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Utility of Pupillary Light Reflex Metrics as a Physiologic Biomarker for Adolescent Sport-Related Concussion

Educational Objective
To determine the potential utility of pupillary light reflex metrics as physiological biomarkers for concussion.
1 Credit CME
Key Points

Question  Do quantitative metrics of the pupillary light reflex (PLR) distinguish athletes with concussion from healthy control individuals?

Findings  In this cohort study, 8 PLR metrics (maximum and minimum pupillary diameter, percentage constriction, peak and average constriction velocity, peak and average dilation velocity, and time to 75% pupillary redilation) were greater among adolescent athletes with concussion compared with healthy control individuals.

Meaning  These results suggest that quantitative metrics of the pupillary light reflex are enhanced in adolescent sport-related concussion and distinguish athletes with concussion from healthy control individuals and may serve as a fast, portable, objective physiologic biomarker for adolescent sport concussion.


Importance  Concussion diagnosis remains clinical, without objective diagnostic tests available for adolescents. Known deficits in visual accommodation and autonomic function after concussion make the pupillary light reflex (PLR) a promising target as an objective physiological biomarker for concussion.

Objective  To determine the potential utility of PLR metrics as physiological biomarkers for concussion.

Design, Setting, and Participants  Prospective cohort of adolescent athletes between ages 12 and 18 years recruited between August 1, 2017, and December 31, 2018. The study took place at a specialty concussion program and private suburban high school and included healthy control individuals (n = 134) and athletes with a diagnosis of sport-related concussion (SRC) (n = 98). Analysis was completed June 30, 2020.

Exposures  Sports-related concussion and pupillometry assessments.

Main Outcomes and Measures  Pupillary light reflex metrics (maximum and minimum pupillary diameter, peak and average constriction/dilation velocity, percentage constriction, and time to 75% pupillary redilation [T75]).

Results  Pupillary light reflex metrics of 134 healthy control individuals and 98 athletes with concussion were obtained a median of 12.0 days following injury (interquartile range [IQR], 5.0-18.0 days). Eight of 9 metrics were significantly greater among athletes with concussion after Bonferroni correction (maximum pupil diameter: 4.83 mm vs 4.01 mm; difference, 0.82; 99.44% CI, 0.53-1.11; minimum pupil diameter: 2.96 mm vs 2.63 mm; difference, 0.33; 99.4% CI, 0.18-0.48; percentage constriction: 38.23% vs 33.66%; difference, 4.57; 99.4% CI, 2.60-6.55; average constriction velocity: 3.08 mm/s vs 2.50 mm/s; difference, 0.58; 99.4% CI, 0.36-0.81; peak constriction velocity: 4.88 mm/s vs 3.91 mm/s; difference, 0.97; 99.4% CI, 0.63-1.31; average dilation velocity, 1.32 mm/s vs 1.22 mm/s; difference, 0.10; 99.4% CI, 0.00-0.20; peak dilation velocity: 1.83 mm/s vs 1.64 mm/s; difference, 0.19; 99.4% CI, 0.07-0.32; and T75: 1.81 seconds vs 1.51 seconds; difference, 0.30; 0.10-0.51). In exploratory analyses, sex-based differences were observed, with girls with concussion exhibiting longer T75 (1.96 seconds vs 1.63 seconds; difference, 0.33; 99.4% CI, 0.02-0.65). Among healthy control individuals, diminished PLR metrics (eg, smaller maximum pupil size 3.81 mm vs 4.22 mm; difference, −0.41; 99.4% CI, −0.77 to 0.05) were observed after exercise.

Conclusions and Relevance  These findings suggest that enhancement of PLR metrics characterize acute adolescent concussion, while exercise produced smaller pupil sizes and overall slowing of PLR metrics, presumably associated with fatigue. Quantifiable measures of the PLR may serve in the future as objective physiologic biomarkers for concussion in the adolescent athlete.

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Article Information

Corresponding Author: Christina L. Master, MD, Sports Medicine and Performance Center, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, 2nd Floor Wood Building, Philadelphia, PA 19104 (masterc@email.chop.edu).

Accepted for Publication: July 28, 2020.

Published Online: September 24, 2020. doi:10.1001/jamaophthalmol.2020.3466

Author Contributions: Dr Master had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Master, Podolak, Ciuffreda, Metzger, Joshi, McDonald, Grady, Arbogast.

Acquisition, analysis, or interpretation of data: Master, Podolak, Ciuffreda, Metzger, Joshi, McDonald, Margulies, Arbogast.

Drafting of the manuscript: Master, Podolak, Ciuffreda, Metzger, Margulies.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Master, Ciuffreda, Metzger, Joshi.

Obtained funding: Master, Margulies, Arbogast.

Administrative, technical, or material support: Master, Podolak, Ciuffreda, Grady.

Supervision: Master, Ciuffreda, Arbogast.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported in part by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (grant R01NS0975NIH) and the Pennsylvania Department of Health (grant SAP4100077078).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentations: Preliminary data from this analysis were presented in part at the following conferences: National Neurotrauma Symposium, Toronto, Ontario, Canada, 2018; 3rd International Pediatric Brain Injury Society Meeting, Belfast, Ireland, 2018; American Academy of Pediatrics National Conference and Exhibit, Orlando, Florida, 2018; University of Pennsylvania Center for Brain Injury and Repair Retreat, Swarthmore, Pennsylvania, 2018; Children’s Hospital of Philadelphia Biomedical Postdoctoral Research Symposium, Philadelphia, Pennsylvania, 2018; Pediatric Research in Sports Medicine Annual Meeting, Atlanta, Georgia, 2019; Pediatric Academic Societies Meeting, Baltimore, MD, 2019; Pediatric Research in Sports Medicine Annual Meeting, Glendale, Arizona, 2020.

Additional Contributions: We thank Ronni S. Kessler, MS, Fairuz Mohammed, MS, MPH, Ari Fish, BS, Shelly Sharma, BA, and Julia Vanni, BS, of Children’s Hospital of Philadelphia for their contribution to data collection for this study. In addition, we thank the students and parents from the Shipley School for their participation. We appreciate the support from the Shipley School administration, faculty and athletic department: Steve Piltch, MEd, EdD, Mark Duncan, MEd, Katelyn Taylor, BS, Dakota Carroll, MS, Kimberly Shaud, BS, Kayleigh Jenkins, BS, and Michael Turner, MEd, without whose support this research would not have been possible.

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