Clinical Research

A New Way of Thinking About Brain Function and the Fundamentals of Autism Screening

Healthcare professional discussing care with a parent and child.

Screening for Autism in Children

The American Academy of Pediatrics recommends screening children for autism spectrum disorder (ASD) at 18 and 24 months of age. Currently, the most widely used behavioral screening tool is the Modified Checklist for Toddlers, Revised with Follow-Up, which relies on a two-stage parent-report process, producing results based on subjective reporting and observation. To date, there is limited availability of an objective screening mechanism for ASD. The average age of diagnosis in the United States is 47 months. This is considered late for children to fully benefit from early interventions shown to make a significant difference in long-term outcomes and quality of life.  

The Neuroscience Behind the Technology

Eye tracking technology has emerged as a promising adjunctive measure to current screening practices. Whereas eye tracking measures can be influenced by social motivation, environment, and visual attention, innovative research at SEL Bioengineering explores an involuntary response: the pupillary light reflex (PLR). The PLR is a sensitive, objective physical marker of the likelihood of ASD. This research focuses on aspects of the visual pathway influenced by neural activity originating in the locus coeruleus (LC), deep within the brainstem. The LC releases norepinephrine (NE), and the LC-NE system modulates arousal and stress response. The LC-NE system regulates cranial nerves impacting essential functions such as hearing, breathing, oral motor movement, and vision. This research focuses on noninvasive measurement of the efficiency of the cranial nerves that activate the pupil response to indirectly assess this system.  
Screen displaying pupillary light reflex measurement data.
Detailed view of a child's eye showing the pupil and iris.

Typical and Atypical Pupillary Light Reflex

The PLR is controlled by the autonomic nervous system. This two-part system is responsible for sensory and physical regulation, including the stress response known as “fight or flight.” Balance in this system is necessary for adaptation in one’s environment and for regulating physical and behavioral responses. In the presence of light, the pupil constricts, indicating activation of the parasympathetic nervous system. Under dark conditions, the pupil dilates to let more light into the eye. This dilation indicates adaptation to the environment, activation of the sympathetic nervous system, and the release of norepinephrine.   Multiple studies have shown that children with ASD demonstrate a hypervigilant autonomic nervous system, which can be observed in an atypical PLR. In young children with ASD, the pupil initially constricts faster and then dilates more slowly than in a typical PLR. This pupil response can be an early sign of atypical neurodevelopment and correlates with outcomes from standardized tools assessing the behavioral and sensory characteristics of ASD.  

Clinical Studies

For further reading about clinical research related to the PLR and ASD, see the articles listed below.
  1. Nyström, P., Gliga, T., Jobs, E. N., Gredebäck, G., Charman, T., Johnson, M. H., Bölte, S., & Falck-Ytter, T. (2018). Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood. Nature Comm 9(1):1-5. https://doi.org/10.1038/s41467-018-03985-4
  2. Fan, X., Miles, J. H., Takahashi, N., & Yao, G. (2009). Abnormal transient pupillary light reflex in individuals with autism spectrum disorders. J Autism Dev Disorders 39(11):1499-1508. https://pubmed.ncbi.nlm.nih.gov/19499319/
  3. Dinalankara, D. M., Miles, J. H., Nicole Takahashi, T., & Yao, G. (2017). Atypical pupillary light reflex in 2–6‐year‐old children with autism spectrum disorders. Autism Research, 10(5):829-838. https://onlinelibrary.wiley.com/doi/full/10.1002/aur.1745 
  4. Kercher, C., Azinfar, L., Dinalankara, D. M., Takahashi, T. N., Miles, J. H., & Yao, G. (2020). A longitudinal study of pupillary light reflex in 6-to 24-month children. Scientific Reports 10(1):1-9. https://doi.org/10.1038/s41598-020-58254-6
  5. Lynch, G. T., James, S. M., Cardon, T. A., & McPherson, S. M. (2022). Sensitivity and specificity of pupillary light reflex measures for ASD using monocular pupillometry. Neurological Sciences, 43(7), 4537-4545. https://link.springer.com/article/10.1007/s10072-022-05976-2
  6. Nyström, P., Gredebäck, G., Bölte, S., & Falck-Ytter, T. (2015). Hypersensitive pupillary light reflex in infants at risk for autism. Molecular Autism 6(1):10. https://pubmed.ncbi.nlm.nih.gov/25750705/
  7. Daluwatte, C., Miles, J. H., Sun, J., & Yao, G. (2015). Association between pupillary light reflex and sensory behaviors in children with autism spectrum disorders. Research in Developmental Disabilities, 37, 209-215. https://pmc.ncbi.nlm.nih.gov/articles/PMC4314503/
  8. Lynch G. Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD. Behavioral Sciences. 2018; 8(11):108. https://pmc.ncbi.nlm.nih.gov/articles/PMC6262612/

The APS Detect Handheld Pupillometer is not cleared for safety and effectiveness by the FDA.

Clinical Research | SEL Bioengineering