Pupillary Light Response Research Articles

Quantitative assessment of visual pathway function in blind retinitis pigmentosa patients

ObjectiveThe current methods used to assess visual function in blind retinitis pigmentosa (RP) patients are mostly subjective. We aimed to identify effective, objective methods. MethodsWe enrolled patients diagnosed with blindness associated with RP; we finally selected 26 patients (51 eyes) with a visual field radius less than 10 degrees and divided them into the following 4 groups by best-corrected visual acuity (BCVA): group 1, no light perception (NLP, 4 eyes); group 2, light perception (LP, 12 eyes); group 3, hand movement or finger counting (faint form perception, FFP, 22 eyes); and group 4, BCVA from 0.1 to 0.8 (form perception, FP, 13 eyes). All patients underwent optometry, optical coherence tomography (OCT), color fundus photography, fundus autofluorescence (FAF), full field electroretinography (ffERG), pattern electroretinography (PERG), multifocal electroretinography (mf-ERG), pattern visual evoked potential (PVEP), flash visual evoked potential (FVEP), and pupillary light response (PLR) assessments. Five patients in groups 1, 2, and 3 (1, 2, and 2 subjects, respectively) underwent functional magnetic resonance imaging (fMRI) scans and were compared with five healthy subjects. ResultsThe outer plexiform layer was thinner in group 1, and the outer nuclear layer was thinner in groups 1 and 2. The ffERG, PERG, and mf-ERG findings were unrecordable in all four groups. The P2 amplitude of the FVEP was significantly lower in groups 1 and 2, while the P100 amplitude of the PVEP was higher in groups 2, 3 and 4 than in group 1. After white- and blue-light stimuli, the PLR thresholds in the patients without form perception were significantly higher. The threshold of the PLR stimulated by blue and white light was negatively correlated with the amplitudes of P2 and P100. Moreover, the fMRI findings showed that some RP patients have significant visual cortex activation in response to certain types of stimulation. However, statistical analysis was not performed because of the small number of cases. ConclusionsOCT, VEP, PLR and fMRI assessments can evaluate residual visual pathway function in blind RP patients. SignificanceOur study may have clinical significance for the potential prediction of RP patient prognoses and the effects after clinical trials.

Deep learning-based pupil model predicts time and spectral dependent light responses

Although research has made significant findings in the neurophysiological process behind the pupillary light reflex, the temporal prediction of the pupil diameter triggered by polychromatic or chromatic stimulus spectra is still not possible. State of the art pupil models rested in estimating a static diameter at the equilibrium-state for spectra along the Planckian locus. Neither the temporal receptor-weighting nor the spectral-dependent adaptation behaviour of the afferent pupil control path is mapped in such functions. Here we propose a deep learning-driven concept of a pupil model, which reconstructs the pupil’s time course either from photometric and colourimetric or receptor-based stimulus quantities. By merging feed-forward neural networks with a biomechanical differential equation, we predict the temporal pupil light response with a mean absolute error below 0.1 mm from polychromatic (2007 pm 1 K, 4983 pm 3 K, 10,138 pm 22 K) and chromatic spectra (450 nm, 530 nm, 610 nm, 660 nm) at 100.01 ± 0.25 cd/m2. This non-parametric and self-learning concept could open the door to a generalized description of the pupil behaviour.

Pupillary Complexity for the Screening of Glaucoma

Glaucoma is a leading cause of irreversible visual field loss. The early detection and diagnosis of the disease are therefore necessary to prevent blindness. Pupillary light responses are an interesting new technique for the detection of glaucoma. However, the analysis of pupillary signals has been associated with manual supervision or involved high computational costs. The present paper is to propose an analysis framework to automatically investigate changes in the complexity of pupillary signals under ambient light conditions for the screening of glaucoma. In this work, pupillary data of 13 glaucoma patients, 13 age-matched controls, and 11 young controls were recorded at the light intensity of 100 cd/m2 using a commercial eye tracker. The pupillary complexity of the participants was analysed using Higuchi’s fractal dimension, permutation entropy, and conditional entropy. We found that there was a statistically significant difference in the pupillary complexity between glaucoma patients and control groups (P < 0.0001). Specifically, the difference was more pronounced when using the fractal dimension measure. These results confirm the potential of using pupillary complexity for the screening of glaucoma using commercial devices.

