Pupillary Light Reflex Research Articles

Quantum Mechanics/Molecular mechanics calculations predict A1, not A2, is present in melanopsin (Opn4m) of red-eared slider turtles (Trachemys scripta elegans)

Melanopsin is a photopigment that plays a role in non-visual, light-driven, cellular processes such as modulation of circadian rhythms, retinal vascular development, and the pupillary light reflex (PLR). In this study, computational methods were used to understand which chromophore is harbored by melanopsin in red-eared slider turtles (Trachemys scripta elegans). In mammals, the vitamin A derivative 11-cis-retinal (A1) is the chromophore, which provides functionality for melanopsin. However, in red-eared slider turtles, a member of the reptilian class, the identity of the chromophore remains unclear. Red-eared slider turtles, similar to other freshwater vertebrates, possess visual pigments that harbor a different vitamin A derivative, 11-cis-3,4-didehydroretinal (A2), making their pigments more sensitive to red-light than blue-light, therefore, suggesting the chromophore to be the A2 derivative instead of the A1. To help resolve the chromophore identity, in this work, computational homology models of melanopsin in red-eared slider turtles were first constructed. Next, quantum mechanics/molecular mechanics (QM/MM) calculations were carried out to compare how A1 and A2 derivatives bind to melanopsin. Time dependent density functional theory (TDDFT) calculations were then used to determine the excitation energy of the pigments. Lastly, calculated excitation energies were compared to experimental spectral sensitivity data from responses by the irises of red-eared sliders. Contrary to what was expected, our results suggest that melanopsin in red-eared slider turtles is more likely to harbor the A1 chromophore than the A2. Furthermore, a glutamine (Q622.56) and tyrosine (Y853.28) residue in the chromophore binding pocket are shown to play a role in the spectral tuning of the chromophore.

0648 Retinal responsivity is associated with light and season-related cognitions in older adults with seasonal depression

Abstract Introduction Maladaptive cognitions associated with lower light availability in winter and the changing of the seasons are elevated in winter depression and are treatment targets in psychotherapy. Mechanisms underlying the development of SAD-specific cognitions may be related to seasonal variation in melanopsin-driven retinal responsivity to light. Prior work has shown reduced retinal responsivity to light during the winter in seasonal depression. We hypothesized maladaptive seasonal cognitions would be associated with reduced retinal responses to light. We also tested whether age moderated this relationship, hypothesizing that this learned association may only appear in older individuals who have experienced a greater number of seasonal depressive episodes. Methods Participants ages 19-65 (M=36.13, SD=12.81) with seasonal depression (n=37) and non-depressed controls (n=32) completed assessments in winter months (21st December to 21st March). Maladaptive seasonal cognitions were measured by the Seasonal Beliefs Questionnaire (SBQ). Melanopsin-driven retinal responsivity was assessed using the post illumination pupil response (PIPR). Net PIPR as a percent of baseline was averaged across the 10-30 seconds post-stimulus for use in analyses. Using multiple regression, we tested (1) if seasonal beliefs predict the PIPR and (2) if an interaction between seasonal beliefs and age predicts the PIPR, controlling for gender, the pupillary light reflex (PLR), and circadian time of testing from Dim Light Melatonin Onset. Results Seasonal beliefs were not associated with the PIPR (b= -0.86e-5, SE=0.27e-3, p=0.98). There was a significant interaction between seasonal beliefs and age on the PIPR (b= -0.56e-4, SE=0.23e-4, p=0.02), in which greater seasonal beliefs were associated with reduced PIPR in older individuals but not younger individuals. The Johnson-Neyman interval indicated that in participants above age 49, greater seasonal beliefs were significantly associated with lower retinal responsivity (PIPR; p< 0.05). Conclusion Greater seasonal beliefs were associated with reduced retinal responsivity, but only in older adults with seasonal depression. It is possible that reduced retinal responsivity creates learned maladaptive schemas regarding seasonal changes that are reinforced with annually recurring winter depressive episodes. However, longitudinal data focused on changes in seasonal beliefs resulting from reduced retinal sensitivity is necessary to test whether retinal responsivity is a mechanism in the formation of these seasonal-specific cognitions. Support (if any)

