A differential of the left eye and right eye neurological pupil index is associated with discharge modified Rankin scores in neurologically injured patients.

BACKGROUND: Automated infrared pupillometry (AIP) and the Neurological Pupil index (NPi) provide an objective means of assessing and trending the pupillary light reflex (PLR) across a broad spectrum of neurological diseases. NPi quantifies the PLR and ranges from 0 to 5; in healthy individuals, the NPi of both eyes is expected to be ≥ 3.0 and symmetric. AIP values demonstrate emerging value as a prognostic tool with predictive properties that could allow practitioners to anticipate neurological deterioration and recovery. The presence of an NPi differential (a difference ≥ 0.7 between the left and right eye) is a potential sign of neurological abnormality. METHODS: We explored NPi differential by considering the modified Rankin Score at discharge (DC mRS) among patients admitted to neuroscience intensive care units (NSICU) of 4 U.S. and 1 Japanese hospitals and for two cohorts of brain injuries: stroke (including subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and aneurysm, 1,200 total patients) and 185 traumatic brain injury (TBI) patients for a total of more than 54,000 pupillary measurements. RESULTS: Stroke patients with at least 1 occurrence of an NPi differential during their NSICU stay have higher DC mRS scores (3.9) compared to those without an NPi differential (2.7; P < .001). Patients with TBI and at least 1 occurrence of an NPi differential during their NSICU stay have higher discharge modified Rankin Scale scores (4.1) compared to those without an NPi differential (2.9; P < .001). When patients experience both abnormalities, abnormal (NPi < 3.0) and an NPi differential, the latter has an anticipatory relationship with respect to the former (P < .001 for z-score skewness analysis). Finally, our analysis confirmed ≥ 0.7 as the optimal cutoff value for the NPi differential (AUC = 0.71, P < .001). CONCLUSION: The NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units. TRIAL REGISTRATION: NCT02804438 , Date of Registration: June 17, 2016.

Clinical Correlation Between Vertical Gaze Palsy and Midbrain Volume in Progressive Supranuclear Palsy.

BACKGROUND: Supranuclear vertical gaze palsies and slowed vertical saccades are characteristic clinic features of progressive supranuclear palsy (PSP). The "hummingbird sign," reflective of midbrain atrophy, is a classic radiographic sign of PSP. Correlation between eye movement abnormalities and radiographic findings in PSP has been reported previously. However, due to the use of clinical criteria not commonly employed in neuro-ophthalmic practice and neuroimaging techniques that are not widely available, it remains unclear whether correlation between midbrain structure and characteristic ocular-motor disturbances can be helpful to neuro-ophthalmologists seeking to adjudicate difficult or unusual diagnostic cases. METHODS: Patients with a diagnosis of probable PSP according to Movement Disorders Society criteria were studied retrospectively. A neuroradiologist calculated brainstem volumes in enrolled participants and normal controls. Spearman correlations were used to correlate the extent of eye movement limitation as assessed by 2 neuro-ophthalmologists with brainstem volumes. RESULTS: Fourteen participants with PSP and 15 healthy controls with similar age and gender distribution were enrolled and evaluated retrospectively. All 14 participants with PSP had undergone MRIs. Midbrain atrophy significantly correlated with the PSP rating scale (P < 0.001). PSP patients had significantly reduced volumes in the midbrain (P -0.0026), tegmentum (0.0001), tectum (0.0001), and medulla (P = 0.0024) compared with normal controls. Notes documenting quantified ocular motor function were available in 7 of 14 participants with PSP. Midbrain atrophy significantly correlated with in the extent of upward gaze limitation (P = 0.03). CONCLUSIONS: The severity of upward gaze limitation correlates with the severity of midbrain atrophy in patients with PSP. Recognition of this correlation may help to adjudicate diagnostic dilemmas and guide further evaluation.

Eye-tracking technology for real-time monitoring of transverse chromatic aberration.

