No abstract available

To evaluate the efficacy and safety of a hinged pupil expansion device (PED) in eyes with small pupils undergoing phacoemulsification.

Recent scientific investigations suggest that people automatically mimic each other's pupil sizes during interaction. However, instead of being a social mimicry effect, it could also be the result of brightness perception. When observers look at individuals with dilated pupils, little of the brighter iris is visible, leading to the perception of a relatively low-illuminated eye region. In the current study we tested whether pupil mimicry remains present when pupils and irises are equalized for luminance values across pupil sizes. We tested several stimulus sets, including faces with static pupils that varied in size across images and dynamic pupils that changed in size over time in videos. Results showed that for traditional, not-luminance-equalized videos, participants' pupil sizes adapted to the observed pupils, showing a pattern that is roughly in line with pupil mimicry. However, no such pupil response in line with mimicry was seen for static images (regardless of whether they were equalized for luminance) nor for luminance-equalized videos. These findings suggest that only salient, dynamic stimuli attract enough attention to the luminance in the eye region to evoke a pupillary response. However, although such responses suggest pupil mimicry, the underlying factor is the change in brightness within the eye as a function of pupil size rather than social mimicry.

Although it has been hypothesized that moderate to vigorous exercise immediately modulates cognition via ascending arousal system activation, such activation during very-light to light exercise has remained uncertain. Here, we aimed to uncover the exact exercise intensity necessary for ascending arousal system activation using pupillometry. The pupil diameter, psychological arousal, and ventilation during graded exercise of 26 young males were analyzed based on %[Formula: see text]. Pupils dilated with very-light exercise compared to rest, stabilized, and then drastically increased again with moderate exercise and above. Pupil dilation with very-light exercise was positively correlated with increases in psychological arousal. Thus, we have shown that there are two phases of pupil dilation during graded exercise: one with very-light exercise coinciding with psychological arousal response, and the other with moderate exercise or above similar to the ventilation increase pattern. This unique pupil dilation pattern provides physiological evidence of ascending arousal system activation with very-light exercise.

Transcutaneous auricular vagus nerve stimulation (taVNS) bears therapeutic potential for a wide range of medical conditions. However, previous studies have found substantial interindividual variability in responsiveness to taVNS, and no reliable predictive biomarker for stimulation success has been developed so far. In this study, we investigate pupil size and event-related pupil response as candidate biomarkers. Both measures have a direct physiological link to the activity of the locus coeruleus (LC), a brainstem structure and the main source of norepinephrine in the brain. LC activation is considered one of the key mechanisms of action of taVNS, therefore, we expected a clear increase of the pupillary measures under taVNS compared to sham (placebo) stimulation, such that it could serve as a prospective predictor for individual clinical and physiological taVNS effects in future studies. We studied resting pupil size and pupillary responses to target stimuli in an auditory oddball task in 33 healthy young volunteers. We observed stronger pupil responses to target than to standard stimuli. However, and contrary to our hypothesis, neither pupil size nor the event-related pupil response nor behavioral performance were modulated by taVNS. We discuss potential explanations for this negative finding and its implications for future clinical investigation and development of taVNS.

Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.

The photoreceptor classes driving the flicker pupil light response (fPLR) to monochromatic sinusoidal temporal modulation are largely unknown. Here, we determine the photoreceptor inputs to the fPLR.

Ocular somatosensory-autonomic reflexes play critical roles in maintaining homeostasis of the eye. The purpose of this study was to investigate the pupil response to nociceptive corneal stimuli.

To compare pupillary responses in patients with Coronavirus disease-2019 (COVID-19) during active infection and at 3rd months post-infection.

Although luminance is the main determinant of pupil size, the amplitude of the pupillary light response is also modulated by stimulus appearance and attention. Here we ask whether perceived numerosity modulates the pupillary light response. Participants passively observed arrays of black or white dots of matched physical luminance but different physical or illusory numerosity. In half the patterns, pairs of dots were connected by lines to create dumbbell-like shapes, inducing an illusory underestimation of perceived numerosity; in the other half, connectors were either displaced or removed. Constriction to white arrays and dilation to black were stronger for patterns with higher perceived numerosity, either physical or illusory, with the strength of the pupillary light response scaling with the perceived numerosity of the arrays. Our results show that even without an explicit task, numerosity modulates a simple automatic reflex, suggesting that numerosity is a spontaneously encoded visual feature.