0628 Retinal responsivity increases after light therapy and is associated with improved depression: Preliminary findings from a RCT

Abstract Introduction Light therapy is a first line treatment for seasonal depression but is not effective for everyone. Understanding mechanisms of light therapy may help predict who will successfully respond to treatment. Individual differences in the retina’s responsivity to light may underlie differences in treatment response given prior work linking reduced retinal responsivity in seasonal depression. This study tested if retinal responsivity changed across a light therapy intervention and whether changes in retinal responsivity were associated with improved depression. Methods Participants diagnosed with Major Depressive Disorder, With Seasonal Pattern were randomized to 6 weeks of light therapy or cognitive behavioral therapy for seasonal affective disorder (CBT-SAD). Participants in the light therapy group (N=52) were on average 41.9 years (SD=14.8) and predominantly women (72%). Retinal responsivity was assessed using the post-illumination pupil response (PIPR), measured mid-day in winter pre- and post-treatment. The net PIPR (red minus blue) was calculated as a percent of baseline 10-30 seconds post stimulus. Depression severity was measured using the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder version (SIGH-SAD). Using multilevel models, we tested 1) if the PIPR changed from pre- to post-treatment and 2) if changes in the PIPR predicted improvements in depression. All analyses included a random intercept of participant ID and controlled for age, gender, time of testing, and the pupillary light reflex (PLR). Results There was a significant main effect of time on the PIPR, such that PIPR increased from pre- to post-light treatment (b=0.29; SE=0.13; p=0.03). There was a significant negative association between changes in PIPR and changes in depression, such that increases in PIPR were associated with decreases in depression symptom severity (b= -0.18; SE=0.06; p=0.01). Conclusion Retinal responsivity increased across a light therapy intervention and increases in retinal responsivity were associated with improved depression. It is possible an upregulation in retinal responsivity drives antidepressant effects of light therapy, either through direct or circadian pathways. However, changes in retinal responsivity measured throughout treatment are required to discern whether these changes are mechanistic. Support (if any)

0653 The effects of light exposure on retinal responsivity in seasonal affective disorder

Abstract Introduction Seasonal affective disorder (SAD) is characterized as patterned depressed mood that emerges during the fall/winter and enters remission during the spring/summer. Retinal responsivity is lower in SAD in the winter and may contribute to the seasonal pattern of mood disruption (Roecklein et al., 2021). Light exposure in the month prior has been shown to influence retinal responsivity (Kawasaki et al., 2018). No work to date has investigated how more proximal prior light history may influence retinal responsivity differently in individuals with SAD versus controls. This study sought to examine group differences in how environmental blue light exposure impacts retinal responsivity in the 2 hours prior. Methods Participants included 19 never depressed controls (Mean Age = 33, SD = 11), and 17 individuals diagnosed with SAD (Mean Age = 36, SD = 10). SAD episode criteria were assessed using the SCID-5 and SIGH-SAD. Retinal responsivity was measured using the Post-Illumination Pupil Response (PIPR) in the winter months. The PIPR was calculated as percent of baseline difference between the blue and red stimuli from 10-30 secs. Light exposure was measured using the Phillips Actiwatch blue light levels in photon flux in 30-second epochs for 2 hours before the PIPR. Means were calculated and cube transformed to account for right skew. Covariates included circadian time of PIPR testing, calculated from DLMO, and Pupil Light Reflex as a measure of retinal irradiance. Results Multiple regressions were performed for the SAD and control groups, separately. Results indicated that the mean blue-light exposure 2-hours before the PIPR did not significantly predict PIPR in either group (Control group: b = -13e-7, p = 0.31/ SAD group: b = -12e-7, p = 0.13). Conclusion This is the first study to find that light exposure within the prior 2 hours does not influence retinal responsivity in SAD or control participants. Future studies should evaluate different light exposure parameters, such as a longer duration of light exposure before the PIPR, variation in light exposure across different timeframes, and circadian time of light exposure. Support (if any)

