Diagnostic Value of Point-of-Care Ultrasound-Guided Assessment of Relative Afferent Pupillary Defect in Adult Ocular Trauma Patients Presenting to the Emergency Department: A Prospective Cohort Study.

OBJECTIVES: Early diagnosis of relative afferent pupillary defects (RAPDs) in patients with ocular trauma is crucial for timely management and improved outcomes. However, clinical examination can be challenging for patients with periorbital ecchymosis. This study aimed to compare the diagnostic accuracy of point-of-care ultrasound (POCUS) and clinical examination by emergency physicians for detecting RAPD in adult ocular trauma patients and to evaluate the proportion of RAPD in patients with ocular trauma who presented to the ED. METHODS: This prospective cohort study was conducted at an academic emergency department in South India. Adult ocular trauma patients were assessed for RAPD using clinical examinations by emergency physicians and POCUS. The diagnostic accuracies of both methods were compared, with the ophthalmologist's final diagnosis serving as the gold standard. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both techniques. RESULTS: A total of 376 patients (median age, 35 years) were included in this study. RAPD was identified in 14.63% of the patients. The sensitivity and specificity of POCUS in detecting RAPD were 92.73% and 99.38%, respectively, which were higher than those of clinical examination, with a sensitivity of 81.82% and specificity of 99.07%. The PPV and NPV of the clinical examination were 93.75% and 96.95%, respectively, whereas the PPV and NPV of POCUS were 96.23% and 98.76%, respectively. POCUS accurately diagnosed RAPD in patients with periorbital ecchymosis. CONCLUSION: POCUS-guided RAPD assessment proves to be a better diagnostic adjunct compared to clinical examination in patients with ocular trauma presenting to the emergency department.

Noninvasive Intracranial Pressure Monitoring: Are We There Yet?

There is an urgent unmet need for a reliable noninvasive tool to detect elevations in intracranial pressure (ICP) above guideline-recommended thresholds for treatment. Gold standard invasive ICP monitoring is unavailable in many settings, including resource-limited environments, and in situations such as liver failure in which coagulopathy increases the risk of invasive monitoring. Although a large number of noninvasive techniques have been evaluated, this article reviews the potential clinical role, if any, of the techniques that have undergone the most extensive evaluation and are already in clinical use. Elevations in ICP transmitted through the subarachnoid space result in distension of the optic nerve sheath. The optic nerve sheath diameter (ONSD) can be measured with ultrasound, and an ONSD threshold can be used to detect elevated ICP. Although many studies suggest this technique accurately detects elevated ICP, there is concern for risk of bias and variations in ONSD thresholds across studies that preclude routine use of this technique in clinical practice. Multiple transcranial Doppler techniques have been used to assess ICP, but the best studied are the pulsatility index and the Czosnyka method to estimate cerebral perfusion pressure and ICP. Although there is inconsistency in the literature, recent prospective studies, including an international multicenter study, suggest the estimated ICP technique has a high negative predictive value (> 95%) but a poor positive predictive value (≤ 30%). Quantitative pupillometry is a sensitive and objective method to assess pupillary size and reactivity. Proprietary indices have been developed to quantify the pupillary light response. Limited data suggest these quantitative measurements may be useful for the early detection of ICP elevation. No current noninvasive technology can replace invasive ICP monitoring. Where ICP monitoring is unavailable, multimodal noninvasive assessment may be useful. Further innovation and research are required to develop a reliable, continuous technique of noninvasive ICP assessment.

Factors associated with favourable neurological outcomes following cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A retrospective multi-centre cohort study.

