Changes In Pupillary Light Reflex Research Articles

Quantitative assessments of pupillary light reflexes in neurocritically ill patients

The pupillary light reflex (PLR) is a component of bedside neurological examinations in neurological intensive care units (neuroICUs). A quantitative pupillometer provides a non-invasive and objective pupil reactivity parameter clinically significant for changes in PLR in neuroICUs. This article reviews the physiology and importance of the PLR and the parameters of quantitative pupillometers. Moreover, this review discusses the clinical applications of quantitative pupillometers for post-cardiac arrest prognostication and monitoring of elevated intracranial pressure and neurological worsening in stroke, seizures, and other neurological diseases in the neuroICU. Quantitative pupillometry is a routine part of neurological examinations and an important monitoring tool for neurological diseases in neuroICUs.

Morphological alterations of intrinsically photosensitive retinal ganglion cells after ablation of mouse photoreceptors with selective photocoagulation

In this work, we investigated changes in the morphology of intrinsically photosensitive retinal ganglion cells (ipRGCs), M1 subtype, and pupillary light reflex following local and selective ablation of photoreceptors in mice. Laser photocoagulation was used to selectively destroy four patches of photoreceptors per eye at around 4 papillary diameters from the optic disc and at the 3, 6, 9, and 12 o'clock positions between the retinal vessels in the adult mouse retina, leaving cells in the inner retina intact. Morphological parameters of individual M1 cells specifically labeled by the antibody against melanopsin (PA1-780), including dendritic field size, total dendritic length, and dendritic branch number, were examined 1, 2, 4, and 8 weeks after photocoagulation with Neurolucida software. A considerable reduction in these parameters in M1 cells in the “lesioned areas” was found at all the four time points after photocoagulation, as compared with those in the “unlesioned areas”. Although M1 cells in the lesioned areas showed significant changes as early as 1 week after laser treatment and the changes gradually increased, reaching a peak value at 2 weeks, morphological restoration was clearly seen in these cells over time. However, no difference in the morphological parameters of M1 cells was observed between the unlesioned areas of laser-treated mice and the corresponding areas of age-matched normal mice without laser lesions. Fluorescence intensity of the somata of melanopsin-positive M1 cells located inside the lesioned areas was significantly decreased at all the four time points after photocoagulation, whereas no changes in pupillary light reflex were detected at different light irradiations, indicating that photocoagulation-induced local photoreceptor loss and alterations of ipRGCs may be insufficient to cause abnormalities in non-image-forming (NIF) visual functions. The results suggest that intact photoreceptors could be crucial for maintaining the expression levels of melanopsin and normal morphology of M1 cells.

Pupillary Light Reflex Variability as a Predictor of Clinical Outcomes in Subarachnoid Hemorrhage.

A change in the pupillary light reflex (PLR) is a sensitive indicator for detecting expanding intracranial lesions. Changes in PLR may be a prognostic marker for patients with intracranial lesions. The purpose of this analysis was to explore how PLR readings, size, constriction velocity (CV), dilation velocity (DV), Neurologic Pupil Index (NPi), and latency predict clinical outcome in patients with subarachnoid hemorrhage. This is a secondary analysis of prospectively collected multicenter registry data. The within-subject standard deviation (WSD) of PLR values, NPi, size, CV, DV, and latency were explored as predictors of discharge modified Rankin Scale (mRS) in patients with subarachnoid hemorrhagic. Among 4403 pupillary readings from 82 patients with a diagnosis of subarachnoid hemorrhage, with a mean age of 57.7 years, the admission Glasgow Coma Scale median score was 14 (eye, 4; verbal, 4; motor, 6), and the mRS median was 0 on admission and 4 at discharge. Correlation between standard deviation of PLR values and discharge mRS was moderate and negative (r = -0.3 to -0.47, P < .01). The standard deviations for NPi, size, CV, and DV were significant for predicting discharge mRS (r = 0.23-0.28, P < .05) after controlling for admission Glasgow Coma Scale. Patients with higher WSD PLR values showed better outcomes (ie, lower mRS at discharge), suggesting that patients with narrower WSD PLR are at a higher risk for poor outcomes.

Effects of cold-pressor and mental arithmetic on pupillary light reflex

Dynamic pupillary light reflex (PLR) is a simple neurological test that can be useful for assessment of autonomic disorders. In this study, we investigated the changes in PLR induced by mental arithmetic task and cold pressor trials which are often applied in research as model systems to elicit autonomic responses. PLR was recorded before, during and after mental arithmetic and cold pressor tasks in 20 healthy adults (ten males and ten females). Stress-induced sympathetic activation was evident as shown in the increased blood pressure during both tasks. Although the pupillary constriction amplitude did not show significant changes, both constriction time and redilation time changed during the tasks. A significant gender effect was observed in cold pressor that suggested more sympathetic activation in males and faster parasympathetic activation in females in response to light stimulation under cold pressor.

