Evaluating the utility of quantitative pupillometry in a neuro-critical care setting for the monitoring of intracranial pressure: A prospective cohort study.

INTRODUCTION: Assessment of the pupillary light reflex (PLR) is key in intensive care monitoring of neurosurgical patients, particularly for monitoring intracranial pressure (ICP). Quantitative pupillometry using a handheld pupillometer is a reliable method for PLR assessment. However, many variables are derived from such devices. We therefore aimed to assess the performance of these variables at monitoring ICP. METHODS: Sedated patients admitted to neurocritical care in a tertiary neurosurgical centre with invasive ICP monitoring were included. Hourly measurement of ICP, subjective pupillometry (SP) using a pen torch device, and quantitative pupillometry (QP) using a handheld pupillometer were performed. RESULTS: 561 paired ICP, SP and QP pupillary observations from nine patients were obtained (1122 total pupillary observations). SP and QP had a moderate concordance for pupillary size (κ=0.62). SP performed poorly at detecting pupillary size changes (sensitivity=24%). In 40 (3.6%) observations, SP failed to detect a pupillary response whereas QP did. Moderate correlations with ICP were detected for maximum constriction velocity (MCV), dilation velocity (DV), and percentage change in pupillary diameter (%C). Discriminatory ability at an ICP threshold of >22 mmHg was moderate for MCV (AUC=0.631), DV (AUC=0.616), %C (AUC=0.602), and pupillary maximum size (AUC=0.625). CONCLUSION: QP is superior to SP at monitoring pupillary reactivity and changes to pupillary size. Although effect sizes were moderate to weak across assessed variables, our data indicates MCV and %C as the most sensitive variables for monitoring ICP. Further study is required to validate these findings and to establish normal range cut-offs for clinical use.

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).

Feasibility of USG-Guided Objective Initial Assessment of Pupillary Size and Pupillary Reflexes Versus Clinical Examination in Patients With Altered Mental Status: A Cross-Sectional Study.

BACKGROUND: Pupillary assessment is an important part of the neurological assessment which provides vital information in critically ill patients. However, clinical pupillary assessment is subjective. The ultrasound-guided pupillary examination is objective. There are limited pieces of literature regarding its use in assessing patients with altered mental status. So, we studied the extent of agreement of B-mode ultrasound with clinical examination for assessment of the pupillary size and reflex in patients with altered mental status. OBJECTIVES: The primary objective was to determine the extent of agreement between clinical examination and ultrasound-based examination for assessing pupillary reflex and size in patients with altered mental status in two settings (trauma and non-trauma patients). METHODS: Exactly 200 subjects (158 males, mean [range] age 43.56 [18-92 years]) with no history of partial globe rupture or dementia were included in this cross-sectional study from March 2019 to March 2020. B-mode ultrasound was performed with the subject's eyes closed using a 7-12 MHz linear probe and a standardized light stimulus. ICC score, paired t-test, kappa, Wilcoxon signed-rank test, and Bland-Altman plots were used for statistical analysis. RESULTS: The clinical-USG agreement for pupillary light reflex examination (Pupillary Diameter [PD] at rest, after direct light stimulation [Dstim ] and consensual light stimulation [Cstim ]) was excellent (ICC, 0.93-0.96). The Kappa coefficient (0.74 ± 0.07) showed an agreement of 87.36% between clinical and USG examination for pupillary reflex (reactive or non-reactive). CONCLUSION: USG-guided pupillary examination proves to be a better adjunct to neurological assessment in patients with altered mental status.

Nociception assessment with videopupillometry in deeply sedated intensive care patients: Discriminative and criterion validations.

