Quantitative pupillometry as a biomarker for prediction of return to play in mild traumatic brain injury: a Military Traumatic Brain Injury Initiative study.

OBJECTIVE: This study aimed to determine the validity of quantitative pupillometry to predict the length of time for return to full activity/duty after a mild traumatic brain injury (mTBI) in a cohort of injured cadets at West Point. METHODS: Each subject received baseline (T0) quantitative pupillometry, in addition to evaluation with the Balance Error Scoring System (BESS), Standardized Assessment of Concussion (SAC), and Sport Concussion Assessment Tool 5th Edition Symptom Survey (SCAT5). Repeat assessments using the same parameters were conducted within 48 hours of injury (T1), at the beginning of progressive return to activity (T2), and at the completion of progressive return to activity protocols (T3). Pupillary metrics were compared on the basis of length of time to return to full play/duty and the clinical scores. RESULTS: The authors' statistical analyses found correlations between pupillometry measures at T1, including end-initial diameter and maximum constriction velocity, with larger change and faster constriction predicting earlier return to play. There was also an association with maximum constriction velocity at baseline (T0), predicting faster return to play. CONCLUSIONS: The authors conclude that that pupillometry may be a valuable tool for assessing time to return to duty from mTBI by providing a measure of baseline resiliency to mTBI and/or autonomic dysfunction in the acute phase after mTBI.

Differences in the pupillary responses to evening light between children and adolescents.

BACKGROUND: In the mammalian retina, intrinsically-photosensitive retinal ganglion cells (ipRGC) detect light and integrate signals from rods and cones to drive multiple non-visual functions including circadian entrainment and the pupillary light response (PLR). Non-visual photoreception and consequently non-visual sensitivity to light may change across child development. The PLR represents a quick and reliable method for examining non-visual responses to light in children. The purpose of this study was to assess differences in the PLRs to blue and red stimuli, measured one hour prior to bedtime, between children and adolescents. METHODS: Forty healthy participants (8-9 years, n = 21; 15-16 years, n = 19) completed a PLR assessment 1 h before their habitual bedtime. After a 1 h dim-light adaptation period (< 1 lx), baseline pupil diameter was measured in darkness for 30 s, followed by a 10 s exposure to 3.0 × 1013 photons/cm2/s of either red (627 nm) or blue (459 nm) light, and a 40 s recovery in darkness to assess pupillary re-dilation. Subsequently, participants underwent 7 min of dim-light re-adaptation followed by an exposure to the other light condition. Lights were counterbalanced across participants. RESULTS: Across both age groups, maximum pupil constriction was significantly greater (p < 0.001, ηp2 = 0.48) and more sustained (p < 0.001, ηp2 = 0.41) during exposure to blue compared to red light. For adolescents, the post-illumination pupillary response (PIPR), a hallmark of melanopsin function, was larger after blue compared with red light (p = 0.02, d = 0.60). This difference was not observed in children. Across light exposures, children had larger phasic (p < 0.01, ηp2 = 0.20) and maximal (p < 0.01, ηp2 = 0.22) pupil constrictions compared to adolescents. CONCLUSIONS: Blue light elicited a greater and more sustained pupillary response than red light in children and adolescents. However, the overall amplitude of the rod/cone-driven phasic response was greater in children than in adolescents. Our findings using the PLR highlight a higher sensitivity to evening light in children compared to adolescents, and continued maturation of the human non-visual photoreception/system throughout development.

Pupillary Light Reflex Reveals Melanopsin System Alteration in the Background of Myopia-26, the Female Limited Form of Early-Onset High Myopia.

