Autism Spectrum Disorder (ASD) is an early-onset neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive patterns of behavior. Diagnostic criteria from DSM-5 are used.
The prevalence of ASD is about 1 in 36 children, with boys being diagnosed approximately four times more often than girls. The etiology is not fully understood, but various genetic and environmental factors related to early brain development are thought to contribute.
Children with ASD are at risk for various ophthalmic conditions. Despite a high incidence of refractive errors, amblyopia, and strabismus, eye diseases are often overlooked due to poor cooperation and communication difficulties. About 15–25% of children with ASD are nonverbal, making standard eye examinations challenging.
In children with developmental disorders, even when visual acuity and binocular vision are good, smooth pursuit and saccadic eye movements may be impaired, leading to skipping lines while reading or difficulty copying from the blackboard. Eye movement development is closely related to gross motor development and heavily involves sensory integration. Additionally, due to communication problems with peers and academic stress, self-esteem may decline, and some children may present with psychogenic visual disturbances.
Ophthalmic findings are also common in ASD-related genetic mutation syndromes. In HIST1H1E mutation (Rahman syndrome), eye deformities were observed in 19 of 52 cases (37%) 1). In ASH1L mutation-related syndrome, 60% of reported cases had ophthalmic abnormalities such as hyperopia, astigmatism, strabismus, and nystagmus 2). Strabismus has also been reported in multiple patients with MYT1L gene 2p25.3 microduplication syndrome 3).
The prevalence of ASD is about 1 in 36 children. Boys are about four times more likely to be diagnosed than girls. Because it encompasses a wide range of conditions, there is great individual variation in symptom severity.
Children with ASD rarely complain of eye symptoms. Since many are nonverbal, it is necessary to infer eye problems from behavioral signs such as the following.
Ophthalmic findings in children with ASD are diverse.
Refractive Error
Refractive error: Found in up to 42% of children with ASD. Hyperopia, myopia, and astigmatism can all occur.
Amblyopia: Secondary to refractive errors or strabismus. If the critical period of visual development passes without appropriate correction, irreversible visual impairment remains.
Abnormal Eye Movements
Strabismus: Frequently observed in children with ASD. It is thought to be caused by impaired eye movement or atypical visual tracking.
Atypical gaze patterns: Features such as looking at other parts of the face or avoiding eye contact.
When amblyopia is unilateral, it is accompanied by strabismus in 19–50% of cases and by refractive errors in 46–79% of cases. This tendency is similar in children with ASD, making precise evaluation of strabismus and anisometropia important.
Refractive errors are found in up to 42% of children with ASD. Strabismus and amblyopia are also more frequent than in typically developing children, and comprehensive ophthalmologic examination is recommended.
The causes of ophthalmologic problems associated with ASD are multifactorial.
In ASD-related genetic mutation syndromes, the rate of ophthalmic abnormalities is high.
Children with cerebral visual impairment (CVI) may also have developmental delays or ASD. Ophthalmic complications such as strabismus (31–94%), optic atrophy (16–42%), and nystagmus (11–92%) are common in children with CVI.
Ophthalmic examination of children with ASD requires special consideration. Since standard examination procedures are often difficult, the following approaches are recommended.
The AAO (American Academy of Ophthalmology) Pediatric Eye Evaluation Preferred Practice Pattern recommends automated or instrument-based screening protocols for children with ASD.
Pediatric visual acuity assessment involves a stepwise approach. Starting with evaluation of fixation and pursuit, combined with the PL method, Teller Acuity Card method, and visual evoked potentials (VEP), it is possible to estimate visual acuity even in children who have difficulty with verbal responses. In children with intellectual developmental delay, fixation and pursuit at around 3 months of age may not always be good. After confirming the absence of obvious ocular disease, it is important to follow up and re-examine.
The following behavioral techniques are effective in obtaining cooperation from children with ASD during examinations.
| Technique | Description |
|---|---|
| Social Story | Explain the examination content in advance using pictures |
| Visual schedule | Present examination steps with photos |
| Shaping | Progress examination step by step |
When behavioral techniques alone are insufficient, oral midazolam (0.5 mg/kg, maximum 15 mg) may be considered. A retrospective cohort study reported that the completion rate in previously untestable children increased to 98%.
When a complete eye examination cannot be performed, information from parents serves as an important supplement to the evaluation. Structured questionnaires can provide information about how the child interacts visually with the environment.