BACKGROUND: Nociceptive assessment in deeply sedated patients is challenging. Validated instruments are lacking for this unresponsive population. Videopupillometry is a promising tool but has not been established in intensive care settings. AIM/OBJECTIVE: To test the discriminate validity of pupillary dilation reflex (PDR) between non-noxious and noxious procedures for assessing nociception in non-neurological intensive care unit (ICU) patients and to test the criterion validity of pupil dilation using recommended PDR cut-off points to determine nociception. METHODS: A single-centre prospective observational study was conducted in medical-surgical ICU patients. Two independent investigators performed videopupillometer measurements during a non-noxious and a noxious procedure, once a day (up to 7 days), when the patient remained deeply sedated (Richmond Agitation-Sedation Scale score: -5 or -4). The non-noxious procedures consisted of a gentle touch on each shoulder and the noxious procedures were endotracheal suctioning or turning onto the side. Bivariable and multivariable general linear mixed models were used to account for multiple measurements in same patients. Sensitivity and specificity, and areas under the curve of the receiver operating characteristic curve were calculated. RESULTS: Sixty patients were included, and 305 sets of 3 measurements (before, during, and after), were performed. PDR was higher during noxious procedures than before (mean difference between noxious and non-noxious procedures = 31.66%). After testing all variables of patient and stimulation characteristics in bivariable models, age and noxious procedures were kept in the multivariable model. Adjusting for age, noxious procedures (coefficient = -15.14 (95% confidence interval = -20.17 to -15.52, p < 0.001) remained the only predictive factor for higher pupil change. Testing recommended cut-offs, a PDR of >12% showed a sensitivity of 65%, and a specificity of 94% for nociception prediction, with an area under the receiver operating curve of 0.828 (95% confidence interval = 0.779-0.877). CONCLUSIONS: In conclusion, PDR is a potentially appropriate measure to assess nociception in deeply sedated ICU patients, and we suggest considering its utility in daily practices. REGISTRATION: This study was not preregistered in a clinical registry. TWEETABLE ABSTRACT: Pupillometry may help clinicians to assess nociception in deeply sedated ICU patients.

Linear integration of multisensory signals in the pupil.

The pupil of the eye responds to various salient signals from different modalities, but there is no consensus on how these pupillary responses are integrated when multiple signals appear simultaneously. Both linear and nonlinear integration have been found previously. The current study aimed to reexamine the nature of pupillary integration, and specifically focused on the early, transient pupillary responses due to its close relationship with orienting. To separate the early pupillary responses out of the pupil time series, we adopted a pupil oscillation paradigm in which sensory stimuli were periodically presented. The simulation analysis confirmed that the amplitude of the pupil oscillation, induced by stimuli repeatedly presented at relatively high rates, can precisely reflect the early, transient pupillary responses without involving the late and sustained pupillary responses. The experimental results then showed that the amplitude of pupil oscillation induced by a series of simultaneous audiovisual stimuli equaled to a linear summation of the oscillatory amplitudes when unisensory stimuli were presented alone. Moreover, the tonic arousal levels, indicated by the baseline pupil size, cannot shift the summation from linear to nonlinear. These findings together support the additive nature of multisensory pupillary integration for the early, orienting-related pupillary responses. The additive nature of pupillary integration further implies that multiple pupillary responses may be independent of each other, irrespective of their potential cognitive and neural drivers.

Chromatic Pupillometry - a New Technique for Assessing Function in Glaucoma? / Chromatische Pupillometrie ­ ein neuer Weg zur funktionellen Glaukomdiagnostik?

Chromatic pupillometry allows quantification of photoreceptor-driven (extrinsic) and melanopsin-driven (intrinsic) responses of the intrinsic-photosensitive retinal ganglion cells (ipRGCs). This small subpopulation of retinal ganglion cells is also affected by glaucoma, making chromatic pupillometry a potential diagnostic tool. Studies show reduced phasic and tonic responses in glaucoma patients. The diagnostic value in earlier studies depended on the technical details and the study design. The purpose of this article is to give an introduction into the principles of chromatic pupillometry and to discuss the potential applications in the management of glaucoma.

The photic blink reflex as an index of photophobia.

Two recent studies of eye closure triggered by intense luminance increase suggest that this behavior reflects the melanopsin-based retinal activity known to underlie photophobia, the pathological aversion to light (Kardon, 2012; Kaiser et al., 2021). Early studies of the photic blink reflex (PBR) are reviewed to help guide future research on this possible objective index of photophobia. Electromyographic recordings of the lid-closure muscle, orbicularis oculi, reveal distinct bursts with typical onset latencies of 50 and 80 ms, R50 and R80, respectively. The latter component appears to be especially sensitive to visual signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) and to prior trigeminal nociceptive stimuli. The authors argue that the R80's function, in addition to protecting the eyeballs from physical contact, is to shape the upper and lower eyelids into a narrow slit to restrict incoming light. This serves to prevent retinal bleaching or injury, while allowing continued visual function.

