Differences in the pupillary responses to evening light between children and adolescents.

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 × 1013 photons/cm2/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, ηp2 = 0.48) and more sustained (p < 0.001, ηp2 = 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, ηp2 = 0.20) and maximal (p < 0.01, ηp2 = 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.

Correlated color temperature and light intensity: Complementary features in non-visual light field.

An appropriate exposure to the light-dark cycle, with high irradiances during the day and darkness during the night is essential to keep our physiology on time. However, considering the increasing exposure to artificial light at night and its potential harmful effects on health (i.e. chronodisruption and associated health conditions), it is essential to understand the non-visual effects of light in humans. Melatonin suppression is considered the gold standard for nocturnal light effects, and the activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) through the assessment of pupillary light reflex (PLR) has been recently gaining attention. Also, some theoretical models for melatonin suppression and retinal photoreceptors activation have been proposed. Our aim in this study was to determine the influence of correlated color temperature (CCT) on melatonin suppression and PLR, considering two commercial light sources, as well as to explore the possible correlation between both processes. Also, the contribution of irradiance (associated to CCT) was explored through mathematical modelling on a wider range of light sources. For that, melatonin suppression and PLR were experimentally assessed on 16 healthy and young volunteers under two light conditions (warmer, CCT 3000 K; and cooler, CCT 5700 K, at ~5·1018 photons/cm2/sec). Our experimental results yielded greater post-stimulus constriction under the cooler (5700 K, 13.3 ± 1.9%) than under the warmer light (3000 K, 8.7 ± 1.2%) (p < 0.01), although no significant differences were found between both conditions in terms of melatonin suppression. Interestingly, we failed to demonstrate correlation between PLR and melatonin suppression. Although methodological limitations cannot be discarded, this could be due to the existence of different subpopulations of Type 1 ipRGCs differentially contributing to PLR and melatonin suppression, which opens the way for further research on ipRGCs projection in humans. The application of theoretical modelling suggested that CCT should not be considered separately from irradiance when designing nocturnal/diurnal illumination systems. Further experimental studies on wider ranges of CCTs and light intensities are needed to confirm these conclusions.

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.

A noncanonical inhibitory circuit dampens behavioral sensitivity to light.

Retinal ganglion cells (RGCs) drive diverse, light-evoked behaviors that range from conscious visual perception to subconscious, non-image-forming behaviors. It is thought that RGCs primarily drive these functions through the release of the excitatory neurotransmitter glutamate. We identified a subset of melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) in mice that release the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at non-image-forming brain targets. GABA release from ipRGCs dampened the sensitivity of both the pupillary light reflex and circadian photoentrainment, thereby shifting the dynamic range of these behaviors to higher light levels. Our results identify an inhibitory RGC population in the retina and provide a circuit-level mechanism that contributes to the relative insensitivity of non-image-forming behaviors at low light levels.

Central autonomic regulation assessed by pupillary light reflex is impaired in children with attention deficit hyperactivity disorder.

It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0+/-2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81+/-1.23 % vs. -30.32+/-1.31 %, p<0.05, left eye: -25.44+/-1.65 % vs. -30.35+/-0.98 %, p<0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p<0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.

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.

Do pupil-based binocular video eye trackers reliably measure vergence?

A binocular eye tracker needs to be accurate to enable the determination of vergence, distance to the binocular fixation point and fixation disparity. These measures are useful in e.g. the research fields of visual perception, binocular control in reading and attention in 3D. Are binocular pupil-based video eye trackers accurate enough to produce meaningful binocular measures? Recent research revealed potentially large idiosyncratic systematic errors due to pupil-size changes. With a top of the line eye tracker (SR Research EyeLink 1000 plus), we investigated whether the pupil-size artefact in the separate eyes may cause the eye tracker to report apparent vergence when the eyeballs do not rotate. Participants were asked to fixate a target at a distance of 77 cm for 160 s. We evoked pupil-size changes by varying the light intensity. With increasing pupil size, horizontal vergence reported by the eye tracker decreased in most subjects, up to two degrees. However, this was not due to a rotation of the eyeballs, as identified from the absence of systematic movement in the corneal reflection (CR) signals. From this, we conclude that binocular pupil-CR or pupil-only video eye trackers using the dark pupil technique are not accurate enough to be used to determine vergence, distance to the binocular fixation point and fixation disparity.

