Constriction Latency Research Articles

Measuring the Pupillary Light Reflex Using Portable Instruments in Applied Settings.

The early components of the pupillary light reflex (PLR) are governed by the parasympathetic nervous system. The use of cheap, portable pupillometry devices may allow for the testing of parasympathetic-system health in field settings. We examined the reliability of two portable instruments for measuring the PLR and their sensitivity to individual differences known to modulate the PLR. Parameters of the PLR were measured in a community sample (N = 108) in a variety of field settings. Measurements were taken using a commercial pupillometer (NeuroLight, IDMED) and an iPhone using the Reflex Pro PLR analyser (Brightlamp). The parameters of baseline pupil diameter, constriction latency, amplitude and relative amplitude of constriction, and constriction velocity were measured. Individual differences related to age, levels of anxiety, and post-traumatic stress disorder (PTSD) symptomology were assessed. Some measures could not be attained using the iPhone under these field conditions. The reliability of the measures was high, save for the measurement of contraction latency which was particularly unreliable for the iPhone system. The parameters of the PLR showed the same internal relationships as those established in laboratory-based measurements. Age was negatively correlated with all the reliable PLR parameters for both systems. Effects of anxiety and PTSD symptomology were also apparent. The study demonstrated that a hand-held portable infrared pupillometer can be used successfully to measure the PLR parameters under field settings and can be used to examine individual differences. This may allow these devices to be used in workplaces, sports fields, roadsides, etc., to examine parasympathetic activity where needed.

Diagnostic accuracy test of quantitative pupillary light reflex as an indicator of increased intracranial pressure in traumatic brain injury patients: a cross-sectional study

Introduction: The gold standard of intracranial pressure (ICP) measurement is an invasive procedure of inserting ICP monitor and one of the limitations of its surrogate, ultrasonography-based (US) optic nerve sheath diameter (ONSD) measurement is operator-dependent. Quantitative pupillary light reflex (PLR) measurement provides objective data promisingly able to predict ICP elevation. The aim of this study was to evaluate diagnostic accuracy of PLR as an indicator of ICP elevation in traumatic brain injury (TBI) patients compared to US-ONSD measurement. Methods: This was a cross-sectional study involving moderate and severe TBI patients aged 18-65 years without any eye lesion, nor medication and illness that may influence PLR. Healthy volunteers were recruited as control group. ONSD and quantitative PLR measurements (baseline diameter, maximum constriction, constriction velocity, latency and amplitude) were assessed to both groups. The Student t-test or Mann-Whitney U-test was used to compare the ONSD and PLR between case and control group. Further analyses were done to determine the sensitivity, specificity and cut-off value of PLR compared to ONSD in case group. Result: ONSD measurements or parameters were significantly different between case and control group (p<0.001), while all PLR parameters were significantly different (p<0.005) except for right eye constriction latency. The baseline diameter of the right eye had the highest accuracy with cut-off value of >3.9 mm (specificity of 100%, sensitivity of 50%). Other PLR components had variable in accuracy. Conclusion: The baseline diameter of the right eye was the most accurate PLR component as an indicator of ICP elevation, represented by ONSD.

Chromatic Pupillometry as a Putative Screening Tool for Heritable Retinal Disease in Rhesus Macaques.

Non-human primates (NHPs) are useful models for human retinal disease. Chromatic pupillometry has been proposed as a noninvasive method of identifying inherited retinal diseases (IRDs) in humans; however, standard protocols employ time-consuming dark adaptation. We utilized shortened and standard dark-adaptation protocols to compare pupillary light reflex characteristics following chromatic stimulation in rhesus macaques with achromatopsia to wild-type (WT) controls with normal retinal function. Nine rhesus macaques homozygous for the p.R656Q mutation (PDE6C HOMs) and nine WT controls were evaluated using chromatic pupillometry following 1-minute versus standard 20-minute dark adaptations. The following outcomes were measured and compared between groups: pupil constriction latency, peak constriction, pupil constriction time, and constriction velocity. Pupil constriction latency was significantly longer in PDE6C HOMs with red-light (P = 0.0002) and blue-light (P = 0.04) stimulation versus WT controls. Peak constriction was significantly less in PDE6C HOMs with all light stimulation compared to WT controls (P < 0.0001). Pupil constriction time was significantly shorter in PDE6C HOMs versus WT controls with red-light (P = 0.04) and white-light (P = 0.003) stimulation. Pupil constriction velocity was significantly slower in PDE6C HOMs versus WT controls with red-light (P < 0.0001), blue-light (P < 0.0001), and white-light (P = 0.0002) stimulation. Dark adaptation time only significantly affected peak (P = 0.008) and time of pupil constriction (P = 0.02) following blue-light stimulation. Chromatic pupillometry following 1- and 20-minute dark adaptation is an effective tool for screening NHPs for achromatopsia. Rapid identification of NHPs with IRDs will provide animal research models to advance research and treatment of achromatopia in humans.