Aim: To investigate the factors associated with favourable neurological outcomes in adult patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). Methods: This retrospective observational study used secondary analysis of the SAVE-J II multicentre registry data from 36 institutions in Japan. Between 2013 and 2018, 2157 patients with OHCA who underwent ECPR were enrolled in SAVE-J II. A total of 1823 patients met the study inclusion criteria. Adult patients (aged ≥ 18 years) with OHCA, who underwent ECPR before admission to the intensive care unit, were included in our secondary analysis. The primary outcome was a favourable neurological outcome at hospital discharge, defined as a Cerebral Performance Category score of 1 or 2. We used a multivariate logistic regression model to examine the association between factors measured at the incident scene or upon hospital arrival and favourable neurological outcomes. Results: Multivariable analysis revealed that shockable rhythm at the scene [odds ratio (OR); 2.11; 95% confidence interval (CI), 1.16-3.95] and upon hospital arrival (OR 2.59; 95% CI 1.60-4.30), bystander CPR (OR 1.63; 95% CI 1.03-1.88), body movement during resuscitation (OR 7.10; 95% CI 1.79-32.90), gasping (OR 4.33; 95% CI 2.57-7.28), pupillary reflex on arrival (OR 2.93; 95% CI 1.73-4.95), and male sex (OR 0.43; 95% CI 0.24-0.75) significantly correlated with neurological outcomes. Conclusions: Shockable rhythm, bystander CPR, body movement during resuscitation, gasping, pupillary reflex, and sex were associated with favourable neurological outcomes in patients with OHCA treated with ECPR.

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).

Prognostic Performance of Initial Clinical Examination in Predicting Good Neurological Outcome in Cardiac Arrest Patients Treated with Targeted Temperature Management.

Prognostication studies of cardiac arrest patients have mainly focused on poor neurological outcomes. However, an optimistic prognosis for good outcome could provide both justification to maintain and escalate treatment and evidence-based support to persuade family members or legal surrogates after cardiac arrest. The aim of the study was to evaluate the utility of clinical examinations performed after return of spontaneous circulation (ROSC) in predicting good neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). This retrospective study included OHCA patients treated with TTM from 2009 to 2021. Initial clinical examination findings related to the Glasgow coma scale (GCS) motor score, pupillary light reflex, corneal reflex (CR) and breathing above the set ventilator rate were assessed immediately after ROSC and before the initiation of TTM. The primary outcome was good neurological outcome at 6 months after cardiac arrest. Of 350 patients included in the analysis, 119 (34%) experienced a good neurological outcome at 6 months after cardiac arrest. Among the parameters of the initial clinical examinations, specificity was the highest for the GCS motor score, and sensitivity was the highest for breathing above the set ventilator rate. A GCS motor score of >2 had a sensitivity of 42.0% (95% confidence interval [CI] = 33.0-51.4) and a specificity of 96.5% (95% CI = 93.3-98.5). Breathing above the set ventilator rate had a sensitivity of 84.0% (95% CI = 76.2-90.1) and a specificity of 69.7% (95% CI = 63.3-75.6). As the number of positive responses increased, the proportion of patients with good outcomes increased. Consequently, 87.0% of patients for whom all four examinations were positive experienced good outcomes. As a result, the initial clinical examinations predicted good neurological outcomes with a sensitivity of 42.0-84.0% and a specificity of 69.7-96.5%. When more examinations with positive results are achieved, a good neurological outcome can be expected.

Neurological Pupillary Index (NPi) Measurement Using Pupillometry and Outcomes in Critically Ill Children.