Purpose: The purpose of this study was to evaluate pupillary light reflex (PLR) to chromatic flashes in patients with early-onset high-myopia (eoHM) without (myopic controls = M-CTRL) and with (female-limited myopia-26 = MYP-26) genetic mutations in the ARR3 gene encoding the cone arrestin. Methods: Participants were 26 female subjects divided into 3 groups: emmetropic controls (E-CTRL, N = 12, mean age = 28.6 ± 7.8 years) and 2 myopic (M-CTRL, N = 7, mean age = 25.7 ± 11.5 years and MYP-26, N = 7, mean age = 28.3 ± 15.4 years) groups. In addition, one hemizygous carrier and one control male subject were examined. Direct PLRs were recorded after 10-minute dark adaptation. Stimuli were 1-second red (peak wavelength = 621 nm) and blue (peak wavelength = 470 nm) flashes at photopic luminance of 250 cd/m². A 2-minute interval between the flashes was introduced. Baseline pupil diameter (BPD), peak pupil constriction (PPC), and postillumination pupillary response (PIPR) were extracted from the PLR. Group comparisons were performed with ANOVAs. Results: Dark-adapted BPD was comparable among the groups, whereas PPC to the red light was slightly reduced in patients with myopia (P = 0.02). PIPR at 6 seconds elicited by the blue flash was significantly weaker (P < 0.01) in female patients with MYP-26, whereas it was normal in the M-CTRL group and the asymptomatic male carrier. Conclusions: L/M-cone abnormalities due to ARR3 gene mutation is currently claimed to underlie the pathological eye growth in MYP-26. Our results suggest that malfunction of the melanopsin system of intrinsically photosensitive retinal ganglion cells (ipRGCs) is specific to patients with symptomatic MYP-26, and may therefore play an additional role in the pathological eye growth of MYP-26.

Association Between Pupil Light Reflex and Delirium in Adults With Traumatic Brain Injury: Preliminary Findings.

ABSTRACT: BACKGROUND: Delirium is a common neurological complication in patients admitted to the intensive care unit (ICU) after moderate to severe traumatic brain injury (TBI). Although current clinical guidelines prioritize delirium prevention, no specific tool is tailored to detect early signs of delirium in TBI patients. This preliminary 2-phase observational study investigated the correlation between the pupillary light reflex (PLR), measured with a pupillometer during mechanical ventilation, and the development of postextubation delirium in TBI patients. METHODS: A convenience sample of 26 adults with moderate to severe TBI under mechanical ventilation was recruited during their ICU stay. In phase I, PLR measurements were performed in the first 3 days of ICU admission using automated infrared pupillometry. In phase II, 2 raters independently extracted delirium data in the 72 hours post extubation period from medical records. Delirium was confirmed with a documented medical diagnosis. Point-biserial correlations ( rpb ) were used to examine the association between PLR scores and the presence of postextubation delirium. Student t tests were also performed to compare mean PLR scores between patients with and without delirium. RESULTS: Ten TBI patients (38%) were diagnosed with postextubation delirium, whereas 16 (62%) were not. Significant correlations between delirium and 2 PLR variables were found: pupil constriction percentage ( rpb (24) = -0.526, P = .006) and constriction velocity ( rpb (24) = -0.485, P = .012). The t test also revealed a significant difference in constriction percentage and velocity scores between TBI patients with and without delirium ( P ≤ .01). CONCLUSION: Our findings suggest that the use of pupillometry in the first 3 days of mechanical ventilation during an ICU stay may help identify TBI patients at risk for delirium after extubation. Although further research is necessary to support its validity, this technological tool may enable ICU nurses to better screen TBI patients for delirium and prevent its development.

High-speed eye tracking based on a synchronized imaging mechanism by a dual-ring infrared lighting source.

It is a challenge for conventional monocular-camera single-light source eye-tracking methods to achieve high-speed eye tracking. In this work, a dual-ring infrared lighting source was designed to achieve bright and dark pupils in high speed. The eye-tracking method used a dual-ring infrared lighting source and synchronized triggers for the even and odd camera frames to capture bright and dark pupils. A pupillary corneal reflex was calculated by the center coordinates of the Purkinje spot and the pupil. A map function was established to map the relationship between the pupillary corneal reflex and gaze spots. The gaze coordinate was calculated based on the mapping function. The average detection time of each gaze spot was 3.76 ms.

Influencing Factors on Pupillary Light Responses as a Biomarker for Local Retinal Function in a Large Normative Cohort.