Specific thresholds of quantitative pupillometry parameters predict unfavorable outcome in comatose survivors early after cardiac arrest

AimQuantitative pupillometry is the guideline-recommended method for assessing pupillary light reflex for multimodal prognostication in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). However, threshold values predicting an unfavorable outcome have been inconsistent across studies; therefore, we aimed to identify specific thresholds for all quantitative pupillometry parameters. MethodsComatose post-OHCA patients were consecutively admitted to the cardiac arrest center at Copenhagen University Hospital Rigshospitalet from April 2015 to June 2017. The parameters of quantitatively assessed pupillary light reflex (qPLR), Neurological Pupil index (NPi), average/max constriction velocity (CV/MCV), dilation velocity (DV), and latency of constriction (Lat) were recorded on the first three days after admission. We evaluated the prognostic performance and identified thresholds achieving zero percent false positive rate (0% PFR) for an unfavorable outcome of 90-day Cerebral Performance Category (CPC) 3–5. Treating physicians were blinded for pupillometry results. ResultsOf the 135 post-OHCA patients, the primary outcome occurred for 53 (39%) patients.On any day during hospitalization, a qPLR < 4%, NPi < 2.45, CV < 0.1 mm/s, and an MCV < 0.335 mm/s predicted 90-day unfavorable neurological outcome with 0% FPR (95%CI: 0–0%), with sensitivities of 28% (17–40%), 9% (2–19%), 13% (6–23%), and 17% (8–26%), respectively on day 1. ConclusionWe found that specific thresholds of all quantitative pupillometry parameters, measured at any time following hospital admission until day 3, predicted a 90-day unfavorable outcome with 0% FPR in comatose patients resuscitated from OHCA. However, at 0% FPR, thresholds resulted in low sensitivity. These findings should be further validated in larger multicenter clinical trials.

187 Use of Quantitative Pupillometry in Mild Traumatic Brain Injury to Diagnose and Predict Symptom Severity

INTRODUCTION: Concussion screening using the Military Acute Concussion Evaluation (MACE 2) and imaging modalities can be subjective, time intensive, and monopolize scarce resources in a forward deployed environment. The Pupillary light reflex (PLR) has shown recent promise in identifying mild traumatic brain injuries. METHODS: Freshman entering a military service academy had baseline PLR measurements (starting pupillary diameter, ending pupillary diameter, average constriction velocity, average dilation velocity, constriction latency, constriction percentage, T75 and pupillary wave form) completed using a Neuroptic PLR-3000. If a subject experienced a concussion they returned for PLR measurements and Sport Concussion Assessment Tool (SCAT) scores within 48 hours of injury. RESULTS: Five hundred and fourteen cadets (383 males and 131 females) completed baseline PLR measurements. Sixteen cadets subsequently sustained an mTBI and performed full post-injury assessments. The one-way MANCOVA performed on PLR metrics controlling for symptom severity revealed a marginally significant difference in combined PLR metrics between baseline and post-injury time points [Wilks’ λ = .578, F(8,22) = 2.01, p = .094, partial η = .422]. A significant difference in outcomes between baseline and post-injury were observed for starting pupillary diameter [F(1,29) = 3.10, p = .089, partial η2 = .097], average constriction velocity [F(1,29) = 5.79, p = .023, partial η2 = .167], and maximum constriction velocity [F(1,29) = 4.54, p =.042, partial η2 = .135]. Correlation coefficients demonstrated that post-injury changes in pupillary metrics were strongly associated with post-injury changes in symptom severity, particularly for starting pupillary diameter, constriction percentage, average constriction velocity, maximum constriction velocity, and T75. CONCLUSIONS: In this evaluation of service academy cadets there are measurable differences in pupillary dynamics after sustaining an mTBI which correlates with symptom severity.