Physiology and miRNA expression in confined sows with different pupillary light reflex

Long-term physical restriction may lead to affective and physiological disorders in sows; pupillary light reflex (PLR) characteristics might be a good indicator to diagnose these symptoms. Accordingly, the physiological and psychological states of sows with different PLR characteristics were investigated in this study. Gestating sows of three parities (parity 0, 2, and 5) were divided into strong reflex (SR) and weak reflex (WR) groups, according to a PLR test. In each group, miRNA expression and serum physiological indices were detected. Compared with the SR group, WR group showed lower 5-hydroxytryptamine levels and higher cortisol, interleukin-6, and beta-endorphin levels (p < .05) in all parities; higher immunoglobulin A and tumour necrosis factor-α levels in the parity 0 and 2 sows (p < .05); and lower miR-335, miR-16, and miR-1202 expression (p < .05) and higher miR-132, miR-504, miR-34a, and miR-30e expression in the parity 2 and 5 sows. Compared with the parity 0 sows, parity 5 sows showed higher cortisol, interleukin-6, tumour necrosis factor-α, and beta-endorphin levels; higher miR-504 and miR-34a expression (p < .05); and lower miR-335, miR-16, miR-134, and miR-1202 expression in both groups. Thus, psychophysiological state differs among sows with different PLR characteristics, and, that of sows with weak PLR characteristics, is consistent with depression disorder, and as parity increases, these psychophysiological differences widen. HIGHLIGHTS PLR characteristics could reflect different physiological states including neurophysiological and immunological states in sows. The miRNA molecular markers and serum physiological indices of sows with weak pupillary light responses were consistent with depression disorder. Long-term physical restriction might worsen physiological and psychological disorders in sows.

The Index of Cognitive Activity - Eligibility for task-evoked informational strain and robustness towards visual influences

Various researchers have proposed pupillometric indicators to assess a person's cognitive strain. However, to distinguish the variation of pupil light response from psychosensory pupil response in experimental field conditions is a challenge. The Index of Cognitive Activity (ICA) addresses this problem by wavelet separation. This research investigates the ICA's sensitivity for multiple level task-evoked cognitive activity and visual influences concerning informational work tasks. Objective and subjective measures assessed cognitive strain of participants (N = 22) during various tasks. In a first experiment, mental arithmetic tasks were used to induce different levels of cognitive activity. In a second experiment, influences of screen polarity and presentation of information were investigated (N = 18). The results indicate that eye metrics are rarely sensitive to slight variations in task difficulty. Moreover, the ICA is likely to be sensitive towards constant screen illumination and shows tendencies regarding changes in displayed information. Possible ramifications for the objective assessment of cognitive strain are discussed.

A Pilot Study of Automated Pupillometry in the Treatment of Opioid Use Disorder.

Introduction/Background:A rough, visual estimate of pupil size is used in grading the severity of opioid withdrawal. Few studies have examined the clinical utility of more precise automated pupillometry measurements.Methods:This prospective cohort study enrolled 27 patients receiving opioid agonist therapy (OAT) to treat cravings or withdrawal during an acute hospitalization. Six sets of automated pupillometry measurements were obtained at regular intervals before and after administration of OAT. Clinical Opiate Withdrawal Scale measurements were performed pre and post OAT. Primary outcomes included pupil size in dark and bright illumination (mm). Latency of the pupillary light response (s), constriction and dilation velocity (mm/s), and percent constriction (%) were secondary outcomes.Results:The mean predosing pupil size in dark and bright illumination was 4.33 ± 1.40 mm and 2.96 ± 0.79 mm, respectively. A significantly decreased mean pupil size was first detected at 15 minutes postdosing (4.01 ± 1.34 mm, P = 0.0115 for dark illumination; 2.71 ± 0.72 mm, P = 0.0003 for bright illumination) and this reduction in pupil size persisted at later postdosing timepoints. Those with Clinical Opiate Withdrawal Scale <5 after dosing had a greater decrease in dark pupil size (10.6% ± 13.2 vs 3.2% ± 3.2, P = 0.043). There was no significant change in the remaining pupil reactivity parameters.Conclusions:Automated pupillometry demonstrated a small but significant change in mean pupil size that occurred within 15 minutes of OAT dosing and was associated with low withdrawal scores. This pilot may inform future work to incorporate pupillometry measurement into OAT dosing assessments.