When observers search for a specific target, it is assumed that they activate a representation of the task relevant object in visual working memory (VWM). This representation - often referred to as the template - guides attention towards matching visual input. In two experiments we tested whether the pupil response can be used to differentiate stimuli that match the task-relevant template from irrelevant input. Observers memorized a target color to be searched for in a multi-color visual search display, presented after a delay period. In Experiment 1, one color appeared at the start of the trial, which was then automatically the search template. In Experiments 2, two colors were presented, and a retro-cue indicated which of these was relevant for the upcoming search task. Crucially, before the search display appeared, we briefly presented one colored probe stimulus. The probe could match either the relevant-template color, the non-cued color (irrelevant), or be a new color not presented in the trial. We measured the pupil response to the probe as a signature of task relevance. Experiment 1 showed significantly smaller pupil size in response to probes matching the search template than for irrelevant colors. Experiment 2 replicated the template matching effect and allowed us to rule out that it was solely due to repetition priming. Taken together, we show that the pupil responds selectively to participants' target template prior to search.

The brain's arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus, one of the key regulators of central arousal and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the locus coeruleus and other brainstem structures involved in arousal control. Furthermore, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brain's arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioural and clinical applications across various domains, including stress-related and anxiety disorders.

We investigated the mechanisms for evaluating perceived gaze-shift duration. Timing relies on the accumulation of endogenous physiological signals. Here we focused on arousal, measured through pupil dilation, as a candidate timing signal. Participants timed gaze-shifts performed by face stimuli in a Standard/Probe comparison task. Pupil responses were binned according to "Longer/Shorter" judgements in trials where Standard and Probe were identical. This ensured that pupil responses reflected endogenous arousal fluctuations opposed to differences in stimulus content. We found that pupil hazard rates predicted the classification of sub-second intervals (steeper dilation = "Longer" classifications). This shows that the accumulation of endogenous arousal signals informs gaze-shift timing judgements. We also found that participants relied exclusively on the 2nd stimulus to perform the classification, providing insights into timing strategies under conditions of maximum uncertainty. We observed no dissociation in pupil responses when timing equivalent neutral spatial displacements, indicating that a stimulus-dependent timer exploits arousal to time gaze-shifts.

Adie's pupil, also called tonic pupil, is mainly seen in young women. Most patients have unilateral eye involvement. The pupil of the affected side is significantly larger than that on the healthy side. The direct and indirect light reflection from the pupil on the affected side disappears. The pupil on the affected side is sensitive to low concentrations of pilocarpine. The pathogeneses of Adie's pupil are complex, some of which are insidious and lack corresponding specific diseases. Through a literature review, we found that Adie's pupil is mainly associated with infectious diseases, most commonly syphilis, followed by immune diseases and paraneoplastic syndromes. The ophthalmological symptoms and pupil abnormalities can disappear after active treatment of the primary disease. Pilocarpine can be used to treat ophthalmologic symptoms, such as blurred vision, for which patients might visit an ophthalmologist or neurologist. It is essential for clinicians to improve their understanding of the disease to avoid misdiagnosis. Differential diagnosis between Adie's pupil, oculomotor nerve palsy, anticholinergic drug overdose, Argyll-Robertson pupil, and congenital mydriasis need to be identified by the physician. Here, the clinical manifestations, pathogenesis, relationship between Adie's pupil and diseases, and differential diagnosis of Adie's pupil are reviewed.

Pupil diameter, under constant illumination, is known to reflect individuals' internal states, such as surprise about observation and environmental uncertainty. Despite the growing use of pupillometry in cognitive learning studies as an additional measure for examining internal states, few studies have used pupillometry in human motor learning studies. Here, we provide the first detailed characterization of pupil diameter changes in a short-term reach adaptation paradigm. We measured pupil changes in 121 human participants while they adapted to abrupt, gradual, or switching force field conditions. Sudden increases in movement error caused by the introduction/reversal of the force field resulted in strong phasic pupil dilation during movement accompanied by a transient increase in tonic premovement baseline pupil diameter in subsequent trials. In contrast, pupil responses were reduced when the force field was gradually introduced, indicating that large, unexpected errors drove the changes in pupil responses. Interestingly, however, error-induced pupil responses gradually became insensitive after experiencing multiple force field reversals. We also found an association between baseline pupil diameter and incidental knowledge of the gradually introduced perturbation. Finally, in all experiments, we found a strong co-occurrence of larger baseline pupil diameter with slower reaction and movement times after each rest break. Collectively, these results suggest that tonic baseline pupil diameter reflects one's belief about environmental uncertainty, whereas phasic pupil dilation during movement reflects surprise about a sensory outcome (i.e., movement error), and both effects are modulated by novelty. Our results provide a new approach for nonverbally assessing participants' internal states during motor learning.NEW & NOTEWORTHY Pupil diameter is known as a noninvasive window into individuals' internal states. Despite the growing use of pupillometry in cognitive learning studies, it receives little attention in motor learning studies. Here, we characterized the pupil responses in a short-term reach adaptation paradigm by measuring pupil diameter of human participants while they adapted to abrupt, gradual, or switching force field conditions. Our results demonstrate how surprise and uncertainty reflected in pupil diameter develop during motor adaptation.