Recommendation of using both initial pupil size and constriction latency in pupillary light reflex as objective indicators reflecting subacute pain-related mental fatigue

A previous study examining clinical subacute pain models under different methodological conditions showed that pain-induced mental fatigue can be associated with decreased initial pupil size (INIT)/shortened constriction latency (LAT) in the pupillary light reflex (PLR). We aimed to investigate the potential of INIT/LAT as objective indicators reflecting mental fatigue under the same methodological conditions. We recruited 118 patients planning to undergo three types of representative otolaryngological head and neck surgery procedures. We used the numerical rating scale (NRS) to assess subjective pain intensity and two mental fatigue-related mood categories of the Profile of Mood States, as well as INIT and LAT measurements (1) in the afternoon one day before surgery (pre1-surgery), (2) in the morning of the day of surgery (pre2-surgery), and (3) in the morning of the day following surgery (post-surgery). We assessed time point-dependent changes using one- or two-way analysis of variance, as well as responses of PLR parameters to mental fatigue using linear mixed-effects models (LMMs). As a result, NRS scores, the two mood categories, as well as LAT and INIT, showed significant time point-dependent changes. In post-hoc analyses, only INIT showed significant changes between the two pre-surgery time points. Thus, INIT values fluctuated even under pain-free conditions due to differences in the time of the day. LMMs demonstrated decreased INIT/shortened LAT related to mental fatigue. All surgical groups showed similar associations between mental fatigue and INIT/LAT findings. As each parameter has advantages and disadvantages, it is recommended to use both INIT and LAT as the indicators.

Early quantitative pupillary response parameters have high predictive value for 30-day mortality in patients resuscitated from out-of-hospital cardiac arrest

Abstract Background Despite adequate post-resuscitation treatment following out-of-hospital cardiac arrest (OHCA), early risk of death remains high due to irreversible anoxic brain injury. Objective Neuroprognostication is pivotal, and automated quantitative pupillometry has become an essential part of early multimodal approach. Several quantitative pupillary response parameters are now available, but little evidence exist on their value and timing in neuroprognostication. Purpose To evaluate prognostic value of standard parameters of quantitative pupillometry in OHCA patients. Methods In this observational study we included 138 comatose patients resuscitated from OHCA admitted to a tertiary cardiac intensive care unit. With quantitative pupillometry, change in pupil size (%CH, %), Neurological Pupil index (NPi, scalar value 0–5), constriction velocity (CV, mm/s), maximum CV (MCV, mm/s), dilation velocity (DV, mm/s) and latency of constriction (Lat, s) were measured at admission, at the 24 hours (24h), and 48-hours (48h) time points. Receiver operating characteristics (ROC) curves with calculation of area under the curve (AUC) were applied for assessment of association with 30-day mortality. Results The population were predominantly males, had a mean age of 61±12 years, and 120 (87%) had shockable primary rhythm, 122 (88%) had witnessed cardiac arrest and 51 (37%) died in the first 30 days. Median %CH, CV, MCV, DV and NPi values were significantly lower for diseased patients compared to survivors. ROC analyses (Figure 1) present all parameters, except NPi, at admission with numerically highest values of AUC at 0.82, 0.76, 0.73, and 0.81 for %CH, CV, MCV, and DV respectively, and for NPi at 48h with AUC at 0.81. The admission time point still presented the highest AUC values, &amp;gt;0.84, for CV, MCV, and DV in an adjusted model. Of all the parameters, %CH and NPi maintained the highest prognostic values through all time points, and %CH performed best at admission with AUC at 0.87 and NPi at 24h with AUC at 0.91. At admission the threshold value with 100% specificity for predicting 30-day mortality were 3.75, 0.09, 0.33, and 0.05, with negative predictive value (NPV [95% confidence interval]) at 71% [67–74], 66% [64–69], 67% [65–70], and 69% [66–72] for %CH, CV, MCV, and DV respectively. NPi had best performance at 24h with a cutoff value of 2.90 and NPV at 64% [63–64]. Conclusion %CH and NPi were the strongest prognostic tools for 30-day mortality. Values below 3.75% for %CH at admission and 2.90 for NPi at 24h after archived 100% specificity for 30-day mortality, with NPV at 71% [67–74] and 64% [63–64] respectively. Although performance was persistently high, %CH, CV, MCV, and DV presented numerically highest AUC at admission. Additional parameters of CV, MCV, and DV were also significantly associated with outcome and future research should focus on validation and possible combining these measures into useful indices. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk Foundation

Impact of acute intoxication on quantitative pupillometry assessment in the emergency department.

