Search Results (27)

Background: Handheld quantitative pupilometers (QPs) measure each phase of the pupillary light reflex (PLR) and provide a summary score based on these values. One phase of the PLR is the period of time from the onset of light exposure to the maximum constriction of the pupil, also known as time to maximum constriction (tMC). Although tMC has been found to vary significantly among patients with neurological injury, there are no studies reporting tMC in healthy controls. This study addresses this gap. Methods: Subjects in this prospective observational study were healthy controls who provided paired (left and right eye) QP readings during four separate observations over the course of 2 days. The tMC was derived by determining the smallest observed pupil size during videos filmed at 30 frames per second, and we assessed within-subject variability using the coefficient of variance and intraclass correlation coefficient (ICC). Results: Fifty subjects provided 380 QP readings (190 left eye and 190 right eye). Subjects primarily identified as female (80%), non-Hispanic (86%), white (62%), and <40 years old (74%). The mean tMC was 1.0 (0.14) seconds (s) for the left eye and 1.0 (0.17) s for the right eye; the coefficient of variance ranged from 11.6% to 18.8% and the ICC ranged from 0.25 to 0.40. For the between-subject comparisons across the four observation periods, the left and right eye mean differences ranged from 0.001 to 0.063 and the ICC ranged from 0.12 to 0.52. Conclusions: The tMC values vary significantly in healthy controls. Changes in pupil function as a clinical biomarker of intracranial pathology are not fully understood. Identifying clinical correlations of tMC variation may provide insight for the prognostication and treatment of neurocritically ill patients. Full article

Background: Quantitative pupillometry has been proposed as an objective means to diagnose acute sports-related concussion (SRC). Objective: To assess the diagnostic accuracy of a smartphone-based quantitative pupillometer in the acute diagnosis of SRC. Methods: Division I college football players had baseline pupillometry including pupillary light reflex (PLR) parameters of maximum resting diameter, minimum diameter after light stimulus, percent change in pupil diameter, latency of pupil constriction onset, mean constriction velocity, maximum constriction velocity, and mean dilation velocity using a smartphone-based app. When an SRC occurred, athletes had the smartphone pupillometry repeated as part of their concussion testing. All combinations of the seven PLR parameters were tested in machine learning binary classification models to determine the optimal combination for differentiating between non-concussed and concussed athletes. Results: 93 football athletes underwent baseline pupillometry testing. Among these athletes, 11 suffered future SRC and had pupillometry recordings repeated at the time of diagnosis. In the machine learning pupillometry analysis that used the synthetic minority oversampling technique to account for the significant class imbalance in our dataset, the best-performing model was a random forest algorithm with the combination of latency, maximum diameter, minimum diameter, mean constriction velocity, and maximum constriction velocity PLR parameters as feature inputs. This model produced 91% overall accuracy, 98% sensitivity, 84.2% specificity, area under the curve (AUC) of 0.91, and an F1 score of 91.6% in differentiating between baseline and SRC recordings. In the machine learning analysis prior to oversampling of our imbalanced dataset, the best-performing model was k-nearest neighbors using latency, maximum diameter, maximum constriction velocity, and mean dilation velocity to produce 82% accuracy, 40% sensitivity, 87% specificity, AUC of 0.64, and F1 score of 24%. Conclusions: Smartphone pupillometry in combination with machine learning may provide fast and objective SRC diagnosis in football athletes. Full article

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. Full article

(1) Background: Defining the optimum center for laser refractive corrections is difficult, with many of the available approaches having pros and cons. Decentered ablations result in undesirable side effects like halos, glare, monocular diplopia, and a reduction in visual acuity; (2) Methods: The ideal centration in refractive corrections should fulfil three requirements: covering a scotopic pupil; respecting the visual axis; and minimizing tissue removal. The implications of different centration strategies are discussed and shown graphically; (3) Results: Oversized asymmetric offset ablation faces fewer difficulties in registering static cyclotorsion, features less tissue wastage compared to a symmetric offset, and includes a certain amount of coma (and trefoil) in the profile, benefiting eyes with a pupil offset, which typically present with relevant amounts of coma and trefoil corneal aberrations due to decentered optics; (4) Conclusions: There is a need for a flexible choice of centration in refractive procedures to design customized and non-customized treatments optimally. An ideal optical zone covering the pupil with the widest entrance may be as important as a centration reference. Full article