An Investigation of the Role of Macular Pigment in Attenuating Photostress through Comparison between Blue and Green Photostress Recovery Times.

PURPOSE: Photostress recovery time (PSRT) is the time required for the macula to return to its normal functioning after the bleaching of cone photopigments due to light exposure, usually white. This work investigates the role of macular pigment (MP) as an optical filter that attenuates photostress by analyses of PSRT at different wavelengths. METHODS: Thirty-nine subjects (19-28 years) were exposed to blue/green photostress varying in irradiance. During photostress, pupil constriction (Cp) was measured. Twenty-seven subjects (20-27 years) were exposed to white photostress. After 25 s of photostress, the time (PSRT) required to read correctly a 0.2 logMAR letter was measured. Correlation was studied between PSRT, CP, and irradiance. Statistical significance of differences between PSRTs was evaluated at Log(irradiance(quanta s-1 cm-2)) = 14 by Student's t statistics. RESULTS: Cp and PSRT were found linearly correlated to Log(irradiance) for blue, green, and white. At Log(irradiance(quanta s-1 cm-2)) = 14, blue and green mean PSRTs resulted different (p < 0.001) with 3.8 ± 0.8 s and 6.7 ± 1.7 s, respectively. After correcting irradiance for the optical absorption of MP, mean blue PSRT became 6.6 ± 0.8 s, at the logarithm of MP-corrected irradiance in quanta s-1 cm-2 equal to 14 (p = 0.571 compared to green PSRT). For white light, at the logarithm of MP-corrected irradiance in quanta s-1 cm-2 equal to 14, mean PSRT was 7.5 ± 2.2 s, not significantly different from blue and green PSRT (p > 0.05). CONCLUSIONS: MP plays the role of an optical filter attenuating photostress. PSRT was substantially proportional to the number of incident photons corrected for the MP optical absorption, regardless of their wavelength.

Pulses of Melanopsin-Directed Contrast Produce Highly Reproducible Pupil Responses That Are Insensitive to a Change in Background Radiance.

Purpose: To measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally narrowband stimuli. Methods: Three-second unipolar pulses were used to elicit pupil responses in human subjects across three sessions. Thirty subjects were studied in session 1, and most returned for sessions 2 and 3. The stimuli of primary interest were "silent substitution" cone- and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, whereas session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape. Results: Group average pupil responses for all stimuli overlapped extensively across sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone- and melanopsin-directed pupil responses from session 3 were highly similar to those from sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light. Conclusions: The group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.

Effects of pupillary responses to luminance and attention on visual spatial discrimination.

The optic quality of the eyes is, at least in part, determined by pupil size. Large pupils let more light enter the eyes, but degrade the point spread function, and thus the spatial resolution that can be achieved (Campbell & Gregory, 1960). In natural conditions, the pupil is mainly driven by the luminance (and possibly the color and contrast) at the gazed location, but is also modulated by attention and cognitive factors. Whether changes in eyes' optics related to pupil size modulation by luminance and attention impacts visual processing was assessed in two experiments. In Experiment 1, we measured pupil size using a constantly visible display made of four disks with different luminance levels, with no other task than fixating the disks in succession. The results confirmed that pupil size depends on the luminance of the gazed stimulus. Experiment 2, using similar settings as Experiment 1, used a two-interval forced-choice design to test whether discriminating high spatial frequencies that requires covert attention to parafoveal stimuli is better during the fixation of bright disks that entails a small pupil size, and hence better eyes' optics, as compared to fixating dark disks that entails a large pupil size, and hence poorer eyes' optics. As in Experiment 1, we observed large modulations of pupil size depending on the luminance of the gazed stimulus, but pupil dynamics was more variable, with marked pupil dilation during stimulus encoding, presumably because the demanding spatial frequency discrimination task engaged attention. However, discrimination performance and mean pupil size were not correlated. Despite this lack of correlation, the slopes of pupil dilation during stimulus encoding were correlated to performance, while the slopes of pupil dilation during decision-making were not. We discuss these results regarding the possible functional roles of pupil size modulations.