Development and Validation of a Prediction Model for 30-Day Mortality and Functional Outcome in Patients with Primary Brainstem Hemorrhage

Introduction: Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is associated with poor prognosis. We aimed to develop a prediction model for predicting 30-day mortality and functional outcome in patients with PBSH. Methods: We reviewed records of 642 consecutive patients with first-time PBSH from three hospitals between 2016 and 2021. Multivariate logistic regression was used to establish a nomogram in a training cohort. Cutoff points of the variables were determined by receiver operating characteristic curve analysis, and certain points were assigned to these predictors to produce the PBSH score. The nomogram and PBSH score were compared with other scoring systems for PBSH. Results: Five independent predictors, comprised of temperature, pupillary light reflex, platelet-to-lymphocyte ratio, Glasgow Coma Scale (GCS) score on admission, and hematoma volume, were incorporated to construct the nomogram. The PBSH score consisted of 4 independent factors with individual points assigned as follows: temperature, ≥38°C (=1 point), <38°C (=0 points); pupillary light reflex, absence (=1 point), presence (=0 points); GCS score 3–4 (=2 points), 5–11 (=1 point), and 12–15 (=0 points); PBSH volume >10 mL (=2 points), 5–10 mL (=1 point), and <5 mL (=0 points). Results showed that the nomogram was discriminative in predicting both 30-day mortality (area under the ROC curve [AUC] of 0.924 in the training cohort, and 0.931 in the validation cohort) and 30-day functional outcome (AUC of 0.887). The PBSH score was discriminative in predicting both 30-day mortality (AUC of 0.923 in the training cohort and 0.923 in the validation cohort) and 30-day functional outcome (AUC of 0.887). The prediction performances of the nomogram and the PBSH score were superior to the intracranial hemorrhage (ICH) score, primary pontine hemorrhage (PPH) score, and new PPH score. Conclusions: We developed and validated two prediction models for 30-day mortality and functional outcome in patients with PBSH. The nomogram and PBSH score could predict 30-day mortality and functional outcome in PBSH patients.

Reproducibility of the pupillary light reflex over short intervals in psychiatric patients and community volunteers.

The pupillary light reflex (PLR) is a method for measuring dynamic responses within the autonomic nervous system, and would have potential value as a point-of-care test in a psychiatry clinic if reproducible results could be obtained in a short period of time. We collected PLR from adult community volunteers and depressed outpatients with the purpose of demonstrating (1) that valid data could be obtained >90% of the time from both the community volunteers and the patients, and (2) that reproducible results could be obtained with repeated measurement over short periods of time. Valid data were captured for 90.3% of 76 participants, allowing for two attempts of the PLR per participant. Success rates were similar for depressed patients and community volunteers. Eighteen of these 76 participants provided repeated paired measurements after 5 and 10 min of dark adaptation, producing high correlations for maximum constriction velocity (MCV) between assay 1 and 2 (Pearson's r = 0.71, p < 0.001), but there was a significant 8% increase in velocity for MCV between assay 1 and 2 (∆ = 0.34 ± 0.59 mm/s, p < 0.05). In contrast, PLR measurements were stable when tested in a separate cohort of 21 additional participants at 10 and 15 min of dark adaptation with an MCV Pearson's correlation of r = 0.84, p < 0.001, with a nonsignificant 1% difference between the two timepoints. These findings indicate an acceptable rate of collecting valid and reproducible PLR data when contrasting twomeasurements of PLR after 10 or 15 min of dark adaptation in depressed and suicidal patients.

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

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

Neurophysiological Effects of Repeated Soccer Heading in Youth.

