Large scale validation of an early-age eye-tracking biomarker of an autism spectrum disorder subtype (original) (raw)

Few clinically validated biomarkers of ASD exist which can rapidly, accurately, and objectively identify autism during the first years of life and be used to support optimized treatment outcomes and advances in precision medicine. As such, the goal of the present study was to leverage both simple and computationally-advanced approaches to validate an eye-tracking measure of social attention preference, the GeoPref Test, among 1,863 ASD, delayed, or typical toddlers (12-48 months) referred from the community or general population via a primary care universal screening program. Toddlers participated in diagnostic and psychometric evaluations and the GeoPref Test: a 1-min movie containing side-by-side dynamic social and geometric images. Following testing, diagnosis was denoted as ASD, ASD features, LD, GDD, Other, typical sibling of ASD proband, or typical. Relative to other diagnostic groups, ASD toddlers exhibited the highest levels of visual attention towards geometric images and those with especially high fixation levels exhibited poor clinical profiles. Using the 69% fixation threshold, the GeoPref Test had 98% specificity, 17% sensitivity, 81% PPV, and 65% NPV. Sensitivity increased to 33% when saccades were included, with comparable validity across sex, ethnicity, or race. The GeoPref Test was also highly reliable up to 24 months following the initial test. Finally, fixation levels among twins concordant for ASD were significantly correlated, indicating that GeoPref Test performance may be genetically driven. As the GeoPref Test yields few false positives (~ 2%) and is equally valid across demographic categories, the current findings highlight the ability of the GeoPref Test to rapidly and accurately detect autism before the 2nd birthday in a subset of children and serve as a biomarker for a unique ASD subtype in clinical trials. Autism spectrum disorder (ASD) begins during prenatal life 1,2 , yet most children do not receive a diagnosis and start treatment until 3-4 years later 3,4. Although genetic, neural, metabolomic, and molecular systems are adversely impacted in ASD 2,5,6 , it is nevertheless detected and diagnosed using clinical judgement. There has been a recent surge in research designed to discover biologically-based markers of ASD which can increase the pace of diagnosis, remove the requirement for highly-trained professionals, provide prognostic information, guide treatment plans, or be used as outcome measures in clinical trials 7. Currently, only two ASD biomarkers are being considered for the FDA Biomarker Qualification Program 8,9. However, they were established at "late" ages in children and therefore may not be generalizable to toddlers and infants, for whom biomarkers are of greatest utility. Moreover, these biomarkers only identify a subset of ASD children, indicating that additional biomarkers for other ASD subtypes are needed. Dramatically reduced attention to social information is a key feature of ASD noted since its discovery in 1943 10. Unsurprisingly, considerable effort has been leveraged to understand and quantify social visual attention abnormalities, most recently using eye-tracking 11-29. Despite varying stimuli and participant age, a meta-analysis