Accounting for Effects of Variation in Luminance in Pupillometry for Field Measurements of Cognitive Workload

Eye-tracking is now above and beyond the sole measurement of visual attention. Amongst the multiple measures it provides, some have been explored as a measure of cognitive workload (CW). One such measure is pupil diameter. Although the relationship between pupil size and CW has been extensively documented, pupil diameter is primarily impacted by luminance variations while the cognitive workload has a relatively minor influence. Therefore luminance variations have to be accounted for, either in the experimental design or in the data processing to avoid the masking of the CW effects. This has meant that the use of pupillometry for the measurement of anything but the pupillary light response, has been restricted to highly controlled lighting conditions in a laboratory. This study proposes a new method that uses point of view (POV) video in conjunction with a luminance measurement sensor to dynamically estimate the luminance of the visual stimuli. As currently available off the shelf eye trackers are usually not equipped to record luminance variations, a luminance sensor was added to a commercial eye tracker. Eye-tracking gaze data, POV video recording of the operator/observer and a head-mounted (POV) luminance sensor together estimate the expected pupil diameter. This estimate over time is due to sole influence of luminance variations. This expected pupil diameter is used as baseline for the cognitive workload. The method was validated in laboratory conditions with controlled visual stimuli. The method reliably measures induced cognitive workload despite luminance variation.

Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence.

Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed and showed similar diseased phenotypes to their human counterparts. Proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including electroretinograms, pupillary light responses, and object avoidance behaviors. Positive results in animal models led to Phase 1 human studies using adeno-associated viral vectors. Results in these initial human studies also showed positive impact on visual function and acceptable safety. A landmark Phase 3 study was then conducted by Spark Therapeutics using a dose of 1.5 x1011 vector genomes after dose-escalation studies confirmed its efficacy and safety. Multi-luminance mobility testing was used to measure the primary efficacy endpoint due to its excellent reliability in detecting the progression of inherited retinal diseases. After the study met its primary endpoint, the Food and Drug Administration approved voretigene neparvovec (Luxturna®) for use in RPE65-associated inherited retinal diseases.

Melanopsin Cell Dysfunction is Involved in Sleep Disruption in Parkinson's Disease.

Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) signal the environmental light to mediate circadian photoentrainment and sleep-wake cycles. There is high prevalence of circadian and sleep disruption in people with Parkinson's disease, however the underlying mechanisms of these symptoms are not clear. Based on recent evidence of anatomical and functional loss of melanopsin ganglion cells in Parkinson's disease, we evaluate the link between melanopsin function, circadian, and sleep behavior. The pupil light reflex and melanopsin-mediated post-illumination pupil response were measured using chromatic pupillometry in 30 optimally medicated people with Parkinson's disease and 29 age-matched healthy controls. Circadian health was determined using dim light melatonin onset, sleep questionnaires, and actigraphy. Ophthalmic examination quantified eye health and optical coherence tomography measured retinal thickness. The melanopsin-mediated post-illumination pupil response amplitudes were significantly reduced in Parkinson's disease (p < 0.0001) and correlated with poor sleep quality (r2 = 33; p < 0.001) and nerve fiber layer thinning (r2 = 0.40; p < 0.001). People with Parkinson's disease had significantly poorer sleep quality with higher subjective sleep scores (p < 0.05) and earlier melatonin onset (p = 0.01). Pupil light (outer retinal) response metrics, daily light exposure and outer retinal thickness were similar between the groups (p > 0.05). Our evidence-based data identify a mechanism through which inner retinal ipRGC dysfunction contributes to sleep disruption in Parkinson's disease in the presence of normal outer retinal (rod-cone photoreceptor) function. Our findings provide a rationale for designing new treatment approaches in Parkinson's disease through melanopsin photoreceptor-targeted light therapies for improving sleep-wake cycles.

Using Attentional Modulation of the Pupillary Light Response to Study the Mechanisms Underlying Object-Based Attention.

Using Attentional Modulation of the Pupillary Light Response to Study the Mechanisms Underlying Object-Based Attention.

Concussion Alters Dynamic Pupillary Light Responses in Children.