Pupillary dilation reflex and behavioural pain scale: Study of diagnostic test.

BACKGROUND: The objective of this study was to assess the value of the pupillary dilation reflex as an assessment pain tool in critically ill patients. It is important to continue working for the well-being and security of critically ill patients. METHODS: We studied the diagnostic accuracy of the pupillary dilation reflex against the Behavioral Pain Scale. Inclusion criteria were: age greater than 18, receiving mechanical ventilation, with a basal score of the Behavioural Pain Scale of three and a Richmond Agitation and Sedation score between -1 and -4. We studied the responses to a non-painful stimulus, four calibrated stimuli, after a tracheal aspiration and with and without pain. The receiver operating curve was plotted and we calculated the area under the curve. We identified the cut-off points showing the highest sensitivity and specificity and studied diagnostic performance based on negative predictive value, positive predictive value, and accuracy. These were reported with their 95% confidence intervals. RESULTS: 183 measurements were performed. An AUC of 0.88(95% CI 0.83-0.94) was obtained. The pupillary dilation reflex of 11.5% had a sensitivity of 89.8%(95% CI 78.2-95.6) and a specificity of 78.4%(95% CI 70.6-84.5) with an accuracy of 81.4(75.2-86.4). The pupillary dilation reflex detected nociceptive pain response in 15.8% of the measurements that did not show pain according to the Behavioural Pain Scale. CONCLUSIONS: Pupillometry may be a valid alternative for identifying pain in critically ill patients.

[Paying attention to the clinical significance of pupil abnormalities].

Pupil abnormalities may be physiological, pathological or pharmacological. It can indicate the underlying disease of the visual afferent system or visual efferent system. Examination of the pupils is therefore a part of eye examination. Insufficient knowledge and inconsistent methods in the pupillary examination by some ophthalmologists lead to mistakes or unreliable results, hampering the disease diagnosis and clinical assessment. This article emphasizes the significance of pupillary examination outcomes, advocates for standardized examination methods, and highlights the need to enhance the awareness of pupillary abnormalities, aiming to provide a guide on how to recognize and interpret the clinical implications of pupillary abnormalities, and to offer valuable insights for clinical practice.

Review on age-related differences in non-visual effects of light: melatonin suppression, circadian phase shift and pupillary light reflex in children to older adults.

Physiological effects of light exposure in humans are diverse. Among them, the circadian rhythm phase shift effect in order to maintain a 24-h cycle of the biological clock is referred to as non-visual effects of light collectively with melatonin suppression and pupillary light reflex. The non-visual effects of light may differ depending on age, and clarifying age-related differences in the non-visual effects of light is important for providing appropriate light environments for people of different ages. Therefore, in various research fields, including physiological anthropology, many studies on the effects of age on non-visual functions have been carried out in older people, children and adolescents by comparing the effects with young adults. However, whether the non-visual effects of light vary depending on age and, if so, what factors contribute to the differences have remained unclear. In this review, results of past and recent studies on age-related differences in the non-visual effects of light are presented and discussed in order to provide clues for answering the question of whether non-visual effects of light actually vary depending on age. Some studies, especially studies focusing on older people, have shown age-related differences in non-visual functions including differences in melatonin suppression, circadian phase shift and pupillary light reflex, while other studies have shown no differences. Studies showing age-related differences in the non-visual effects of light have suspected senile constriction and crystalline lens opacity as factors contributing to the differences, while studies showing no age-related differences have suspected the presence of a compensatory mechanism. Some studies in children and adolescents have shown that children's non-visual functions may be highly sensitive to light, but the studies comparing with other age groups seem to have been limited. In order to study age-related differences in non-visual effects in detail, comparative studies should be conducted using subjects having a wide range of ages and with as much control as possible for intensity, wavelength component, duration, circadian timing, illumination method of light exposure, and other factors (mydriasis or non-mydriasis, cataracts or not in the older adults, etc.).