Study Hypothesis/ObjectiveThis prospective cohort study aimed to assess whether and to what extent different quantitative pupillometry (QP) metrics are associated with different intoxicant drug classes as well as investigate the potential benefit of QP as a tool in the rapid assessment of clinically intoxicated patients in the emergency department (ED).MethodsBetween February 25, 2019 and April 24, 2021, 325 patients were enrolled in the EDs of the Hospital of the University of Pennsylvania (HUP) and Penn Presbyterian Medical Center (PPMC). Patients deemed clinically intoxicated or in withdrawal by an attending emergency physician were considered for eligibility. Patients <18 years old, with a chief complaint indicative of head trauma or stroke or without a urine drug screen (UDS) positive for drugs of abuse were excluded. QP data were also collected from a cohort of 82 healthy control subjects.ResultsNeurological Pupil index (NPi) values did not vary significantly between control and study groups nor between study group patients with a UDS positive for opioids. With exception of latency of constriction, all other QP metrics for the study group were depressed relative to controls (P < 0.005).ConclusionsThis work demonstrated the feasibility of QP measurement in the ED, finding that NPi remains unaffected by clinical intoxication and therefore can potentially be used for ED patient evaluation without risk of confounding by key intoxicants of abuse. Future work will evaluate the value of QP as a means of rapid and reproducible neurological assessment to identify various pathologies.

Decreased initial pupil size and shortened constriction latency due to negative mood states and mental fatigue in clinical subacute pain models

Previous clinical studies on pupillary light reflex parameters showed shortened constriction latency (LAT) and decreased initial pupil size (INIT) due to increased numeric rating scale (NRS) scores, reflecting subjective pain intensity, in subacute pain models. As noxious stimulation causes pupil dilation, decreased INIT (pupil constriction) was an unexpected finding. Pain-related negative moods and mental fatigue might have caused this finding. We aimed to investigate how psychological states affect LAT/INIT in two subacute pain models. For psychological assessment, we used the Profile of Mood States (POMS) and calculated the total mood disturbance (TMD) score using six mood categories. We collected data on NRS scores, POMS-related scores, LAT, and INIT through a longitudinal study. Using linear mixed-effects models, we evaluated the association of TMD scores with NRS scores, LAT, and INIT. Furthermore, we performed subanalyses targeting two mood categories that represent mental fatigue: Fatigue–Inertia (Fatigue) and Vigor–Activity (Vigor). We investigated whether obtained results can be identical in both models. In total, 141 patients were enrolled. Increased NRS scores were associated with increased TMD/Fatigue scores and decreased Vigor scores, being associated with shortened LAT/decreased INIT in both models. Score changes in NRS, TMD, Fatigue, and Vigor indicated that increased subjective pain intensity can be associated with negative mood states, especially mental fatigue. This study revealed that negative moods and mental fatigue induced by acute pain can be associated with shortened LAT/decreased INIT in both models, indicating clinical potential of LAT/INIT as objective indicators reflecting the psychological states for pain assessment.

Exploring Finger Digit Ratios (2D:4D) in Surgeons, Professional Rugby Players, and Political Journalists to Form a Directional Hypothesis: Could Finger Length Predict Attention and Focus?

In this short report we explore the predictive nature of finger digit ratio (i.e., second/index finger length divided by fourth/ring finger length; 2D:4D) and achievement. This research, with niche and specialized populations, was intended to support and grow on knowledge obtained from other large population 2D:4D studies and help form a directional hypothesis for future work exploring finger digit ratio and “success.” Twenty-nine professional rugby players aged 25.1 ± 4.2 years, height 185.2 ± 6.3 cm and weight 101.9 ± 11.8 kg; n = 16 orthopedic surgeons aged 55.3 ± 9.3 years with height 183.8 ± 10.2 cm and weight 90.8 ± 14.0 kg; and n = 18 political journalists with age, height and weight of 38.8 ± 7.3 years, 182.8 ± 7.8 cm, and 84.4 ± 11.4 kg, respectively, were recruited. Three experiments were conducted where we (1) explored relationships for 2D:4D with testosterone and cortisol responsiveness to low stress exercise, (2) explored relationships for 2D:4D with pupil constriction and pupil constriction latency (pupillometry measures related to testosterone and cortisol responsiveness and to attentiveness), and (3) compared 2D:4D between rugby players, surgeons, and journalists. Our results revealed 2D:4D was not predictive of testosterone and cortisol responsiveness to low-level exercise stress. However, relationships exist for 2D:4D and pupillometry measures (p < 0.05). Journalists right minus left 2D:4D difference was significantly different to rugby players’ and surgeons (p < 0.05). We argue 2D:4D is likely predictive of testosterone sensitivity and associated ability to focus attention; a skill important to high achievement in various contexts.

