Search

Background: In the mammalian retina, intrinsically-photosensitive retinal ganglion cells (ipRGC) detect light and integrate signals from rods and cones to drive multiple non-visual functions including circadian entrainment and the pupillary light response (PLR). Non-visual photoreception and consequently non-visual sensitivity to light may change across child development. The PLR represents a quick and reliable method for examining non-visual responses to light in children. The purpose of this study was to assess differences in the PLRs to blue and red stimuli, measured one hour prior to bedtime, between children and adolescents., Methods: Forty healthy participants (8-9 years, n = 21; 15-16 years, n = 19) completed a PLR assessment 1 h before their habitual bedtime. After a 1 h dim-light adaptation period (< 1 lx), baseline pupil diameter was measured in darkness for 30 s, followed by a 10 s exposure to 3.0 × 10 13 photons/cm 2 /s of either red (627 nm) or blue (459 nm) light, and a 40 s recovery in darkness to assess pupillary re-dilation. Subsequently, participants underwent 7 min of dim-light re-adaptation followed by an exposure to the other light condition. Lights were counterbalanced across participants., Results: Across both age groups, maximum pupil constriction was significantly greater (p < 0.001, η p 2  = 0.48) and more sustained (p < 0.001, η p 2  = 0.41) during exposure to blue compared to red light. For adolescents, the post-illumination pupillary response (PIPR), a hallmark of melanopsin function, was larger after blue compared with red light (p = 0.02, d = 0.60). This difference was not observed in children. Across light exposures, children had larger phasic (p < 0.01, η p 2  = 0.20) and maximal (p < 0.01, η p 2  = 0.22) pupil constrictions compared to adolescents., Conclusions: Blue light elicited a greater and more sustained pupillary response than red light in children and adolescents. However, the overall amplitude of the rod/cone-driven phasic response was greater in children than in adolescents. Our findings using the PLR highlight a higher sensitivity to evening light in children compared to adolescents, and continued maturation of the human non-visual photoreception/system throughout development., (© 2024. The Author(s).)

Study Objectives: Altered light sensitivity may be an underlying vulnerability for disrupted circadian photoentrainment. The photic information necessary for circadian photoentrainment is sent to the circadian clock from melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). The current study tested whether the responsivity of ipRGCs measured using the post-illumination pupil response (PIPR) was associated with circadian phase, sleep timing, and circadian alignment, and if these relationships varied by season or depression severity., Methods: Adult participants (N = 323, agem = 40.5, agesd = 13.5) with varying depression severity were recruited during the summer (n = 154) and winter (n = 169) months. Light sensitivity was measured using the PIPR. Circadian phase was assessed using Dim Light Melatonin Onset (DLMO) on Friday evenings. Midsleep was measured using actigraphy. Circadian alignment was calculated as the DLMO-midsleep phase angle. Multilevel regression models covaried for age, gender, and time since wake of PIPR assessment., Results: Greater light sensitivity was associated with later circadian phase in summer but not in winter (β = 0.23; p = 0.03). Greater light sensitivity was associated with shorter DLMO-midsleep phase angles (β = 0.20; p = 0.03) in minimal depression but not in moderate depression (SIGHSAD < 6.6; Johnson-Neyman region of significance)., Conclusions: Light sensitivity measured by the PIPR was associated with circadian phase during the summer but not in winter, suggesting ipRGC functioning in humans may affect circadian entrainment when external zeitgebers are robust. Light sensitivity was associated with circadian alignment only in participants with minimal depression, suggesting circadian photoentrainment, a possible driver of mood, may be decreased in depression year-round, similar to decreased photoentrainment in winter., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

To increase computational flexibility, the processing of sensory inputs changes with behavioural context. In the visual system, active behavioural states characterized by motor activity and pupil dilation 1,2 enhance sensory responses, but typically leave the preferred stimuli of neurons unchanged 2-9 . Here we find that behavioural state also modulates stimulus selectivity in the mouse visual cortex in the context of coloured natural scenes. Using population imaging in behaving mice, pharmacology and deep neural network modelling, we identified a rapid shift in colour selectivity towards ultraviolet stimuli during an active behavioural state. This was exclusively caused by state-dependent pupil dilation, which resulted in a dynamic switch from rod to cone photoreceptors, thereby extending their role beyond night and day vision. The change in tuning facilitated the decoding of ethological stimuli, such as aerial predators against the twilight sky 10 . For decades, studies in neuroscience and cognitive science have used pupil dilation as an indirect measure of brain state. Our data suggest that, in addition, state-dependent pupil dilation itself tunes visual representations to behavioural demands by differentially recruiting rods and cones on fast timescales., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2022. The Author(s).)

Purpose: Two-photon vision relies on the perception of pulsed infrared light due to two-photon absorption in visual pigments. This study aimed to measure human pupil reaction caused by a two-photon 1040-nm stimulus and compare it with pupil responses elicited by 520-nm stimuli of similar color., Methods: Pupillary light reflex (PLR) was induced on 14 dark-adapted healthy subjects. Three types of fovea-centered stimuli of 3.5° diameter were tested: spirals formed by fast scanning 1040-nm (infrared [IR] laser) or 520-nm (visible [VIS] laser) laser beams and uniformly filled circle created by 520-nm LED (VIS light-emitting diode [LED]). The power of visible stimuli was determined with a dedicated procedure to obtain the same perceived brightness equivalent as for 800 µW used for two-photon stimulation., Results: The minimum pupil diameter for IR laser was 88% ± 10% of baseline, significantly larger than for both VIS stimuli: 74% ± 10% (laser) and 69% ± 9% (LED). Mean constriction velocity and time to maximum constriction had significantly smaller values for IR than for both VIS stimuli. Latency times were similar for IR and VIS lasers and slightly smaller for VIS LED., Conclusions: The two-photon stimulus caused a considerably weaker pupil reaction than one-photon stimuli of the same shape, brightness, and similar color. The smaller pupil response may be due to weaker two-photon stimulation of rods relative to cones as previously observed for two-photon vision. Contrary to normal vision, in a two-photon process the stray light is not perceived, which might reduce the number of stimulated photoreceptors and further weaken the PLR.

Background: We investigated the effectiveness of automated pupillometry on monitoring cardiopulmonary resuscitation (CPR) and predicting return of spontaneous circulation (ROSC) in a swine model of cardiac arrest (CA)., Methods: Sixteen male domestic pigs were included. Traditional indices including coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO 2 ), regional cerebral tissue oxygen saturation (rSO 2 ) and carotid blood flow (CBF) were continuously monitored throughout the experiment. In addition, the pupillary parameters including the initial pupil size before constriction (Init, maximum diameter), the end pupil size at peak constriction (End, minimum diameter), and percentage of change (%PLR) were measured by an automated quantitative pupillometer at baseline, at 1, 4, 7 min during CA, and at 1, 4, 7 min during CPR., Results: ROSC was achieved in 11/16 animals. The levels of CPP, ETCO 2 , rSO 2 and CBF were significantly greater during CPR in resuscitated animals than those non-resuscitated ones. Init and End were decreased and %PLR was increased during CPR in resuscitated animals when compared with those non-resuscitated ones. There were moderate to good significant correlations between traditional indices and Init, End, and %PLR (|r| = 0.46-0.78, all P < 0.001). Furthermore, comparable performance was also achieved by automated pupillometry (AUCs of Init, End and %PLR were 0.821, 0.873 and 0.821, respectively, all P < 0.05) compared with the traditional indices (AUCs = 0.809-0.946)., Conclusion: The automated pupillometry may serve as an effective surrogate method to monitor cardiopulmonary resuscitation efficacy and predict ROSC in a swine model of cardiac arrest., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Transient variations in pupil size (PS) under constant luminance are coupled to rapid changes in arousal state, 1-3 which have been interpreted as vigilance, 4 salience, 5 or a surprise signal. 6-8 Neural control of such fluctuations presumably involves multiple brain regions 5 , 9-11 and neuromodulatory systems, 3 , 12 , 13 but it is often associated with phasic activity of the noradrenergic system. 9 , 12 , 14 , 15 Serotonin (5-HT), a neuromodulator also implicated in aspects of arousal 16 such as sleep-wake transitions, 17 motivational state regulation, 18 and signaling of unexpected events, 19 seems to affect PS, 20-24 but these effects have not been investigated in detail. Here we show that phasic 5-HT neuron stimulation causes transient PS changes. We used optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DRN) of head-fixed mice performing a foraging task. 5-HT-driven modulations of PS were maintained throughout the photostimulation period and sustained for a few seconds after the end of stimulation. We found no evidence that the increase in PS with activation of 5-HT neurons resulted from interactions of photostimulation with behavioral variables, such as locomotion or licking. Furthermore, we observed that the effect of 5-HT on PS depended on the level of environmental uncertainty, consistent with the idea that 5-HT could report a surprise signal. 19 These results advance our understanding of the neuromodulatory control of PS, revealing a tight relationship between phasic activation of 5-HT neurons and changes in PS., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

