Amplitude Of Pupillary Light Reflex Research Articles

Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behavior Disorder.

BackgroundMelanopsin retinal ganglion cell (mRGC)‐mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α‐synucleinopathies.ObjectivesTo quantitatively compare PLR and mRGC‐mediated contribution to PLR in 16 iRBD patients and 16 healthy controls.MethodsiRBD and controls underwent extensive neuro‐ophthalmological evaluation and chromatic pupillometry. In iRBD, PLR metrics were correlated with clinical variables and with additional biomarkers including REM atonia index (RAI), DaTscan, and presence of phosphorylated‐α‐synuclein (p‐α‐syn) deposition in skin biopsy.ResultsWe documented higher baseline pupil diameter and decreased rod‐transient PLR amplitude in iRBD patients compared to controls. PLR rod‐contribution correlated with RAI. Moreover, only iRBD patients with evidence of p‐α‐syn deposition at skin biopsy showed reduced PLR amplitude compared to controls.ConclusionThe observed PLR abnormalities in iRBD might be considered as potential biomarkers for the risk stratification of phenoconversion of the disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Pupillary reflex and behavioral masking responses to light as functional measures of retinal degeneration in mice.

Pre-clinical testing of retinal pathology and treatment efficacy depends on reliable and valid measures of retinal function. The electroretinogram (ERG) and tests of visual acuity are the ideal standard, but can be unmeasurable while useful vision remains. Non-image-forming responses to light such as the pupillary light reflex (PLR) are attractive surrogates. However, it is not clear how accurately such responses reflect changes in visual capability in specific disease models. The purpose of this study was to test whether measures of non-visual responses to light correlate with previously determined visual function in two photoreceptor degenerations. The sensitivity of masking behavior (light induced changes in running wheel activity) and the PLR were measured in 3-month-old wild-type mice (WT) with intact inner retinal circuitry, Pde6b-rd1/rd1 mice (rd1) with early and rapid loss of rods and cones, and Prph2-Rd2/Rd2 mice (Rd2) with a slower progressive loss of rods and cones. In rd1 mice, negative masking had increased sensitivity, positive masking was absent, and the sensitivity of the PLR was severely reduced. In Rd2 mice, positive masking identified useful vision at higher light levels, but there was a limited decrease in the irradiance sensitivity of negative masking and the PLR, and the amplitude of change for both underestimated the reduction in irradiance sensitivity of image-forming vision. Together these data show that in a given disease, two responses to light can be affected in opposite ways, and that for a given response to light, the change in the response does not accurately represent the degree of pathology. However, the extent of the deficit in the PLR means that even a limited rescue of rod/cone function might be measured by increased PLR amplitude. In addition, positive masking has the potential to measure effective treatment in both models by restoring responses or shifting thresholds to lower irradiances.

Chromatic Pupillometry Findings in Alzheimer’s Disease

Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribution of rods, cones, and mRGCs to the PLR. In particular, post-illumination pupil response (PIPR) is the most reliable pupil metric of mRGC function. We have previously described, in post-mortem investigations of AD retinas, a loss of mRGCs, and in the remaining mRGCs, we demonstrated extensive morphological abnormalities. We noted dendrite varicosities, patchy distribution of melanopsin, and reduced dendrite arborization. In this study, we evaluated, with chromatic pupillometry, the PLR in a cohort of mild-moderate AD patients compared to controls. AD and controls also underwent an extensive ophthalmological evaluation. In our AD cohort, PIPR did not significantly differ from controls, even though we observed a higher variability in the AD group and 5/26 showed PIPR values outside the 2 SD from the control mean values. Moreover, we found a significant difference between AD and controls in terms of rod-mediated transient PLR amplitude. These results suggest that in the early stage of AD there are PLR abnormalities that may reflect a pathology affecting mRGC dendrites before involving the mRGC cell body. Further studies, including AD cases with more severe and longer disease duration, are needed to further explore this hypothesis.

Early outcome prediction with quantitative pupillary response parameters after out-of-hospital cardiac arrest: A multicenter prospective observational study​.