Clinical potential of pupillary light reflex and heart rate variability parameters as objective indicators of tonsillectomy-induced pain

Objective. Establishing objective indicators of subjective pain intensity is important in pain assessment. Pupillary light reflex (PLR) and heart rate variability (HRV) indicate autonomic nervous system (ANS) activity and may serve as pain indicators because pain can affect ANS activity. In this prospective longitudinal study, we aimed to investigate the potential of PLR/HRV parameters as objective indicators of subjective pain intensity after tonsillectomy. Approach. Sixty-seven patients undergoing tonsillectomy were enrolled. Subjective pain intensity based on a numeric rating scale (NRS) and eight PLR/HRV parameters were assessed at five time points. We investigated the changes in the NRS values over time. We estimated regression coefficients reflecting parameter changes per unit change in the NRS score using linear mixed-effects models. Main Results. The mean NRS score was 0 at two pre-surgery time points, 5 on postoperative days (PODs) 1 and 2, and 0 at postoperative week 3. Two parameters (initial pupil size [INIT] and constriction latency [LAT]) showed significant changes on POD1 and POD2 in comparison to baseline data measured at the pre-surgery time point. Among these parameters, only LAT showed no significant changes between POD1 and POD2. Significant regression coefficients with the narrowest 95% confidence intervals were observed for INIT and LAT. Increased NRS scores were associated with decreased INIT and shortened LAT. Significance. LAT was a robust indicator of subjective pain intensity. Our patients showed decreased INIT with increased NRS scores, indicating the predominance of the parasympathetic, not sympathetic, tone in pupils. Further studies are required to investigate factors causing this predominance.

Repeatability and clinical use of pupillary light reflex measurement using RAPDx® pupillometer.

To evaluate the repeatability of pupillary light reflex metrics measured by the RAPDx® dynamic pupillometer in healthy subjects and clinical application in patients with unilateral optic neuritis (ON). Sixty eyes of 30 healthy volunteers were measured three times consecutively by the same technician. The amplitude of constriction (AC), the latency of constriction (LOC), the velocity of peak constriction (VC) of light-evoked pupillary constriction, RAPD score for amplitude and latency were measured using RAPDx® dynamic pupillometer. The repeatability of above metrics was assessed by the intraclass correlation coefficient (ICC) and coefficient of variation (Cov). Furthermore, pupillary light reflex measurements were performed in 48 eyes of 24 patients diagnosed with unilateral optic neuritis (ON). Interocular symmetry was evaluated both in the healthy subjects and the ON-involved patients. High repeatability of AC, LOC, and VC in healthy subjects was displayed, presenting with the ICC value over 0.80 and the Cov less than 8.00%. But the RAPD score for amplitude (ICC: 0.67) and RAPD score for latency (ICC: 0.65) showed only moderate repeatability. Furthermore, a slight declining trend was found in amplitude and peak velocity when continuous and multiple measurements in the healthy subjects. Good symmetry of the AC, LOC, and VC of pupillary light constriction between the two eyes was displayed in the healthy subjects (P > 0.05). By contrast, there was a distinct decrease of AC and VC (P < 0.01), and a mild increase of LOC (P < 0.01) in the ON-involved eye in direct pupillary light reflex. Pupillary light reflex measured by the RAPDx® pupillometer achieved overall good repeatability and interocular symmetry in healthy subjects. The device also presented decent preliminary results in patients with unilateral ON, suggesting its potential value to be developed as a tool in optic nerve diseases.