Aim/objective Neurological Pupil Index (NPi), measured by automated pupillometry (AP), allows the objective assessment of pupillary light reflex (PLR). NPi ranges from 0 (non-reactive) to 5 (normal). In this study, we aimed to compare neurologic and functional outcomes in children admitted for neurologic injury with normal (≥3) versus abnormal (<3) NPi measured during their pediatric intensive care unit (PICU) stay. Materials and methods We conducted a retrospective chart review of children between one month and 18 years admitted to our PICU with a diagnosis of neurologic injury between January 2019 and June 2022. We collected demographic, clinical, pupillometer, and outcome data, including mortality, Pediatric Cerebral Performance Category (PCPC), Pediatric Overall Performance Category (POPC), and Functional Status Score (FSS) at admission, at discharge, and at the three to six-month follow-up. We defined abnormal pupil response as any NPi <3 at any point during the PICU stay. Using the student's t-test and chi-square test, we compared the short-term and long-term outcomes of children with abnormal NPi (<3) versus those with normal NPi (≥3). Results There were 49 children who met the inclusion criteria and who had pupillometry data available for analysis. The mean (SD) Glasgow Coma Scale (GCS) in the study cohort was 5.6 (4.3), and 61% had low (<3) NPi during ICU stay. Mortality was significantly higher among patients with an abnormal NPi as compared to those with normal NPi. Children with abnormal NPi exhibited significant worsening of neurologic and functional status (ΔPCPC, ΔPOPC, and ΔFSS) from admission to discharge (mean (SD): 3.55(1.5), 3.45(1.43), 16.75(7.85), p<0.001) as compared to those with normal NPi (mean (SD): 1.45(0.93), 1.73(0.90), 3.55(2.07), p>0.05). The significant difference in neurologic and functional status persisted at the three to six-month follow-up between the two groups - children with abnormal NPi (mean (SD): 2.0(1.41), 2.08(1.38), 6.92(6.83), p<0.01) and children with normal NPi (mean (SD): 0.82(1.01), 0.94(1.03), 1.53(1.70), p>0.05). Conclusion In our retrospective cohort study, children admitted to the PICU for a neuro injury and with abnormal NPi (< 3) have higher mortality, and worse short-term and long-term neurologic and functional outcomes as compared to those with normal NPi (≥ 3) measured during the PICU course. AP provides an objective assessment of PLR and has potential applications for neuro-prognostication. More research needs to be done to elucidate the prognostic value of NPi in pediatrics.

The Role of Pupillometry in the Assessment of Pain in Children Under General Anesthesia: A Prospective Single-Blinded Observational Study.

Background and objective The management and treatment of nociception remain one of the major challenges in anesthesiology, and hemodynamic variations may occur due to inadequate analgesia, which at times can be injurious. Pupillometry is a new noninvasive tool to assess nociception during anesthesia. The amount of pupillary reflex dilation (PRD) is directly proportional to the intensity of nociceptive stimuli and inversely proportional to the opioid dosage. This study aimed to assess the use of pupillometry as reflex pupillary dilatation in response to surgical stimulus in children under general anesthesia and to guide intraoperative opioid consumption. Materials and methods After obtaining approval from the institutional ethics committee and written consent from parents, children with an American Society of Anesthesiology (ASA) classification of I and II and aged 2-12 years who were undergoing surgery under general anesthesia were enrolled in this prospective randomized observational study. General anesthesia was standardized with propofol, sevoflurane, and O2 and N2O (50:50%), and fentanyl administration was guided by pupil diameter changes. The primary outcome was to measure pupillary dilatation in response to pain and fentanyl administration guided by it. Results A total of 72 patients were included in the study. The mean pupil diameter significantly increased after surgical stimulus from 1.37 ±0.87 to 2.40 ±1.95 mm (p<0.001). The heart rate (116.2 ±12.25 to 118.50 ±8.20 beats/minute, p=0.18) and systolic BP (114.60 ±17.73 to 118.50 ±12.25 mmHg, p=0.12) did not change significantly on stimulus. The mean fentanyl consumption was 2.4 ug/kg and the side effects were not remarkable. Conclusion Based on our findings, pain has a significant influence on the pupil dilatation reflex in anesthetized children, and opioid administration based on pupil diameter can be valuable in clinical settings. We recommend the use of pupillometry as a pain index in children undergoing surgery under general anesthesia, and it can be a beneficial tool for assessing intraoperative pain. Newer techniques and developments are required in this field.

Feasibility of the pupillary pain index as a guide for depth of analgesia during opioid-sparing anesthesia with continuous infusion of dexmedetomidine.