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that modulates the noradrenergic activity of the locus coeruleus (LC). Yet, there is still uncertainty about the most effective stimulation and reliable outcome parameters. In a double blind, sham-controlled study including a sample of healthy young individuals (N = 29), we compared a shorter (3.4 s) and a longer (30 s) stimulation duration and investigated the effects of taVNS (real vs. sham) on saliva samples (alpha amylase and cortisol concentration), pupil (pupillary light reflex and pupil size at rest) and EEG data (alpha and theta activity at rest, ERPs for No-Go signals), and cognitive tasks (Go/No-Go and Stop Signal Tasks). Salivary alpha amylase concentration was significantly increased in the real as compared to sham stimulation for the 30 s stimulation condition. In the 3.4 s stimulation condition, we found prolonged reaction times and increased error rates in the Go/No-Go task and increased maximum acceleration in the pupillary light reflex. For the other outcomes, no significant differences were found. Our results show that prolonged stimulation increases salivary alpha-amylase, which was expected from the functional properties of the LC. The finding of longer response times to short taVNS stimulation was not expected and cannot be explained by an increase in LC activity. We also discuss the difficulties in assessing pupil size as an expression of taVNS-mediated LC functional changes. Full article

Background: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. Methods: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics^®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable’s β coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. Results: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. Conclusions: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS. Full article

This article employed pupillometry as a non-invasive technique to analyze pupillary light reflex (PLR) using LED flash stimuli. Particularly, for the experiments, only the red LED with a wavelength of 600 nm served as the light stimulation source. To stabilize the initial pupil size, a pre-stimulus (PRE) period of 3 s was implemented, followed by a 1 s stimulation period (ON) and a 4 s post-stimulus period (POST). Moreover, an experimental, low-cost pupillometer prototype was designed to capture pupillary images of 13 participants. The prototype consists of a 2-megapixel web camera and a lighting system comprising infrared and RGB LEDs for image capture in low-light conditions and stimulus induction, respectively. The study reveals several characteristic features for classifying the phenomenon, notably the mobility of Hjórth parameters, achieving classification percentages ranging from 97% to 99%, and offering novel insights into pattern recognition in pupillary activity. Moreover, the proposed device successfully captured the PLR from all the participants with zero reported incidents or health affectations. Full article

Chromatic Pupillometry, used to assess Pupil Light Reflex (PLR) to a coloured light stimulus, has regained interest since the discovery of melanopsin in the intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). This technique has shown the potential to be used as a screening tool for neuro-ophthalmological diseases; however, most of the pupillometers available are expensive and not portable, making it harder for them to be used as a widespread screening tool. In this study, we developed a smartphone-based system for chromatic pupillometry that allows targeted stimulation of the ipRGCs. Using a smartphone, this system is portable and accessible and takes advantage of the location of the ipRGCs in the perifovea. The system incorporates a 3D-printed support for the smartphone and an illumination system. Preliminary tests were carried out on a single individual and then validated on eleven healthy individuals with two different LED intensities. The average Post-Illumination Pupil Light Response 6 s after the stimuli offsets (PIPR-6s) showed a difference between the blue and the red stimuli of 9.5% for both intensities, which aligns with the studies using full-field stimulators. The results validated this system for a targeted stimulation of the ipRGCs for chromatic pupillometry, with the potential to be a portable and accessible screening tool for neuro-ophthalmological diseases. Full article