Purpose: Investigating influencing factors on the pupillary light response (PLR) as a biomarker for local retinal function by providing epidemiological data of a large normative collective and to establish a normative database for the evaluation of chromatic pupil campimetry (CPC). Methods: Demographic and ophthalmologic characteristics were captured and PLR parameters of 150 healthy participants (94 women) aged 18 to 79 years (median = 46 years) were measured with L-cone- and rod-favoring CPC protocols. Linear-mixed effects models were performed to determine factors influencing the PLR and optical coherence tomography (OCT) data were correlated with the pupillary function volume. Results: Relative maximal constriction amplitude (relMCA) and latency under L-cone- and rod-favoring stimulation were statistically significantly affected by the stimulus eccentricity (P < 0.0001, respectively). Iris color and gender did not affect relMCA or latency significantly; visual hemifield, season, and daytime showed only minor influence under few stimulus conditions. Age had a statistically significant effect on latency under rod-specific stimulation with a latency prolongation ≥60 years. Under photopic and scotopic conditions, baseline pupil diameter declined significantly with increasing age (P < 0.0001, respectively). Pupillary function volume and OCT data were not correlated relevantly. Conclusions: Stimulus eccentricity had the most relevant impact on relMCA and latency of the PLR during L-cone- and rod-favoring stimulation. Latency is prolonged ≥60 years under scotopic conditions. Considering the large study collective, a representative normative database for relMCA and latency as valid readout parameters for L-cone- and rod-favoring stimulation could be established. This further validates the usability of the PLR in CPC as a biomarker for local retinal function.

Altered pupil light and darkness reflex and eye-blink responses in late-life depression.

BACKGROUND: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD. METHODS: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups. RESULTS: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes. CONCLUSIONS: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.

Evidence of the protective role of Carvacrol in a retinal degeneration animal model.

Neurodegenerative pathologies affecting the posterior segment of the eye, are characterized by being devastating and responsible for the majority of visual dysfunctions worldwide. These diseases are primarily degenerative, progressing chronically, and can inflict gradual harm to the optic nerve, retinal ganglion cells (RGC), photoreceptors, and other retinal cells. This retinal damage leads to a progressive loss of vision, marking these conditions as a significant health concern worldwide. The intravitreal administration of the phytochemical Carvacrol (CAR) is expected to demonstrate a neuroprotective and antiapoptotic effect on retinal cells, with a specific focus on RGC. This effect will be observed in a retinal degeneration model (RDM) in rabbits induced by cytotoxic and oxidative agents, namely glutamate (GLUT) and L-buthionine-S, R-sulfoximine (BSO). An in vivo study was conducted using New Zealand rabbits in which retinal damage was created to evaluate the effectiveness of CAR. The effectiveness of CAR on the functionality of retinal neuronal cells in RDM was evaluated using pupillary light reflection (PLR). Furthermore, the phytotherapeutic's influence on cell viability was determined through flow cytometry analysis. Finally, the neuroprotective and antiapoptotic capabilities of CAR were specifically scrutinized in RGC through histological studies, quantifying cell survival, and employing immunohistochemical assays to detect the apoptotic index (%) using the TUNEL technique. Our results demonstrated that CAR promoted the recovery of the pupillary contraction profile over time, maintaining the functionality of retinal cells as healthy controls. Additionally, it showed increased cell viability under oxidative and cytotoxic conditions given by GLUT-BSO agents. Finally, we found that CAR protects the survival of RGC and decreases the percentage of apoptotic cells when compared to RDM. CAR demonstrated to have positive effects on the functionality of photoreceptive nerve cells by restoring pupillary contraction. Likewise, it was shown to have neuroprotective and antiapoptotic effects when evaluated in a general and specific way on retinal nerve cells.

A pupillary contrast response in mice and humans: Neural mechanisms and visual functions.

In the pupillary light response (PLR), increases in ambient light constrict the pupil to dampen increases in retinal illuminance. Here, we report that the pupillary reflex arc implements a second input-output transformation; it senses temporal contrast to enhance spatial contrast in the retinal image and increase visual acuity. The pupillary contrast response (PCoR) is driven by rod photoreceptors via type 6 bipolar cells and M1 ganglion cells. Temporal contrast is transformed into sustained pupil constriction by the M1's conversion of excitatory input into spike output. Computational modeling explains how the PCoR shapes retinal images. Pupil constriction improves acuity in gaze stabilization and predation in mice. Humans exhibit a PCoR with similar tuning properties to mice, which interacts with eye movements to optimize the statistics of the visual input for retinal encoding. Thus, we uncover a conserved component of active vision, its cell-type-specific pathway, computational mechanisms, and optical and behavioral significance.

Good outcome prediction after out-of-hospital cardiac arrest: A prospective multicenter observational study in Korea (the KORHN-PRO registry).