We evaluated changes in the pupillary light reflex (PLR) of ethambutol (EMB)-induced optic neuropathy and analyzed the correlations between PLR parameters and other structural changes in EMB-induced optic neuropathy. This retrospective, observational, case-control study involved thirty-two eyes of 17 patients with EMB-induced optic neuropathy (EON group), sixty eyes of 60 patients without EMB-induced optic neuropathy (non-EON group) while taking ethambutol, and forty-five eyes of 45 normal controls. PLR was measured by digital pupillometry. The clinical characteristics, optical coherence tomography measurements and PLR parameters including pupil diameter, constriction latency, constriction ratio/velocity, and dilation velocity were noted. The differences in PLR measurements were compared among the three groups. Correlations between PLR parameters and other structural parameters in EMB-induced optic neuropathy were evaluated. The pupillary constriction ratio, constriction and dilation velocities were significantly reduced in the EON group compared to the non-EON group and controls (all P < 0.05). In EMB-induced optic neuropathy, average outer macular ganglion cell layer (mGCL) thickness showed a significant correlation with the pupillary constriction ratio (ß = 4.14, P = 0.003) and maximal constriction velocity (ß = 1.08, P < 0.001). This study confirmed that pupillary constriction and dilation velocities were significantly decreased in patients with EMB-induced optic neuropathy, compared to normal controls. Digital pupillometry may be a useful tool in the evaluation of EMB-induced optic neuropathy.

The purpose of this pilot study was to investigate the light-induced pupillary and lacrimation responses mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) in migraine. Ten participants with episodic migraine and normal tear production, as well as eleven visually normal controls participated in this study. Following an initial baseline trial (no light flash), participants received seven incremental and alternating red and blue light flashes. Pupillometry recording of the left eye and a 1-min anesthetized Schirmer's test of the right eye (using 0.5% proparacaine) were performed simultaneously. Intrinsic and extrinsic ipRGC photoactivities did not differ between migraine participants and controls across all intensities and wavelengths. Migraine participants, however, had significantly lower lacrimation than controls following the highest blue intensity. A positive correlation was found between melanopsin-driven post-illumination pupillary responses and lacrimation following blue stimulation in both groups. Our results show that participants with self-reported photophobia have normal ipRGC-driven responses, suggesting that photophobia and pupillary function may be mediated by distinct ipRGC circuits. The positive correlation between melanopsin-driven pupillary responses and light-induced lacrimation suggests the afferent arm of the light-induced lacrimation reflex is melanopsin-mediated and functions normally in migraine. Lastly, the reduced melanopsin-mediated lacrimation at the highest stimulus suggests the efferent arm of the lacrimation reflex is attenuated under certain conditions, which may be a harbinger of dry eye in migraine., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Human and animal studies suggest that light-mediated dopamine release may underlie the protective effect of time outdoors on myopia development. Melanopsin-containing retinal ganglion cells may be involved in this process by integrating ambient light exposure and regulating retinal dopamine levels. The study evaluates this potential involvement by examining whether melanopsin-driven pupillary responses are associated with adult refractive error., Methods: Subjects were 45 young adults (73% female, 24.1 ± 1.8 years) with refractive errors ranging from -6.33 D to +1.70 D. The RAPDx (Konan Medical) pupillometer measured normalized pupillary responses to three forms of square-wave light pulses alternating with darkness at 0.1 Hz: alternating long wavelength (red, peak at 608 nm) and short wavelength (blue, peak at 448 nm), followed by red only and then blue only., Results: Non-myopic subjects displayed greater pupillary constriction in the blue-only condition and slower redilation following blue light offset than subjects with myopia (P = 0.011). Pupillary responses were not significantly different between myopic and non-myopic subjects in the red-only condition (P = 0.15). More hyperopic/less myopic refractive error as a continuous variable was linearly related to larger increases in pupillary constriction in response to blue-only stimuli (r = 0.48, P = 0.001)., Conclusions: Repeated light exposures to blue test stimuli resulted in an adaptation in the pupillary response (more constriction and slower redilation), presumably due to increased melanopsin-mediated input in more hyperopic/less myopic adults. This adaptive property supports a possible role for these ganglion cells in the protective effects of time outdoors on myopia development.

Pupil size changes with light. For this reason, researchers studying the effect of attention, contextual processing, and arousal on the pupillary response have matched the mean luminance of their stimuli across conditions to eliminate the contribution of differences in light levels. Here, we argue that the match of mean luminance is not enough. In Experiment 1, we presented a circular sinewave grating on a gray background for 2 seconds. The area of the grating could be 3°, 6°, or 9°. The mean luminance of each grating was equal to the luminance of the gray background, such that regardless of the size of the grating there was no change in mean luminance between conditions. Participants were asked to fixate the center of the grating and passively view it. We found that in all size conditions, there was a pupil constriction starting at about 300 ms after stimulus onset, and the pupil constriction increased with the size of the grating. In Experiment 2, when a small grating was presented immediately after the presentation of a large grating (or vice versa), the pupil constriction changed accordingly. In Experiment 3, we replicated Experiment 1 but had the subjects perform an attention-demanding fixation task in one session, and passively view the stimuli in the other. We found that the main effect of task was not significant. In sum, our results show that stimulus size can modulate pupil size robustly and steadily even when the luminance is matched across the different stimuli.

Purpose: To determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans., Methods: Twenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength "blue," or long wavelength "red" light, or darkness. Choroidal thickness, imaged with spectral domain optical coherence tomography, axial length, determined from biometry, and rod/cone- and intrinsically photosensitive retinal ganglion cell-driven pupil responses were measured before and after exposure. Pupil stimuli were six 1 second alternating red (651 nm) and blue (456 nm) stimuli, 60 seconds apart. Pupil metrics included maximum constriction and the 6 second post-illumination pupil response (PIPR)., Results: Compared with before exposure, the choroid significantly thinned after broadband light, red light, and dark exposure (all P < 0.05), but not after blue light exposure (P = 0.39). The maximum constriction to 1 second red stimuli significantly decreased after all light exposures (all P < 0.001), but increased after dark exposure (P = 0.02), compared with before exposure. Maximum constriction and 6-second PIPR to 1 second blue stimuli significantly decreased after all light exposures compared with before exposure (all P < 0.005), with no change after dark exposure (P > 0.05). There were no differences in axial length change or 6-second PIPR to red stimuli between exposures., Conclusions: Narrowband blue and red light exposure induced differential changes in choroidal thickness. Maximum constriction, a function of rod/cone activity, and the intrinsically photosensitive retinal ganglion cell-mediated PIPR were attenuated after all light exposures. Findings demonstrate differing effects of short-term narrowband light and dark exposure on the choroid, rod/cone activity, and intrinsically photosensitive retinal ganglion cells.