Clinical potential of pupillary light reflex parameters as objective indicators reflecting chronic rhinosinusitis-specific quality of life: a 12-month prospective longitudinal study

Pupillary light reflex (PLR) and heart rate variability (HRV) parameters can be objective indicators of chronic rhinosinusitis (CRS) status from the viewpoint of autonomic nervous system activity. This study aimed to establish objective indicators for CRS using the 22-item Sino-Nasal Outcome Test (SNOT-22) and PLR/HRV parameters. Sixty-seven patients were prospectively and longitudinally followed up after surgical treatment. We investigated changes in SNOT-22 scores, representing CRS-specific quality of life (QOL). We prepared two models: linear regression model adjusting clinical factors as predictor variables (model 1) and linear mixed-effects model adjusting clinical factors and among-individual variability (model 2). We compared Akaike’s information criterion (AIC) values and regression coefficients. The model with lower AIC values was defined as the better-fit model. Model 2 showed lower AIC values in all parameters (better-fit model). Three parameters showed opposite results between the two models. The better-fit models showed significances in the five PLR parameters but not in any HRV parameters. Among these PLR parameters, constriction latency can be the most robust indicator because of the narrowest 95% confidence intervals. Adjusting the among-individual variability while investigating clinical potential of PLR/HRV parameters to reflect CRS-specific QOL can improve the model fit, thereby reaching robust conclusions from obtained data.

Development of the pupillary light reflex from 9 to 24 months: association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis.

Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24months in a sample of infants (N=264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD ) were calculated for 190 infants. While infants showed a decrease in latency between 9 and 14months, higher PGSASD was associated with a smaller decrease in latency in the first year (β=-.16, 95% CI=-0.31, -0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative 'catch-up') between 14 and 24months relative to those with other outcomes (typical: β=.54, 95% CI=0.08, 0.99; other: β=.53, 95% CI=0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (β=.08, 95% CI=0.01, 0.14) and RRB (β=.05, 95% CI=0.004, 0.11) traits. These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.

Commentary: The utility of automated pupillometry in retinal disorders.

Pupillary light reflex (PLR) remains an integral part of ocular examination providing an insight into the retinal, optic nerve, and brain stem functions. An altered PLR has significance in a multitude of ocular disorders such as third nerve palsies, optic neuritis, and central retinal vein occlusion.[123] A relative afferent pupillary defect (RAPD), detected by the swinging flashlight test, is indicative of an asymmetrical/unilateral retinal pathology or an optic nerve lesion and was first described by Levatin in 1959. Although the use of neutral density filters and standardized clinical grading has helped in quantifying RAPD, these methods remain limited by variable test conditions and observer bias.[4] The evaluation of RAPD with a swinging flashlight test is further hampered in patients with dark irides and small and/or poorly reacting pupils. Automated pupillometry helps in eliminating these barriers and provides an objective, standardized, and reproducible assessment of the pupillary function. In addition, the automated pupillometer is capable of assessing multiple variables, including pupillary size, constriction velocity, dilation velocity, and the latency of PLR. One of the earliest utilization of pupillometry in ophthalmology was described by Bloom et al.[3] in their study of central retinal vein occlusion. In eyes developing rubeosis, they observed a greater mean RAPD using neutral density filters, while infrared pupillometry revealed greater pupillary diameter and latency of constriction with a slower rate of pupillary constriction. They also concluded that because of the subjective nature of RAPD assessment, pupillometry was a more specific test generating a higher amount of measurable data and hence recommended its further development. Using pupillometry, Jain et al.[5] observed altered pupillary dynamics in the early stages of diabetic retinopathy and further observed that the dynamics deteriorated with the increasing severity of retinopathy. The importance of pupil assessment is heightened in neuro-ophthalmology cases to clinch the diagnosis. Kim et al.[1] evaluated the pupillary response in isolated third nerve palsy cases using an automated, infrared pupillometer. The ability of the automated pupillometer to quantify the pupillary response enabled them to calculate the pupillary constriction ratio, which they found to be highly specific for detecting third nerve palsy due to compressive etiologies. They were also able to distinguish microvascular ischemic third nerve palsy from those due to compressive lesions using digital pupillometry. Optic nerve disorders, including optic neuritis and nonarteritic anterior ischemic optic neuropathy (NAION), can significantly affect the PLR. Yoo et al.[2] observed a decreased pupillary constriction velocity, constriction ratio, and latency in acute optic neuritis and NAION using automated pupillometry. They also concluded that a delayed constriction latency and PLR recovery were features suggestive of optic neuritis over NAION. Although the role of PLR and automated pupillometer in age-related macular degeneration (ARMD) has been described in previous studies, the current study demonstrated its role in assessing macular lesions in choroidal neovascular membranes (CNVM) and also correlated the structural dimensions assessed on optical coherence tomography with RAPD scores.[678] Although the current study provides useful insights into the role of pupillometry in ARMD, the cross-sectional design does not address the role of evaluating the PLR in monitoring treatment response and disease progression, thus warranting further studies. Also, it would be interesting to evaluate the role of CNVM components such as subretinal fluid, intraretinal fluid, and subretinal hemorrhage on the RAPD scores. To conclude, automated pupillometry has a potential role to play in the monitoring of disease progression and response to therapy in ARMD and myriad other retinal disorders. Further studies are needed to expand the horizons about the role of this noninvasive, objective test for retinal pathologies. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Pupil light reflex in Parkinson's disease patients with and without freezing of gait symptoms