Repeated head loading in sports is associated with negative long-term brain health, and there is growing evidence of short-term neurophysiological changes after repeated soccer heading. The objective of this study was to quantify the head kinematics and effects of repetitive soccer headers in adolescents using an instrumented mouthguard. Adolescent soccer players aged 13-18 years were randomly assigned to a kicking control, frontal heading, or oblique heading group. Participants completed neurophysiological assessments at three-time points: immediately prior to, immediately after, and approximately 24 h after completing 10 headers or kicks. The suite of assessments included the Post-Concussion Symptom Inventory, visio-vestibular exam, King-Devick test, modified Clinical Test of Sensory Interaction and Balance with force plate sway measurement, pupillary light reflex, and visual evoked potential. Data were collected for 19 participants (17 male). Frontal headers resulted in significantly higher peak resultant linear acceleration (17.4 ± 0.5 g) compared to oblique headers (12.1 ± 0.4 g, p < 0.001), and oblique headers resulted in significantly higher peak resultant angular acceleration (frontal: 1147 ± 45 rad/s2, oblique: 1410 ± 65 rad/s2, p < 0.001). There were no neurophysiological deficits for either heading group or significant differences from controls at either post-heading timepoint, and therefore, a bout of repeated headers did not result in changes in the neurophysiological measures evaluated in this study. The current study provided data regarding the direction of headers with the goal to reduce the risk of repetitive head loading for adolescent athletes.

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.

A case report of long-delayed diagnosis of pseudorabies virus encephalitis with endophthalmitis: lessons from metagenomic next generation sequencing

BackgroundPseudorabies virus (PRV) was thought to only infect animals. Recent studies have shown that it can also infect human.Case presentationWe report a case of pseudorabies virus encephalitis and endophthalmitis, diagnosed 89 days after onset, confirmed with intraocular fluid metagenomic next generation sequencing (mNGS) after the result of two cerebrospinal fluid (CSF) mNGS tests were negative. Although treatment with intravenous acyclovir, foscarnet sodium, and methylprednisolone improved the symptoms of encephalitis, significant diagnostic delay resulted in permanent visual loss.ConclusionsThis case suggests that pseudorabies virus (PRV) DNA in the intraocular fluid may have a higher positivity than that in the CSF. PRV may persist in the intraocular fluid for an extended period and may thus require extended antiviral therapy. Patients with severe encephalitis and PRV should be examined with the focus on pupil reactivity and light reflex. A fundus examination should be performed in patients with a central nervous system infection, specifically, those in a comatose state, to help reduce eye disability.

Assessment of increased intracranial pressure in patients with brain injury

Background: Monitoring and managing elevated intracranial pressure (ICP) is one of the core topics in neurocritical care. Although invasive methods are regarded as standard means, the recent development of non-invasive monitoring devices help clinicians handle ICP issues without additional risks of device-related complications.Current Concepts: According to the Monro–Kellie hypothesis, any brain injury that can cause a mass effect will lead to ICP elevation. Therefore, an ICP surge beyond the capacity of a compensatory reserve will decrease cerebral blood flow and may end up causing secondary brain damage. Indications for invasive ICP monitoring may vary according to the underlying conditions or the severity of brain damage. Regardless, ICP monitoring is considered when there is a risk of ICP elevation. In addition to pressure monitoring, external ventricular drainage catheters are used therapeutically to drain cerebrospinal fluid to reduce ICP. Several ICP monitoring probes are available based on pressure measurement types. Recently, non-invasive ICP monitoring methods have been developed and are increasingly used in patients with severe brain injuries. Pulsatility index from transcranial Doppler ultrasonography, quantitative pupillary light reflex from an automated pupillometer, and optic nerve sheath diameter using ultrasonography are commonly used surrogates for ICP surges in neurointensive care units.Discussion and Conclusion: ICP monitoring is essential for managing patients with severe brain injuries. Understanding the differences among the ICP monitors and determining the appropriate methods for ICP monitoring is necessary for optimizing patients’ care in the neurocritical care unit.

Use of Prognostication Instruments in Prognostication Procedures of Postanoxic Coma Patients over Time: A Retrospective Study.