AIM: To assess the ability of clinical examination, biomarkers, electrophysiology and brain imaging, individually or in combination to predict good neurological outcomes at 6 months after CA. METHODS: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0, which included adult out-of-hospital cardiac arrest (OHCA) patients (≥18 years). Good outcome predictors were defined as both pupillary light reflex (PLR) and corneal reflex (CR) at admission, Glasgow Coma Scale Motor score (GCS-M) >3 at admission, neuron-specific enolase (NSE) <17 µg/L at 24-72 h, a median nerve somatosensory evoked potential (SSEP) N20/P25 amplitude >4 µV, continuous background without discharges on electroencephalogram (EEG), and absence of anoxic injury on brain CT and diffusion-weighted imaging (DWI). RESULTS: A total of 1327 subjects were included in the final analysis, and their median age was 59 years; among them, 412 subjects had a good neurological outcome at 6 months. GCS-M >3 at admission had the highest specificity of 96.7% (95% CI 95.3-97.8), and normal brain DWI had the highest sensitivity of 96.3% (95% CI 92.9-98.4). When the two predictors were combined, the sensitivities tended to decrease (ranging from 2.7-81.1%), and the specificities tended to increase, ranging from81.3-100%. Through the explorative variation of the 2021 European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) prognostication strategy algorithms, good outcomes were predicted, with a specificity of 83.2% and a sensitivity of 83.5% in patients by the algorithm. CONCLUSIONS: Clinical examination, biomarker, electrophysiology, and brain imaging predicted good outcomes at 6 months after CA. When the two predictors were combined, the specificity further improved. With the 2021 ERC/ESICM guidelines, the number of indeterminate patients and the uncertainty of prognostication can be reduced by using a good outcome prediction algorithm.

Prediction for the prognosis of diffuse axonal injury using automated pupillometry.

OBJECTIVE: Previous studies have reported various predictive indicators of diffuse axonal injury (DAI), but no consensus has not been reached. Although the efficiency of automated pupillometry in patients with consciousness disorder has been widely reported, there are few reports of its use in patients with DAI. This study aimed to investigate the significance of pupillary findings in predicting the prognosis of DAI. PATIENTS AND METHODS: We included patients admitted to our center with a diagnosis of DAI from June 1, 2021 to June 30, 2022. Pupillary findings in both eyes were quantitatively measured by automated pupillometry every 2 hours after admission. We statistically examined the correlations between automated pupillometry parameters, the patients' characteristics, and outcomes such as the Glasgow Outcome Scale Extended (GOSE) after 6 months from injury, the time to follow command, and so on. RESULTS: Among 22 patients included in this study, five had oculomotor nerve palsy. Oculomotor nerve palsy was correlated with all outcomes, whereas Marshall computed tomography (CT) classification, Injury severity score (ISS) and DAI grade were correlated with few outcomes. Some of the automated pupillometry parameters were significantly correlated with GOSE at 6 months after injury, and many during the first 24 hours of measurement were correlated with the time to follow command. Most of these results were not affected by adjustment using sedation period, ISS or Marshall CT classification. A subgroup analysis of patients without oculomotor nerve palsy revealed that many of the automated pupillometry parameters during the first 24 hours of measurement were significantly correlated with most of the outcomes. The cutoff values that differentiated a good prognosis (GOSE 5-8) from a poor prognosis (GOSE 1-4) were constriction velocity (CV) 1.43 (AUC = 0.81(0.62-1), p = 0.037) and maximum constriction velocity (MCV) 2.345 (AUC = 0.78 (0.58-0.98), p = 0.04). The cutoff values that differentiated the time to follow command into within 7 days and over 8 days were percentage of constriction 8 (AUC = 0.89 (0.68-1), p = 0.011), CV 0.63 (AUC = 0.92 (0.78-1), p = 0.013), MCV 0.855 (AUC = 0.9 (0.74-1), p = 0.017) and average dilation velocity 0.175 (AUC = 0.95 (0.86-1), p = 0.018). CONCLUSIONS: The present results indicate that pupillary findings in DAI are a strong predictive indicator of the prognosis, and that quantitative measurement of them using automated pupillometry could facilitate enhanced prediction for the prognosis of DAI.

Evaluating the utility of quantitative pupillometry in a neuro-critical care setting for the monitoring of intracranial pressure: A prospective cohort study.

