Chromatic Pupillometry Research Articles

Binocular Summation in Postillumination Pupil Response Driven by Melanopsin-Containing Retinal Ganglion Cells.

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. 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. 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. 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.

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

Background/aimsWe 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...

Chromatic Pupillometry in Children.

Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from −3.15 to −1.15 log cd/m2 after 3 min of dark adaptation, five red (622 nm) stimuli of −1.15, −0.7, −0.15, 0.3, and 0.85 log cd/m2 after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m2 and one bright red of 2 log cd/m2. The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma

To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. Cross-sectional study. Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of-6 decibels or better on automated perimetry. Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P= 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r= 0.51, P < 0.001; red: r= 0.45, P= 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.

Issue Information

PsyCh Journal's December issue opens with a special collection on chronobiology, the topic taking the 2017 Nobel Prize in Medicine, starting with an editorial introduction titled “Chronobiology—Circadian Oscillators in Neuroscience.” An original article then reports a suggested association between sleep length and depression in a large sample of Chinese adolescents, followed by review articles discussing research on the impacts of chronotype on education, and on interactions of the circadian system with the stress system which may include disruptions of the circadian clock by repeated psychosocial stress. Two short communications close out the collection with a report on the potential use of sleep‐time indices as a proxy for in‐lab melatonin measures of circadian phase, and a proposal for using chromatic pupillometry for testing the functionality of arousal‐promoting non‐visual effects of light in older adults.The December issue also includes an original article validating the Asian American Family Conflict Scale in a study among Chinese Americans, plus special reports examining the impact of characteristics of the urban environment on the way‐finding strategies of the blind, and a consideration of how problem‐oriented research might best be organized given the heuristic assumption of a world lacking universities as we know them. There are also short communications reporting an fMRI study showing different patterns for self‐serving and other‐serving decisions in a tempting‐decision task, and the results of a survey on the link between jealousy and relationship satisfaction among dating adults in Indonesia. A final contribution reports research results from China relevant to the question of whether neural markers can be identified for temporal segmentation in the domain of a few seconds. image

Pupillary light reflex and circadian synchronization in the elderly.

Most elderly lack a synchronized circadian rhythm and often cannot benefit from light therapy. Non-visual effects of light are mediated through intrinsic photosensitive retinal ganglion cells (ipRGCs). With chromatic pupillometry, the functionality of ipRGCs and their functional circuit in the brain can be tested.

Pupillary responses to light are not affected by narrow irido-corneal angles

Chromatic pupillometry is an emerging method for evaluating ocular health that relies upon the differential stimulation of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it has been investigated in conditions affecting the outer or inner retina, there is a paucity of studies in conditions where the anterior chamber of the eye is affected. Primary angle closure suspects (PACS) are defined as eyes with narrow anterior chamber angles and intact retina. PACS patients are at risk of developing primary angle closure glaucoma and are prophylactically treated by performing laser peripheral iridotomy (LPI). Here we evaluated pupillary responses to monchromatic lights in 18 PACS before and after LPI, and compared the results with those of 36 age-matched controls who had gonioscopically open angles. Dose response curves for pupillary constriction were similar between PACS patients and controls (p = 0.98 for blue and 0.90 for red light) and within subjects pre- and post-LPI (p = 0.58 for blue and 0.20 for red light). Baseline-adjusted pupillary constriction responses to blue and red lights were similar in controls and PACS, and not altered after LPI. Our findings suggest that narrow irido-corneal angles and LPI do not influence pupillary responses in PACS.

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.

Choroideremia: melanopsin-mediated postillumination pupil relaxation is abnormally slow.

To investigate the rod-cone and melanopsin pupillary light response (PLR) pathways in choroideremia. Eight patients with choroideremia and 18 healthy age-matched controls underwent chromatic pupillometry by applying blue (463nm) and red light (643nm) at 100lux intensity to the right eye while recording pupil diameters. Absolute baseline pupil size (mm), normalized maximal pupil constriction and the early and late postillumination pupillary dilation, from 0 to 10seconds and 10 to 30seconds after the end of illumination, respectively, were determined. Postillumination responses to blue light were considered to be primarily driven by melanopsin activation of the intrinsic photosensitive retinal ganglion cells. Baseline pupil diameters were comparable in patients with choroideremia and control subjects (p=0.48). The maximum pupil constriction in patients with choroideremia was severely weakened in red light but only mildly weakened in blue light (p<0.05). Postillumination dilation of the pupil was normal after red illumination but extremely protracted after blue illumination. Also, in contrast to healthy subjects, no abrupt change in the dilation curve was seen in the patients after the end of blue illumination, the early-phase dilation being completely abolished (p<0.01). Rod-cone-driven pupil responses were decreased as expected in an outer retinal degeneration, and near-normal pupil constriction in blue light supports that the melanopsin system is normal. In contrast, the lack of brisk early-phase dilation after blue illumination in choroideremia is remarkable and may be interpreted to mean that the absence of photoreceptor inhibition promotes a tonic contraction of the pupil.

Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response.

PurposeThe purpose of this study was to evaluate a chromatic pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs.MethodsChromatic pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function, and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry.ResultsMean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB), and photopic bright red (phBR) lights in WT dogs were 21.3% ± 10.6%, 50.0% ± 17.5%, and 19.4% ± 7.4%, respectively. Melanopsin-mediated responses to scBB persisted for several minutes (7.7 ± 4.6 min) after stimulus offset. In dogs with inherited retinal degeneration, loss of rod function resulted in absent scDB responses, followed by decreased phBR responses with disease progression and loss of cone function. Primary loss of cone function abolished phBR responses but preserved those responses to blue light (scDB and scBB). Although melanopsin/Opn4 expression was diminished with retinal degeneration, melanopsin-expressing ipRGCs were identified for the first time in both WT and degenerated canine retinas.ConclusionsPupil responses elicited by light stimuli of different colors and intensities allowed differential functional assessment of canine rods, cones, and ipRGCs. Chromatic pupillometry offers an effective tool for diagnosing retinal and optic nerve diseases.

The effect of blue-blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery.

To compare the long-term effect on circadian photoentrainment and sleep in patients implanted with neutral and blue-blocking intraocular lenses 1year after cataract surgery. Randomized, controlled trial involving 67 patients with age-related cataract. Intervention was cataract surgery with implantation of either a neutral or a blue-blocking intraocular lens (IOL). Main outcome was activation of the intrinsically photosensitive retinal ganglion cells (ipRGC) measured by chromatic pupillometry. The circadian rhythm was analysed by 24-hr melatonin profiles and actigraphy; the latter was also used to determine objective sleep quality. The Pittsburgh Sleep Quality Index determined subjective sleep quality. One year after surgery, peak melatonin concentration was 3.3pg/ml (95% CI, 2-5.5) corresponding to 50% lower for the participants allocated to blue-blocking IOLs compared with participants allocated to neutral IOLs. Compared with preoperative levels, the ipRGC response had increased by 13.7% (95% confidence interval [CI], 3.2-22.6) 1year after surgery. Objective sleep quality was also improved as the time of wakefulness after sleep onset had improved by 5min (95% CI, 1-10) for the entire population while sleep efficiency had increased by two percentage points (95% CI, 0.42-3.65) although exclusively, for the participants allocated to blue-blocking IOLs. Blue-blocking IOLs increased sleep efficiency but lowered nocturnal melatonin secretion compared with neutral IOLs. Cataract surgery improved the response of ipRGCs and sleep quality. However, the effect of cataract surgery on sleep quality may be unrelated to circadian photoentrainment.

Determination of Rod and Cone Influence to the Early and Late Dynamic of the Pupillary Light Response.

PurposeThis study aims to identify which aspects of the pupil light reflex are most influenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor deficiency.MethodsOne-month-old wild type (WT), rodless (Rho−/−), coneless (Cnga3−/−), or photoreceptor less (Cnga3−/−; Rho−/− or Gnat1−/−) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the first 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude.ResultsRho−/− mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3−/− mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3−/− mice demonstrated marked prolongation of the pupillary constriction. Cnga3−/−; Rho−/− mice had no pupil response to red light of low and medium intensity.ConclusionsFrom specific gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models.

Factors influencing the pupillary light reflex in healthy individuals.