Background: Concussion examination is based primarily on clinical evaluation and symptomatic reporting. Pupillary light reflex (PLR) metrics may provide an objective physiological marker to inform concussion diagnosis and recovery, but few studies have assessed PLR, and normative data are lacking, particularly for adolescents. Aim: To capture PLR data in adolescent rugby players and examine the effects of concussion history and biological sex. Design: Cross-sectional. Methods: Male and female adolescent rugby union players aged 16 to 18 years were recruited at the start of the 2022–2023 playing season. PLR was recorded using a handheld pupillometer which provided seven different metrics relating to pupil diameter, constriction/dilation latency, and velocity. Data were analysed using a series of 2 × 2 ANOVAs to examine the main effects of independent variables: biological sex, concussion history, and their interactions, using adjusted p-values (p < 0.05). Results: 149 participants (75% male) were included. A total of 42% reported at least one previous concussion. Most metrics were unaffected by the independent variables. There were however significant main effects for concussion history (F = 4.11 (1); p = 0.05) and sex (F = 5.42 (1); p = 0.02) in end pupil diameters, and a main effect for sex in initial pupil diameters (F = 4.45 (1); p = 0.04). Although no significant interaction effects were found, on average, females with a concussion history presented with greater pupillary diameters and velocity metrics, with many pairwise comparisons showing large effects (SMD > 0.8). Conclusions: Pupillary diameters in adolescent athletes were significantly affected by concussion history and sex. The most extreme PLR metrics were recorded in females with a history of concussion (higher pupillary diameters and velocities). This highlights the importance of establishing baseline PLR metrics prior to interpretation of the PLR post-concussion. Long-standing PLR abnormalities post-concussion may reflect ongoing autonomic nervous system dysfunction. This warrants further investigation in longitudinal studies. Full article

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol’s pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation between pupillary response and tramadol PK. Our objective was to evaluate pupillometry as a phenotyping method to assess CYP2D6 activity in children treated with tramadol. We included 41 children (mean age 11 years) receiving a first dose of tramadol (2 mg/kg) in the emergency room (ER) as part of their routine care. CYP2D6 phenotyping and genotyping were performed. The concentrations of tramadol and its active metabolite, M1, were measured, and static and dynamic pupillometry was conducted using a handheld pupillometer at the time of tramadol administration and during the ER stay. Pupillometric measurements were obtained for 37 children. Tramadol affected pupillary parameters, with a decrease in pupil diameter in 83.8% of children (p = 0.002) (mean decrease 14.1 ± 16.7%) and a decrease in reflex amplitude constriction in 78.4% (p = 0.011) (mean decrease 17.7 ± 34.5%) at T150 compared to T0. We were unable to identify a correlation between pupillometry measurements and CYP2D6 activity. Likely confounding factors include light intensity, pain, and stress, making the procedure less feasible in paediatric emergency settings. Full article

Pupillary light reflex (PLR) assessment is a crucial examination for evaluating brainstem function, particularly in patients with acute brain injury and neurosurgical conditions. The PLR is controlled by neural pathways modulated by both the sympathetic and parasympathetic nervous systems. Altered PLR is a strong predictor of adverse outcomes after traumatic and ischemic brain injuries. However, the assessment of PLR needs to take many factors into account since it can be modulated by various medications, alcohol consumption, and neurodegenerative diseases. The development of devices capable of measuring pupil size and assessing PLR quantitatively has revolutionized the non-invasive neurological examination. Automated pupillometry, which is more accurate and precise, is widely used in diverse clinical situations. This review presents our current understanding of the anatomical and physiological basis of the PLR and the application of automated pupillometry in managing neurocritical patients. We also discuss new technologies that are being developed, such as smartphone-based pupillometry devices, which are particularly beneficial in low-resource settings. Full article

Automated pupil light reflex (PLR) is a valid indicator of dysfunctional autonomic brain function following traumatic brain injury. PLR’s use in identifying disturbed autonomic brain function following repeated head impacts without outwardly visible symptoms has not yet been examined. As a combat sport featuring repeated ‘sub-concussive’ head impacts, mixed martial arts (MMA) sparring may provide a model to understand such changes. The aim of this pilot study was to explore which, if any, PLR variables are affected by MMA sparring. A cohort of n = 7 MMA athletes (age = 24 ± 3 years; mass = 76.5 ± 9 kg; stature = 176.4 ± 8.5 cm) took part in their regular sparring sessions (eight rounds × 3 min: 1 min recovery). PLR of both eyes was measured immediately pre- and post-sparring using a Neuroptic NPi-200. Bayesian paired samples t-tests (BF₁₀ ≥ 3) revealed decreased maximum pupil size (BF₁₀ = 3), decreased minimum pupil size (BF₁₀ = 4) and reduced PLR latency (BF₁₀ = 3) post-sparring. Anisocoria was present prior to sparring and increased post-sparring, with both eyes having different minimum and maximum pupil sizes (BF₁₀ = 3–4) and constriction velocities post-sparring (BF₁₀ = 3). These pilot data suggest repeated head impacts may cause disturbances to autonomic brain function in the absence of outwardly visible symptoms. These results provide direction for cohort-controlled studies to formally investigate the potential changes observed. Full article