PURPOSE:Freezing of gait (FOG) is considered as a motor disorder that affects some Parkinson’s disease (PD) patients; however, sensory systems may also be involved in FOG. The pupil light reflex (PLR) is a reliable measure of the autonomic nervous system. Different dilation and constriction pupil parameters may be used to investigate the integrity of the autonomic nervous system in PD patients with and without FOG symptoms. This study aimed to look at the integrity of autonomic nervous system and to investigate the nonmotor functions mediated by the cholinergic system in Parkinson’s patients with and without FOG symptoms.METHODS:Constriction and dilation pupil light reflexes were measured by using a handheld pupillometer. Twenty-two patients with FOG symptoms, 25 patients without FOG symptoms, and 25 aged-matched healthy controls participated in this study.RESULTS:The results showed that most of the constriction parameters and dilation latency of both patient groups differed significantly from healthy controls. FOG patients showed larger pupil size under light condition and larger deficits in constriction latency than nonFOG patients. Both the groups of PD patients had longer dilation latencies than healthy controls.CONCLUSION:This study suggests that the cholinergic autonomic nervous system is affected in PD patients more than the adrenergic system. FOG patients had larger impairments in nondopaminergic mediated functions such as pupil light reflexes, which suggests that FOG patients have greater impairment in functions that involve cholinergic neurotransmitters.

Pupillary light reflex in ethambutol-induced optic neuropathy

We evaluated changes in the pupillary light reflex (PLR) of ethambutol (EMB)-induced optic neuropathy and analyzed the correlations between PLR parameters and other structural changes in EMB-induced optic neuropathy. This retrospective, observational, case–control study involved thirty-two eyes of 17 patients with EMB-induced optic neuropathy (EON group), sixty eyes of 60 patients without EMB-induced optic neuropathy (non-EON group) while taking ethambutol, and forty-five eyes of 45 normal controls. PLR was measured by digital pupillometry. The clinical characteristics, optical coherence tomography measurements and PLR parameters including pupil diameter, constriction latency, constriction ratio/velocity, and dilation velocity were noted. The differences in PLR measurements were compared among the three groups. Correlations between PLR parameters and other structural parameters in EMB-induced optic neuropathy were evaluated. The pupillary constriction ratio, constriction and dilation velocities were significantly reduced in the EON group compared to the non-EON group and controls (all P < 0.05). In EMB-induced optic neuropathy, average outer macular ganglion cell layer (mGCL) thickness showed a significant correlation with the pupillary constriction ratio (ß = 4.14, P = 0.003) and maximal constriction velocity (ß = 1.08, P < 0.001). This study confirmed that pupillary constriction and dilation velocities were significantly decreased in patients with EMB-induced optic neuropathy, compared to normal controls. Digital pupillometry may be a useful tool in the evaluation of EMB-induced optic neuropathy.