Many survivors of cardiovascular arrest remain in a postanoxic coma. The neurologist's task is to provide the most accurate assessment of the patient's neurologic prognosis through a multimodal approach of clinical and technical tests. The aim of this study is to analyze differences and developments in the concept of neurological prognosis assessment and in-hospital outcome of patients over a five year-period. This retrospective observational study included 227 patients with postanoxic coma treated in the medical intensive care unit of the University Hospital, Mannheim from January 2016 to May 2021. We retrospectively analyzed patient characteristics, post-cardiac arrest care, and the use of clinical and technical tests for neurological prognosis assessment and patient outcome. Over the observation period, 215 patients received a completed neurological prognosis assessment. Regarding the multimodal prognostic assessment, patients with poor prognosis (54%) received significantly fewer diagnostic modalities than patients with very likely poor (20.5%), indeterminate (24.2%), or good prognosis (1.4%; p = 0.001). The update of the DGN guidelines in 2017 had no effect on the number of performed prognostic parameters per patient. The finding of bilaterally absent pupillary light reflexes or severe anoxic injury on CT contributed most to a poor prognosis category (OR 8.38, 95%CI 4.01-7.51 and 12.93, 95%CI 5.55-30.13, respectively), whereas a malignant EEG pattern and NSE > 90 µg/L at 72 h resulted in the lowest OR (5.11, 95%CI 2.32-11.25, and 5.89, 95%CI 3.14-11.06, respectively) for a poor prognosis category. Assessment of baseline NSE significantly increased over the years (OR 1.76, 95%CI 1.4-2.22, p < 0.001), and assessment of follow-up NSE at 72 h trended to increase (OR 1.19, 95%CI 0.99-1.43, p = 0.06). In-hospital mortality was high (82.8%), remained unchanged over the observation period, and corresponded to the number of patients in whom life-sustaining measures were discontinued. Among comatose survivors of cardiac arrest, the prognosis remains poor. Prognostication of a poor outcome led nearly exclusively to withdrawal of care. Prognostic modalities varied considerably with regard to their contribution to a poor prognosis category. Increasing enforcement of a standardized prognosis assessment and standardized evaluation of diagnostic modalities are needed to avoid false-positive prognostication of poor outcomes.

Combat Sports as a Model for Measuring the Effects of Repeated Head Impacts on Autonomic Brain Function: A Brief Report of Pilot Data.

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

Guillain-Barré Syndrome Mimicking Brainstem Death Following Traumatic Intracerebral Hemorrhage (P12-7.006)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 73-year-old man attended the ED following an assault where he sustained multiple traumatic blows to the head. He was alert, complained of headache but provided a detailed account. There were facial injuries but no clinical signs of cranial or skull base fractures. There was injury to the right eye, in which he had pre-existing visual impairment from previous injury. Vision was normal in the left. Right pupillary light reflex was absent but left was normal. The remainder of the neurological examination was unremarkable. CT-Head identified a small traumatic subarachnoid hemorrhage over the left cerebral convexity and a small contusion in the left temporo-parietal region. Vitreous hemorrhage was evident in the right eye. Clinically stable, follow-up CT on day 3 showed small intra-cerebral haemorrhage within the contusion, with minimal mass effect. However, on day 8, his GCS dropped and he was admitted to the ITU for airway management. Both pupils were non-responsive to light. Expansion of haemorrhage was suspected, however repeat CT was stable. EEG showed slowing over the left hemisphere without epileptiform activity. MRI excluded alternative causes for his neurological status such as brainstem ischaemia. With no clinical improvement, formal brainstem death testing was initiated. No potential confounders were recognised. The pupillary, corneal, oculocephalic, cough and gag reflexes were absent. Unexpectedly, deep tendon reflexes were absent in all limbs. A peripheral nerve stimulator using a train-of-four test protocol found no response. Post-traumatic Guillain-Barré syndrome (GBS) was suspected. Intravenous immunoglobulin was commenced. Nerve conduction studies found absent motor and sensory responses in all limbs. EMG showed fibrillation potentials and sharp waves. These findings were consistent with acute motor-sensory axonal neuropathy (AMSAN) variant of GBS. Serum Anti-GM1 antibodies were identified. After multiple rounds of plasmapheresis the patient was weaned from the ventilator. Nevertheless, severe neurological disability remained. <h3>Conclusions:</h3> NA <b>Disclosure:</b> Dr. Finegan has nothing to disclose. Dr. Ryan has nothing to disclose. Michael J. Hennessy has nothing to disclose. Kevin Murphy has nothing to disclose. Dr. Crowley has nothing to disclose. Dr. Elamin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche .

Quantitative Pupillometry is Not Impacted By IV Opioid or Sedative Bolus Dosing (P11-7.005)

<h3>Objective:</h3> Evaluate effect of intermittent intravenous opioids and sedatives on Neurological Pupil Index (NPi) using Quantitative Pupillometry (QP). <h3>Background:</h3> Opioids and sedatives are widely used in the Neuroscience ICU (NSICU). NPi, an objective measurement of pupillary light reflex (PLR), is a critical component of the neurologic examination and is measured routinely using QP. Yet whether NPi values are affected by opioid or sedative bolus in acutely ill patients is unknown. <h3>Design/Methods:</h3> Prospective, observational, pragmatic study of adult patients (≥18 years old) admitted to the NSICU with any admission diagnosis who received bolus doses of IV opioids or sedatives. 100 patients will be enrolled for final analysis. NPi was assessed using the NPi-300 pupillometer within 30 minutes prior to and 15 minutes after administration of IV opioid or sedative administration. Opioids and sedatives utilized include hydromorphone, fentanyl, morphine, and midazolam. Descriptive data were obtained for demographics. Paired t-test was used to compare pre and post NPi values. <h3>Results:</h3> 39 patients were included in the interim analysis: 54% female, median age 48 (IQR 39–65). Of 39 patients, 35 (90%) received hydromorphone, 2 (5%) received morphine, 1 (2.5%) received fentanyl, and 1 (2.5%) received midazolam. Mean premedication NPi of the RIGHT eye was 4.25 (0.47), and mean premedication NPi of the LEFT eye was 4.27 (0.47). Mean post-medication NPi of the RIGHT eye was 4.26 (0.47), <i>P</i>=0.73. Mean post-medication NPi of the LEFT eye was 4.27 (0.46), <i>P</i>=0.99. Numbers in parenthesis represent standard deviation unless otherwise noted. <h3>Conclusions:</h3> NPi does not significantly differ from before to after administration of bolus IV opioids or sedatives. Significant changes in NPi are unlikely to be related to medication administration and should be correlated clinically. <b>Disclosure:</b> Dr. Battley has nothing to disclose. Ms. Marshall has nothing to disclose. DaiWai Olson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Minnetronix. The institution of DaiWai Olson has received research support from Neuroptics. The institution of DaiWai Olson has received research support from Ceribell. Sonja Stutzman, 10738 has received publishing royalties from a publication relating to health care. Dr. Reyes has nothing to disclose.

OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.

OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.

Posterior Ischemic Optic Neuropathy after Surgery: A Case Report and Review of Literature

We propose in this work to report a case of perioperative posterior ischemic optic neuropathy, after a cardiac surgery. This is a 45-year-old patient, operated for Coronary Angioplasty and Stenting. 24h after the surgery he noticed a bilateral loss of vision. Examination of the both eyes revealed visual acuity decreased to no light perception, absent pupillary light reflexes and normal fundus. The neurological examinationis normal, macular OCT and cerebral magnetic imaging were normal. Visual evoked potentials were absent confirming the diagnosis of right retrobulbar optic neuropathy. The evolution was marked by no improvement of vision and the development of optic nerve atrophy. Perioperative posterior ischemic optic neuropathy during cataract surgery is an extremely rare incident. Posterior ischemic optic neuropathy is an uncommon complication Its physiopathology is multifactorial and dominated by hypotension and anemia. Its prognosis is bad and visual recovery is generally poor.