To investigate the impact of concussion on pupillary function in children by examining pupillometric parameters and assessing for differences in children reporting photosensitivity. Retrospective chart review was performed of pediatric patients referred for visual symptoms after concussion from 2017 to 2018 seen in a single academic outpatient clinic. Pupillometry data of 92 patients were included. Outcomes were compared to normative pediatric data from the same institution by 2-sample t tests. The association between photosensitivity and each outcome was assessed by use of linear mixed models with photosensitivity as a fixed effect and random patient effect. Outcomes of 181 eyes in 92 concussion patients were averaged by patient and compared to normative values in scotopic conditions. Concussion patients had an average age of 13.8 ± 2.64 years. Average constriction velocity (P = .0008), maximum constriction velocity (P = .0012), and average dilation velocity (P = .0034) were faster in concussion patients, whereas 75% recovery times (P = .0027) was increased. Photosensitivity did not significantly affect measured pupillary responses. Dynamic pupillary responses may be increased in pediatric concussion. Pupillometry may provide insight into the complex pathophysiological changes underlying pediatric concussion.

Adaptations for amphibious vision in sea otters (Enhydra lutris): structural and functional observations.

Sea otters (Enhydra lutris) are amphibious mammals that maintain equal in-air and underwater visual acuity. However, their lens-based underwater accommodative mechanism presumably requires a small pupil that may limit sensitivity across light levels. In this study, we consider adaptations for amphibious living by assessing the tapetum lucidum, retina, and pupil dynamics in sea otters. The sea otter tapetum lucidum resembles that of terrestrial carnivores in thickness and fundic coverage. A heavily rod-dominated retina appears qualitatively similar to the ferret and domestic cat, and a thick outer nuclear layer relative to a thinner inner nuclear layer is consistent with nocturnal vertebrates and other amphibious carnivores. Pupil size range in two living sea otters is smaller relative to other amphibious marine carnivores (pinnipeds) when accounting for test conditions. The pupillary light response seems slower than other aquatic and terrestrial species tested in comparable brightness, although direct comparisons require further assessment. Our results suggest that sea otters have retained features for low-light vision but rapid adjustments and acute underwater vision may be constrained across varying light levels by a combination of pupil shape, absolute eye size, and the presumed coupling between anterior lens curvature and pupil size during accommodation.

Effects of stimulus size, eccentricity, luminance, and attention on pupillary light response examined by concentric stimulus

Previous studies show that the amplitude of pupillary light response (PLR) depends on the corneal flux density (CFD), which is the product of stimulus area by luminance. However, the contribution of CFD has been investigated only when the stimulus was centered on the fovea, whereas perceived luminance to pupillary response would reduce with stimulus eccentricity. Additionally, it has been shown recently that attentional state modulates pupillary response. In this study, we aimed to clarify the complete mechanisms of PLR by manipulating the stimulus size, eccentricity, luminance, and the participants’ attentional states. We focused on four indices to examine PLR, that is, pupillary latency (PL), maximum constriction velocity (MCV), maximum constriction (MC), and mean pupil change (MPC). Results showed that PL was a function of CFD, whereas MCV, MC, and MPC were functions of both CFD and stimulus eccentricity. Furthermore, the magnitude of effect due to stimulus eccentricity for MCV and MC was different from that for MPC. These results provided new evidence that the different processing systems in PLR existed.

Treatment of Limbal Melanocytoma with Full Excision and a Fresh Homologous Corneoscleral Graft in a Dog