We aimed to determine the characteristics of quantitative pupillary response parameters other than amplitude of pupillary light reflex (PLR) early after return of spontaneous circulation (ROSC) and their implications for predicting neurological outcomes early after cardiac arrest (CA). Fifty adults resuscitated after non-traumatic out-of-hospital CA from four emergency hospitals were enrolled. Pupil diameters, PLR, constriction velocity (CV), maximum CV (MCV), dilation velocity (DV), latency of constriction, and Neurological Pupil index (NPi) were quantitatively measured at 0, 6, 12, 24, 48, and 72 h post-ROSC using an automated pupillometer. Change over time of each parameter was compared between favorable (Cerebral Performance Category [CPC] 1 or 2) and unfavorable neurological outcome (CPC 3-5) groups. Prognostic values of 90-day favorable outcome by these parameters and when combined with clinical predictors (witness status, bystander cardiopulmonary resuscitation, initial shockable rhythm, implementation of target temperature management) were tested. Thirteen patients achieved favorable outcome. CV, MCV, DV (P < 0.001), and NPi (P = 0.005) were consistently greater in the favorable group than in the unfavorable outcome group. Change over time was not statistically different between the groups in all parameters. CV, MCV, DV (ρ = 0.96 to 0.97, P < 0.001, respectively), and NPi (ρ = 0.65, P < 0.001) positively correlated with PLR. The prognostic value of 0-hour CV (area under the curve, AUC [95% confidence interval]: 0.92 [0.80-1.00]), DV (0.84 [0.68-0.99]), and NPi (0.88 [0.74-1.00]) was equivalent to that of PLR (0.84 [0.69-0.98]). Prognostic values improved to AUC of 0.95-0.96 when 0-hour PLR, CV, DV, or NPi was combined with clinical predictors. The 0-hour CV, MCV, and NPi showed equivalent prognostic values to PLR alone/in combination with clinical predictors. Using PLR among several quantitative pupillary response parameters for early neurological prognostication of post-CA patients is a simple and effective strategy.

In Response.

We thank Hrishi and colleagues1 for their comments on our recently published study.2 They give us the opportunity to clarify some points related to the use of quantitative pupillometry in critically ill patients. Two pupillary reflexes can be measured using portable infrared pupillometry: pupillary light reflex (PLR) in response to light stimulus and pupil reflex dilation (PRD) in response to noxious stimulus. By providing information on the brainstem integrity through the second and third cranial nerves, there is a growing interest in using quantitative PLR to estimate prognosis after cardiac arrest and traumatic brain injury. Contrary to the widely held opinion, PLR amplitude is relatively resistant to opioids, propofol, volatile agents, and neuromuscular blocking agents.3 We did not use PLR to assess nociception in our study. On the other way, PRD is an evoked reflex mediated through the ophthalmic nerve to detect painful reactions in nonverbal patients. It is largely admitted that opioids depress PRD in a dose-related fashion. Because γ-aminobutyric acid type A (GABAa) receptors might be involved in generating PRD,3 GABAa agonists such as propofol and midazolam could interfere with PRD measurements. Given that critically ill patients usually receive both opioids and sedatives, monitoring analgesia using PRD implies necessarily considering the level of sedation. In our study, all patients were kept sedated at Richmond Agitation Sedation Scale (RASS) −5 to −4, as shown in Table 2. The choice of noxious stimulus is critical to appropriately assess nociception in nonverbal patients. Laryngoscopy, tracheal intubation, and surgical incision are stimuli of very different uncontrolled noxious intensities. Tetanic stimulation is a more predictable source of painful stimulus than these procedures. Nursing, as used in the referenced poster presentation,4 is a multifaceted procedure that cannot be standardized to assess nociception. Nursing has been never used to validate any pain instrument. The pupillary pain index (PPI) is an elegant approach to estimate nociception while avoiding unnecessary pain and poor tolerance with the application of predefined intensity of electric stimulation. The maximal 13% dilation threshold from baseline was chosen to prevent systemic reactions such as tachycardia and arterial hypertension during tetanic stimulus. Accordingly, we found no changes in these systemic parameters or in Behavioral Pain Scale (BPS) scores during tetanic stimulation. Assessing nociception in brain-injured patients implies the integrity of PRD reflex pathway. Otherwise, PRD measurements can be used as an indicator of peripheral nerve block efficacy or to detect hemispheric brain lesion in a sedated patient. In the present study, there was no evidence of focal neurological lesion according to the computed tomography (CT) scan and PLR measurements. In the rare case of asymmetric PRD response, the highest PPI was taken for the analysis to detect patients with true nociception during endotracheal suctioning. Marc Vinclair, MDClotilde Schilte, MDGilles Francony, MDJean-Francois Payen, MD, PhDDepartment of Anesthesia and Critical CareGrenoble Alpes University HospitalGrenoble, France[email protected]