Mortality Prediction in Severe Traumatic Brain Injury Using Traditional and Machine Learning Algorithms.

Prognostic prediction of traumatic brain injury (TBI) in patients is crucial in clinical decision and health care policy making. This study aimed to develop and validate prediction models for in-hospital mortality after severe traumatic brain injury (sTBI). We developed and validated logistic regression (LR), LASSO regression, and machine learning (ML) algorithms including support vector machines (SVM) and XGBoost models. Fifty-four candidate predictors were included. Model performance was expressed in terms of discrimination (C-statistic) and calibration (intercept and slope). For model development, 2804 patients with sTBI in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China Registry study were included. External validation was performed in 1113 patients with sTBI in the CENTER-TBI European Registry study. XGBoost achieved high discrimination in mortality prediction, and it outperformed logistic and LASSO regression. The XGBoost model established in this study also outperformed prediction models currently available, including the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) core and International Mission for Prognosis and Analysis of Clinical Trials (CRASH) basic models. When including 54 variables, XGBoost and SVM reached C-statistics of 0.87 (95% confidence interval [CI]: 0.81-0.92) and 0.85 (95% CI: 0.79-0.90) at internal validation, and 0.88 (95% CI: 0.87-0.88) and 0.86 (95% CI: 0.85-0.87) at external validation, respectively. A simplified version of XGBoost and SVM using 26 variables selected by recursive feature elimination (RFE) reached C-statistics of 0.87 (95% CI: 0.82-0.92) and 0.86 (95% CI: 0.80-0.91) at internal validation, and 0.87 (95% CI: 0.87-0.88) and 0.87 (95% CI: 0.86-0.87) at external validation, respectively. However, when the number of variables included decreased, the difference between ML and LR diminished. All the prediction models can be accessed via a web-based calculator. Glasgow Coma Scale (GCS) score, age, pupillary light reflex, Injury Severity Score (ISS) for brain region, and the presence of acute subdural hematoma were the five strongest predictors for mortality prediction. The study showed that ML techniques such as XGBoost may capture information hidden in demographic and clinical predictors of patients with sTBI and yield more precise predictions compared with LR approaches.

Use of gene therapy for optic nerve protection: Current concepts.

Gene therapy has become an essential treatment for optic nerve injury (ONI) in recent years, and great strides have been made using animal models. ONI, which is characterized by the loss of retinal ganglion cells (RGCs) and axons, can induce abnormalities in the pupil light reflex, visual field defects, and even vision loss. The eye is a natural organ to target with gene therapy because of its high accessibility and certain immune privilege. As such, numerous gene therapy trials are underway for treating eye diseases such as glaucoma. The aim of this review was to cover research progress made in gene therapy for ONI. Specifically, we focus on the potential of gene therapy to prevent the progression of neurodegenerative diseases and protect both RGCs and axons. We cover the basic information of gene therapy, including the classification of gene therapy, especially focusing on genome editing therapy, and then we introduce common editing tools and vector tools such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -Cas9 and adeno-associated virus (AAV). We also summarize the progress made on understanding the roles of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), phosphatase-tensin homolog (PTEN), suppressor of cytokine signal transduction 3 (SOCS3), histone acetyltransferases (HATs), and other important molecules in optic nerve protection. However, gene therapy still has many challenges, such as misalignment and mutations, immunogenicity of AAV, time it takes and economic cost involved, which means that these issues need to be addressed before clinical trials can be considered.

Photoreceptor contributions to the human pupil light reflex

The pupil reacts to the amount of light reaching the eye. It reduces its size when the light is high and dilates at low light levels to allow the entrance of more photons. This behavior is called pupil light reflex (PLR). Recent investigations in humans were conducted to understand how the photoreceptor signals are combined to drive the pupil light reflex. This review is about the physiological processes that govern the pupil in humans. In particular, how cone-opsins, rhodopsin, and melanopsin photoreception contribute to governing the PLR. We also summarize investigations on the assessment of the PLR in clinical settings.