The Pupillary Light Reflex as a Biomarker of Concussion

The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term changes in brain function secondary to injury should cause a change in the parameters of the PLR. We performed a retrospective clinical review of the PLR of our patients using the BrightLamp Reflex iPhone app. The PLR variables of latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered a concussion and those that had not. There were also significant differences in PLR metrics over the life span and between genders and those subjects with and without symptoms. The differences in PLR metrics are modulated not only by concussion history but also by gender and whether or not the person has symptoms associated with a head injury. A concussive injury to the brain is associated with changes in the PLR that persist over the life span, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making.

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Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD

Behavioral Sciences ◽

10.3390/bs8110108 ◽

2018 ◽

Vol 8 (11) ◽

pp. 108 ◽

Cited By ~ 2

Author(s):

Georgina Lynch

Keyword(s):

Pupil Diameter ◽

Pupillary Response ◽

Autism Spectrum ◽

Pupillary Light Reflex ◽

Clinical Population ◽

Experimental Conditions ◽

Light Reflex ◽

Pupillary Light ◽

Rigorous Study ◽

Future Work

With recent advances in technology, there has been growing interest in use of eye-tracking and pupillometry to assess the visual pathway in autism spectrum disorder (ASD). Within emerging literature, an atypical pupillary light reflex (PLR) has been documented, holding potential for use as a clinical screening biomarker for ASD. This review outlines dominant theories of neuropathology associated with ASD and integrates underlying neuroscience associated with the atypical PLR through a reciprocal model of brainstem involvement and cortical underconnectivity. This review draws from animal models of ASD demonstrating disruption of cranial motor nuclei and brain imaging studies examining arousal and the influence of the locus coeruleus norepinephrine (LC-NE) system on the pupillary response. Pupillometry methods are explained in relation to existing data examining the PLR in ASD and pupillary parameters of constriction latency and tonic pupil diameter as key parameters for investigation. This focused review provides preliminary data toward future work developing pupillometry metrics and offers direction for studies aimed at rigorous study replication using pupillometry with the ASD population. Experimental conditions and testing protocol for capturing pupil parameters with this clinical population are discussed to promote clinical research and translational application.

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Characteristics of the Pupillary Light Reflex in the Alert Rhesus Monkey

Journal of Neurophysiology ◽

10.1152/jn.01131.2002 ◽

2003 ◽

Vol 89 (6) ◽

pp. 3179-3189 ◽

Cited By ~ 44

Author(s):

Robert J. Clarke ◽

Hongyu Zhang ◽

Paul D. R. Gamlin

Keyword(s):

Rhesus Monkey ◽

Neural Control ◽

Pupil Diameter ◽

Sympathetic Innervation ◽

Experimental Studies ◽

Pupillary Light Reflex ◽

Light Reflex ◽

Pupillary Light ◽

Pupillary Responses ◽

Dilator Muscle

This study investigated the static and dynamic characteristics of the pupillary light reflex (PLR) in the alert rhesus monkey. Temporal characteristics of the PLR were investigated with Maxwellian viewing during sinusoidal changes in illumination of a 36° stimulus in both monkeys and humans. Bode plots of the PLR response were fitted by a linear model composed of a delay combined with a cascaded first- and second-order filter. The Bode magnitude plots conformed to this model with a sharp roll-off above 1.3 Hz for the human PLR and 1.9 Hz for the monkey PLR. Bode phase angle plots were fitted by this model with a delay of 280 ms for humans and 160 ms for monkeys. To investigate the influence of the sympathetic innervation of the iris on steady-state pupil diameter, dynamics of pupillary responses, and the latency of the PLR, we blocked this innervation pharmacologically with a selective alpha-1 adrenoreceptor antagonist. Although there was a resultant miosis (decrease in pupil diameter) from the relaxation of the pupil dilator muscle, no other measures of the PLR, including the dynamics and latency, were significantly affected by this treatment. We examined the pupillary responses evoked by visual stimuli presented either binocularly or monocularly at various locations on a 80 × 60° tangent screen. These pupillomotor fields revealed that, as has been reported for humans, stimuli at the fovea and surrounding macular region of monkeys produce substantially larger pupillary responses than more peripheral stimuli and that binocular responses are substantially greater than can be accounted for by the linear summation of binocular retinal illuminance. In conclusion, we found that the spatial characteristics of the PLR of the rhesus monkey are very similar, in all important aspects, to those reported for humans and that the temporal responses of the PLR are comparable between the two species. The rhesus monkey thus provides an excellent model for experimental studies of the neural control of the pupil.