Pre-use of social stories and visual schedules is effective. The examination should be conducted in a quiet, low-stimulation environment, using a shaping approach that proceeds step by step. It is also important to reduce the burden of verbal responses through device-based screening.
Treatment for eye problems in children with ASD follows the same principles as for typically developing children, but requires consideration of communication difficulties.
If refractive error is found, prescribe glasses. Perform refraction under cycloplegia and have the child wear fully corrective glasses. Children with ASD may have sensory hypersensitivity to wearing glasses due to tactile defensiveness, so gradual habituation may be necessary. Tactile hypersensitivity often delays acceptance of glasses, but with cooperation from therapeutic and educational institutions, most children can wear glasses. Prescribe glasses for children with disabilities using the same criteria as for typically developing children.
For strabismic amblyopia and refractive amblyopia, in addition to refractive correction, perform occlusion therapy (eye patch) or cycloplegic eye drops (atropine). Children with ASD may have difficulty accepting patches, so combine with behavioral therapy approaches. Actively use the amblyopic eye for near tasks such as reading and coloring.
Depending on the type and angle of strabismus, prism glasses or surgery are selected. Children with ASD may have strong anxiety about general anesthesia, so preoperative use of social stories is useful.
Vitamin A and B12 deficiency due to unbalanced diet can cause optic neuropathy. Perform nutritional assessment and supplement vitamins as needed.
In cases of sensory hypersensitivity, a shaping approach of gradual habituation is effective. Start with short periods of wear and provide positive reinforcement when worn. Choosing frames with consideration for material and lightness is also important.
The mechanism by which ophthalmic problems frequently occur in children with ASD is based on the following neurodevelopmental foundations.
In children with ASD, atypical processing of the magnocellular and koniocellular systems has been reported. Impairment of S-cone photoreceptor function and altered retinal ganglion cell activity are thought to cause color vision abnormalities.
Developmental abnormalities of the fusiform gyrus are considered the neurological basis for facial recognition difficulties in children with ASD. This abnormality is associated with atypical gaze patterns (a tendency to look at parts of the face other than the eyes).
Many of the gene mutations that cause ASD are also involved in eye development.
Zhao et al. (2023) analyzed 52 cases of HIST1H1E mutations and found eye deformities in 19 cases (37%). In the Ala144 frameshift mutation group, eye deformities were observed in 50%, which was higher than in other mutation sites (32%) 1).
Cordova et al. (2024) studied 15 cases of ASH1L mutation-related syndrome (literature cases + 3 new BGR cases) and found hyperopia, astigmatism, strabismus, and nystagmus in 60%. Among the BGR cases, one had dysmetria and ataxic gait, and another had astigmatism 2).
Sheth et al. (2023) reported two sisters with NEUROG1 gene mutations. Both cases presented with congenital cranial nerve deficiency syndrome and ASD. Corneal opacity, ptosis, facial asymmetry, bilateral cochlear hypoplasia, and hypoplasia of the eighth cranial nerve were observed 4).
In children with cerebral visual impairment (CVI), co-occurrence of developmental disorders and ASD is known. Ocular complications in children with CVI include strabismus in 31–94%, optic atrophy in 16–42%, and nystagmus in 11–92%. Refractive correction and strabismus treatment should be actively performed even in children with CVI.
The elucidation of the genetic basis of ASD is progressing rapidly. Numerous genes have been identified as ASD susceptibility genes, and research is ongoing into how mutations in these genes affect eye development.
Zhao et al. (2025) reported the first case in China of a nonsense mutation in the ANK2 gene (c.3007C>T, p.R1003*). A comprehensive analysis of 16 cases with ANK2 mutations revealed 9 cases of ASD, 10 of epilepsy, 5 of intellectual disability, and 11 of language communication disorder. ANK2 mutations are attracting attention as a causative gene for a novel neurodevelopmental disorder involving ASD, epilepsy, and intellectual disability5).
Ma et al. (2024) reported a 9-year-old child with type 22 primary microcephaly due to NCAPD3 gene mutation complicated by ASD. Strabismus was noted from 10 months of age, and after stent treatment for cerebral ischemic covert vessel dissection, improvements were observed in social interaction, language, strabismus, and eye movements 7).
Standardization of ophthalmic care protocols for children with ASD is progressing. Efforts are being made to improve the accuracy of device-based screening, systematize behavioral techniques, and develop parent questionnaires to detect and appropriately treat ophthalmic problems in children with ASD early.