BACKGROUND: The pupillary dilation reflex (PDR) is an objective indicator of analgesic levels in anesthetized patients. Through measurement of the PDR during increasing tetanic stimulation (10-60 mA), it is possible to obtain the pupillary pain index (PPI), a score that assesses the level of analgesia. OBJECTIVES: The depth of analgesia during opioid-sparing anesthesia (OSA) with continuous infusion of dexmedetomidine in addition to general anesthesia was assessed. DESIGN: Observational prospective feasibility pilot study SETTING: This study was performed in the operating rooms of the Spedali Civili University-affiliated hospital of Brescia, Italy. PATIENTS: Forty-five adults who underwent elective open (5-cm incision) surgery under general anesthesia (78% inhalation anesthesia), from Feb. 18th to Aug. 1st, 2019, were enrolled. Exclusion criteria were as follows: implanted pacemaker or ICD, ophthalmological comorbidities, chronic opioid use, peripheral neuropathy, other adjuvant drugs, epidural analgesia, or locoregional block. MAIN OUTCOME MEASURES: The first aim was to verify the feasibility of applying a study protocol to evaluate the depth of analgesia during intraoperative dexmedetomidine administration using an instrumental pupillary evaluation. The secondary outcome was to evaluate appropriate analgesia, drug dosage, anesthesia depth, heart rate, blood pressure, transient side effects, postoperative nausea and vomiting (PONV), and pain numerical rating scale (NRS) score. RESULTS: Thirty out of 50 patients (60%) treated with dexmedetomidine during the study period were included in the DEX group (8 males, age 42 ± 13 years, BMI 45 ± 8), and 15 other patients were included in the N-DEX group (8 males, age 62 ± 13 years, BMI 26 ± 6). Patients who underwent bariatric, abdominal, or plastic surgery were enrolled. At least 3 pupillary evaluations were taken for each patient. PPI ≤ 3 was observed in 97% of patients in the DEX group and 53% in the N-DEX group. Additionally, the DEX group received less than half the remifentanil dose than the N-DEX group (0.13 ± 0.07 vs 0.3 ± 0.11 mcg kg-1 min-1). The average dose of dexmedetomidine administered was 0.17 ± 0.08 mcg kg-1 h-1. CONCLUSION: The feasibility of applying the protocol was verified. An OSA strategy involving dexmedetomidine may be associated with improved analgesic stability: a randomized controlled trial is necessary to verify this hypothesis. TRIAL REGISTRATION: Trial.gov registration number: NCT05785273.

Modern Sedation and Analgesia Strategies in Neurocritical Care.

PURPOSE OF REVIEW: Patients with acute neurologic injury require a specialized approach to critical care, particularly with regard to sedation and analgesia. This article reviews the most recent advances in methodology, pharmacology, and best practices of sedation and analgesia for the neurocritical care population. RECENT FINDINGS: In addition to established agents such as propofol and midazolam, dexmedetomidine and ketamine are two sedative agents that play an increasingly central role, as they have a favorable side effect profile on cerebral hemodynamics and rapid offset can facilitate repeated neurologic exams. Recent evidence suggests that dexmedetomidine is also an effective component when managing delirium. Combined analgo-sedation with low doses of short-acting opiates is a preferred sedation strategy to facilitate neurologic exams as well as patient-ventilator synchrony. Optimal care for patients in the neurocritical care population requires an adaptation of general ICU strategies that incorporates understanding of neurophysiology and the need for close neuromonitoring. Recent data continues to improve care tailored to this population.

Postoperative Nausea and Vomiting following Endoscopic Sinus Surgery under the Guidance of Adequacy of Anesthesia or Pupillometry with Intravenous Propofol/Remifentanil.