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Concussion History Does Not Predict Pupillary Light Reflex or Visual Sensory Performance in Young Adults

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000560801.23086.0a ◽

2019 ◽

Vol 51 (Supplement) ◽

pp. 102

Author(s):

Cassie B. Ford ◽

Christina B. Vander Vegt ◽

Nikki Barczak ◽

Patricia R. Combs ◽

Jamie DeCicco ◽

...

Keyword(s):

Young Adults ◽

Pupillary Light Reflex ◽

Light Reflex ◽

Pupillary Light ◽

Concussion History

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THE UTILITY OF PUPILLARY LIGHT REFLEX AS AN OBJECTIVE BIOMARKER OF ACUTE CONCUSSION IN THE ADOLESCENT ATHLETE

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967119s00155 ◽

2019 ◽

Vol 7 (3_suppl) ◽

pp. 2325967119S0015

Author(s):

Olivia E. Podolak ◽

Nabin Joshi ◽

Kenneth Ciuffreda ◽

Fairuz Mohamed ◽

Shelly Sharma ◽

...

Keyword(s):

Nervous System ◽

Autonomic Nervous System ◽

Pupil Diameter ◽

Light Stimulus ◽

Pupillary Light Reflex ◽

Post Injury ◽

Light Reflex ◽

Autonomic Nervous ◽

Pupillary Light ◽

Over Time

Background: Visual deficits and autonomic dysfunction have been well recognized following pediatric concussion. Testing of the pupillary light reflex (PLR) is a simple, non-invasive, and objective approach to examine the autonomic nervous system by accessing the brain pathways. The aim of this study was to objectively evaluate adolescent pupillary responses to a light stimulus after a physician-diagnosed concussion and compare them to baseline responses. Methods: In this prospective cohort study, PLR was assessed in 135 adolescent athletes (ages 14-18) during their sport pre-season. All of the athletes were not recovering from a concussion at the time of their baseline assessment. Within this cohort, seven athletes (ages 14-17) sustained a concussion during their sport season and had longitudinal post-injury assessments of PLR through their recovery. The PLR was obtained in response to a brief step-input (0.8 seconds) white light stimulus using a hand-held pupillometer (stimulus recording duration= 5 seconds, light intensity= 150 lux). Pre-set and automated device-generated parameters used for analysis include the minimum and maximum pupil diameter, response amplitude and latency, mean constriction and dilation velocities and the maximum constriction velocity of the eye in response to a light stimulus. During each assessment, three monocular trials were performed in each eye alternatively, and the responses for each eye were subsequently averaged. Results: Six out of the seven concussed adolescents showed response enhancement of about 20% (IQR 11-33%). Enhancement was noted in the steady state diameter with a mean of 24% (median 18%), minimum pupil diameter mean of 17% (median 11%) and maximum constriction velocity mean of 28% (median 33%) following concussion, which decreased during the recovery process (days to weeks post-injury) to pre-injury or below initial pre-injury baseline measurements. Pupillary responsivity was found to be significantly enhanced after concussion compared to baseline measurements, waning over time. Maximum constriction velocity better highlighted the enhancement compared to the baseline pupil diameter. Conclusions/Significance: Pupil responsivity was found to be significantly enhanced after concussion compared to baseline measurements which waned over time during recovery. Assessment of dynamic PLR responses has potential utility as an objective biomarker to aid in concussion diagnosis on the sidelines or in the office, allowing physicians to quantify function (and dysfunction) of the autonomic nervous system under parasympathetic and sympathetic control after concussion.