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 time points. These findings indicate an acceptable rate of collecting valid and reproducible PLR data when contrasting two measurements of PLR after 10 or 15 min of dark adaptation in depressed and suicidal patients.

Blue-light stimulation of the blind-spot constricts the pupil and enhances contrast sensitivity.

Short- and long-wavelength light can alter pupillary responses differently, allowing inferences to be made about the contribution of different photoreceptors on pupillary constriction. In addition to classical retinal photoreceptors, the pupillary light response is formed by the activity of melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC). It has been shown in rodents that melanopsin is expressed in the axons of ipRGCs that bundle at the optic nerve head, which forms the perceptual blind-spot. Hence, the first aim of this study was to investigate if blind-spot stimulation induces a pupillary response. The second aim was to investigate the effect of blind-spot stimulation by using the contrast sensitivity tests. Fifteen individuals participated in the pupil response experiment and thirty-two individuals in the contrast sensitivity experiment. The pupillary change was quantified using the post-illumination pupil response (PIPR) amplitudes after blue-light (experimental condition) and red-light (control condition) pulses in the time window between 2 s and 6 s post-illumination. The contrast sensitivity was assessed using two different tests: the Freiburg Visual Acuity Test and Contrast Test and the Tuebingen Contrast Sensitivity Test, respectively. Contrast sensitivity was measured before and 20 minutes after binocular blue-light stimulation of the blind-spot at spatial frequencies higher than or equal to 3 cycles per degree (cpd) and at spatial frequencies lower than 3 cpd (control condition). Blue-light blind-spot stimulation induced a significantly larger PIPR compared to red-light, confirming a melanopsin-mediated pupil-response in the blind-spot. Furthermore, contrast sensitivity was increased after blind-spot stimulation, confirmed by both contrast sensitivity tests. Only spatial frequencies of at least 3 cpd were enhanced. This study demonstrates that stimulating the blind-spot with blue-light constricts the pupil and increases the contrast sensitivity at higher spatial frequencies.

Automated pupillometry in space neuroscience.

Modern pupillometers are automated, thereby providing an objective, accurate, and reliable evaluation of various aspects of the pupillary light reflex at precision levels that were previously unobtainable. There are many gaps in knowledge regarding pupil size and pupillary light reflex in nervous system changes related to space travel given the previous lack of a precise method to quantitatively measure it. Automated pupillometry has not been used previously in space. This novel tool has promising uses in altered gravity environments as a sensitive non-invasive tool to determine alterations due to headward fluid shifts and elevated intracranial pressure. This article discusses the potential use of automated pupillometry in space for monitoring of astronaut health and neurological pathology.

Investigating the development of the autonomic nervous system in infancy through pupillometry.

We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24 months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, [Formula: see text] = 0.13), latency to constriction (F(3,326.41) = 3.84, p = 0.010, [Formula: see text] = 0.03) and relative constriction amplitude(F(3,282.53) = 3.70, p = 0.012, [Formula: see text] = 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001, [Formula: see text] = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, [Formula: see text] = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value.

Evaluation of Static and Dynamic Pupillary Functions in Early-Stage Primary Open Angle Glaucoma.

PRCIS: The dynamic parameters of the pupil, evaluated with an automated pupillometry device, differ in newly diagnosed early-stage primary open angle glaucoma (POAG) patients compared with healthy individuals, and this may guide us in early diagnosis and follow-up of glaucoma. INTRODUCTION AND AIM: To quantitatively determine static and dynamic pupillary functions in treatment-naive, newly diagnosed early-stage POAG patients and compare them with healthy controls. METHODS: Forty eye of forty subjects with early POAG were compared with 71 eye of 71 age- matched and sex-matched healthy controls in terms of static and dynamic pupillary functions in this prospective and cross-sectional study. Static and dynamic pupillary functions were obtained with an automated pupillometry device. Static pupillometry parameters are pupil diameter (mm) in high photopic (100 cd/m 2 ), low photopic (10 cd/m 2 ), mesopic (1 cd/m 2 ), and scotopic (0.1 cd/m 2 ) light conditions. Dynamic pupillometry parameters are resting diameter (mm), amplitude (mm), latency (ms), duration (ms), and velocity (mm/s) of pupil contraction and dilation. Measured data were evaluated and compared with t test for independent groups. RESULTS: Duration of pupil contraction was lower, ( P =0.04) latency of pupil dilation time was longer, ( P =0.03) duration of pupil dilation was shorter ( P =0.04) and velocity of pupil dilation was lower ( P =0.02) in the POAG group. There was no significant difference between the 2 groups in terms of static pupillometry characteristics and the resting pupil diameter ( P >0.05 for all values). CONCLUSION: These results suggest that dynamic pupillary light responses may be affected in early-stage POAG compared with the normal population. Longitudinal studies with larger series are needed to better understand the quantitative changes in dynamic pupillometry functions in early-stage POAG.