Postoperative nausea and vomiting (PONV) constitutes an adverse event after endoscopic sinus surgery (ESS) under general anesthesia (GA) with intravenous opioids, such as remifentanil (RMF). Monitoring the nociception/antinociception balance using the surgical pleth index (SPI) or pupillary dilatation reflex (PRD) helps guide intravenous RMF infusion. We aimed to investigate whether their employment could help reduce the incidence of PONV in patients undergoing ESS. The data of 30 patients from the GA group, 31 from the SPI group, and 28 from the PRD group were analyzed. The initial RMF infusion rate of 0.25 µg/kg body weight/minute was increased by 50% when the SPI, PRD, or Boezaart Bleeding Scale (BBS) were elevated by >15, >5%, or >2 points, respectively, until they normalized. PONV was present in 7/89 patients (7.9%): 2/31 patients (6.5%) of the SPI group, 1/30 patients (3.3%) of the GA group, and 4/28 patients (14.3%) of the PRD group. Neither PRD nor SPI guidance for RMF administration reduced the incidence of PONV compared to standard practice. Further studies are required in order to investigate the possibility of PONV eradication in patients undergoing ESS under GA when it is possibly combined with paracetamol/metamizole preventive analgesia, as well as those using antiemetic prophylaxis based on the Apfel Score and premedication with midazolam.

Evaluating the Reliability of Neurological Pupillary Index as a Prognostic Measurement of Neurological Function in Critical Care Patients.

Background Neurological pupil index (NPi) is a novel method of assessing pupillary size and reactivity using pupillometry to reduce human subjectivity. This paper aims to evaluate the use of NPi as a potential prognostic tool in a broad population of neurocritical care patients by observing the correlation between NPi, modified Rankin Scale (mRS), and Glasgow Coma Scale (GCS). Methods Our data was collected from 194 patients in the neurosurgical intensive care unit (ICU) at Arrowhead Regional Medical Center (ARMC), as determined by the power calculation. We utilized the Kolmogorov-Smirnova and Shapiro-Wilk normality tests with Lilliefors significance correction. Pearson product-moment correlation was performed between average final NPi and final GCS. Multi-variate linear regression and analysis of variance (ANOVA) were used to evaluate the association and predictive capabilities of NPi on GCS and discharge mRS. Finally, we evaluated whether age, ethnicity, sex, length of stay (LOS), or discharge location were significantly associated with NPi.  Results We observed a significant correlation between final GCS and NPi (r=0.609, p<0.001). Our regression analysis revealed that NPi significantly predicted GCS and mRS scores; however, no associations were found between age, ethnicity, sex, LOS, or discharge location. Limitations of our study include a single institutional study with a lack of disease subtyping and the inability to quantify the predictive ability of NPi. Conclusion The analysis revealed a strong correlation between final GCS and average final NPi. NPi was also able to significantly predict GCS and mRS scores. The correlation between NPi and established methods to determine neurological function, such as mRS and GCS, suggests that NPi can be a good prognostication tool for neurological diseases.

The association between perioperative pupillary parameters and postoperative acute pain: A pilot cross-sectional study.

OBJECTIVE: We aim to explore the capacity of perioperative pupillary variables to predict acute pain in the post-anesthesia care unit (PACU). METHODS: Patients scheduled to undergo thoracic or abdominal surgery under general anesthesia between April 2021 and June 2021 were enrolled. We measured the pupil diameter, pupillary light reflex (PLR), and pupillary reflex dilatation 5 min before anesthesia induction (T1), 5 min after intubation (T2), at the end of anesthesia (T3), immediately before extubation (T4), and 5 min after extubation (T5). We assessed the early postoperative pain intensity in the PACU using Numeric Rating Scales (NRS) at recovery, 5 min after recovery, and 10 min after recovery. Logistic regression models were used to evaluate the association between perioperative pupillary variables and postoperative pain intensity. RESULTS: Fifty-one patients were enrolled, 50 of whom were included in the final analysis. A total of 13 patients (26%) needed remedial analgesia in the PACU. Pupil parameters at T1, T2, T3, and T5 were not associated with NRS in the PACU. Multiple logistic regression models and receiver operating characteristic (ROC) curves indicated that only latency of PLR at T4 can predict postoperative acute pain. The ROC analysis showed that the cutoff value for latency of PLR at T4 was 0.29 s to discriminate between no pain and pain, and the area under the curve was 0.778 (95% CI 0.634-0.922, p = 0.002) with sensitivity 50.0% and specificity 91.7%. CONCLUSION: The latency of PLR immediately before extubation may be a useful predictor for postoperative acute pain in the PACU.