The common degu (Octodon degus) is an emerging model in biomedical science research due to its longevity and propensity to develop human-like conditions. However, there is a lack of standardized techniques for this non-traditional laboratory animal. In an effort to characterize the model, we developed a chromatic pupillometry setup and analysis protocol to characterize the pupillary light reflex (PLR) in our animals. The PLR is a biomarker to detect early signs for central nervous system deterioration. Chromatic pupillometry is a non-invasive and anesthesia-free method that can evaluate different aspects of the PLR, including the response of intrinsically photosensitive retinal ganglion cells (ipRGCs), the disfunction of which has been linked to various disorders. We studied the PLR of 12 degus between 6 and 48 months of age to characterize responses to LEDs of 390, 450, 500, 525 and 605 nm, and used 5 with overall better responses to establish a benchmark for healthy PLR (PLR+) and deteriorated PLR (PLR-). Degu pupils contracted up to 65% of their horizontal resting size before reaching saturation. The highest sensitivity was found at 500 nm, with similar sensitivities at lower tested intensities for 390 nm, coinciding with the medium wavelength and short wavelength cones of the degu. We also tested the post-illumination pupillary response (PIPR), which is driven exclusively by ipRGCs. PIPR was largest in response to 450 nm light, with the pupil preserving 48% of its maximum constriction 9 s after the stimulus, in contrast with 24% preserved in response to 525 nm, response driven mainly by cones. PLR- animals showed maximum constriction between 40% and 50% smaller than PLR+, and their PIPR almost disappeared, pointing to a disfunction of the iPRGCs rather than the retinal photoreceptors. Our method thus allows us to non-invasively estimate the condition of experimental animals before attempting other procedures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate three measures of inner retina function, the pattern electroretinogram (pERG), the photopic negative response (PhNR), and the post-illumination pupil response (PIPR) in diabetics with and without nonproliferative diabetic retinopathy (NPDR)., Methods: Fifteen non-diabetic control subjects and 45 type 2 diabetic subjects participated (15 have no clinically apparent retinopathy [NDR], 15 have mild NPDR, and 15 have moderate/severe NPDR). The pERG was elicited by a contrast-reversing checkerboard pattern, and the PhNR was measured in response to a full-field, long-wavelength flash presented against a short-wavelength adapting field. The PIPR was elicited by a full-field, 450 cd/m 2 , short-wavelength flash. All responses were recorded and analyzed using conventional techniques. One-way ANOVAs were performed to compare the pERG, PhNR, and PIPR among the control and diabetic groups., Results: ANOVA indicated statistically significant differences among the control and diabetic subjects for all three measures. Holm-Sidak post hoc comparisons indicated small, nonsignificant reductions in the pERG (8%), PhNR (8%), and PIPR (10%) for the NDR group compared to the controls (all p > 0.25). In contrast, there were significant reductions in the pERG (35), PhNR (34%), and PIPR (30%) for the mild NPDR group compared to the controls (all p < 0.01). Likewise, there were significant reductions in the pERG (40%), PhNR (32%), and PIPR (32%) for the moderate/severe NPDR group compared to the controls (all p < 0.01)., Conclusion: Abnormalities of the pERG, PhNR, and PIPR suggest inner retina neural dysfunction in diabetics who have clinically apparent vascular abnormalities. Taken together, these measures provide a noninvasive, objective approach to study neural dysfunction in these individuals.

Pupillary examination has fundamental diagnostic and prognostic values in clinical practice. However, pupillary assessment was relied until present on manual, qualitative, examination, using manual flash penlights or lamps. Quantitative examination with the use of automated infrared video-pupillometers allows an objective assessment of several pupillary parameters and may be superior to manual subjective examination. The potential for quantitative pupillometry is multiple in the setting of critical care, for the monitoring and detection of secondary cerebral insults and to assess brainstem dysfunction and early coma outcome prognostication, and in the intra-operative anesthesiology setting, to assess analgesia and opioid requirement. Here, we describe the pupillometry technique and review recent critical care and anesthesiology studies that demonstrate the value and potential clinical utility of quantitative pupillometry as neuromonitoring bedside modality.

Background/aims: We wished to determine whether the pupillary light reaction can differentiate preclinical Alzheimer's disease (AD) subjects from normal ageing controls. We performed a prospective study evaluating the pupillary light reaction in a cohort of well-characterised subjects with preclinical AD versus normal ageing controls., Methods: We recruited 57 subjects from our institution's Memory and Aging Project, part of our Alzheimer's Disease Research Center. All subjects completed PET-PiB imaging, cerebrospinal fluid analysis and at least 1 neuropsychiatric assessment after their baseline assessment. All participants were assigned a clinical dementia rating and underwent a complete neuro-ophthalmic examination. Participants were divided into a dementia biomarker+ (preclinical AD) and biomarker- (normal ageing) group based on preclinical risk for Alzheimer's dementia. Pupillometry measurements were performed by using the NeurOptics PLR-200 Pupillometer., Results: A total of 57 subjects were recruited with 24 dementia biomarker+ and 33 dementia biomarker- individuals. A variety of pupil flash response (PLR) parameters were assessed. Comparisons between groups were analysed using generalised estimating equations. None of the pupillary parameters showed a significant difference between groups., Conclusions: We found no significant differences in PLR between preclinical AD subjects and normal ageing controls. This suggests that the disease effect on the PLR may be small and difficult to detect at the earliest stages of the disease. Future studies could include larger sample size and chromatic pupillometry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pupillary dysfunction is recognized as a sign of acute neurological deterioration due to worsening mass effect in patients with hemispheric strokes. Recent neuroimaging studies suggest that horizontal displacement of brain structures may be more important than vertical displacement in explaining these pupillary findings. Pupillometers allow objective and standardized evaluation of the pupillary light reflex. We hypothesized that pupillary data (Neurological Pupil index [NPi] and constriction velocity [CV]) obtained with a hand-held pupilometer, correlate with horizontal intracranial midline shift in patients with ischemic and hemorrhagic strokes., Methods: The ENDPANIC registry is a prospective database of pupillometer readings in neurological patients. There were 134 patients in the database with an acute ischemic stroke or intracerebral hemorrhage who had at least 2 neurologic imaging studies (CT or MRI) and pupillometer assessments performed within 6 hours of the imaging. Horizontal shift of the septum pellucidum (SPS) was measured in 293 images. We computed the correlation between SPS and the following pupillary variables: size, NPi, CV (left, right, and left-right difference), followed by a regression model to control for confounders., Results: There were 94 patients (70.1%) with an ischemic stroke and 40 patients (29.9%) had an intracerebral hemorrhage. After controlling for age, race, and gender, there was a significant correlation between the SPS and NPi (left [P < .001], right [P < .001]), CV (left [P < .005], right [P < .001]) pupillary asymmetry (absolute difference between right and left; P < .05), but not between SPS and pupillary size (left or right). There was a significant correlation between the NPi and CV for the right pupil when there was a right-to-left SPS (P < .001 and P < .05, respectively), but none between the NPi and CV for the left pupil and left-to-right SPS., Conclusions: In patients with ischemic and hemorrhagic strokes, there is a significant correlation between SPS and the NPi, CV and pupillary asymmetry, but not with pupillary size., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pupillary reflex has been used as a method to examine psychological problems in human clinics and mental disease research. Intensive animal farming has been shown to lead to chronic stress resulting in depression; however, comparing with humans we lack an effective clinical method to clinically inspect these psychological problems in animals. The goal of this study was to investigate the effect of age and housing conditions (confined crates vs. group pens) on pupillary light reflex (PLR) of sows to explore whether PLR can be used as an effective way to measure the psychological state of farm animals. In total, 270 pregnant sows were selected for PLR testing and divided into 6 treatments (45 sows per treatment) of 2 different environments (group-housed pen and confined gestation crates) and 3 parities (first, third, and fifth parities). Six selected pupil parameters: 1) latency of the pupil constriction onset (LAT); 2) the percent of the constriction (CON); 3) average constriction velocity (ACV); 4) maximum constriction velocity (MCV); 5) average dilation velocity (ADV); and 6) time of 75% recovery after constriction (T75) were examined. The results showed that there was no difference found in these PLR parameters between the breeds (P > 0.05) but the significant effects were found on LAT, CON, ACV, and MCV by age (P < 0.01). The group-housed sows had significantly higher CON, ACV, and MCV than those in the confined crates (P < 0.05). In conclusion, the pupillary light reflex of the sows was not affected by breed but by age. The results also indicate that some of PLR parameters were sensitive to housing conditions and suggest that ACV and MCV have potential to be sensitive indicators in relation to the psychological problem of sows., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tear-film dynamics were analyzed by a synchronizing recording of double-pass (DP) and pupil retro-illumination (RI) images with contrast sensitivity (CS) measurements. Simultaneous DP and RI images were acquired in three subjects wearing contact lenses while keeping the eye open. Changes in contrast sensitivity for an 18 c/deg green grating were also estimated. From the DP retinal images, the effect of the tear film is described through the objective scattering index (OSI). This presented a negative correlation with the increase in CS during tear-film deterioration (as observed by RI imaging). These results show a relationship between visual outcome degradation due to tear-film breakup and the increase in intraocular scattering. This work shows a combined methodology for the evaluation of tear-film dynamics.

