± 1.91 years) underwent corneal confocal microscopy (CCM) and quantification of corneal nerve fiber morphology. Corneal nerve fibre density (fibers/mm²) (28.61 ± 5.74 vs. 40.42 ± 8.95, p = 0.000), corneal nerve fibre length (mm/mm²) (16.61 ± 3.26 vs. 21.44 ± 4.44, p = 0.001), corneal nerve branch density (branches/mm²) (43.68 ± 22.71 vs. 62.39 ± 21.58, p = 0.018) and corneal nerve fibre tortuosity (0.037 ± 0.023 vs. 0.074 ± 0.017, p = 0.000) were significantly lower and inferior whorl length (mm/mm²) (21.06 ± 6.12 vs. 23.43 ± 3.95, p = 0.255) was comparable in children with ASD compared to controls. CCM identifies central corneal nerve fiber loss in children with ASD. These findings, urge the need for larger longitudinal studies to determine the utility of CCM as an imaging biomarker for neuronal loss in different subtypes of ASD and in relation to disease progression.