Corrigendum: Large-Area Photoreceptor Degeneration Model in Rabbits by Photocoagulation and Oxidative Stress in the Retina.

[This corrects the article DOI: 10.3389/fnins.2021.617175.].

Zfhx3 modulates retinal sensitivity and circadian responses to light.

Mutations in transcription factors often exhibit pleiotropic effects related to their complex expression patterns and multiple regulatory targets. One such mutation in the zinc finger homeobox 3 (ZFHX3) transcription factor, short circuit (Sci, Zfhx3Sci/+ ), is associated with significant circadian deficits in mice. However, given evidence of its retinal expression, we set out to establish the effects of the mutation on retinal function using molecular, cellular, behavioral and electrophysiological measures. Immunohistochemistry confirms the expression of ZFHX3 in multiple retinal cell types, including GABAergic amacrine cells and retinal ganglion cells including intrinsically photosensitive retinal ganglion cells (ipRGCs). Zfhx3Sci/+ mutants display reduced light responsiveness in locomotor activity and circadian entrainment, relatively normal electroretinogram and optomotor responses but exhibit an unexpected pupillary reflex phenotype with markedly increased sensitivity. Furthermore, multiple electrode array recordings of Zfhx3Sci/+ retina show an increased sensitivity of ipRGC light responses.

Selective glycinergic input from vGluT3 amacrine cells confers a suppressed-by-contrast trigger feature in a subtype of M1 ipRGCs in the mouse retina.

KEY POINTS: M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) are known to encode absolute light intensity (irradiance) for non-image-forming visual functions (subconscious vision), such as circadian photoentrainment and the pupillary light reflex. It remains unclear how M1 cells respond to relative light intensity (contrast) and patterned visual signals. The present study identified a special form of contrast sensitivity (suppressed-by-contrast) in M1 cells, suggesting a role of patterned visual signals in regulating non-image-forming vision and a potential role of M1 ipRGCs in encoding image-forming visual cues. The study also uncovered a synaptic mechanism and a retinal circuit mediated by vesicular glutamate transporter 3 (vGluT3) amacrine cells that underlie the suppressed-by-contrast response of M1 cells. M1 ipRGC subtypes (M1a and M1b) were revealed that are distinguishable based on synaptic connectivity with vGluT3 amacrine cells, receptive field properties, intrinsic photo sensitivity and membrane excitability, and morphological features, suggesting a division of visual tasks among discrete M1 subpopulations. ABSTRACT: The M1 type ipRGC (intrinsically photosensitive retinal ganglion cell) is known to encode ambient light signals for non-image-forming visual functions such as circadian photo-entrainment and the pupillary light reflex. Here, we report that a subpopulation of M1 cells (M1a) in the mouse retina possess the suppressed-by-contrast (sbc) trigger feature that is a receptive field property previously found only in ganglion cells mediating image-forming vision. Using optogenetics and the dual patch clamp technique, we found that vesicular glutamate transporter 3 (vGluT3) (vGluT3) amacrine cells make glycinergic, but not glutamatergic, synapses specifically onto M1a cells. The spatiotemporal and pharmacological properties of visually evoked responses of M1a cells closely matched the receptive field characteristics of vGluT3 cells, suggesting a major role of the vGluT3 amacrine cell input in shaping the sbc trigger feature of M1a cells. We found that the other subpopulation of M1 cells (M1b), which did not receive a direct vGluT3 cell input, lacked the sbc trigger feature, being distinctively different from M1a cells in intrinsic photo responses, membrane excitability, receptive-field characteristics and morphological features. Together, the results reveal a retinal circuit that uses the sbc trigger feature to regulate irradiance coding and potentially send image-forming cues to non-image-forming visual centres in the brain.

