The purpose of this study was to investigate pupillary light reflex (PLR) in 2-6-years-old children with autism spectrum disorders (ASD). A total of 117 medication-free 2-6-year-old boys participated in this study. Sixty participants were diagnosed with ASD (the "ASD group") and the other 57 were in the control group of typical development (the "TD group"). A questionnaire was completed by the parent/guardian for assessing potential dysfunctions in the autonomic nervous system (ANS). The base pupil radius, PLR latency, and constriction time showed a significant age-related trend in both the ASD and TD groups. The base pupil size increased with age in the typically developing children, but not in the ASD group. The ASD group showed more symptoms related to ANS dysfunctions. An association between abnormal sweating with base pupil radius and PLR constriction was observed in the TD group but not the ASD group. The different association of PLR parameters with ANS dysfunction may suggest disrupted autonomic controls in children with ASD. Autism Res 2017, 10: 829-838. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Pupillary light reflex (PLR) is an involuntary response where the pupil size changes with luminance. Studies have shown that PLR response was altered in children with autism spectrum disorders (ASDs) and other neurological disorders. However, PLR in infants and toddlers is still understudied. We conducted a longitudinal study to investigate PLR in children of 6-24 months using a remote pupillography device. The participants are categorized into two groups. The 'high risk' (HR) group includes children with one or more siblings diagnosed with ASDs; whereas the 'low risk' (LR) group includes children without an ASD diagnosis in the family history. The participants' PLR was measured every six months until the age of 24 months. The results indicated a significant age effect in multiple PLR parameters including resting pupil radius, minimal pupil radius, relative constriction, latency, and response time. In addition, the HR group had a significantly larger resting and minimal pupil size than the LR group. The experimental data acquired in this study revealed not only general age-related PLR changes in infants and toddlers, but also different PLRs in children with a higher risk of ASD. Autism Spectrum Disorders (ASDs) are complicated disorders that are marked by persistent deficits in social communication and interactions and by restricted, repetitive patterns of behavior, interests or activities 1. Initially chronicled 75 years ago 2 , ASDs now affect about 2.47% children and adolescents in USA alone 3. Although the etiology of ASD is still not fully understood, our understanding of this disorder has since been significantly improved owing to a large amount of physiological, psychological, and neurological studies. Evidence supports that the outcome in children with ASDs can be greatly improved by using early behavioral intervention 4,5. Unfortunately, most children do not receive an ASD diagnosis until after the age of four 6 , although early signs may appear as young as 12 months of age 7. Therefore, there is a great interest in finding effective biological markers for early screening of risk of autism and assessing responses to interventions. Pupillary light reflex (PLR) is the involuntary and nearly instantaneous pupil size change that occurs as a response to the luminous intensity of light that falls on the retina. The pupil size is controlled by the dilator and sphincter muscles innervated primarily by the sympathetic and parasympathetic branches of the autonomic nervous system (ANS), respectively 8. In 1961, Rubin observed that the pupils in 7 to 12 years old children with ASD constricted slower in responses to light adaption compared to typically developing children 9. Using a computerized pupillography system, Fan et al. discovered that pupils of children with ASD took a greater amount of time to respond to short (0.1 s) light stimuli and constricted less and more slowly than those with typical development 10. Similar atypical PLR responses were also reported in subsequent studies in children with ASD of diffe...

Pupillary light reflex (PLR) is a simple noninvasive neurological test that can reveal a great amount of information of the neural system. We report here a novel imaging system for measuring PLR without using any restraints to limit the subject’s movement. Our system incorporates a tracking component that can locate the subject’s eye position and redirect the pupillary imaging component to follow the subject’s movement. This system can measure PLR, at a distance from the subject, with high spatial resolution (<50 µm) and temporal resolution (120 Hz). Because this new PLR device can accommodate the subject’s movement, it is well positioned to test in young children and other people who have difficulty remaining voluntarily still during tests.

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Pupillary light reflex (PLR) is a phenomenon wherein the pupil size changes according to retina illumination. PLR of adults and children has been investigated in various studies. However, its significance in the medical care of young children and infants has been limited due to the lack of reliable instrumentation. Traditional PLR devices need to restrain subject or have to be worn on the head, which is not suitable for young children. A remote PLR measuring device was developed which allows the subject to sit far from the device during the PLR test. The device can capture high resolution images at a high sample rate similar to what can be found in a desktop system, but without the need for a restraint. The device follows the subject by tracking their eye movements during the PLR test. The device has been used to test PLR in typical developing (TD) children and children with autism spectrum disorders (ASDs), who were between ages of two to six years old. It was found that PLR latency in children with ASDs was longer than in typical developing children. The PLR constriction of the ASD subjects was slightly smaller than the TD subjects, but that difference was not statistically significant in our test. Moreover, the base pupil radius increased and latency decreased with age in the TD children but not in the ASD group. We found that PLR parameters are associated with autonomic nervous system (ANS) dysfunction. TD children with abnormal sweating issues showed a larger PLR constriction and smaller base pupil radius. We found that children with ASD did not show such differences. However, constriction time is negatively correlated with the normalized high frequency component of heart rate variability power spectrum in the ASD group, but not in the TD group. Nine TD children and eight ASD children were tested again 1-1.5 years from their first test date. The PLR parameter differences between the first and second tests were calculated, and we found that latency difference was negatively correlated to base pupil radius difference. Moreover, constriction difference was found to be positively correlated to the base pupil radius difference in TD children, but not in the ASD group. Remote PLR device camera setup was changed to capture the test subject's motion by a one camera while the other camera captures a high resolution pupil image. Because the two cameras are off axis, 3D location of the eye position is directly calculated using stereo vision base method, which helped to remove the need of physical measurement. The entire space occupied by the new rPLR device is about 50% of the previous device.