Background: Limbal melanoma has been diagnosed in dogs and due to progression may cause vision loss and eyeball removal. Definitive diagnosis is made through histopathological examination. Therapeutic options include full thickness resection and repair by homologous corneal tissue, synthetic graft material, and enucleation. In this report, we describe a case of limbal melanocitoma in a dog that has been treated successfully with fresh homologous corneoscleral graft.Case: A 5-year-old female Labrador was referred to the Ophthalmology Veterinary Section of the Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil, with a history of a pigmented mass located on the left eye. Ophthalmic examination revealed a pigmented mass located at the left temporal limbus with corneal involvement. Surgical excision followed by reconstruction using fresh homologous corneoscleral was recommended. The patient was premedicated with acepromazine (0.05 mg/kg, IM) and meperidine (20 mg/kg, IM). Anaesthesia was induced with propofol (10 mg/kg, IV) and maintained with isoflurane. Atracurium (0.2 mg/kg, IV) was administered to maintain a central eye position. The mass and a free margin were removed by full-thickness corneoscleral resection. A corneoscleral graft was harvested from a dogthat had been euthanised for reasons unrelated to this study and sutured with 9-0 polyglactin 910 using a simple interrupted pattern. The mass was immediately fixed in 10% neutral buffered formalin and submitted for histological sectioning and routine staining. Based on the histopathological analysis it was confirmed limbal melanocytoma. Postoperative treatment consisted of topical administration of 0.3% flurbiprofen every 6 h for 15 days, and a combination of topical ciprofloxacin/dexamethasone eye drops every 6 h for 30 days. Systemic carprofen (4 mg/kg per day, VO) was prescribed for 10 days. Topical tropicamide was used twice daily for 1 week. Cyclosporin 0.2% eye drops were applied twice daily for 2 months. Examination of the left eye two months after surgery revealed decreased corneal vascularization, and the results of pupillary light response and vision testing were normal. The values of intraocular pressure remained normal in all postoperativeevaluations. The patient was followed for 36 months postoperatively, during which time there was no recurrence.Discussion: Limbal melanomas are the most common ocular melanomas in dogs. Most of them develop slowly and are located closely to the superior limbus. The tumors tend to grow more rapidly in younger dogs and more slowly in older dogs. Labrador Retrievers and German shepherds appear to be affected more frequently than other breeds. The present case involved a 5-year-old Labrador breed. The clinical presentation included a pigmented limbal mass extending intothe adjacent cornea, sclera and conjunctival tissue. A tissue biopsy is necessary to confirm the diagnosis. In the present case, the diagnosis of limbal melanocytoma was based on clinical signs and confirmed by histopathological examination. The choice of treatment is influenced by the tumour size and location, availability of equipment and materials, clinician expertise and the cost of treatment. Some techniques for removing the mass and repairing the resultant corneoscleral defect has been described. In the present case, due to the location and size of the mass and the absence of intraocular invasion, surgical removal including a margin of normal tissue was performed. With this surgical procedure, the intention was to preserve the eyeball and maintain vision. In this case, surgical excision of a limbal melanocytoma combined with homologous corneoscleral graft was effective for repairing a full-thickness corneoscleral defect and preserving ocular function.

Pupillary light responses in type 1 and type 2 diabetics with and without retinopathy.

We assessed the function of rod/cones and melanopsin in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) with and without non-proliferative diabetic retinopathy (NPDR). We performed pupillometry on 22 healthy controls and four diabetic groups: 12 T1DM patients without NPDR and 12 with moderate NPDR, and 16 T2DM patients without NPDR and 12 with moderate NPDR. Monocular stimulations of 20seconds with red (λ=633nm) and blue light (λ=463nm) at ~15log quanta/cm2 /second were performed. The primary outcome was the melanopsin-mediated late redilation phase of postillumination pupillary light response (PIPRL ate ) to blue light. The secondary outcomes were the mixed rod/cone and melanopsin responses, that is maximal pupil constriction and the early redilation phase of PIPR (PIPRE arly ). Late redilation phase of PIPR (PIPRL ate ) to blue and red light stimuli was not significantly different between healthy control and the four diabetic groups (n.s.). The maximal pupil contractions to blue light stimulus were significantly reduced in T1DM patients as well as in T2DM patients with NPDR (p≤0.02), whereas for red light stimuli, the maximal pupil constriction was only reduced in T2DM with NPDR (p<0.01). Early redilation phase of PIPR (PIPRE arly ) to blue and red light stimuli was not significantly different between healthy controls and diabetic patients (n.s.). Neither the PIPRE arly nor the PIPRL ate was significantly reduced in diabetics with or without NPDR compared to healthy controls. The reduced maximal pupil constrictions in diabetics with NPDR indicate decreased mixed rod/cone and melanopsin responses.

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease.

Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD. We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

The pupillary light response reflects visual working memory content.

