Christina L Master1,2,3, Olivia E Podolak2, Kenneth J Ciuffreda4, Kristina B Metzger2, Nabin R Joshi4, Catherine C McDonald2,3,5, Susan S Margulies6, Matthew F Grady1,3, Kristy B Arbogast2,3. 1. Sports Medicine and Performance Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 2. Center for Injury Research and Prevention, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 3. Perelman School of Medicine, University of Pennsylvania, Philadelphia. 4. College of Optometry, State University of New York, New York. 5. University of Pennsylvania School of Nursing, Philadelphia. 6. Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta.
Abstract
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.
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.
Authors: Divya Jain; Kristy B Arbogast; Catherine C McDonald; Olivia E Podolak; Susan S Margulies; Kristina B Metzger; David R Howell; Mitchell M Scheiman; Christina L Master Journal: Optom Vis Sci Date: 2022-07-14 Impact factor: 2.106
Authors: Lynn B McGrath; Jessica Eaton; Isaac Joshua Abecassis; Anthony Maxin; Cory Kelly; Randall M Chesnut; Michael R Levitt Journal: Front Neurosci Date: 2022-07-01 Impact factor: 5.152
Authors: Tara L Alvarez; Chang Yaramothu; Mitchell Scheiman; Arlene Goodman; Susan A Cotter; Kristine Huang; Angela M Chen; Matthew Grady; Anne E Mozel; Olivia E Podolak; Chris G Koutures; Christina L Master Journal: Vision Res Date: 2021-04-23 Impact factor: 1.984
Authors: Adam C Raikes; Natalie S Dailey; Brittany Forbeck; Anna Alkozei; William D S Killgore Journal: Front Neurol Date: 2021-02-05 Impact factor: 4.003
Authors: Jason H Boulter; Margaret M Shields; Melissa R Meister; Gregory Murtha; Brian P Curry; Bradley A Dengler Journal: Front Neurol Date: 2021-07-12 Impact factor: 4.003