The pupillary light reflex, which has been seen as an important noninvasive and objective indicator of autonomic nervous system function, can be used for evaluating the impact of different lighting conditions in buildings on circadian behaviors, assessing ipRGC function in healthy and diseased retinas, and explaining luminance adaptation. However, the mechanism by which the intrinsic and extrinsic signals of ipRGCs regulate the steady-state pupil size under continuous lighting stimuli is still not clearly understood after decades of exploration. This paper presents a new experimental protocol with a large hemisphere LED screen as the stimulation device, allowing for a more realistic and comprehensive study in architectural spaces, which can potentially inform the design of lighting systems in buildings that promote healthy vision and comfort. Results reveal that both intrinsic and extrinsic signals participated in the process of regulating pupil size under continuous lighting conditions. Based on the findings, a new mathematical model was further proposed to calculate the contribution of these two signal sources to the changing intensity of melanopic radiance. The research outcomes also provide new insight into the mechanism of visual perception and adaptation and the nonvisual effect of eyes under different light conditions. Results suggest that the contribution of extrinsic signals may have been underestimated in previous studies since the extrinsic signal increases with reducing intensity in photopic conditions with lower melanopic radiance. Full article

Neurological disorders and traumatic brain injury (TBI) are among the leading causes of death and disability. The pupillary light reflex (PLR) is an emerging diagnostic tool for concussion in humans. We compared PLR obtained with a commercially available pupillometer in the 4 week old piglet model of the adolescent brain subject to rapid nonimpact head rotation (RNR), and in human adolescents with and without sports-related concussion (SRC). The 95% PLR reference ranges (RR, for maximum and minimum pupil diameter, latency, and average and peak constriction velocities) were established in healthy piglets (N = 13), and response reliability was validated in nine additional healthy piglets. PLR assessments were obtained in female piglets allocated to anesthetized sham (N = 10), single (sRNR, N = 13), and repeated (rRNR, N = 14) sagittal low-velocity RNR at pre-injury, as well as days 1, 4, and 7 post injury, and evaluated against RRs. In parallel, we established human PLR RRs in healthy adolescents (both sexes, N = 167) and compared healthy PLR to values obtained <28 days from a SRC (N = 177). In piglets, maximum and minimum diameter deficits were greater in rRNR than sRNR. Alterations peaked on day 1 post sRNR and rRNR, and remained altered at day 4 and 7. In SRC adolescents, the proportion of adolescents within the RR was significantly lower for maximum pupil diameter only (85.8%). We show that PLR deficits may persist in humans and piglets after low-velocity head rotations. Differences in timing of assessment after injury, developmental response to injury, and the number and magnitude of impacts may contribute to the differences observed between species. We conclude that PLR is a feasible, quantifiable involuntary physiological metric of neurological dysfunction in pigs, as well as humans. Healthy PLR porcine and human reference ranges established can be used for neurofunctional assessments after TBI or hypoxic exposures (e.g., stroke, apnea, or cardiac arrest). Full article

Saccadic eye movements are directed to the objects of interests and enable high-resolution visual images in the exploration of the visual world. There is a trial-to-trial variation in saccade dynamics even in a simple task, possibly attributed to arousal fluctuations. Previous studies have showed that an increase of fatigue level over time, also known as time-on-task, can be revealed by saccade peak velocity. In addition, pupil size, controlled by the autonomic nervous system, has long been used as an arousal index. However, limited research has been done with regards to the relation between pupil size and saccade behavior in the context of trial-to-trial variation. To investigate fatigue and arousal effects on saccadic and pupillary responses, we used bright and emotional stimuli to evoke pupillary responses in tasks requiring reactive and voluntary saccade generation. Decreased voluntary saccade peak velocities, reduced tonic pupil size and phasic pupillary responses were observed as time-on-task increased. Moreover, tonic pupil size affected saccade latency and dynamics, with steeper saccade main sequence slope as tonic pupil size increased. In summary, saccade dynamics and tonic pupil size were sensitive to fatigue and arousal level, together providing valuable information for the understanding of human behavior. Full article