This paper aims to compare the image quality between centration on the coaxially sighted corneal light reflex (CSCLR) and on the entrance pupil center (EPC). Myopic laser ablation was simulated on eye models, and the optical performances were compared. Centration on the EPC leads to higher wavefront aberrations and lower modulation transfer function. The two centration methods give nearly identical retinal images for angle kappa less than 5°. Because of less tissue removal, centration on the EPC is probably preferable for angle kappa less than 5°, but CSCLR centration may be preferable for angle kappa larger than 5°. The degree of tilt of the post-surgery anterior corneal surface explains the differences between the two methods.

Chromatic pupillometry is an emerging modality in the assessment of retinal and optic nerve disorders. Herein, we evaluate the effect of low and moderate refractive errors on pupillary responses to blue- and red-light stimuli in a healthy older population. This study included 139 participants (≥50 years) grouped by refractive error: moderate myopes (>-6.0D and ≤-3.0D, n = 24), low myopes (>-3.0D and <-0.5D, n = 30), emmetropes (≥-0.5D and ≤0.5D, n = 31) and hyperopes (>0.5D and <6.0D, n = 54). Participants were exposed to logarithmically ramping-up blue (462 nm) and red (638 nm) light stimuli, designed to sequentially activate rods, cones and intrinsically-photosensitive retinal ganglion cells. Pupil size was assessed monocularly using infra-red pupillography. Baseline pupil diameter correlated inversely with spherical equivalent (R = -0.26, P < 0.01), and positively with axial length (R = 0.37, P < 0.01) and anterior chamber depth (R = 0.43, P < 0.01). Baseline-adjusted pupillary constriction amplitudes to blue light did not differ between groups (P = 0.45), while constriction amplitudes to red light were greater in hyperopes compared to emmetropes (P = 0.04) at moderate to bright light intensities (12.25-14.0 Log photons/cm²/s). Our results demonstrate that low and moderate myopia do not alter pupillary responses to ramping-up blue- and red-light stimuli in healthy older individuals. Conversely, pupillary responses to red light should be interpreted cautiously in hyperopic eyes.

Background: It is well known that light containing the blue component stimulates the intrinsically photosensitive retinal ganglion cells (ipRGCs) and plays a role in melatonin suppression and pupillary constriction. In our previous studies, we verified that simultaneous exposure to blue and green light resulted in less pupillary constriction than blue light exposure. Hence, we hypothesized that the nonvisual effects of polychromatic white light might be increased by blocking the green component. Therefore, we conducted an experiment using optical filters that blocked blue or green component and examined the nonvisual effects of these lights on pupillary constriction and electroencephalogram power spectra., Methods: Ten healthy young males participated in this study. The participant sat on a chair with his eyes facing an integrating sphere. After 10 min of light adaptation, the participant's left eye was exposed to white pulsed light (1000 lx; pulse width 2.5 ms) every 10 s with a blue-blocking glasses, a green-blocking glasses, or control glasses (no lens), and pupillary constriction was measured. Then, after rest for 10 min, the participant was exposed a continuous white light of 1000 lx with a blue- or green-blocking glasses or control glasses and electroencephalogram was measured., Results: Pupillary constriction with the blue-blocking glasses was significantly less than that observed with the green-blocking glasses. Furthermore, pupillary constriction under the green-blocking glasses was significantly greater than that observed with the control glasses., Conclusions: A reduction in the green component of light facilitated pupillary constriction. Thus, the effects of polychromatic white light containing blue and green components on ipRGCs are apparently increased by removing the green component.

Purpose: To assess the effect of stimulus intensity on rod- and cone-mediated pupil light reflex (PLR) to small stimuli presented at central and peripheral visual field (VF) locations., Methods: The PLR to small (0.43°) chromatic stimuli was tested in the right eye of healthy subjects. Blue (485 ± 20 nm) and red (625 ± 15 nm) stimuli were presented at incremental light intensities (0.5-3.75 log cd/m2) at peripheral (21.21°) and central (4.24°) VF locations using a chromatic pupilloperimeter under mesopic or blue light adaptation conditions. The percentage of pupil contraction (PPC), maximal pupil contraction velocity (MCV), latency of MCV (LMCV) and the ratio of central to peripheral responses for PPC (QPPC value) were determined., Results: Under mesopic light adaptation conditions, the mean PPC recorded in response to red stimuli was lower than blue stimuli in all VF locations and light intensities, and the QPPC values were higher in response to red compared with blue light stimuli across the light intensity range tested. With blue background light, the pupil responses for red and blue light stimuli were approximately the same in the peripheral VF. LMCV was nearly constant in all VF locations for blue and red stimuli, respectively., Conclusions: The chromatic pupilloperimeter enables the assessment of rod- and cone- contribution to the PLR in different VF locations. The optimal light intensities determined here for the assessment of focal activation of the two photoreceptor systems may be used for clinical evaluation of photoreceptor health.

Purpose: To investigate how melanopsin-mediated intrinsically photosensitive retinal ganglion cell (ipRGC) signals are integrated binocularly using chromatic pupillometry. We hypothesized that if the melanopsin system is summative, there will be a greater postillumination pupillary response (PIPR) under binocular conditions after viewing bright blue light., Methods: Pupillary responses in 10 visually normal participants were recorded with an eye tracker following full-field stimulation of red (long wavelength) and blue (short wavelength) light of equal intensity (dim: 0.1 cd [candela]/m2, bright: 60 cd/m2) and duration (400 ms). Individual monocular (left eye) pupil responses were measured first, followed by binocular responses. Each participant repeated the same protocol on 3 separate days, at similar times of day. PIPR was recorded for bright red and blue conditions only, whereas maximum pupillary constriction (MPC) was measured under both bright and dim conditions during red and blue light stimulation., Results: Bright blue light stimulation induced greater PIPR under binocular than monocular viewing conditions (F(1,9) = 79.52, P < 0.001). Bright red light stimulation induced minimal PIPR and showed no significant difference between viewing conditions post Bonferroni correction (F(1,9) = 5.49, P = 0.04). MPC was greater during binocular than monocular viewing conditions for all light stimuli, but was greatest following blue compared to red light stimulation., Conclusions: A larger PIPR was induced using a binocular than a monocular full-field stimulus of equal intensity and duration, demonstrating that melanopsin-mediated ipRGC signals are summated binocularly. This study expands our current understanding of the melanopsin system and may be used as an additional marker to stratify diseases according to their etiologies.