Correlation between Pupilometer and the Vestibular/Ocular Motor Screening in Division I Female Collegiate Soccer Athletes

The objective of this study was to explore the correlation between pupilometer and Vestibular Ocular Motor Screening on Division 1 female collegiate soccer players. Concussions are one of the most prevalent acquired neurologic conditions occurring in young adults with an estimated 1.6 to 3.8 million head injuries.1,2 Concussions are assessed with a variety of measures such as the Vestibular/Ocular Motor Screen (VOMS). Visual disruptions are frequently observed following concussion with an estimated 65%-90% of patients complaining of visual disruption.4,5 A pupilometer measures objective pupillary activity such as pupil constriction latency, diameter, speed of constriction and dilation, and reflex recovery time.5 DESIGN/METHODS: This prospective study recruited Division I female soccer athletes aged 18 to 28. Athletes were excluded if they had a lower extremity injury in the past 3 months that caused the athlete to miss more than 1 day of practice, had a history of a head injury in the past 6 months, or were diagnosed with a visual, vestibular, or balance disorder. Twenty-six female Division I collegiate soccer athletes (mean age of 20.46 ± 2.36 years) completed baseline pupilometer and VOMS testing. Three of the twenty-six had borderline pupillary index scores and five had abnormal VOMS scores at baseline. One athlete had a concussion during the 2019 season and at retest, pupilometer results were normal but two VOMS components were abnormal. The pupilometer and VOMS were poorly correlated. While the neurocognitive consequences of participation in soccer is becoming uncertain, the current study suggests that 11% of female soccer athletes without a diagnosis of a concussion had abnormal pupilometer results and 19% had abnormal VOMS scores. Evidence is mounting that repetitive hits to the head can lead to potential neurocognitive impairments. Future studies are warranted to examine baseline measures across age in female soccer athletes.

Elucidation of Cellular Mechanisms That Regulate the Sustained Contraction and Relaxation of the Mammalian Iris.

PurposeIn mammals, pupil constriction and dilation form the pupillary light reflex (PLR), which is mediated by both brain-regulated (parasympathetic) and local iris-driven reflexes. To better understand the cellular mechanisms that regulate pupil physiological dynamics via central and local photoreception, we have examined the regulation of the PLR via parasympathetic and local activation, respectively.MethodsIn this study, the PLR was examined in mouse enucleated eyes ex vivo in real-time under different ionic conditions in response to acetylcholine and/or blue light (480 nm). The use of pupillometry recordings captured the relaxation, contraction, and pupil escape (redilation) processes for 10 minutes up to 1 hour.ResultsAmong others, our results show that ryanodine receptor channels are the main driver for iridal stimulation–contraction coupling, in which extracellular influx of Ca2+ is required for amplification of pupil constriction. Both local and parasympathetic iridal activations are necessary, but not sufficient for sustained pupil constriction. Moreover, the degree of membrane potential repolarization in the dark is correlated with the latency and velocity of iridal constriction. Furthermore, pupil escape is driven by membrane potential hyperpolarization where voltage-gated potassium channels play a crucial role.ConclusionsTogether, this study presents new mechanisms regulating synchronized pupil dilation and contraction, sustained pupil constriction, iridal stimulation-contraction coupling, and pupil escape.

Is There a Link between Stress and Cognition, and Capacity to Execute Motor Skill?

This study aimed to examine the link between stress (measured via salivary cortisol and testosterone), cognition (measured via pupillometry, with greater pupil constriction and reduced pupil constriction latency associated with increased attention and improved information processing), and motor skill capacity (measured via somatosensory processing). Twenty-five professional rugby players participated in this study. Saliva samples were collected upon waking, before pupillometry and somatosensory processing testing, and after testing. Testing times varied for participants; however, it was always in the morning, and the order of testing was randomized. Very small differences in hormone concentrations were seen across the morning (effect size = 0.01). Moderate to large differences in left eye pupil constriction for direct (left eye) versus consensual (right eye) stimulus were also seen (P < 0.01; effect size = 0.51 to 1.04). No differences for pupil constriction latency were seen for direct versus consensual stimulus. Some positive weak to moderate relationships were seen for testosterone and pupil constriction latency (r = 0.37 to 0.39, P < 0.05). Moderate to strong inverse relationships were seen for hormones with left eye pupil constriction difference between direct and consensual stimulus, and for pre- to posttest testosterone-to-cortisol ratio decline with left eye pupil constriction for direct and consensual stimulus (r = 0.41 to 0.52, P < 0.05). Weak to moderate inverse relationships for testosterone-to-cortisol ratio decline and somatosensory processing were seen (r = 0.36 to 0.47, P < 0.05). Stress may affect ability to receive information and ability to execute motor tasks. Thus, stress may compromise ability to make appropriate objective decisions and consequently execute skill/task behavior. Strategies to help mitigate negative stress responses are noted.