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Operational implications of varying ambient light levels and time-of-day effects on saccadic velocity and pupillary light reflex

Ophthalmic and Physiological Optics ◽

10.1111/j.1475-1313.2006.00450.x ◽

2007 ◽

Vol 27 (2) ◽

pp. 130-141 ◽

Cited By ~ 12

Author(s):

Minzhong Yu ◽

Mary A. Kautz ◽

Maria L. Thomas ◽

Dagny Johnson ◽

Edwin R. Hotchkiss ◽

...

Keyword(s):

Time Of Day ◽

Pupillary Light Reflex ◽

Ambient Light ◽

Light Reflex ◽

Light Levels ◽

Pupillary Light ◽

Saccadic Velocity

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Central Autonomic Regulation Assessed by Pupillary Light Reflex is Impaired in Children With Attention Deficit Hyperactivity Disorder

Physiological Research ◽

10.33549/physiolres.934589 ◽

2021 ◽

pp. S513-S521

Author(s):

A HAMRAKOVA ◽

I ONDREJKA ◽

N SEKANINOVA ◽

L BONA OLEXOVA ◽

Z VISNOVCOVA ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Pupil Diameter ◽

Light Stimulus ◽

Autonomic Regulation ◽

Pupillary Light Reflex ◽

Light Reflex ◽

Hyperactivity Disorder ◽

Non Invasive ◽

Pupillary Light

It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0±2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81±1.23 % vs. -30.32±1.31 %, p<0.05, left eye: -25.44±1.65 % vs. -30.35±0.98 %, p˂0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p˂0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.

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A Novel Method for Measuring the Pupil Diameter and Pupillary Light Reflex of Healthy Volunteers and Patients With Intracranial Lesions Using a Newly Developed Pupilometer

Frontiers in Medicine ◽

10.3389/fmed.2021.598791 ◽

2021 ◽

Vol 8 ◽

Author(s):

Joji Kotani ◽

Hiroyuki Nakao ◽

Isamu Yamada ◽

Atsushi Miyawaki ◽

Naomi Mambo ◽

...

Keyword(s):

Visible Light ◽

Healthy Volunteers ◽

Pupil Diameter ◽

Video Recording ◽

Healthy Adults ◽

Pupillary Light Reflex ◽

Infrared Light ◽

Light Reflex ◽

Pupillary Light ◽

Intracranial Lesions

Background: Physicians currently measure the pupil diameter and the pupillary light reflex with visual observations using a ruler and a traditional penlight, leading to possibly inaccurate and subjective assessments. Although a mobile pupillometer has been developed and is available in clinical settings, this device can only assess one pupil at a time. Hence, an indirect pupillary light reflex, including those under irradiation to the opposite side of pupil, cannot be evaluated. Consequently, we have developed a new automatic mobile pupilometer, the Hitomiru®, with Hitomiru Co., Ltd. (Tokyo, Japan). This device is a two-glass type pupilometer with a video recording system. The pupil diameter and light reflex of both pupils can be measured simultaneously; therefore, both indirect and direct light reflexes can be assessed.Purpose: To evaluate the clinical ability of the Hitomiru® pupilometer to assess the pupil diameter and the pupillary light reflex of healthy volunteers and patients with intracranial lesions in an intensive care unit (ICU).Methods: Twenty-five healthy volunteers and five ICU patients with intracranial lesions on only the left side were assessed using the Hitomiru® pupilometer. The protocol was as follows: infrared light was applied to both pupils, followed by visible light to the right pupil, infrared light to both pupils, visible light to the left pupil, and then infrared light to both pupils. All the intervals were 2 s, and the dynamics of pupil diameters on both sides were continuously recorded.Results: The healthy adults had approximately 0.5 mm anisocoria, miosis was harder, and mydriasis was less with increased age. There were several differences in miosis rates, miosis times, and mydriasis rates between the healthy adults and the patients with intracranial lesions with both direct irradiation and indirect irradiation.Conclusions: The initial trial estimated and digitally recorded direct and indirect light reflexes, including rapidity of miosis after direct and indirect lights on, and mydriasis after direct and indirect lights off. The Hitomiru® pupilometer was a useful device to digitally record and investigate the relationship between pupil reflexes and intracranial diseases.

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