Large-Area Photoreceptor Degeneration Model in Rabbits by Photocoagulation and Oxidative Stress in the Retina.

Photocoagulation is used for the treatment of retinal ischemic disease. However, due to the invasive nature of photocoagulation and variety of melanin concentrations between individuals, it is challenging to avoid damaging the adjacent photoreceptors and inducing several side effects. Previous studies indicate the role of laser power, duration, and spot size on retinal lesions, but the effect of interspot distance of the laser pulses needs to be considered in panretinal photocoagulation. In this study, we examine different parameters of photocoagulation on lesions of the retina in rabbit, finding that the lesion level of the outer nuclear layer of the retina depended on the pulse duration and laser spot size, and decreasing interspot distance could completely abolish the photoreceptor layer. The degeneration of the photoreceptor by photocoagulation occurred in 24 h and was not restored afterward. We then conducted panretinal photocoagulation in rabbit and found that oxidative stress was decreased in the inner nuclear layer of the retina, and pupillary light reflex and ERG signals were impaired. Our study could provide a rabbit model to explore the mechanism of photoreceptor degeneration and therapies for the side effects after photocoagulation.

Abnormal neurological pupil index is associated with malignant cerebral edema after mechanical thrombectomy in large vessel occlusion patients.

BACKGROUND AND OBJECTIVES: Malignant cerebral edema (MCE) is a feared complication in patients suffering from large vessel occlusion. Variables associated with the development of MCE have not been clearly elucidated. Use of pupillometry and the neurological pupil index (NPi) as an objective measure in patients undergoing mechanical thrombectomy (MT) has not been explored. We aim to evaluate variables significantly associated with MCE in patients that undergo MT and hypothesize that abnormal NPi is associated with MCE in this population. METHODS: A retrospective analysis of patients with acute ischemic stroke who had undergone MT at our institution between 2017 and 2020 was performed. Baseline and outcome variables were collected, including NPi values from pupillometry readings of patients within 72 h after the MT. Patients were divided into two groups: MCE versus non-MCE group. A univariate and multivariate analysis was performed. RESULTS: Of 284 acute ischemic stroke patients, 64 (22.5%) developed MCE. Mean admission glucose (137 vs. 173; p < 0.0001), NIHSS on admission (17 vs. 24; p < 0.01), infarct core volume (27.9 vs. 17.9 mL; p = 0.0036), TICI score (p = 0.001), and number of passes (2.9 vs. 1.8; p < 0.0001) were significantly different between the groups. Pupillometry data was present for 64 patients (22.5%). Upon multivariate analysis, abnormal ipsilateral NPi (OR 21.80 95% CI 3.32-286.4; p = 0.007) and hemorrhagic conversion were independently associated with MCE. CONCLUSION: Abnormal NPi and hemorrhagic conversion are significantly associated with MCE in patients following MT. Further investigation is warranted to better define an association between NPi and patient outcomes in this patient population.

Melanopsin-mediated pupillary responses in bipolar disorder-a cross-sectional pupillometric investigation.

BACKGROUND: Visible light, predominantly in the blue range, affects mood and circadian rhythm partly by activation of the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). The light-induced responses of these ganglion cells can be evaluated by pupillometry. The study aimed to assess the blue light induced pupil constriction in patients with bipolar disorder (BD). METHODS: We investigated the pupillary responses to blue light by chromatic pupillometry in 31 patients with newly diagnosed bipolar disorder, 22 of their unaffected relatives and 35 healthy controls. Mood state was evaluated by interview-based ratings of depressive symptoms (Hamilton Depression Rating Scale) and (hypo-)manic symptoms (Young Mania Rating Scale). RESULTS: The ipRGC-mediated pupillary responses did not differ across the three groups, but subgroup analyses showed that patients in remission had reduced ipRGC-mediated responses compared with controls (9%, p = 0.04). Longer illness duration was associated with more pronounced ipRGC-responses (7% increase/10-year illness duration, p = 0.02). CONCLUSIONS: The ipRGC-mediated pupil response to blue light was reduced in euthymic patients compared with controls and increased with longer disease duration. Longitudinal studies are needed to corroborate these potential associations with illness state and/or progression.