INTRODUCTION: Assessment of the pupillary light reflex (PLR) is key in intensive care monitoring of neurosurgical patients, particularly for monitoring intracranial pressure (ICP). Quantitative pupillometry using a handheld pupillometer is a reliable method for PLR assessment. However, many variables are derived from such devices. We therefore aimed to assess the performance of these variables at monitoring ICP. METHODS: Sedated patients admitted to neurocritical care in a tertiary neurosurgical centre with invasive ICP monitoring were included. Hourly measurement of ICP, subjective pupillometry (SP) using a pen torch device, and quantitative pupillometry (QP) using a handheld pupillometer were performed. RESULTS: 561 paired ICP, SP and QP pupillary observations from nine patients were obtained (1122 total pupillary observations). SP and QP had a moderate concordance for pupillary size (κ=0.62). SP performed poorly at detecting pupillary size changes (sensitivity=24%). In 40 (3.6%) observations, SP failed to detect a pupillary response whereas QP did. Moderate correlations with ICP were detected for maximum constriction velocity (MCV), dilation velocity (DV), and percentage change in pupillary diameter (%C). Discriminatory ability at an ICP threshold of >22 mmHg was moderate for MCV (AUC=0.631), DV (AUC=0.616), %C (AUC=0.602), and pupillary maximum size (AUC=0.625). CONCLUSION: QP is superior to SP at monitoring pupillary reactivity and changes to pupillary size. Although effect sizes were moderate to weak across assessed variables, our data indicates MCV and %C as the most sensitive variables for monitoring ICP. Further study is required to validate these findings and to establish normal range cut-offs for clinical use.

Pupillary Responses Reflect Dynamic Changes in Multiple Cognitive Factors During Associative Learning in Primates.

Associative learning involves complex interactions of multiple cognitive factors. While adult subjects can articulate these factors verbally, for model animals such as macaques, we rely on behavioral outputs. In our study, we used pupillary responses as an alternative measure to capture these underlying cognitive changes. We recorded the dynamic changes in the pupils of three male macaques when they learned the associations between visual stimuli and reward sizes under the classical Pavlovian experimental paradigm. We found that during the long-term learning process, the gradual changes in the pupillary response reflect the changes in the cognitive state of the animals. The pupillary response can be explained by a linear combination of components corresponding to multiple cognitive factors. These components reflect the impact of visual stimuli on the pupils, the prediction of reward values associated with the visual stimuli, and the macaques' understanding of the current experimental reward rules. The changing patterns of these factors during interday and intraday learning clearly demonstrate the enhancement of current reward-stimulus association and the weakening of previous reward-stimulus association. Our study shows that the dynamic response of pupils can serve as an objective indicator to characterize the psychological changes of animals, understand their learning process, and provide important tools for exploring animal behavior during the learning process.

Melanopsin retinal ganglion cell function in Alzheimer's vs. Parkinson's disease an exploratory meta-analysis and review of pupillometry protocols.

BACKGROUND: Neurodegenerative diseases share retinal abnormalities. Chromatic pupillometry allows in vivo assessment of photoreceptor functional integrity, including melanopsin-expressing retinal ganglion cells. This exploratory meta-analysis assesses retinal photoreceptor functionality in Alzheimer's vs. Parkinson's disease and conducts an in-depth review of applied pupillometric protocols. METHODS: Literature reviews on PubMed and Scopus from 1991 to August 2023 identified chromatic pupillometry studies on Alzheimer's disease (AD; n = 42 patients from 2 studies) and Parkinson's disease (PD; n = 66 from 3 studies). Additionally, a pre-AD study (n = 10) and an isolated REM Sleep Behavior Disorder study (iRBD; n = 10) were found, but their results were not included in the meta-analysis statistics. RESULTS: Melanopsin-mediated post-illumination pupil response to blue light was not significantly impaired in Alzheimer's (weighted mean difference = -1.54, 95% CI: 4.57 to 1.49, z = -1.00, p = 0.319) but was in Parkinson's (weighted mean difference = -9.14, 95% CI: 14.19 to -4.08, z = -3.54, p < 0.001). Other pupil light reflex metrics showed no significant differences compared to controls. Studies adhered to international standards of pupillometry with moderate to low bias. All studies used full-field stimulation. Alzheimer's studies used direct while Parkinson's studies used consensual measurement. Notably, studies did not control for circadian timing and Parkinson's patients were on dopaminergic treatment. CONCLUSION AND RELEVANCE: Results affirm chromatic pupillometry as a useful method to assess melanopsin-related retinal cell dysfunction in Parkinson's but not in Alzheimer's disease. While adhering to international standards, future studies may analyze the effects of local field stimulation, dopaminergic treatment, and longitudinal design to elucidate melanopsin dysfunction in Parkinson's disease.