A novel method of inducing endogenous pupil oscillations to detect patients with unilateral optic neuritis.

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).

Subadditive responses to extremely short blue and green pulsed light on visual evoked potentials, pupillary constriction and electroretinograms.

BACKGROUND: The simultaneous exposure to blue and green light was reported to result in less melatonin suppression than monochromatic exposure to blue or green light. Here, we conducted an experiment using extremely short blue- and green-pulsed light to examine their visual and nonvisual effects on visual evoked potentials (VEPs), pupillary constriction, electroretinograms (ERGs), and subjective evaluations. METHODS: Twelve adult male subjects were exposed to three light conditions: blue-pulsed light (2.5-ms pulse width), green-pulsed light (2.5-ms pulse width), and simultaneous blue- and green-pulsed light with white background light. We measured the subject's pupil diameter three times in each condition. Then, after 10 min of rest, the subject was exposed to the same three light conditions. We measured the averaged ERG and VEP during 210 pulsed-light exposures in each condition. We also determined subjective evaluations using a visual analog scale (VAS) method. RESULTS: The pupillary constriction during the simultaneous exposure to blue- and green-pulsed light was significantly lower than that during the blue-pulsed light exposure despite the double irradiance intensity of the combination. We also found that the b/|a| wave of the ERGs during the simultaneous exposure to blue- and green-pulsed light was lower than that during the blue-pulsed light exposure. We confirmed the subadditive response to pulsed light on pupillary constriction and ERG. However, the P100 of the VEPs during the blue-pulsed light were smaller than those during the simultaneous blue- and green-pulsed light and green-pulsed light, indicating that the P100 amplitude might depend on the luminance of light. CONCLUSIONS: Our findings demonstrated the effect of the subadditive response to extremely short pulsed light on pupillary constriction and ERG responses. The effects on ipRGCs by the blue-pulsed light exposure are apparently reduced by the simultaneous irradiation of green light. The blue versus yellow (b/y) bipolar cells in the retina might be responsible for this phenomenon.

Pupil response components: attention-light interaction in patients with Parinaud's syndrome.

Covertly shifting attention to a brighter or darker image (without moving one's eyes) is sufficient to evoke pupillary constriction or dilation, respectively. One possibility is that this attentional modulation involves the pupillary light response pathway, which pivots around the olivary pretectal nucleus. We investigate this possibility by studying patients with Parinaud's syndrome, where the normal pupillary light response is strongly impaired due to lesions in the pretectal area. Four patients and nine control participants covertly attended (while maintaining fixation at the center of a monitor screen) to one of two disks located in the left and right periphery: one brighter, the other darker than the background. Patients and control subjects behaved alike, showing smaller pupils when attending to the brighter stimulus (despite no eye movements); consistent results were obtained with a dynamic version of the stimulus. We interpret this as proof of principle that attention to bright or dark stimuli can dynamically modulate pupil size in patients with Parinaud's syndrome, suggesting that attention acts independently of the pretectal circuit for the pupillary light response and indicating that several components of the pupillary response can be isolated - including one related to the focus of covert attention.

Pupillometric evaluation of the melanopsin containing retinal ganglion cells in mitochondrial and non-mitochondrial optic neuropathies.

In recent years, chromatic pupillometry is used in humans to evaluate the activity of melanopsin expressing intrinsic photosensitive retinal ganglion cells (ipRGCs). Blue light is used to stimulate the ipRGCs and red light activates the rod/cone photoreceptors. The late re-dilation phase of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among the diseases, which have been subject to pupillometric studies. The ipRGCs are differentially affected in these various optic neuropathies. In mitochondrial optic neuropathies, the ipRGCs are protected against degeneration, whereas in glaucoma, NAION, optic neuritis and IIH the ipRGCs are damaged. Here, we will review the results of pupillometric, histopathological and animal studies evaluating the ipRGCs in mitochondrial and non-mitochondrial optic neuropathies.