Significance: The response of the pupil to a flash of light, the pupillary light reflex (PLR), is an important measure in optometry and in other fields of medicine that is typically evaluated by qualitative observation. Here we describe a simple, portable, iPhone-based pupillometer that quantifies the PLR in real time., Purposes: The purposes of this study were to describe a novel application that records the PLR and to compare its technical capabilities with a laboratory-based infrared (IR) camera system., Methods: Pupil sizes were measured from 15 visually normal subjects (age, 19 to 65 years) using an IR camera system and the Sensitometer test. This test elicits pupillary constriction using the iPhone flash, records pupil size using the camera, and provides measurements in real time. Simultaneous recordings were obtained with the Sensitometer test and IR camera, and two measures were calculated: (1) dark-adapted steady-state pupil size and (2) minimum pupil size after the flash. The PLR was defined as the difference between these two measures. Pupil size was also recorded during the redilation phase after the flash. Bland-Altman analysis was used to assess the limits of agreement between the two methods., Results: Statistically significant correlations between the IR and Sensitometer test measures were found for the PLR (r = 0.91, P < .001) and redilation size (r = 0.65, P = .03). Bland-Altman analysis indicated a mean PLR difference of 6% between these two methods. The PLR limit of agreement was 14%, indicating that 95% of subjects are expected to have IR and Sensitometer test measurements that differ by 14% or less. Bland-Altman analysis indicated a mean redilation size difference of 1% between the two methods; the limit of agreement was 5%., Conclusions: There is excellent agreement between pupil responses recorded using the Sensitometer test and IR camera. The Sensitometer test provides a highly promising approach for simple, portable, inexpensive pupillary measurements.

The timecourse and extent of changes in pupil area in response to light are reviewed in all classes of vertebrate and cephalopods. Although the speed and extent of these responses vary, most species, except the majority of teleost fish, show extensive changes in pupil area related to light exposure. The neuromuscular pathways underlying light-evoked pupil constriction are described and found to be relatively conserved, although the precise autonomic mechanisms differ somewhat between species. In mammals, illumination of only one eye is known to cause constriction in the unilluminated pupil. Such consensual responses occur widely in other animals too, and their function and relation to decussation of the visual pathway is considered. Intrinsic photosensitivity of the iris muscles has long been known in amphibia, but is in fact widespread in other animals. The functions of changes in pupil area are considered. In the majority of species, changes in pupil area serve to balance the conflicting demands of high spatial acuity and increased sensitivity in different light levels. In the few teleosts in which pupil movements occur they do not serve a visual function but play a role in camouflaging the eye of bottom-dwelling species. The occurrence and functions of the light-independent changes in pupil size displayed by many animals are also considered. Finally, the significance of the variations in pupil shape, ranging from circular to various orientations of slits, ovals, and other shapes, is discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

When addressing the risk of laser-induced retinal injury in daylight, an individual's pupil size (diameter) is of great importance since the retinal illumination varies as the square of the pupil size. Pupil size was measured under daylight conditions for 87 subjects to fill the data gap in over a century of laboratory pupillometry studies. Photography with a fixed chin/head rest and digital camera platform was employed to measure pupil diameter of subjects viewing a full-field neutral screen. The digital images of the pupils of 87 subjects were measured using computer software. Screen luminance values ranged between 790 cd m to 4,300 cd m. The average pupil size for this study was 2.39 mm for an average luminance of 1,473 cd m. Pupil size measurements ranged from 1.44 mm to 3.03 mm. The data were stratified over luminance intervals, sex, eye color, and age.

Purpose: To use and test a new method of inducing endogenously generated pupillary oscillations (POs) in patients with unilateral optic neuritis (ON), to describe a signal analysis approach quantifying pupil activity and to evaluate the extent to which POs permit to discriminate patients from control participants., Method: Pupil size was recorded with an eye-tracker and converted in real time to modulate the luminance of a stimulus (a 20° disk) presented in front of participants. With this biofeedback setting, an increasing pupil size transforms into a high luminance, entraining a pupil constriction that in turn decreases the stimulus luminance, and so on, resulting in endogenously generated POs. POs were recorded for 30 seconds in the affected eye, in the fellow eye and in binocular conditions with 22 patients having a history of unilateral ON within a period of 5 years, and with 22 control participants. Different signal analysis methods were used to quantify the power and frequency of POs., Results: On average, pupil size oscillated at around 1 Hz. The amplitude of POs appears not to be a reliable marker of ON. In contrast, the frequency of POs was significantly lower, and was more variable over time, in the patients' affected eye, as compared to their fellow eye and to the binocular condition. No such differences were found in control participants. Receiver operating characteristic analyses based on the frequency and the variability of POs to classify patients and control participants gave an area under the curve of 0.82, a sensitivity of 82% (95%CI: 60%-95%) and a specificity of 77% (95%CI: 55%-92%)., Conclusions: The new method used to induce POs allowed characterizing the visual afferent pathway defect in ON patients with encouraging accuracy. The method was fast, easy to use, only requiring that participants look ahead, and allows testing many stimulus parameters (e.g. color, stimulus location, size, etc)., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate in patients with primary open-angle glaucoma (POAG) the contribution of the inner and outer retinal photoreceptors to the pupillary light responses (PLRs) correlated with both functional (color vision and visual field perimetry) and morphologic (optical coherence tomography) parameters., Methods: In total, 45 patients with POAG and 25 healthy control participants were evaluated. The PLR was measured as pupil diameter with an eye tracker; stimuli were presented in a Ganzfeld. Pupil responses were measured monocularly, to 1 second blue (470 nm) and red (640 nm) flashes with -3, -2, -1, 0, 1, 2, and 2.4 log cd/m luminance levels. Color vision was evaluated with the Cambridge Color Test, visual field was measured by standard automatic perimetry, and retinal nerve fiber layer thickness was evaluated by optical coherence tomography., Results: Patients with moderate and severe POAG have a significantly decreased PLR that depends on the severity of POAG, for both the 470 and 640 nm stimuli, revealing the reduction of the contributions of the rods, cones, and intrinsically photosensitive retinal ganglion cells to PLR. A significant loss of color discrimination along the blue-yellow axis was observed in all stages of POAG. Correlations among standard automatic perimetry, retinal nerve fiber layer thickness, Cambridge Color Test, PLR, and melanopsin parameters were found., Conclusions: The results provide evidence that in moderate and severe stages of POAG, both the inner and outer retinal contributions to PLR are affected. Also, a worsening in color vision was correlated with reduced PLR responses at high-intensity stimuli. These findings may enhance the clinical management of POAG patients.

Environmental light can exert potent effects on physiology and behaviour, including pupil size, vigilance and sleep. Previous work showed that these non-image forming effects can last long beyond discontinuation of short -wavelength light exposure. The possible functional effects after switching off long -wavelength light, however, have been insufficiently characterized. In a series of controlled experiments in healthy adult volunteers, we evaluated the effects of five minutes of intense red light on physiology and performance during subsequent darkness. As compared to prior darkness, prior red light induced a subsequent sustained pupil dilation. Prior red light also increased subsequent heart rate and heart rate variability when subjects were asked to perform a sustained vigilance task during the dark exposure. While these changes suggest an increase in the mental effort required for the task, it could not prevent a post-red slowing of response speed. The suggestion that exposure to intense red light affects vigilance during subsequent darkness, was confirmed in a controlled polysomnographic study that indeed showed a post-red facilitation of sleep onset. Our findings suggest the possibility of using red light as a nightcap., (© 2018 The Author(s).)