How uncertain are you? Disentangling expected and unexpected uncertainty in pupil-linked brain arousal during reversal learning.

During decision making, we are continuously faced with two sources of uncertainty regarding the links between stimuli, our actions, and outcomes. On the one hand, our expectations are often probabilistic, that is, stimuli or actions yield the expected outcome only with a certain probability (expected uncertainty). On the other hand, expectations might become invalid due to sudden, unexpected changes in the environment (unexpected uncertainty). Several lines of research show that pupil-linked brain arousal is a sensitive indirect measure of brain mechanisms underlying uncertainty computations. Thus, we investigated whether it is involved in disentangling these two forms of uncertainty. To this aim, we measured pupil size during a probabilistic reversal learning task. In this task, participants had to figure out which of two response options led to reward with higher probability, whereby sometimes the identity of the more advantageous response option was switched. Expected uncertainty was manipulated by varying the reward probability of the advantageous choice option, whereas the level of unexpected uncertainty was assessed by using a Bayesian computational model estimating change probability and resulting uncertainty. We found that both aspects of unexpected uncertainty influenced pupil responses, confirming that pupil-linked brain arousal is involved in model updating after unexpected changes in the environment. Furthermore, high level of expected uncertainty impeded the detection of sudden changes in the environment, both on physiological and behavioral level. These results emphasize the role of pupil-linked brain arousal and underlying neural structures in handling situations in which the previously established contingencies are no longer valid.

Recommendation of using both initial pupil size and constriction latency in pupillary light reflex as objective indicators reflecting subacute pain-related mental fatigue.

A previous study examining clinical subacute pain models under different methodological conditions showed that pain-induced mental fatigue can be associated with decreased initial pupil size (INIT)/shortened constriction latency (LAT) in the pupillary light reflex (PLR). We aimed to investigate the potential of INIT/LAT as objective indicators reflecting mental fatigue under the same methodological conditions. We recruited 118 patients planning to undergo three types of representative otolaryngological head and neck surgery procedures. We used the numerical rating scale (NRS) to assess subjective pain intensity and two mental fatigue-related mood categories of the Profile of Mood States, as well as INIT and LAT measurements (1) in the afternoon one day before surgery (pre1-surgery), (2) in the morning of the day of surgery (pre2-surgery), and (3) in the morning of the day following surgery (post-surgery). We assessed time point-dependent changes using one- or two-way analysis of variance, as well as responses of PLR parameters to mental fatigue using linear mixed-effects models (LMMs). As a result, NRS scores, the two mood categories, as well as LAT and INIT, showed significant time point-dependent changes. In post-hoc analyses, only INIT showed significant changes between the two pre-surgery time points. Thus, INIT values fluctuated even under pain-free conditions due to differences in the time of the day. LMMs demonstrated decreased INIT/shortened LAT related to mental fatigue. All surgical groups showed similar associations between mental fatigue and INIT/LAT findings. As each parameter has advantages and disadvantages, it is recommended to use both INIT and LAT as the indicators.

Central retina plays a decisive role in the suppression of pupillary escape.

