Atypical Pupillary Light Reflex in 2 – 6 Year Old Children with Autism Spectrum Disorders

Background:  Atypical pupillary light reflex (PLR) was previously observed in children age 6 – 17 years with autism spectrum disorders (ASDs). Abnormal PLR parameters were also reported in “high risk” 10-month-old infants who have siblings diagnosed with ASD. However, the group differences in PLR parameters appeared to be age dependent. To better understand the age effect, there is a need to evaluate PLR in children 2 – 6 years old, which is lacking in the literature.

Objectives:   To investigate whether atypical PLR parameters also exist in 2 – 6 year old children with ASD.

Methods:  Pupillary light reflex was measured in 55 children with ASD (54.1±16.2 months) and 54 children in the typical development (TD) group (55.0±17.8 months). Tests were conducted using a remote PLR device under two room illuminance levels: 5.6 lux (L1) and 2.7 lux (L2). We measured the following PLR parameters: baseline pupil radius, PLR latency, constriction, and constriction time. In addition, a questionnaire was used to evaluate symptoms related to autonomic nervous system (ANS) and their potential correlations with PLR parameters. A mixed model was used to study the group, age-group, and illuminance level effect on PLR parameters. Linear regression was used to investigate the change of PLR parameters with age.

Results:  The mixed model indicated a significant group effect (F_1,205=31.10, p<0.0001) and age effect (F_1,205=21.37, p<0.0001) on the PLR latency. Overall PLR latency was longer in the ASD group  than in the TD group; the latency in ASD group was 246.17 ± 18.20 ms in L1 and 261.27 ± 15.74 ms in L2 whereas it was 235.76 ± 16.01 ms in L1 and 248.05 ± 12.64 ms in L2 in the TD group. Linear regression confirmed that PLR latency decreased with age in the TD group (r=−0.41, p=0.0026 in L1 and r=−0.31, p=0.023 in L2) and baseline pupil radius increased with age in the TD group (r=0.36, p=0.0084 in L1 and r=0.28, p=0.042 in L2). However these age trends were not observed in the ASD group (p>0.05 in L1 and L2). There was a significant difference between the ASD and TD groups in the averaged ANS score (t₈₀=6.85, p<0.0001). Two-way ANOVA indicated a significant interaction between the group (ASD vs. TD) and abnormal ‘sweat’ symptoms on PLR constriction (F_1,100 =9.84, p=0.0022 in L1 and F_1,102=7.63, p=0.0068 in L2).

Conclusions:  Atypical PLR parameters were also observed in 2 – 6 year old children with ASD. In the TD group, PLR latency decreased with age and baseline pupil radius increased with age; whereas these trends were not observed in the ASD group. Children with ASD showed more symptoms of autonomic nervous system dysfunction. We observed an association between abnormal sweating and PLR constriction in the TD group but not in the ASD group.