Purpose: In this work, we investigated the pupillary conditions during straylight measurement, and the potential effect this might have on the measured straylight., Methods: Five young (26-29-years-old) and 15 older (50-68-years-old) individuals participated in this study. First, the pupil diameter of both eyes was measured at three room illuminances. Next, straylight was assessed at two room illuminances. Simultaneously, the change in pupil size of the fellow eye was registered by a camera., Results: Pupil size decreased with room illuminance and with age (both p<0.05). The dependency of pupil size on age decreased as room illuminance increased (0.018mm/year at 4 lux, 0.014mm/year at 40 lux, and 0.008mm/year at 400 lux illuminances). However, during straylight measurement, pupil sizes hardly differed between 4 and 40 lux illuminances. Respective pupil sizes corresponded with 399 and 451 lux adaptation on average. No statistically significant difference was found between the straylight under the two illuminances with average R 2 =0.85, p<0.05., Conclusion: We conclude that the illuminance of the examination room during straylight assessment does not affect the outcome in normal eyes. In fact, under mesopic and scotopic conditions, the luminance of the test field is so much higher than that of the room so that it determines the pupil size. Regardless of the lighting level, straylight measured in a laboratory, is valid for photopic pupils at an adaptation level corresponding with about 400 lux room illuminance., (Copyright © 2017 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To assess the clinically acceptable range of inlay decentration with respect to the light-constricted pupil center and the coaxially sighted corneal light reflex (CSCLR) for an inlay (Raindrop Near Vision Inlay; ReVision Optics, Inc., Lake Forest, CA) that reshapes the anterior corneal surface., Methods: In this retrospective, observational cohort study of 115 patients with emmetropic or low hyperopic presbyopia who were implanted with a shape-changing corneal inlay, visual acuity, task performance (in good and dim light), reports of halos and glare, and satisfaction data were collected from the preoperative and 3-month postoperative examinations. Inlay centration with respect to the pupil center and CSCLR was determined from the center of the inlay effect derived from iTrace (Tracey Technologies, Houston, TX) wavefront measurements. Multivariate regression models assessed the influence of inlay position on visual outcomes., Results: On average, monocular uncorrected near visual acuity (UNVA) improved 4.9 ± 1.7 lines in the treated eye, with no loss in binocular distance vision. Eighty-three percent of implants were centered radially within 0.5 mm of the pupil center. Multivariate analysis of decentration with respect to both the pupil center and CSCLR revealed no significant interaction with the above clinical outcomes, with the exception of UNVA in the treated eye (all P > .05, α = 0.05). For decentration of less than 0.75 mm, the change in UNVA was less than 1 line., Conclusions: Distance and near visual acuity, task performance, severity of halos and glare, and satisfaction were independent of radial decentration of the Raindrop Near Vision Inlay of less than 0.75 mm from the light-constricted pupil. [J Refract Surg. 2018;34(3):164-170.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To study the effect of the internal fixation lamp on anterior chamber width measured by anterior segment optical coherence tomography., Methods: In a prospective cross sectional observational study, consecutive 22 right eyes of 22 patients (4 men and 18 women) with suspected primary angle closure underwent swept source domain anterior segment optical coherence tomography (AS-OCT), (CASIA SS-1000, Tomey, Nagoya, Japan). Anterior chamber parameters of angle opening distance (AOD), trabecular-iris angle (TIA), angle recess area (ARA) at 500 or 750 µm from scleral spur and pupil diameter were measured by AS-OCT in a three-dimensional mode in 4 quadrants (superior, inferior, temporal and nasal) in dark room setting both with and without internal fixation lamp., Results: Anterior segment parameters of AOD 500 in superior, inferior and temporal quadrants, AOD 750 at superior and nasal, TIA 500 at superior, and inferior and TIA 750 at superior and nasal, and ARA 500 or 750 at superior and inferior with internal fixation lamp were greater and the pupil diameter was significantly (all P < 0.05, paired t test) smaller than when measured without fixation lamp., Conclusions: Internal fixation lamp of the anterior segment OCT makes the pupil constrict and angle wider. When using AS-OCT with usual setting with internal fixation lamp on with eyes in which the anterior chamber angle is narrow but open, it is recommended that the internal fixation lamp be turned off to ensure a clear indication as to whether the angle is open or closed in the dark.

Purpose: To test the hypothesis that marginal ray deviations determine perceived starburst sizes, and to explore different strategies for decreasing starburst size in highly aberrated eyes., Methods: Perceived size of starburst images and visual acuities were measured psychophysically for eyes with varying levels of spherical aberration, pupil sizes, and defocus. Computationally, we use a polychromatic eye model including the typical levels of higher order aberrations (HOAs) for keratoconic and post-LASIK eyes to quantify the image quality (the visually weighted Strehl ratio derived from the optical transfer function, VSOTF) with different pupil sizes at both photopic and mesopic light levels., Results: For distance corrected post-LASIK and keratoconic eyes with a night-time pupil (e.g., 7 mm), the starburst diameter is about 1.5 degrees (1 degree for normal presbyopic eyes), which can be reduced to ≤0.25 degrees with pupil sizes ≤3 mm. Starburst size is predicted from the magnitude of the longitudinal spherical aberration. Refracting the eye to focus the pupil margin also removed starbursts, but, unlike small pupils, significantly degraded visual acuity. Reducing pupil diameter to 3 mm improved image quality for these highly aberrated eyes by about 2.7 ×  to 1.7 ×  relative to the natural pupils when light levels were varied from 0.1 to 1000 cd m -2 , respectively., Conclusion: Subjects with highly aberrated eyes observed larger starbursts around bright lights at night predictable by the deviated marginal rays. These were effectively attenuated by reducing pupil diameters to ≤3 mm, which did not cause a drop in visual acuity or modelled image quality even at mesopic light levels., (© 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.)

Purpose: To predict the magnitude of functional damage [mean deviation (MD) on visual field examination] and structural damage [retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness on spectral domain optical coherence tomography] in glaucoma from monocular pupillary light response measurements using automated pupillography., Methods: In total, 59 subjects (118 eyes) with either a confirmed or suspected diagnosis of glaucoma underwent automated pupillography, along with visual fields and spectral domain optical coherence tomography examinations. Association between pupillary light response measurements of each eye [amplitude of constriction, latency of onset of constriction (Loc), latency of maximal constriction (Lmaxc), velocity of constriction and velocity of redilation] and corresponding MD, average RNFL, and average GCC measurements were evaluated using univariate and multivariate regression analysis after accounting for the multicollinearity. Goodness of fit of the multivariate models was evaluated using coefficient of determination (R)., Results: Multivariate regression models that contained Loc and Lmaxc showed the best association with MD (R of 0.30), average RNFL thickness (R=0.18) and average GCC thickness (R=0.26). The formula that best predicts the MD could be described as: MD=-14.06-0.15×Loc+0.06×Lmaxc. The formula that best predicts the average RNFL thickness could be described as: Average RNFL thickness=67.18-0.22×Loc+0.09×Lmaxc., Conclusions: Glaucomatous damage as estimated by MD, RNFL, and GCC thickness measurements were best predicted by the latency parameters (Loc and Lmaxc) of pupillography. Worsening of glaucomatous damage resulted in a delayed onset of pupillary constriction and a decreased Lmaxc.

Purpose: To compare the chromatic pupillary light responses (PLR) in healthy subjects with those from patients with diseases of the outer or inner retina under various stimulus conditions, and to ascertain the parameters required to optimally distinguish between disease and control groups., Methods: Fifteen patients with retinitis pigmentosa (RP), 19 patients with optic nerve disease (ON), and 16 healthy subjects were enrolled in this prospective study. ON included optic neuritis (NNO) and non-arteritic anterior ischemic optic neuropathy (NAION). For each subject, the PLR was recorded, to red, yellow, green, and blue stimuli for durations of 4 and 12 s, and for stimulus intensities of 4 lx and 28 lx., Results: Comparison between control and RP or ON patient results showed that responses after stimulus onset were significantly different for most stimulus conditions, but the post-stimulus amplitudes at 3 s and 7 s after light extinction were not. On the other hand, the difference between the ON and RP groups was significant only for post-stimuli time-points and only for blue stimuli. Differences between responses to blue and red were significantly different, predominantly at post stimulus time-points. A ROC analysis revealed that the maximal constriction amplitudes to a 4 lx, 4 s yellow stimulus are significantly different in ON vs RP patients, and the responses to a 4 s, 28 lx blue stimulus at 7 s post-stimulus are significantly different in controls vs ON vs RP patients with a high specificity., Conclusions: Pupillary light responses to blue light in healthy, RP, and ON subjects are significantly different from one another. The optimal stimuli for future protocols was found to be a 4 s blue stimulus at 28 lx, and a 4 s yellow stimulus at 4 lx.