Objective measurements of transverse chromatic aberration (TCA) between two or more wavelengths with an adaptive optics scanning laser ophthalmoscope (AOSLO) are very accurate, but frequent measurements are impractical in many experimental settings. Here, we demonstrate a pupil tracker that can accurately measure relative changes in TCA that are caused by small shifts in the pupil relative to the AOSLO imaging beam. Corrections for TCA caused by these shifts improve the measurement of TCA as a function of eccentricity, revealing a strong linear relationship. We propose that pupil tracking be integrated into AOSLO systems, where robust and unobtrusive control of TCA is required.

Pupillary dilations in a Target/Distractor visual task paradigm and attention deficit hyperactivity disorder (ADHD).

ADHD is a neurocognitive disorder characterized by attention difficulties, hyperactivity, and impulsivity, often persisting into adulthood with substantial personal and societal consequences. Despite the importance of neurophysiological assessment and treatment monitoring tests, their availability outside of research settings remains limited. Cognitive neuroscience investigations have identified distinct components associated with ADHD, including deficits in sustained attention, inefficient enhancement of attended Targets, and altered suppression of ignored Distractors. In this study, we examined pupil activity in control and ADHD subjects during a sustained visual attention task specifically designed to evaluate the mechanisms underlying Target enhancement and Distractor suppression. Our findings revealed some distinguishing factors between the two groups which we discuss in light of their neurobiological implications.

Quantification of relative afferent pupillary defect by an automated pupillometer and its relationship with visual acuity and dimensions of macular lesions in age-related macular degeneration.

PURPOSE: The occurrence of relative afferent pupillary defect (RAPD) secondary to optic nerve diseases and widespread retinal disorders is well established. However, only very few reports of RAPD in macular disorders exist in the literature. In this study, we used automated pupillometer to evaluate RAPD in eyes with macular lesions. METHODS: It was a prospective cross-sectional study. A total of 82 patients with choroidal neovascular membrane (CNVM) - 65 unilateral and 17 bilateral macular lesions - were enrolled. RAPD was assessed with an automated pupillometer and macular lesions evaluated with optical coherence tomography (OCT). The length of the ellipsoid zone disruption was measured as the longest length of lesion on the horizontal raster scans and the area of macular lesion was measured manually, mapping the affected area of ellipsoid zone on the enface images. RESULTS: : RAPD scores showed good correlation with the intereye difference in length of maximum ellipsoid zone disruption (r-value = 0.84, P value <0.001) and macular lesion area as measured on OCT in all unilateral cases (r-value = 0.84, P value <0.001). Best-corrected visual acuity was also found to have a significant correlation with lesion size on the OCT as well as the length of ellipsoid zone disruption in unilateral cases. CONCLUSION: : RAPD evaluated with an automated binocular pupillometer is a noninvasive and objective method to assess macular lesions in CNVMs; it shows good correlation with structural lesion dimensions on OCT in unilateral cases. Further longitudinal studies are needed to assess the significance of these findings in disease progression as well as correlation with lesion response to treatment.

Pupil dilation during visual target detection.

It has long been documented that emotional and sensory events elicit a pupillary dilation. Is the pupil response a reliable marker of a visual detection event while viewing complex imagery? In two experiments where viewers were asked to report the presence of a visual target during rapid serial visual presentation (RSVP), pupil dilation was significantly associated with target detection. The amplitude of the dilation depended on the frequency of targets and the time of target presentation relative to the start of the trial. Larger dilations were associated with trials having fewer targets and with targets viewed earlier in the run. We found that dilation was influenced by, but not dependent on, the requirement of a button press. Interestingly, we also found that dilation occurred when viewers fixated a target but did not report seeing it. We will briefly discuss the role of noradrenaline in mediating these pupil behaviors.

Transverse chromatic offsets with pupil displacements in the human eye: sources of variability and methods for real-time correction.

