Evaluation of pupillary light reflex as biomarker of neurodevelopmental disorder

University Of Missouri-Columbia, Columbia MO

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Abstract

DESCRIPTION (provided by applicant): Every one in eight children in the USA is born with a neurodevelopmental disability that will require medical, educational and special services remediation. Autism spectrum disorder (ASD) alone develops in 1 in 88 children in the US (CDC data). Early therapeutic intervention is the only available treatment and has been clinically proven effective in improving these children's outcomes. However, current practice for early identification of neurodevelopmental disorders relies on parent reporting plus behavioral observation that suffers from poor accuracy and sensitivity. Therefore, there is a clinical need for an objective measure (biomarker) that can track normal neurodevelopmental progress in infants and toddlers. Pupillary light reflex (PLR) is a simple functional neurological test that measures the pupil size changes in response to a short light flash. Our recent studies revealed that children with ASD had significantly longer PLR latency, lesser constriction amplitude, and shorter constriction and redilation times than typically developing children. Moreover, the PLR latency decreased significantly from 6 to 8 years of age in typically developing children. This age trend did not occur in children with ASD. These results suggest that PLR may have the potential to meet this aforementioned clinical need of an objective biomarker for the early identification of neurodevelopmental disorders. Unfortunately there is a lack of PLR data in children younger than 6 years old in the literature because existing PLR instrumentation cannot be reliably used in young children. To address this deficiency, we have developed a novel remote imaging system that can measure PLR in children without the need to hold their head still. We propose here to measure PLR in fifty 2 to 6 years old children with ASD (10 children at each age) and equal number of demographically matched (age and gender) typical controls. Specifically, we will test the hypothesis that atypical PLR parameters observed in older children with ASD also exist in younger children from 2 to 6 years old. In addition, we will test the hypothesis that PLR latency decreases with age in typically developing children younger than 6 years old and such age trend fails to occur in young children with ASD. This R21 project will produce data that are currently missing from literature, yet are critical to determining whether PLR can be used as a biomarker for neurodevelopmental disability in children younger than 6 years. If successful, such a simple physical biomarker will improve tremendously the current practice of early identification of neurodevelopmental disorders in children and ensure prompt diagnosis and therapeutic intervention.