Altered pupillary light reflex in PACAP receptor 1-deficient mice

The pupillary light reflex (PLR) is regulated by the classical photoreceptors, rods and cones, and by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin. IpRGCs receive input from rods and cones and project to the olivary pretectal nucleus (OPN), which is the primary visual center involved in PLR. Mice lacking either the classical photoreceptors or melanopsin exhibit some changes in PLR, whereas the reflex is completely lost in mice deficient of all three photoreceptors. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is co-stored with melanopsin in ipRGCs and mediates light signaling to the brain via the specific PACAP receptor 1 (PAC1R). Here, we examined the occurrence of PACAP and PAC1R in the mouse OPN, and studied if lack of PAC1R affected the PLR. PACAP-immunoreactive nerve fibers were shown in the mouse OPN, and by in situ hybridization histochemistry, we demonstrated the presence of PAC1R mRNA. Mice lacking PAC1R exhibited a significantly attenuated PLR compared to wild type mice upon light stimulation, and the difference became more pronounced as light intensity was increased. Our findings accord well with observations of the PLR in the melanopsin-deficient mouse. We conclude that PACAP/PAC1R signaling is involved in the sustained phase of the PLR at high irradiances.

Quantitative analysis of pupillary light reflex by real-time autofluorescent imaging in a diabetic mouse model

Here we (i) introduce a novel laser-based quantitative method of measuring pupillary light reflex (PLR) and applied it for the in vivo PLR monitoring of early diabetic retinopathy (DR) in a mouse model, (ii) investigate if melanopsin-expressing retinal ganglion cells (mRGCs) are implicated in the early progression of DR and, if so, is there an impact on PLR and (iii) determine if changes in PLR precede the onset of retinal hypoperfusion. A base-line PLR measurement is captured from C57BL/6J wild type mice followed by a single intraperitoneal administration of 200 mg/kg streptozotocin (STZ) and citrate buffer (vehicle) for the “diabetic” ( n = 5) and “control” ( n = 5) mice respectively, the very next day. PLR measurements are repeated once a week for four weeks. The PLR data comprises retinal autofluorescence intensity (AFI) values sampled over a 5-min period under confocal excitation with 488 nm high intensity blue laser light. AFI is used here as an indirect measure of pupil size since the amount of excitation light entering and emission light leaving the eye is proportional to the pupil area. Immunohistochemistry (IHC) staining of mRGCs and RT-PCR of melanopsin mRNA are performed at the end-point. The vascular calibre of both control and STZ-treated diabetic mice is assessed via in vivo fluorescein angiography (FA) on day 0 (base-line), 1/2, 1 and 4 months post-STZ treatment. The PLR profile shows a more rapid pupil constriction and slower dilation in diabetic mice compared to the control. Changes in PLR coincide or even precede the onset of retinal hypoperfusion. Extensive dendritic network of the mRGCs in retinal whole-mounts and increased melanopsin mRNA from the whole eye are also observed in diabetic mice. These pathological changes to mRGCs during early DR may in turn contribute towards changes in PLR. We present here a quantitative method of measuring PLR which enables an early detection of DR with potential application in the clinical setting. In contrast to conventional measurements of PLR, we are able to calibrate the amount of light reaching the retina which is a crucial parameter in longitudinal studies.

Pupillary and cardiovascular responses to a video movie in senior human subjects

The effects of watching video movies on autonomic functions were estimated by measuring changes in pupillary and cardiovascular parameters in 10 senior subjects. The subjects looked at a series of video images (with accompanied sounds) taken during the execution of motor vehicles. The images were rear-projected on a large screen for 15 min. Pupil diameter and parameters of the light reflex were measured by an infrared pupillometer before and after the video presentation. Their electrocardiograms (ECG) and blood pressure were measured continuously. Subjects were divided into two groups depending on their values of blood pressure and fasting plasma glucose level. Subjects in Group A had blood pressures of less than 140 mm Hg and a fasting plasma glucose level of less than 7 mmol/dl (normal group). Other subjects were included in Group B (mild hypertension or diabetes mellitus group). While changes in pupillary light reflex after video viewing were minimal in the members of Group A, amplitudes of the pupillary reflex in the members of Group B varied over a significantly wide range. By the spectral analysis of cardiovascular rhythm, %LF and %HF components of blood pressure rhythm were significantly different between the two groups before video viewing. However, the ratios of frequency components before and after video viewing were not significantly different between the two groups. Our findings suggest that pupillary light reflex was less precisely controlled in subjects with mild autonomic dysfunction after prolonged audiovisual stimulation.