Recent studies have shown that the pupillary light response (PLR) is modulated by higher cognitive functions, presumably through activity in visual sensory brain areas. Here we use the PLR to test the involvement of sensory areas in visual working memory (VWM). In two experiments, participants memorized either bright or dark stimuli. We found that pupils were smaller when a prestimulus cue indicated that a bright stimulus should be memorized; this reflects a covert shift of attention during encoding of items into VWM. Crucially, we obtained the same result with a poststimulus cue, which shows that internal shifts of attention within VWM affect pupil size as well. Strikingly, the effect of VWM content on pupil size was most pronounced immediately after the poststimulus cue, and then dissipated. This suggests that a shift of attention within VWM momentarily activates an "active" memory representation, but that this representation quickly transforms into a "hidden" state that does not rely on sensory areas. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Observer‐perceived light aversion behaviour in photophobic subjects with traumatic brain injury

BackgroundPhotophobia is a common sequela of traumatic brain injury (TBI). Diagnostic tools for this debilitating condition are lacking. This investigation sought to determine whether masked observers can distinguish subjects with TBI‐associated photophobia from matched controls based on video recordings of their ocular responses to light stimulation.MethodsCohorts of students (n = 20), photophobic TBI subjects (n = 28) and their matched control subjects (n = 12) were recruited. A custom pupillometer delivered bright (1013–1014 photons/s/cm2), flashing (0.10-Hz) red (625-nm) and blue (470-nm) light stimuli to subjects, and consensual pupil light responses were recorded. Using a five‐point scale, masked observers later graded light aversion behaviour in the pupil video recordings obtained from the student cohort based on observed blinking, tearing and squinting. A grading scale was developed and used by masked observers to grade light aversion behaviour in videos obtained from subjects with post‐TBI photophobia and the matched controls. These subjects also scored their perceived discomfort during each light pulse using a five‐point scale.ResultsThe subjects in the TBI cohort scored both the blue and red flashing stimuli as evoking more discomfort, relative to control subjects, consistent with their reported photophobia. There was strong agreement among the masked observers for their grades of light aversion behaviour in the videos of ocular light stimulation (interclass correlation co‐efficient = 0.78; 29 per cent perfect concordance). However, the median grades for the videos obtained from the TBI subject cohort were not significantly different from those for the control group.ConclusionsClinicians cannot diagnose TBI‐related photophobia based solely on video recordings of ocular responses to light. The need remains for an objective test to diagnose and manage this prevalent post‐TBI symptom.

The flicker Pupil Light Response (fPLR).

PurposeThe photoreceptor classes driving the flicker pupil light response (fPLR) to monochromatic sinusoidal temporal modulation are largely unknown. Here, we determine the photoreceptor inputs to the fPLR.MethodsThe 0.5-Hz fPLR was measured in healthy observers using a Maxwellian view (41° diameter) pupillometer at five narrowband wavelengths (short: 409 nm; intermediate: 462, 507, 530 nm; and long: 592 nm) over ∼10 log units of irradiance spanning scotopic to photopic levels (5.6 to 15.6 log quanta·cm−2·s−1; −6.9 to 3.6 log cd·m−2). The relative photoreceptor contributions to the fPLR were then derived from these amplitude-irradiance functions using a criterion fPLR.ResultsThe fPLR amplitude is small (≤ 3.9 ± 3.1%; mean ± SEM) below 8.0 log quanta·cm−2·s−1 then increases with retinal irradiance in accordance with a Hill function that asymptotes between 13.0 to 15.0 log quanta·cm−2·s−1 (wavelength dependent). The Hill slope is steepest for the intermediate wavelengths. Further increases in irradiance (>15.0 log quanta·cm−2·s−1) produce a distinct suppression of the fPLR for the intermediate wavelengths. The fPLR phase delay shows a linear decrease with increasing irradiance. The spectral sensitivity of the fPLR is dominated by inner retinal melanopsin ganglion cell and outer retinal rod photoreceptor inputs to the afferent pupil control pathway; the relative melanopsin : rhodopsin weighting decreases with the transition from photopic to scotopic lighting.ConclusionsThe fPLR can be used as a marker of melanopsin and rod interactions during the flicker stimulation and to quantify their contributions to the post-illumination pupil response (PIPR).Translational RelevanceThese irradiance and wavelength responses will be useful in standardizing the measurements of the fPLR using chromatic pupillometry.

Quantitative Pupillometry in the Intensive Care Unit.

Quantitative pupillometry provides a noninvasive and objective assessment within the neurological examination. This review details the physiology of the pupillary light response, the clinical significance of changes in pupillary reactivity, and the variables that compose the Neurological Pupil index or NPi are discussed. This article reviews the most recent applications and advances in quantitative pupillometry for noninvasive intracranial pressure monitoring, postcardiac arrest prognostication, and subarachnoid hemorrhage. Also discussed are the limitations and confounders of quantitative pupillometry in the modern neurological intensive care unit.