Tissue macrophages, which are ubiquitously present innate immune cells, play versatile roles in development and organogenesis. During development, macrophages prune transient or unnecessary synapses in neuronal development, and prune blood vessels in vascular development, facilitating appropriate tissue remodeling. In the present study, we identified that macrophages contributed to the development of pupillary morphology. Csf1op/op mutant mice, in which ocular macrophages are nearly absent, exhibited abnormal pupillary edges, with abnormal protrusions of excess iris tissue into the pupillary space. Macrophages located near the pupillary edge engulfed pigmented debris, which likely consisted of unnecessary iris protrusions that emerge during smoothening of the pupillary edge. Indeed, pupillary edge macrophages phenotypically possessed some features of M2 macrophages, consistent with robust tissue engulfment and remodeling activities. Interestingly, protruding irises in Csf1op/op mice were only detected in gaps between regressing blood vessels. Taken together, our findings uncovered a new role for ocular macrophages, demonstrating that this cell population is important for iris pruning during development.

Pupil dynamics can represent an indirect measure of perception; thus, it has been broadly explored in the auditory and visual fields. Although it is crucial for experiencing the outside world, tactile perception is not well-explored. Considering that, we sought to answer the following question via a systematic review: does normal tactile perception processing modulate pupil dilation in mammals (human or not)? The review process was conducted according to PRISMA Statement. We searched on Periódicos CAPES (Brazil) for the following terms: [(touch) OR (cutaneous stimulation) OR (tactile perception) OR (somatosensory) AND (pupil OR pupillary) NOT blind NOT reflex NOT pain NOT fear NOT noxious NOT autism NOT nerve NOT (pupillary block) NOT glaucoma NOT cataract NOT aneurysm NOT syndrome NOT treatment NOT special education]. From the 6,488 papers found, 4,568 were duplicates, and nine fulfilled the inclusion criteria. All papers found a positive relationship between pupil diameter and tactile perception. We found that the pupil is a reliable indirect measure of brain states and can evaluate norepinephrine (NE)/locus coeruleus (LC) action, stimulus inhibition, arousal, cognitive processes, and affection independently of the stimuli category (visual, auditory, or tactile). We also found that the perceptual tactile processing occurs in similar ways as the other perceptual modalities. We verified that more studies should be done, mostly avoiding low sampling rate recording systems, confounders as cue signs, not automated stimulation, and concurrent stimulus and using more reliable equipment.

Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

Pupillometry has become a standard measure for assessing arousal state. However, environmental factors such as luminance, a primary dictator of pupillary responses, often vary across studies. To what degree does luminance interact with arousal-driven pupillary changes? Here, we parametrically assessed luminance-driven pupillary responses across a wide-range of luminances, while concurrently manipulating cognitive arousal using auditory math problems of varying difficulty. At the group-level, our results revealed that the modulatory effect of cognitive arousal on pupil size interacts multiplicatively with luminance, with the largest effects occurring at low and mid-luminances. However, at the level of individuals, there were qualitatively distinct individual differences in the modulatory effect of cognitive arousal on luminance-driven pupillary responses. Our findings suggest that pupillometry as a measure for assessing arousal requires more careful consideration: there are ranges of luminance levels that are more ideal in observing pupillary differences between arousal conditions than others.

Mobile eye-tracking in external environments remains challenging, despite recent advances in eye-tracking software and hardware engineering. Many current methods fail to deal with the vast range of outdoor lighting conditions and the speed at which these can change. This confines experiments to artificial environments where conditions must be tightly controlled. Additionally, the emergence of low-cost eye tracking devices calls for the development of analysis tools that enable non-technical researchers to process the output of their images. We have developed a fast and accurate method (known as "SET") that is suitable even for natural environments with uncontrolled, dynamic and even extreme lighting conditions. We compared the performance of SET with that of two open-source alternatives by processing two collections of eye images: images of natural outdoor scenes with extreme lighting variations ("Natural"); and images of less challenging indoor scenes ("CASIA-Iris-Thousand"). We show that SET excelled in outdoor conditions and was faster, without significant loss of accuracy, indoors. SET offers a low cost eye-tracking solution, delivering high performance even in challenging outdoor environments. It is offered through an open-source MATLAB toolkit as well as a dynamic-link library ("DLL"), which can be imported into many programming languages including C# and Visual Basic in Windows OS (www.eyegoeyetracker.co.uk).