Prospective study examining the impact of cerebral angiography on quantitative pupillometer values in the interventional radiology suite.

OBJECTIVES: The purpose of this pilot study was to obtain baseline quantitative pupillometry (QP) measurements before and after catheter-directed cerebral angiography (DCA) to explore the hypothesis that cerebral angiography is an independent predictor of change in pupillary light reflex (PLR) metrics. DESIGN: This was a prospective, observational pilot study of PLR assessments obtained using QP 30 min before and after DCA. All patients had QP measurements performed with the NPi-300 (Neuroptics) pupillometer. SETTING: Recruitment was done at a single-centre, tertiary-care academic hospital and comprehensive stroke centre in Dallas, Texas. PARTICIPANTS: Fifty participants were recruited undergoing elective or emergent angiography. Inclusion criteria were a physician-ordered interventional neuroradiological procedure, at least 18 years of age, no contraindications to PLR assessment with QP, and nursing transport to and from DCA. Patients with a history of eye surgery were excluded. MAIN OUTCOME MEASURES: Difference in PLR metric obtained from QP 30 min before and after DCA. RESULTS: Statistically significant difference was noted in the pre and post left eye readings for the minimum pupil size (a.k.a., pupil diameter on maximum constriction). The mean maximum constriction diameter prior to angiogram of 3.2 (1.1) mm was statistically larger than after angiogram (2.9 (1.0) mm; p<0.05); however, this was not considered clinically significant. Comparisons for all other PLR metrics pre and post angiogram demonstrated no significant difference. Using change in NPi pre and post angiogram (Δpre=0.05 (0.77) vs Δpost=0.08 (0.67); p=0.62), we calculated the effect size as 0.042. Hence, detecting a statistically significant difference in NPi, if a difference exists, would require a sample size of ~6000 patients. CONCLUSIONS: Our study provides supportive data that in an uncomplicated angiogram, even with intervention, there is no effect on the PLR.

The value of pupillary diameter in evaluating pain perception after awakening in patients undergoing general anesthesia during orthopedic surgery.

BACKGROUND: The pupillary response to tetanic electrical stimulation reflects the balance between nociceptive stimulation and analgesia. Although pupillary pain index (PPI) was utilized to predict postoperative pain, it depended on tetanic stimulation and was complex. We aim to describe the potential relationship between PD in the presence of surgical stimulation and pain levels after awakening. METHODS: According to the Verbal Rating Scale (VRS) score after extubation, the patients were divided into painless group (VRS = 0) and pain group (VRS ≥ 1). Pupillary diameter (PD) and pupillary light reflex velocity (PLRV) were compared between two groups when patients entered the operating room (T1), before incision (T2), 10 s after incision (T3), 30 s after incision (T4), 1 h after incision (T5), at the end of surgery (T6), shortly after extubation (T7), and when patients expressed pain clearly (T8). The magnitude of PD change (ΔPD) compared to the baseline value after anesthesia induction (T2) was calculated. The correlations between pupillary parameters and pain after awakening were calculated. RESULTS: Patients with VRS ≥ 1 had greater PD than painless patients at T3-7 (P = 0.04, 0.04, 0.003, <0.001, <0.001), and it was positively correlated with VRS score after awakening at T4-7 (r = 0.188, 0.217, 0.684, 0.721). The ability of T6ΔPD to predict VRS ≥ 1 was strong [threshold: 20.53%, area under the curve (AUC): 0.93, 95% confidence interval (CI): 0.89-0.97 ]. CONCLUSION: Our study indicates that PD is a useful index to direct the individualized analgesics used during operation, to better avoid the occurrence of pain during the postoperative emergence period. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000040908, registration date: 15/12/2020).

Changes in Listening Effort Through Pupil Response After Atresioplasty in Children With Congenital Aural Atresia.