Pupillary Light Reflexes in Severe Photoreceptor Blindness Isolate the Melanopic Component of Intrinsically Photosensitive Retinal Ganglion Cells.

Purpose: Pupillary light reflex (PLR) is driven by outer retinal photoreceptors and by melanopsin-expressing intrinsically photosensitive retinal ganglion cells of the inner retina. To isolate the melanopic component, we studied patients with severe vision loss due to Leber congenital amaurosis (LCA) caused by gene mutations acting on the outer retina. Methods: Direct PLR was recorded in LCA patients (n = 21) with known molecular causation and severe vision loss. Standard stimuli (2.5 log scot-cd.m-2; ∼13 log quanta.cm-2.s-1; achromatic full-field) with 0.1- or 5-second duration were used in all patients. Additional recordings were performed with higher luminance (3.9 log scot-cd.m-2) in a subset of patients. Results: The LCA patients showed no detectable PLR to the standard stimulus with short duration. With longer-duration stimuli, a PLR was detectable in the majority (18/21) of patients. The latency of the PLR was 2.8 ± 1.3 seconds, whereas normal latency was 0.19 ± 0.02 seconds. Peak contraction amplitude in patients was 1.1 ± 0.9 mm at 6.2 ± 2.3 seconds, considerably different from normal amplitude of 4.2 ± 0.4 mm at 3.0 ± 0.4 seconds. Recordings with higher luminance demonstrated that PLRs in severe LCA could also be evoked with short-duration stimuli. Conclusions: The PLR in severe LCA patients likely represents the activation of the melanopic circuit in isolation from rod and cone input. Knowledge of the properties of the human melanopic PLR allows not only comparison to those in animal models but also serves to define the fidelity of postretinal transmission in clinical trials targeting patients with no outer retinal function.

Selective Modulation of the Pupil Light Reflex by Microstimulation of Prefrontal Cortex.

The prefrontal cortex (PFC) is thought to flexibly regulate sensorimotor responses, perhaps through modulating activity in other circuits. However, the scope of that control remains unknown: it remains unclear whether the PFC can modulate basic reflexes. One canonical example of a central reflex is the pupil light reflex (PLR): the automatic constriction of the pupil in response to luminance increments. Unlike pupil size, which depends on the interaction of multiple physiological and neuromodulatory influences, the PLR reflects the action of a simple brainstem circuit. However, emerging behavioral evidence suggests that the PLR may be modulated by cognitive processes. Although the neural basis of these modulations remains unknown, one possible source is the PFC, particularly the frontal eye field (FEF), an area of the PFC implicated in the control of attention. We show that microstimulation of the rhesus macaque FEF alters the magnitude of the PLR in a spatially specific manner. FEF microstimulation enhanced the PLR to probes presented within the stimulated visual field, but suppressed the PLR to probes at nonoverlapping locations. The spatial specificity of this effect parallels the effect of FEF stimulation on attention and suggests that FEF is capable of modulating visuomotor transformations performed at a lower level than was previously known. These results provide evidence of the selective regulation of a basic brainstem reflex by the PFC.SIGNIFICANCE STATEMENT The pupil light reflex (PLR) is our brain's first and most fundamental mechanism for light adaptation. Although it is often described in textbooks as being an immutable reflex, converging evidence suggests that the magnitude of the PLR is modulated by cognitive factors. The neural bases of these modulations are unknown. Here, we report that microstimulation in the prefrontal cortex (PFC) modulates the gain of the PLR, changing how a simple reflex circuit responds to physically identical stimuli. These results suggest that control structures such as the PFC can add complexity and flexibility to even a basic brainstem circuit.

Effect of quantity and intensity of pulsed light on human non-visual physiological responses.