Automatic Pupillary Light Reflex Detection in Eyewear Computing

There are many benefits to facilitating “always-on” pupillary light reflex (PLR)-aware pupil size measurement in eyewear, including improving the reliability of pupil-based cognitive and affective load monitoring and enabling PLR-based diagnosis of cognitive and eye-related diseases which have neurological symptoms manifested in the form of aberrant PLR responses. However, the detection of PLR responses for application in eyewear devices for everyday usage, beyond PLR measurement in confined clinical sessions, has not been investigated. To this end, a means of characterizing PLRs in less controlled environmental settings is investigated and subsequently a method of PLR detection is developed and evaluated. A low-cost head-mounted Web camera was used to record near-field eye video sequences which were processed with the self-tuning threshold algorithm for pupil diameter estimation and blink detection. PLR was induced by luminance change of a monitor and brightness change of the displayed image on a monitor. A transient model-based PLR detection algorithm which utilizes the general correlation of PLR amplitude and velocity was developed and evaluated on the data sets in terms of false alarm and false rejection rates. The findings from this research suggest that the PLR can be detected reliably using low-cost wearable pupil-measurement systems without using a separate sensor for detecting the luminance conditions. The correlation between pupil diameter amplitude and maximum velocity of PLR was shown to be sufficiently consistent for PLR detection.

Quantitative pupillometry and transcranial Doppler measurements in patients treated with hypothermia after cardiac arrest

BackgroundPredicting outcome after cardiac arrest (CA) is particularly difficult when therapeutic hypothermia (TH) is used. We investigated the performance of quantitative pupillometry and transcranial Doppler (TCD) in this context. MethodsThis prospective observational study included 82 post-CA patients. Quantitative assessment of pupillary light reflex (PLR) and TCD measurements of the two middle cerebral arteries were performed at admission (day 1) and after 24h (day 2) during TH (33–35°C) and sedation. Neurological outcome was assessed at 3 months using cerebral performance category (CPC) scores; patients were classified as having good (CPC 1–2) or poor (CPC 3–5) outcome. Prognostic performance was analyzed using area under the receiver operating characteristic curve (AUC-ROC). ResultsPatients with good outcome (n=27) had higher PLR amplitude than patients with poor outcome (n=55) both at day 1, 13% (10–18) (median, 25th–75th percentile) vs. 8% (2–11) (P<0.001), and at day 2, 17% (13–20) vs. 8% (5–13) (P<0.001), respectively. The AUC-ROC curves at days 1 and 2 were 0.76 (95% confidence interval [CI] 0.65–0.86) and 0.82 (95% CI 0.73–0.92), respectively. The best cut-off values of PLR amplitude to predict a 3-month poor outcome were <9% and <11%, respectively. A PLR amplitude of <7% at day 2 predicted a 3-month poor outcome with a specificity of 100% (95% CI 86–100) and a sensitivity of 42% (95% CI 28–58). No differences in TCD measurements were found between the two patient groups. ConclusionPLR measurements might be informative in the prediction of outcome of post-CA patients even under sedation and hypothermia.