Tracking SLO systems equipped to perform retinally targeted stimulus delivery typically use near-IR wavelengths for retinal imaging and eye tracking and visible wavelengths for stimulation. The lateral offsets between wavelengths caused by transverse chromatic aberration (TCA) must be carefully corrected in order to deliver targeted stimuli to the correct location on the retina. However, both the magnitude and direction of the TCA offset is dependent on the position of the eye's pupil relative to the incoming beam, and thus can change dynamically within an experimental session without proper control of the pupil position. The goals of this study were twofold: 1) To assess sources of variability in TCA alignments as a function of pupil displacements in an SLO and 2) To demonstrate a novel method for real-time correction of chromatic offsets. To summarize, we found substantial between- and within-subject variability in TCA in the presence of monochromatic aberrations. When adaptive optics was used to fully correct for monochromatic aberrations, variability both within and between observers was minimized. In a second experiment, we demonstrate that pupil tracking can be used to update stimulus delivery in the SLO in real time to correct for variability in chromatic offsets with pupil displacements.

Quantification of RAPD by an automated pupillometer in asymmetric glaucoma and its correlation with manual pupillary assessment.

PURPOSE: The relative afferent pupillary defect (RAPD) is an important sign of asymmetrical retinal ganglion cell damage. The purpose of this study was to quantify RAPD by a pupillometer (RAPiDo, Neuroptics) and assess its correlation with asymmetric glaucoma and manual pupillary assessment. METHODS: A total of 173 subjects were enrolled in the study and categorized into glaucoma, n = 130, and control, n = 43. Subjects were all recruited in the Glaucoma Clinic of the Aravind Eye Hospital in Madurai during their follow-up. They were 18 years and older, with best corrected visual acuity of 6/36 or better. Exclusion criteria included all retinal pathologies, optic atrophies, ocular injuries, severe uveitis, cloudy corneas, dense cataracts, or use of mydriatics or miotic drugs. RAPD was assessed in all subjects using an automated pupillometer and the results were compared with the swinging flash light test conducted on the same subjects by an experienced ophthalmologist. We looked at the correlation between RAPD and the intereye difference in cup-to-disc ratio (CDR), mean deviation (MD) of visual field testing, and retinal nerve fiber layer (RNFL) thickness. Sensitivity and specificity were assessed by area under the receiver operator characteristic (AUROC) analysis. RESULTS: Glaucoma patients had significant RAPD (0.55 ± 0.05 log units) when compared with the controls (0.25 ± 0.05 log units), P < 0.001. Significant intereye differences in CDR, MD, and RNFL between glaucoma and control (P < 0.001) were seen. There was a good correlation between the magnitude and sign of RAPD and these intereye differences in CDR (r = 0.52, P < 0.001), MD (r = 0.44, P < 0.001) and RNFL thickness (r = 0.59, P < 0.001). When compared with the experienced ophthalmologist, AUROC was 0.94, with 89% sensitivity and 91.7% specificity. CONCLUSION: The good correlation between the magnitude of RAPD, as measured by the automated pupillometer, and intereye differences in MD, CDR, and RNFL thickness in glaucomatous, and the good sensitivity and specificity when compared with the experienced ophthalmologist, suggest that pupillometry may be useful as a screening tool to assess asymmetric glaucoma.

Image-type dependent eigen-regions-of-interest define conspicuity operators for predicting human scanpath fixation.

Top-down informativeness elaboration and bottom-up conspicuity processing are intimately interconnected in visual perception. An internal cognitive model of the external world must necessarily control not only our recognition but also the scanpath sequence of eye movement/shift of attention jumps. A self-organizing process based on principal component analysis and scanpath experimental data are used in this paper to define spatial visual conspicuity from the eigen-features of the scanpath sequence image loci. Eight different classes of images are used as both training and testing set. We first demonstrate that cognitive-driven scanpath loci can be discriminated in terms of these bottom-up eigen conspicuity features. We can finally define a conspicuity processing algorithm and measure its ability to predict human scanpaths as evidenced by the positional similarity measure Sp. Some computer vision applications will also be discussed.

Pupil examination: validity and clinical utility of an automated pupillometer.