To determine the ocular anatomical factors influencing the pupillary light reactions to different wavelengths of light, measured with chromatic pupillometry. Community-based, cross-sectional study including subjects with normal ocular health (ages 50-79years). Direct pupillary responses to continuously increasing irradiances (6.8 to 13.8 log photons cm(-2) s(-1)) of red (631nm) and blue (469nm) light were measured, using a dedicated infrared pupillometer. All subjects underwent swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) and noncontact partial coherence laser interferometry (Lenstar LS900, Haag-Streit AG, Switzerland). Univariate and multivariable regression analyses were performed to determine the anatomical features influencing pupillographic parameters. Among the 177 included subjects, 167 (94.4%) were Chinese and 116 (65.5%) female. The average baseline pupil diameter in darkness (β = -0.080, p < 0.001) and the amplitude of the relative pupillary constriction (β = -0.233, p = 0.006) to blue light decreased with age. The amplitude of pupillary constriction was significantly larger in patients with a thinner iris, in response to stimulation with blue (β = -0.321, p < 0.001) and red light (β = -0.336, p < 0.001). Other ocular parameters (i.e., lens vault, anterior chamber depth width, iris volume, iris curvature, and lens thickness) were not significantly associated with pupillometric outcomes. The amplitude of the pupillary light constriction to chromatic photic stimuli is reduced with increasing age and iris thickness in subjects with normal ocular health, a finding which needs to be integrated into future pupillometric studies.

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity

To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss. Cross-sectional study. One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older. Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system. Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7-14 log photons/cm(2) per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany). The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r=-0.44; P= 0.005) as well as HRT linear cup-to-disc ratio (r= 0.61; P < 0.001) and several other optic nerve head parameters. In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma.

Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy.

We examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5 log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure.

Test-retest reliability of hemifield, central-field, and full-field chromatic pupillometry for assessing the function of melanopsin-containing retinal ganglion cells.

We evaluated the test-retest reliability of current methods of inducing the melanopsin-driven postillumination pupil response (PIPR) under hemifield, central-field, and full-field stimulation conditions. Pupil response was recorded with an eye tracker in 10 visually normal participants. Light stimuli were presented using a Ganzfeld screen with a custom-built device that allows specific regions of the retina to be stimulated. Blue light stimulation at 400 cd/m(2) intensity was presented for 400 ms to the lower and upper halves of the central 30° fields (hemifields), central 30° field (central-field), and full-field to induce PIPR. Red light full-field stimulation also was presented with the same intensity and duration as a control condition. Test-retest reliability of the PIPR measures was assessed by calculating the intraclass correlation coefficient (ICC) of six repetitions for lower and upper hemifield stimulation, and three repetitions for central-field and full-field stimulation. Hemifield, central-field, and full-field blue light stimulation induced increasingly greater PIPR in ascending order, while full-field red light stimulation induced no PIPR. Mean lower and upper hemifield PIPR was highly symmetric. Mean ICC of blue light PIPR was 0.87 for lower hemifield, 0.88 for upper hemifield, 0.95 for central-field, and 0.94 for full-field stimulation. We validated a new and repeatable method to measure PIPR induced by hemifield, central-field, and full-field light stimulation. Good PIPR measurement reliability was obtained under all conditions. This practical and reliable protocol will facilitate the clinical application of PIPR testing in different disease populations.

Chromatic pupillometry for assessment functional rod and cone patterns in Usher syndrome patients

AbstractPurpose The aim of the study was to characterize the functional rod and cone patterns using chromatic pupillometry in Usher syndrome patients.Methods Prospective case series study enrolled 45 Usher syndrome patients. All patients underwent in‐depth phenotypic examination. Functional rod and cone patterns were obtained using custom‐made chromatic pupillometer(AMTech, Dosenheim, Germany). Pupil diameter was recorded monocular in response to red (640 nm) and blue (462 nm) light stimuli for varied intensity levels (ranged from 1000 cd/m2 to 0.001cd/m2). Response amplitudes were analyzed and compared to the clinical phenotype.Results Pupil responses to rod‐ and cone‐weighted stimulation were significantly diminished in all Usher syndrome patients for all intensity levels (mean decrease 60% and 30%, respectively p&lt;0.001). Lower rod‐weighted responses were related with decreased b‐wave amplitude in full field ERG (r=0.37,p&lt;0.001). Decreased cone‐weighted responses were correlated with diminished photopic ERG b‐wave amplitude (r=0.43,p&lt;0.001) and mfERG amplitudes (r=0.65,p&lt;0.001). Higher cones‐weighted responses were associated with preserved cone mosaic in adaptive optics and presence of inner/outer segment in optical coherence tomography, although not always related with preserved visual field and visual acuity. Rod‐ and cone‐weighted responses were recordable even in a very advanced Usher syndrome cases associated with abolished ERG.Conclusion Chromatic pupillography is an objective tool to assess functional rod and cone patterns in Usher syndrome, which potentially could be used as an outcomes measure to assess safety and efficacy in therapy trials, in particularly in advanced cases.