Purpose: Adrenergic medications may elevate the upper eyelid and dilate the pupil. The effects of topical phenylephrine on Müller's muscle have been well described. Dilute epinephrine (DE) is a sympathomimetic agent commonly administered in blepharoptosis surgery, and has been shown to elevate the upper eyelid margin when injected subcutaneously. The effects of DE applied topically to the eye, whether intentional or inadvertent during surgery have not been characterized. The purpose of this investigation was to quantify and compare the effects of topical DE and phenylephrine on upper eyelid position and pupil size., Methods: Prospective, nonrandomized trial of 41 adults without (n = 25, 25 eyes) and with ptosis (n = 16, 16 eyes). Upper eyelid margin reflex distance (MRD1) and pupil diameter were primary measures and pupil reactivity to light was a secondary measure. MRD1 and pupil diameter were recorded at baseline and at 30-second intervals for 5 minutes after administration of topical 1% lidocaine with epinephrine 1:100,000 (DE). After a washout period of >24 hours, the same measurements were recorded after administration of topical phenylephrine 2.5%., Results: No statistically significant difference was observed between mean baseline and postexposure MRD1 after application of topical DE (p = 0.181). In contrast, a mean increase in MRD1 of 0.51 ± 0.09 mm (effect size 0.33) was observed after exposure to phenylephrine 2.5% (p < 0.001). Baseline-adjusted postexposure mean MRD1 was significantly greater for phenylephrine compared with DE (p < 0.001, analysis of covariance). Mean pupil diameter increased 0.29 ± 0.09 mm (effect size 0.48) in response to DE and 0.27 ± 0.11 mm (effect size 0.41) after application of phenylephrine (p = 0.004 and p = 0.001, respectively). All pupils maintained a constrictive response to light., Conclusions: Although DE is similar to topical phenylephrine in causing mydriasis, it did not have a similar effect on elevating the upper eyelid. These findings may have implications on intraoperative assessment during eyelid surgery. The pupillary changes due to DE offer one explanation for cases of transient pupil dilation during orbitofacial surgery.

Purpose: Photophobia is a common symptom in individuals suffering from traumatic brain injury (TBI). Recent evidence has implicated blue light-sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs) in contributing to the neural circuitry mediating photophobia in migraine sufferers. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing pupillary responses to blue and red light., Methods: Twenty-four case participants (mean age 43.3; 58% female), with mild TBI and self-reported photophobia, and 12 control participants (mean age 42.6; 58% female) were in this study. After 10 minutes of dark adaptation, blue (470 nm, 1 × 10 phots/s/cm) and red (625 nm, 7 × 10 phots/s/cm) flashing (0.1 Hz) light stimuli were delivered for 30 seconds to the dilated left eye while the right pupil was recorded. The amplitude of normalized pupil fluctuation (constriction and dilation) was quantified using Fourier fast transforms., Results: In both case and control participants, the amplitude of pupil fluctuation was significantly less for the blue light stimuli as compared to the red light stimuli, consistent with a contribution of ipRGCs to these pupil responses. There was no significant difference in the mean pupil fluctuation amplitudes between the two participant groups, but case participants displayed greater variability in their pupil responses to the blue stimulus., Conclusions: Case and control participants showed robust ipRGC-mediated components in their pupil responses to blue light. The results did not support the hypothesis that ipRGCs are "hypersensitive" to light in TBI participants with photophobia. However, greater pupil response variability in the case subjects suggests that ipRGC function may be more heterogeneous in this group.

Background: Transgenic mice are widely used for the study of basic visual function and retinal disease, including in psychophysical tests. Mice have a robust pupillary light reflex that controls the amount of light that enters the eye, and the attenuating effects of the pupil must be considered during such tests. Measurement of the size of pupils at various luminance levels requires that mice remain stable over prolonged periods of time; however, sedation of mice with anesthesia and/or manual restraint can influence the size of their pupils., New Method: We present a system to measure the pupillary light response to steady lights of freely behaving mice using a custom-built, portable device that automatically acquires close-up images of their eyes. The device takes advantage of the intrinsic nature of mice to inspect objects of interest and can be used to measure pupillary responses in optomotor or operant behavior testing chambers., Results: The size of the pupils in freely behaving mice decreased gradually with luminance from a maximal area in the dark of 3.8mm 2 down to a minimum 0.14mm 2 at 80 scotopic cd/m 2 . The data was well fit with a Hill equation with Lo equal to 0.21cd/m 2 and coefficient h=0.48., Comparison With Existing Methods: These values agree with prior measurements of the pupillary response of unrestrained mice that use more laborious and time consuming approaches., Conclusions: Our new method facilitates practical, straightforward and accurate measurements of pupillary responses made under the same experimental conditions as those used during psychophysical testing., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To quantify the optimum pupil diameters for presbyopic eyes when environmental light levels vary from high photopic to low mesopic., Methods: We computed the white light visual Strehl ratio from the polychromatic optical transfer function (VSOTF). The impact on image quality of retinal illuminance and the accompanying changes in photon noise were reflected in changing neural contrast sensitivity. VSOTF was calculated for focused and -2D defocused images, over a wide range of photopic and mesopic target luminances, and for pupil diameters ranging from 1 to 7 mm. We compare these modeling data to logMAR visual acuity measured under the same conditions., Results: Optimum pupil depends on the relative gain of optical factors (diffraction and aberrations) and neural thresholds (photon noise effect). When light levels are reduced from 1000 to 2 cd/m, the pupil size that optimizes VSOTF for a well-focused presbyopic eye model also maximizes visual acuity and it increases from 2.5 to 4 mm. A 1-mm-diameter pupil maximizes VSOTF at all light levels when -2D of defocus are included, but at 2 cd/m the optimum pupil diameter for acuity increases slightly to 1.4 mm. At 0.2 cd/m, the pupil size that optimizes VSOTF remains 4 and 1 mm for a focused and -2D defocused eye, respectively, but significantly larger pupils are needed for maximal visual acuity. Reducing pupils to 30% of their natural size is beneficial for distance and near image quality and visual acuity at all light levels, producing more gains for near than for distance., Conclusions: A fixed 2- to 3-mm small pupil or a 30% pupil miosis can both produce near visual acuity gains without significant losses to distance acuity or image quality, and therefore can be considered as optimal for a presbyope experiencing a wide range of light levels.