OBJECTIVES: This study aimed to determine whether the improvement of hearing by surgical treatment alleviates cognitive demands through pupil response in patients with unilateral congenital aural atresia (CAA). DESIGN: A prospective study was performed on patients with unilateral CAA who were scheduled to undergo primary atresioplasty between November 2017 and May 2020. Pure-tone audiometry, auditory digit span test, Korean Speech Perception in Noise test, pupil measurement during speech tests, and questionnaires (Sound-Spatial-Qualities of Hearing Scale; subjective listening effort rating) were performed before and 6 months after surgery. RESULTS: Of 30 consecutive patients who initially enrolled, only 18 patients (12 males and 6 females) were included in the analysis. When the improvement of the air-bone gap and interaural difference of air conduction within 30 dB was defined as a successful hearing outcome, successful hearing improvement was achieved in 50% of the 18 patients. In pupil measurement, the success group had a significantly smaller mean pupil dilation response than the nonsuccess group at 0 and -3 dB signal to noise ratio (SNR) (all p < 0.01). In addition, significant differences were identified between the two groups for peak dilation and peak latency at all noise levels (all p < 0.01). When analyzing the change in pupil response before and after surgery, the difference in relative mean pupil dilation in the success group was significantly greater than that in the nonsuccess group at -3 dB SNR ( p = 0.02). In addition, the success group showed a significantly greater change in peak latency than the nonsuccess group at the -3 dB SNR ( p < 0.01). The difference in peak dilation tended to be greater in the success group than in the nonsuccess group, but the difference was not statistically significant. CONCLUSIONS: Patients with unilateral CAA who achieved surgically improved hearing had a smaller pupil dilation response than those who did not. These results suggest that successful hearing outcomes after surgery in patients with unilateral CAA may reduce the cognitive effort required to understand speech under difficult listening conditions.

Analysis of pupillary responses in pediatric patients with vitamin D deficiency.

PURPOSE: To evaluate the effects of vitamin D deficiency on pupillary responses in the pediatric population. METHODS: The study was conducted using data from the right eyes of 52 children with vitamin D deficiency and 52 healthy children. Measurements were taken under static and dynamic conditions with automatic pupillometry. Static measurements were performed at scotopic, mesopic, and photopic light intensities. The mean pupil dilation speed was calculated by observing the changes in pupil dilation over time according to dynamic measurements. Differences between patient and control groups were analyzed for the static and dynamic measurements and the mean pupil dilation speed. RESULTS: While the two groups were similar in terms of scotopic, mesopic, the first dynamic measurements, and the pupil dilation speed data (p > 0.05), a significant difference was found in the photopic conditions (p = 0.001). The mean pupil diameter of the patient group was 4.46 ± 0.928 mm and 3.95 ± 0.556 mm in the control group under photopic conditions. CONCLUSIONS: Pediatric patients with vitamin D deficiency have significantly larger pupil diameters in photopic conditions than healthy children. These results suggest that there is an autonomic dysfunction in vitamin D deficiency in the pediatric population, especially pointing to the parasympathetic system.

The pupillary dilation reflex to a nociceptive stimulus as a tool for analgesia management: A diagnostic study.

BACKGROUND: More than 70% of patients demonstrate pain after endotracheal aspiration. Tools are needed to objectify the need for analgesia in non-communicative critically ill patients. OBJECTIVE: The objective of this study was to identify the lowest intensity electrical stimulus for detecting pain before daily care interventions. METHODS: Study of diagnostic tests to assess pupillometry to detect pain through the pupillary dilation response to noxious stimuli versus the Behavioural Pain Scale. Patients older than 18 years, under analgosedation, subjected to invasive ventilation, baseline Behavioural Pain Scale of 3, and Richmond Agitation-Sedation Scale between -1 and -4 were studied. We assessed the Behavioural Pain Scale and the pupillary dilation response to 10, 20, 30, and 40 mA stimuli. We studied the diagnostic performance based on sensitivity and specificity, negative predictive value, positive predictive value, and accuracy of the selected points after the different stimulations. AlgiScan® Pupillometer measured the pupillary dilation response. The presence of pain was considered as a Behavioural Pain Scale score of ≥4. Significance was defined as p <0.05. RESULTS: Measurements were performed on 31 patients. In the 20 mA stimulus, we found an area under the curve of 0.85 (0.69-1.0). The cut-off point of pupillary dilation was 11.5%, with a sensitivity of 100% (34.2-100) and a specificity of 75.9% (57.9-87.8). This point had an accuracy of 77.4 (60.2-88.6) and a Youden's Index of 0.8. CONCLUSIONS: Pupillary variation measurement during a 20 mA stimulus could help assess the need for analgesia before potentially painful interventions. Further studies are needed to confirm this. REGISTRATION: Phase 1 of the project PUPIPAIN ClinicalTrials.gov Identifier: NCT04078113.