PURPOSE: To explore the pupil redilation during persistent light exposure (pupillary escape phenomenon) at the macula and periphery with monochromatic light stimuli. METHODS: Forty healthy subjects aged 18-64 years (24 females) were examined by chromatic pupil campimetry (CPC) using red and blue 4-s stimuli of 10° radius at the center and 20°-peripheral locations one per quadrant. One glaucoma patient and one achromatopsia patient served as disease models. For statistical analyses, linear mixed-effects models were performed followed by post hoc t-tests. RESULTS: A distinct pupillary escape could be demonstrated peripherally (blue 0.099%*s, red 0.153%*s); at the central healthy retina, there was no relevant escape, neither for blue nor red stimulation. Comparing central versus peripheral stimulation revealed highly significant differences in the escape (difference blue 0.100 ± 0.013, red 0.144 ± 0.013, < 0.0001, respectively). In the periphery, the escape was significantly more pronounced for red compared with blue stimulation (difference 0.054 ± 0.013; p = 0.0001). Enhanced pupillary escape outside of the 95% confidence interval of the linear mixed-effects model of the healthy population could be exemplarily shown in a patient with glaucomatous ganglion cell damage. In the achromatopsia example, no relevant escape was found for blue stimulation, but for red stimulation in the periphery in a comparable range to healthy controls. CONCLUSION: The results emphasize that an intact inner retinal network of nerve fibers arising from the central macular region is necessary for maintaining pupillary constriction during a bright 4-s light stimulus and preventing increase of pupillary escape. Increasing receptive field sizes towards the periphery on the level of retinal ganglion cells and less input from central 1:1 connections could be one of the driving mechanisms for pupillary escape.

Pupillary response to chromatic light stimuli as a possible biomarker at the early stage of glaucoma: a review.

Glaucoma is a multifactorial neurodegenerative disease of the optic nerve currently considered a severe health problem because of its high prevalence, being the primary cause of irreversible blindness worldwide. The most common type corresponds to Primary Open-Angle Glaucoma. Glaucoma produces, among other alterations, a progressive loss of retinal ganglion cells (RGC) and its axons which are the key contributors to generate action potentials that reach the visual cortex to create the visual image. Glaucoma is characterized by Visual Field loss whose main feature is to be painless and therefore makes early detection difficult, causing a late diagnosis and a delayed treatment indication that slows down its progression. Intrinsically photosensitive retinal ganglion cells, which represent a subgroup of RGCs are characterized by their response to short-wave light stimulation close to 480 nm, their non-visual function, and their role in the generation of the pupillary reflex. Currently, the sensitivity of clinical examinations correlates to RGC damage; however, the need for an early damage biomarker is still relevant. It is an urgent task to create new diagnostic approaches to detect an early stage of glaucoma in a prompt, quick, and economical manner. We summarize the pathology of glaucoma and its current clinical detection methods, and we suggest evaluating the pupillary response to chromatic light as a potential biomarker of disease, due to its diagnostic benefit and its cost-effectiveness in clinical practice in order to reduce irreversible damage caused by glaucoma.

Artificial light at night decreases the pupillary light response of dark-adapted toads to bright light.

Artificial light at night (ALAN) is expanding worldwide. Many physiological effects have been reported in animals, but we still know little about the consequences for the visual system. The pupil contributes to control incoming light onto the retina. Sudden increases in light intensity evokes the pupil light reflex (PLR). Intrinsically photosensitive retinal ganglion cells (ipRGC) affect PLR and melatonin expression, which largely regulate circadian rhythms and PLR itself. IpRCG receive inputs from various photoreptors with different peak sensitivities implying that PLR could be altered by a broad range of light sources. We predicted ALAN to enhance PLR. Contrary to our prediction, dark-adapted cane toads Rhinella marina, exposed to ALAN (5 lx) for 12 days, exhibited a lower PLR than controls and individuals exposed to 0.04 lx, even after 1 h in bright light. We cannot conclude whether ALAN induced a larger pupil size in dark-adapted toads or a slower initial contraction. Nevertheless, the response was triggered by a light source with an emission peak (590 nm) well above the sensitivity peak of melanopsin, the main photoreceptor involved in PLR. Therefore, ALAN alters the capacity of toads to regulate the incoming light in the eye at night, which may reduce the performance of visually guided behaviors, and increase mortality by predators or road kills at night. This first study emphasizes the need to focus on the effect of ALAN on the vision of nocturnal organisms to better understand how this sensory system is altered and anticipate the consequences for organisms.