Purpose: To assess visual field (VF) defects and retinal function objectively in healthy participants and patients with retinitis pigmentosa (RP) using a chromatic multifocal pupillometer., Design: Cross-sectional study., Participants: The right eyes of 16 healthy participants and 13 RP patients., Methods: Pupil responses to red and blue light (peak, 485 and 625 nm, respectively) presented by 76 light-emitting diodes, 1.8-mm spot size at different locations of a 16.2° VF were recorded. Subjective VFs of RP patients were determined using chromatic dark-adapted Goldmann VFs (CDA-GVFs). Six healthy participants underwent 2 pupillometer examinations to determine test-retest reliability., Main Outcome Measures: Three parameters of pupil contraction were determined automatically: percentage of change of pupil size (PPC), maximum contraction velocity (MCV; in pixels per second), and latency of MCV (LMCV; in seconds). The fraction of functional VF was determined by CDA-GVF., Results: In healthy participants, higher PPC and MCV were measured in response to blue compared with red light. The LMCV in response to blue light was relatively constant throughout the VF. Healthy participants demonstrated higher PPC and MCV and shorter LMCV in central compared with peripheral test points in response to red light. Test-retest correlation coefficients were 0.7 for PPC and 0.5 for MCV. In RP patients, test point in which the PPC and MCV were lower than 4 standard errors from the mean of healthy participants correlated with areas that were indicated as nonseeing by CDA-GVF. The mean absolute deviation in LMCV parameter in response to the red light between different test point was significantly higher in RP patients (range, 0.16-0.47) than in healthy participants (range, 0.02-0.16; P < 0.0001) and indicated its usefulness as a diagnostic tool with high sensitivity and specificity (area under the receiver operating characteristic curve (AUC), 0.97, Mann-Whitney-Wilcoxon analysis). Randomly reducing the number of test points to a total of 15 points did not significantly reduce the AUC in RP diagnosis based on this parameter., Conclusions: This study demonstrates the feasibility of using a chromatic multifocal pupillometer for objective diagnosis of RP and assessment of VF defects., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Melanopsin expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) entirely control the post-illumination pupil response (PIPR) from 6 s post-stimulus to the plateau during redilation after light offset. However, the photoreceptor contributions to the early redilation phase of the PIPR (< 6 s post-stimulus) have not been reported. Here, we evaluated the photoreceptor contributions to the early phase PIPR (0.6 s to 5.0 s) by measuring the spectral sensitivity of the criterion PIPR amplitude in response to 1 s light pulses at five narrowband stimulus wavelengths (409, 464, 508, 531 and 592 nm). The retinal irradiance producing a criterion PIPR was normalised to the peak and fitted by either a single photopigment nomogram or the combined melanopsin and rhodopsin spectral nomograms with the +L+M cone photopic luminous efficiency (Vλ) function. We show that the PIPR spectral sensitivity at times ≥ 1.7 s after light offset is best described by the melanopsin nomogram. At times < 1.7 s, the peak PIPR sensitivity shifts to longer wavelengths (range: 482 to 498 nm) and is best described by the combined photoreceptor nomogram, with major contributions from melanopsin and rhodopsin. This first report of melanopsin and rhodopsin contributions to the early phase PIPR is in line with the electrophysiological findings of ipRGC and rod signalling after the cessation of light stimuli and provides a cut-off time for isolating photoreceptor specific function in healthy and diseased eyes., Competing Interests: The authors have declared that no competing interests exist.

Ants of the Australian genus Myrmecia partition their foraging niche temporally, allowing them to be sympatric with overlapping foraging requirements. We used histological techniques to study the light and dark adaptation mechanisms in the compound eyes of diurnal (Myrmecia croslandi), crepuscular (M. tarsata, M. nigriceps) and nocturnal ants (M. pyriformis). We found that, except in the day-active species, all ants have a variable primary pigment cell pupil that constricts the crystalline cone in bright light to control for light flux. We show for the nocturnal M. pyriformis that the constriction of the crystalline cone by the primary pigment cells is light dependent whereas the opening of the aperture is regulated by an endogenous rhythm. In addition, in the light-adapted eyes of all species, the retinular cell pigment granules radially migrate towards the rhabdom, a process that in both the day-active M. croslandi and the night-active M. pyriformis is driven by ambient light intensity. Visual system properties thus do not restrict crepuscular and night-active ants to their temporal foraging niche, while day-active ants require high light intensities to operate. We discuss the ecological significance of these adaptation mechanisms and their role in temporal niche partitioning., (© 2016. Published by The Company of Biologists Ltd.)

Study Objectives: Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN)., Methods: Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8-35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy., Results: All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry., Conclusions: Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep., (© 2016 Associated Professional Sleep Societies, LLC.)

Purpose: To evaluate possible changes in pupil size subsequent to panretinal and focal/grid laser photocoagulation., Methods: Sixty-four eyes of 64 participants were included. Thirty-two eyes with planned panretinal photocoagulation formed Group 1, and 32 eyes with planned focal retinal photocoagulation formed Group 2. The participants underwent full ophthalmologic examination at baseline. Automated infrared pupillometry was performed at baseline and month 1., Results: The mean pupillary measurements (in millimeters) for Group 1 (in order photopic, mesopic, scotopic) were 3.09 ± 0.69 mm, 3.66 ± 0.85 mm, and 3.87 ± 1.01 mm and changed to 3.34 ± 0.74 mm, 3.82 ± 0.92 mm, and 4.03 ± 1.02 mm. There was a significant increase in pupil size at month 1 (P = 0.001, P = 0.001, P = 0.003). For Group 2, they were 2.65 ± 0.87 mm, 3.08 ± 1.08 mm, and 3.18 ± 1.19 mm and changed to 2.92 ± 0.72 mm, 3.45 ± 0.76 mm, and 3.57 ± 0.88 mm. There was no significant difference in pupil size at month 1 (P = 0.151, P = 0.106, P = 0.095)., Conclusion: We have demonstrated through automated infrared pupillary measurements that panretinal laser photocoagulation may significantly influence pupil size and focal/grid laser photocoagulation may not.

Purpose: To assess whether the direct and consensual postillumination (ipRGC-driven) pupil light responses to chromatic light stimuli are equal in healthy subjects., Methods: Pupil responses in healthy volunteers were recorded using a prototype binocular chromatic pupillometer (IdeaMedical, Copenhagen), which is capable of both direct and consensual pupillometry measurements. The device uses a pair of dual monochromatic narrow bandwidth LED light sources, red (660 nm) and blue (470 nm). Pupil light responses were recorded with infrared video cameras and analysed using custom-made circuitry and software. Subjects were randomized to receive light stimuli at either the right or left eye after 5 min of dark adaptation. Pupil light responses were recorded in both eyes for 10 seconds before illumination, during illumination and 50 seconds after illumination with red and blue light. Three variables were defined for the recorded pupil responses: the maximal constriction amplitude (CAmax ), the pupil response during illumination and postillumination pupil response (PIPR)., Results: No difference was found in the pupil response to blue light. With red light, the pupil response during illumination was slightly larger during consensual illumination compared to direct illumination (0.54 and 0.52, respectively, p = 0.027, paired Wilcoxon's test, n = 12), while no differences were found for CAmax or the PIPR., Conclusions: No difference was found between direct and consensual pupil response to either red or blue light in the postillumination period. Direct and consensual responses can readily be compared when examining the postillumination pupil response to blue light as estimation of photosensitive retinal ganglion cell activation., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The pointing direction of cone photoreceptors can be inferred from the Stiles-Crawford Effect of the First Kind (SCE-I) measurement. Healthy retinas have tightly packed cones with a SCE-I function peak either centered in the pupil or with a slight nasal bias. Various retinal pathologies can change the profile of the SCE-I function implying that the arrangement or the light capturing properties of the cone photoreceptors are affected. Measuring the SCE-I may reveal early signs of photoreceptor change before actual cell apoptosis occurs. In vivo retinal imaging with adaptive optics (AO) was used to measure the pointing direction of individual cones at eight retinal locations in four control human subjects. Retinal images were acquired by translating an aperture in the light delivery arm through 19 different locations across a subject's entrance pupil. Angular tuning properties of individual cones were calculated by fitting a Gaussian to the reflected intensity profile of each cone projected onto the pupil. Results were compared to those from an accepted psychophysical SCE-I measurement technique. The maximal difference in cone directionality of an ensemble of cones, ρ¯, between the major and minor axes of the Gaussian fit was 0.05 versus 0.29mm(-2) in one subject. All four subjects were found to have a mean nasal bias of 0.81mm with a standard deviation of ±0.30mm in the peak position at all retinal locations with mean ρ¯ value decreasing by 23% with increasing retinal eccentricity. Results show that cones in the parafoveal region converge towards the center of the pupillary aperture, confirming the anterior pointing alignment hypothesis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)