Pupillometry in perioperative medicine: a narrative review.

PURPOSE: Pupillometry is a technique for objective quantification of nociception that takes into account the central processing of noxious stimuli and its sympathetic response. This narrative review provides an overview of the physiology of the pupil, the principles of pupillometry, and its potential application in the perioperative environment, especially in nociception monitoring and quantifying responses to opioids. SOURCE: Relevant articles, including reports of original investigation, review articles, and meta-analyses were identified from searches of PubMed and Google Scholar databases. Articles that described pupillary physiology and pupillometry, along with original research reports of the application of pupillometry in perioperative and critical care environment were used to synthesize a narrative review. PRINCIPAL FINDINGS: Pupillometry is emerging as an objective measure of nociception, especially in patients under general anesthesia, children, non-verbal patients, and critically ill patients who cannot effectively communicate ongoing pain. Portable automated pupillometers have made accurate quantification of pupillary reflexes, including light reflex and dilatation reflex, possible. This technique has been successfully studied in the perioperative setting for a number of applications, including quantification of nociception, response to analgesia, and assessing efficacy of regional blocks. Pupillary oscillations have shown promise in assessing central opioid effects. Pupillometers can also accurately quantify light reflexes during the neurologic evaluation of critically ill patients. CONCLUSIONS: Pupillometry is an easy to use non-invasive bedside technique to quantify nociception and monitor opioid effects. It has the potential to personalize pain management in perioperative and intensive care unit environments. Additional studies are needed to further understand the utility of pupillometry in this context.

RéSUMé: OBJECTIF: La pupillométrie est une technique de quantification objective de la nociception qui tient compte de l'intégration centrale des stimuli douloureux et de la réponse sympathique de la pupille. Cette revue narrative donne un aperçu de la physiologie de la pupille, des principes de la pupillométrie et de son application potentielle dans le contexte périopératoire, en particulier dans le monitorage de la nociception et la quantification des réponses aux opioïdes. SOURCE: Les articles pertinents, comprenant les comptes rendus de recherche originale, les articles de synthèse et les méta-analyses, ont été identifiés à partir de recherches dans les bases de données PubMed et Google Scholar. Les articles décrivant la physiologie de la pupille et la pupillométrie, ainsi que des comptes rendus de recherche originale portant sur l'application de la pupillométrie dans le contexte périopératoire et des soins intensifs, ont été utilisés pour synthétiser un compte rendu narratif. CONSTATATIONS PRINCIPALES: La pupillométrie est une modalité émergente en tant que mesure objective de la nociception, en particulier chez les patients sous anesthésie générale, les patients pédiatriques, les patients qui ne parlent pas et les patients en état critique qui ne peuvent pas communiquer de façon efficace leur douleur. Les pupillomètres automatisés portatifs ont rendu possible la quantification précise des réflexes pupillaires, y compris du réflexe photomoteur et du réflexe de dilatation. Cette technique a été étudiée avec succès dans le cadre périopératoire pour plusieurs applications, y compris la quantification de la nociception, la réponse à l'analgésie et l'évaluation de l'efficacité des blocs régionaux. Les oscillations pupillaires se sont montrées prometteuses pour l'évaluation des effets centraux des opioïdes. Les pupillomètres peuvent également quantifier avec précision les réflexes photomoteurs lors de l'évaluation neurologique des patients en état critique. CONCLUSION: La pupillométrie est une technique au chevet non invasive facile à utiliser pour quantifier la nociception et surveiller les effets des opioïdes. Cette technique pourrait permettre de personnaliser la prise en charge de la douleur dans les environnements périopératoires et de soins intensifs. D'autres études sont nécessaires pour mieux comprendre l'utilité de la pupillométrie dans ce contexte.