Pupillary size and reactivity have long been a critical component of the clinical assessment of patients with neurological disorders. The pupillary examination may provide critical information related to new or worsening intracranial pathology and facilitate prompt intervention to minimize further neuronal damage. With this in mind, intensive care nurses caring for neurologically impaired patients frequently must perform pupillary examinations in concert with assigning a Glasgow Coma Scale score. The purpose of this study was to test the accuracy and reliability of an automated pupillometer compared with the standard manual examination as a preliminary step in assessing the usefulness of automated pupillometry in the critical care setting. Twenty patients in the intensive care units of a teaching hospital were examined by two groups of three examiners using both the manual examination with a penlight or similar light source and a portable automated pupillometer capable of measuring pupil size and reaction. Measurements by a static pupillometer before and after each pupillary examination were used to determine the mean "true" size of the pupil. This study found that the automated pupillometer is more accurate and reliable than the manual examination in measuring pupil size and reactivity. For these reasons, such a device may be a beneficial addition in the clinical assessment of neurologically impaired patients.

Human-vision-based selection of image processing algorithms for planetary exploration.

Independent and automatic image processing is a fundamental objective of the computer vision community. Understanding the role of the eye movement scan path in human vision is an important step toward the achievement of this objective. This top-down model of higher human vision is a new approach to bottom-up image processing algorithms and provides an important new metric and tool in computer vision. We have demonstrated that a small and manageable collection of image processing algorithms, experimentally selected and then combined together can serve in a task such as predicting human eye fixations identifying geological features. Thus, automatic picture analysis based upon human vision could be an essential element in planetary exploration.

Analysis of microsaccades and pupil dilation reveals a common decisional origin during visual search.

During free viewing visual search, observers often refixate the same locations several times before and after target detection is reported with a button press. We analyzed the rate of microsaccades in the sequence of refixations made during visual search and found two important components. One related to the visual content of the region being fixated; fixations on targets generate more microsaccades and more microsaccades are generated for those targets that are more difficult to disambiguate. The other empathizes non-visual decisional processes; fixations containing the button press generate more microsaccades than those made on the same target but without the button press. Pupil dilation during the same refixations reveals a similar modulation. We inferred that generic sympathetic arousal mechanisms are part of the articulated complex of perceptual processes governing fixational eye movements.

A binocular pupil model for simulation of relative afferent pupil defects and the swinging flashlight test.

Many important intracranial neural pathways are involved in the control of the two muscles of the human pupil and the observation and analysis of pupil responses to light or other stimuli is of great interest in many clinical procedures. The binocular pupil model presented in this document has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It is employed here to simulate responses to the swinging flashlight test, a procedure which is routinely practiced in ophthalmology to diagnose different degrees of relative afferent pupil defects often a consequence of severe optic nerve diseases or retinal dysfunctions. Other, not light-dependent, pupil stimuli are briefly discussed.

On the discriminability of hROIs, human visually selected regions-of-interest.

Many studies have tried to answer an important question: is it possible to predict human visually selected regions-of-interest (hROIs)? hROIs are defined as the loci of eye fixations and they can be analyzed by their spatial distribution over the visual stimulus and their temporal ordering. We used a simplified set of geometrical spatial kernels and linear filter models as bottom-up conspicuity operators that produce algorithmically selected regions-of-interest, aROIs. As a direct approach we measured the ability of these aROIs to predict human scanpaths. The level of prediction is measured by two similarity indices: Sp for spatial similarity and Ss for temporal ordering similarity. At the same time we assessed the discriminability of the hROI loci, in terms of conspicuity, with respect to non-selected (not of interest) regions of an image. We prove that this discrimination is possible and further correlates with the positional similarity index Sp. Other human scanpath experimental conditions are presented in parsing diagrams and discussed. A general top-down/bottom-up scanpath model is finally formulated.

A binocular pupil model for simulation of relative afferent pupil defect, RAPD.

The human pupil is an important element studied in many clinical procedures. The binocular pupil model presented has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It simulates responses to the swinging flashlight test for different degrees of relative afferent pupil defects, RAPD.