Full-field chromatic pupillometry for the assessment of the postillumination pupil response driven by melanopsin-containing retinal ganglion cells.

The postillumination pupil response (PIPR) is produced by intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to refine the testing conditions for PIPR by investigating whether a greater PIPR can be induced using full-field light stimuli of shorter duration and lower intensity than that produced by existing protocols that use central-field stimuli. Pupil response was recorded with an eye tracker in 10 visually-normal subjects. Red and blue light stimuli were presented using a Ganzfeld system. In Experiment 1 (intensity trials), PIPR was induced using 1-second full-field stimuli of increasing intensities from 0.1 to 400 cd/m(2) (11 steps). For comparison, PIPR also was induced using a 60° × 90° central-field blue stimulus of 400 cd/m(2). In Experiment 2 (duration trials), PIPR was induced using 100 and 400 cd/m(2) full-field stimulus of increasing duration from 4 to 1000 ms (10 steps). Results indicated that PIPR increased monotonically with increasing stimulus intensity. Full-field stimulation using blue light at 400 cd/m(2) intensity induced significantly more sustained PIPR than central-field stimulation (P = 0.001). In addition, PIPR increased as the stimulus duration increased from 4 to 200 ms; however, no further increase in PIPR was observed when the duration increased from 400 to 1000 ms. Compared to existing central-field protocols, larger PIPR can be induced with a full-field stimulus with lower intensity and shorter duration, indicating that PIPR is a function of stimulus intensity, stimulus duration, and retinal area stimulated. The testing protocol can be refined with this new knowledge to target particular clinical populations.

Abnormal pupillary light reflex with chromatic pupillometry in Gaucher disease.

The hallmark of neuronopathic Gaucher disease (GD) is oculomotor abnormalities, but ophthalmological assessment is difficult in uncooperative patients. Chromatic pupillometry is a quantitative method to assess the pupillary light reflex (PLR) with minimal patient cooperation. Thus, we investigated whether chromatic pupillometry could be useful for neurological evaluations in GD. In our neuronopathic GD patients, red light-induced PLR was markedly impaired, whereas blue light-induced PLR was relatively spared. In addition, patients with non-neuronopathic GD showed no abnormalities. These novel findings show that chromatic pupillometry is a convenient method to detect neurological signs and monitor the course of disease in neuronopathic GD.

Unilateral Anterior Ischemic Optic Neuropathy: Chromatic Pupillometry in Affected, Fellow Non-Affected and Healthy Control Eyes

The intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin, which is sensitive to blue light. Previous chromatic pupillometry studies have shown that the post-illumination response is considered an indicator of the melanopsin activation. The aim of this study was to investigate the ipRGC mediated pupil response in patients with a unilateral non-arteritic anterior ischemic optic neuropathy (NAION). Consensual pupil responses during and after exposure to continuous 20 s blue (470 nm) or red (660 nm) light of high intensity (300 cd/m2) were recorded in each eye for 10 patients. Comparisons were performed both intra-individually (affected versus non-affected eyes) and inter-individually (compared with healthy controls). The pupil response was calculated both during the illumination and during the post-illumination phase. The pupil responses to blue and red colors were significantly reduced in the NAION-affected eyes, compared with the fellow non-affected eyes. When comparing the affected eyes with the healthy control eyes, the post-illumination responses were not significantly different. In addition, the post-illumination pupil responses after blue light exposure were increased in the fellow non-affected patients’ eyes, compared with the healthy controls. However, significance was only reached for the late post-illumination response. In conclusion, chromatic pupillometry disclosed reduced post-illumination pupil responses in the NAION-affected eyes, compared with the non-affected fellow eyes, suggesting dysfunction of the ipRGCs. Compared with the responses of the healthy controls, the blue light post-illumination pupil responses were similar in the affected eyes and increased in the fellow non-affected eyes. This suggests a possible adaptive phenomenon, involving the ipRGCs of both eyes after unilateral NAION.