BACKGROUND: Exposure to pulsed light results in non-visual physiological responses in humans. The present study aims to investigate whether such non-visual effects are influenced to a greater extent by the intensity of lighting or by the power (quantity) of lighting. METHODS: >Twelve healthy young male participants (23 ± 0.3 years, 21-24 age range) were recruited for the present study. Participants were exposed to light of varying levels of intensity and quantity whose frequency was held constant across the conditions, which consisted of exposure to blue (different intensity, constant quantity) and white (constant intensity, different quantity) LEDs. Pupillary constriction, electroencephalogram (EEG) alpha band ratio, subjective sleepiness, concentration and perception of blueness were measured. RESULTS: Pupillary constriction and subjective concentration were significantly greater under the high-intensity and short pulse width (HS) condition than under the low-intensity and long pulse width (LL) conditions at three time points during exposure to high-intensity light. However, no significant differences were observed among the results at the three time points during exposure to different quantities of pulsed light. CONCLUSIONS: The results of the present study indicate that non-visual influences of pulsed light on physiological function are mainly determined not by the quantity but by the intensity of the emitted light, with relatively higher levels of intensity producing more significant physiological changes, suggesting potent excitation of intrinsically photosensitive retinal ganglion cells.

Interaction of aberrations, diffraction, and quantal fluctuations determine the impact of pupil size on visual quality.

Our purpose is to develop a computational approach that jointly assesses the impact of stimulus luminance and pupil size on visual quality. We compared traditional optical measures of image quality and those that incorporate the impact of retinal illuminance dependent neural contrast sensitivity. Visually weighted image quality was calculated for a presbyopic model eye with representative levels of chromatic and monochromatic aberrations as pupil diameter was varied from 7 to 1 mm, stimulus luminance varied from 2000 to 0.1 cd/m2, and defocus varied from 0 to -2 diopters. The model included the effects of quantal fluctuations on neural contrast sensitivity. We tested the model's predictions for five cycles per degree gratings by measuring contrast sensitivity at 5 cyc/deg. Unlike the traditional Strehl ratio and the visually weighted area under the modulation transfer function, the visual Strehl ratio derived from the optical transfer function was able to capture the combined impact of optics and quantal noise on visual quality. In a well-focused eye, provided retinal illuminance is held constant as pupil size varies, visual image quality scales approximately as the square root of illuminance because of quantum fluctuations, but optimum pupil size is essentially independent of retinal illuminance and quantum fluctuations. Conversely, when stimulus luminance is held constant (and therefore illuminance varies with pupil size), optimum pupil size increases as luminance decreases, thereby compensating partially for increased quantum fluctuations. However, in the presence of -1 and -2 diopters of defocus and at high photopic levels where Weber's law operates, optical aberrations and diffraction dominate image quality and pupil optimization. Similar behavior was observed in human observers viewing sinusoidal gratings. Optimum pupil size increases as stimulus luminance drops for the well-focused eye, and the benefits of small pupils for improving defocused image quality remain throughout the photopic and mesopic ranges. However, restricting pupils to <2 mm will cause significant reductions in the best focus vision at low photopic and mesopic luminances.

Pupillary responses to short-wavelength light are preserved in aging.

With aging, less blue light reaches the retina due to gradual yellowing of the lens. This could result in reduced activation of blue light-sensitive melanopsin-containing retinal ganglion cells, which mediate non-visual light responses (e.g., the pupillary light reflex, melatonin suppression, and circadian resetting). Herein, we tested the hypothesis that older individuals show greater impairment of pupillary responses to blue light relative to red light. Dose-response curves for pupillary constriction to 469-nm blue light and 631-nm red light were compared between young normal adults aged 21-30 years (n = 60) and older adults aged ≥50 years (normal, n = 54; mild cataract, n = 107; severe cataract, n = 18). Irrespective of wavelength, pupillary responses were reduced in older individuals and further attenuated by severe, but not mild, cataract. The reduction in pupillary responses was comparable in response to blue light and red light, suggesting that lens yellowing did not selectively reduce melanopsin-dependent light responses. Compensatory mechanisms likely occur in aging that ensure relative constancy of pupillary responses to blue light despite changes in lens transmission.

The diagnostic accuracy of chromatic pupillary light responses in diseases of the outer and inner retina.

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.