State-dependent pupil dilation rapidly shifts visual feature selectivity.

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 dilation1,2 enhance sensory responses, but typically leave the preferred stimuli of neurons unchanged2-9. 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 sky10. 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.

Arousal-based pupil modulation is dictated by luminance.

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.

Pupillary Light Reflex Induced by Two-Photon Vision.

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.

Automated pupillometry helps monitor the efficacy of cardiopulmonary resuscitation and predict return of spontaneous circulation.

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 (ETCO2), regional cerebral tissue oxygen saturation (rSO2) 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, ETCO2, rSO2 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.

Phasic Activation of Dorsal Raphe Serotonergic Neurons Increases Pupil Size.

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 regions5,9-11 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 arousal16 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.

Pupillary light reflex in ethambutol-induced optic neuropathy.

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.

Investigation of light-induced lacrimation and pupillary responses in episodic migraine.

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.

The Effect of Refractive Error on Melanopsin-Driven Pupillary Responses.

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 is modulated by the size of equal-luminance gratings.

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.

Effects of Narrowband Light on Choroidal Thickness and the Pupil.

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.

Chromatic pupillometry for the characterization of the pupillary light reflex in Octodon degus.

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.

Optical quality comparison between laser ablated myopic eyes with centration on coaxially sighted corneal light reflex and on entrance pupil center.

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.

Tear-film dynamics by combining double-pass images, pupil retro-illumination, and contrast sensitivity.

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.

Electrophysiological and pupillometric measures of inner retina function in nonproliferative diabetic retinopathy.

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/m2, 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.

Role of automated pupillometry in critically ill patients.

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.

Correlation of Objective Pupillometry to Midline Shift in Acute Stroke Patients.

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.

Technical Note: Effects of age and confinement on pupillary light reflex in sows1.

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.

Effects of low and moderate refractive errors on chromatic pupillometry.

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.

Pupillary light reaction in preclinical Alzheimer's disease subjects compared with normal ageing controls.

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.

Effect of Stimulus Intensity and Visual Field Location on Rod- and Cone-Mediated Pupil Response to Focal Light Stimuli.

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.