Pain assessment in the postanaesthesia care unit using pupillometry

Patients assess their own pain with a numerical rating scale (NRS). In the postanaesthesia care unit (PACU), NRS helps to determine and monitor analgesic administration, but is useless in patients who are unable to communicate. In non-PACU patients, acute pain increases pupillary diameter and pupillary light reflex amplitude (PLRA), the difference between pupillary diameter before and after light stimulation. To study the association between postoperative pain (NRS) and pupillary diameter or PLRA in PACU patients after routine anaesthetic care. Cross-sectional cohort study. Bichat-Claude Bernard Hospital, Paris. One hundred and forty-five patients undergoing planned surgery under general anaesthesia. NRS, pupillary diameter and PLRA were measured on arrival in the PACU. When NRS was more than 4, intravenous morphine titration was started and a second measurement performed. Association between NRS and pupillary diameter or PLRA was assessed with Pearson correlation coefficient (r) as was association between changes in these variables after morphine titration. Mean NRS was 4.7, and was more than 4 in 79 patients (55%). No statistically significant association was observed between NRS and pupillary diameter (r = 0.10, P = 0.54) or PLRA (r = 0.03, P = 0.72). Twenty-seven patients (19%) received morphine titration with significant decreases in NRS, pupillary diameter and PLRA afterwards. No association was observed between NRS changes and pupillary diameter or PLRA changes. Acute postoperative pain is not associated with pupillary diameter or PLRA. Further research is required to develop tools to assess pain in the PACU.

Assessment of Pain During Labor with Pupillometry

Pain intensity is usually self-rated by patients with a numeric rating scale (NRS) but this scale cannot be used for noncommunicating patients. In anesthetized patients, experimental noxious stimulus increases pupillary diameter (PD) and pupillary light reflex amplitude (PLRA), the difference between PD before and after light stimulation. Labor pain is an intense acute nonexperimental stimulus, effectively relieved by epidural analgesia. In this prospective observational study, we therefore describe the effects of labor pain and pain relief with epidural analgesia on PD and PLRA, determine their association with pain intensity and determine the ability of a single measurement of PD or PLRA to assess pain. In the first stage, pain (11-point NRS), PD, and PLRA were measured in 4 conditions in 26 laboring women: before and after epidural analgesia and in the presence and absence of a uterine contraction. Pupillometry values among the 4 conditions were compared, and the strength of the association between absolute values of pain and PD or PLRA and between pain and changes in PD or PLRA brought about by uterine contraction was assessed with r(2). In the second stage, 1 measurement was performed in 104 laboring women. The strength of the association between pain and PD or PLRA was assessed with r(2). The ability of PD or PLRA to discriminate pain (NRS > 4) was also assessed. In the first stage, a statistically significant increase in pain, PD, and PLRA was observed during a contraction, and this change was abolished after epidural analgesia. The r(2) for the association between pain and changes in PD (r(2) = 0.25 [95% confidence interval, 0.07-0.46] or PLRA (r(2) = 0.34 [0.14-0.56]) brought about by a uterine contraction was higher than the r(2) for the association between pain and absolute values of PD (r(2) = 0.14 [0.04-0.28]) or PLRA (r(2) = 0.22 [0.10-0.37]) suggesting a stronger association for changes than for absolute values. In the second stage, r(2) was 0.23 [0.10-0.38] for PD and 0.26 [0.11-0.40] for PLRA and the area under the receiver operating characteristics curve was 0.82 [0.73-0.91] and 0.80 [0.71-0.89], respectively. Changes in PD and PLRA brought about by a uterine contraction may be used as a tool to assess analgesia in noncommunicating patients.

Trait anxiety affects the pupillary light reflex in college students

This study was designed to examine whether anxious personality, i.e. trait anxiety, influences the autonomic nervous functions in humans without manipulation of experimental stressors. The degrees of state and trait anxiety, blood pressure, heart rate, pupillary light reflex (PLR), and body temperature were measured at the same hour on four different days in 14 healthy college students. A multiple regression analysis showed that trait anxiety predominantly influenced state anxiety and the PLR parameters. A single regression analysis showed that trait anxiety positively correlated to the initial pupillary diameter and the constricted diameter of PLR and negatively to the amplitude of PLR. It was concluded that trait anxiety predicts state anxiety and a smaller amplitude of PLR in humans at rest.