Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors. It affects approximately 2.2% of children. Both genetic and environmental risk factors have been identified for ASD. Visual comorbidities are relatively common among children with ASD. Between 20 and 44% of ASD children have visually significant refractive error, on-third have strabismus, and one-fifth have amblyopia. In addition, ASD is 30 times more common in children with congenital blindness. It is unknown whether the association of ASD with visual morbidity is causal, comorbid, or contributing. Structural and functional abnormalities have been identified in MRIs of ASD children, and ASD children have been noted to have aberrant eye tracking. ASD children with visually significant refractive errors and poor spectacle compliance (present in 30% of ASD children) offer the opportunity for investigation into how improved visual acuity influences ASD behaviors. In this review, we focus on what is known of the visual system, refractive surgery, and ASD.

Background/purpose: A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated. Methods: IRD genes from RetNet were included in this study. Publicly available data on the genome aggregation database (gnomAD) were used to analyze the number of total and pathogenic missense variants. Metapredict, an accurate and high-performance predictor that reproduces consensus disorder scores, was used to calculate disorder. Main outcome measures: The main outcome measures were percent disorder, percent pathogenicity, number of total missense variants, and percent total missense variation. Results: We included 287 RetNet genes with relevant data available from gnomAD. Mean percent disorder was 26.3% ± 26.0%, mean percent pathogenicity was 5.2% ± 11.0%, mean number of total missense variants was 424.4 ± 450.0, and mean percent total missense was 50.0% ± 13.4%. The percent disorder followed a bimodal distribution with the highest number of occurrences in the 0 to 10th disorder decile. The five outlier proteins in the first disorder decile with a higher-than-expected number of total missense variation were identified (HMCN1, ADGRV, USH2A, DYNC2H1, LAMA1, and SLC38A8). When excluded, % total missense was significantly associated with percent disorder (R = 0.238 and p = 0.0240). Conclusions: This novel study examining all genes implicated in IRDs found that the majority genes had a disorder in the 0 to 10th decile and were relatively intolerant to missense variation. This may have future utility when interpreting variants of undetermined significance and missense variants.