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112 result(s) for "Constable, Paul A."
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Retinal electrophysiology in central nervous system disorders. A review of human and mouse studies
The retina and brain share similar neurochemistry and neurodevelopmental origins, with the retina, often viewed as a “window to the brain.” With retinal measures of structure and function becoming easier to obtain in clinical populations there is a growing interest in using retinal findings as potential biomarkers for disorders affecting the central nervous system. Functional retinal biomarkers, such as the electroretinogram, show promise in neurological disorders, despite having limitations imposed by the existence of overlapping genetic markers, clinical traits or the effects of medications that may reduce their specificity in some conditions. This narrative review summarizes the principal functional retinal findings in central nervous system disorders and related mouse models and provides a background to the main excitatory and inhibitory retinal neurotransmitters that have been implicated to explain the visual electrophysiological findings. These changes in retinal neurochemistry may contribute to our understanding of these conditions based on the findings of retinal electrophysiological tests such as the flash, pattern, multifocal electroretinograms, and electro-oculogram. It is likely that future applications of signal analysis and machine learning algorithms will offer new insights into the pathophysiology, classification, and progression of these clinical disorders including autism, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia, depression, Parkinson’s, and Alzheimer’s disease. New clinical applications of visual electrophysiology to this field may lead to earlier, more accurate diagnoses and better targeted therapeutic interventions benefiting individual patients and clinicians managing these individuals and their families.
OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods
Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.
ISCEV Standard for clinical electro-oculography (2017 update)
The clinical electro-oculogram (EOG) is an electrophysiological test of the outer retina and retinal pigment epithelium (RPE) in which changes in the electrical potential across the RPE are recorded during successive periods of dark and light adaptation. This document presents the 2017 EOG Standard from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org ). This standard has been reorganized and updated to include an explanation of the mechanism of the EOG, but without substantive changes to the testing protocol from the previous version published in 2011. It describes methods for recording the EOG in clinical applications and gives detailed guidance on technical requirements, practical issues and reporting of results with the main clinical measure (the Arden ratio) now termed the light peak:dark trough ratio. The standard is intended to promote consistent quality of testing and reporting within and between clinical centers.
Group comparisons of the individual electroretinogram time trajectories for the ascending limb of the b-wave using a raw and registered time series
Objectives The electroretinogram is a clinical test commonly used in the diagnosis of retinal disorders with the peak time and amplitude of the a- and b-waves used as the main indicators of retinal function. However, subtle changes that affect the shape of the electroretinogram waveform may occur in the early stages of disease or in conditions that have a neurodevelopmental or neurodegenerative origin. In such cases, we introduce a statistical approach to mathematically model the shape of the electroretinogram waveform that may aid clinicians and researchers using the electroretinogram or other biological signal recordings to identify morphological features in the waveforms that may not be captured by the time or time–frequency domains of the waveforms. We present a statistical graphics-based analysis of the ascending limb of the b-wave (AL-b) of the electroretinogram in children with and without a diagnosis of autism spectrum disorder (ASD) with a narrative explanation of the statistical approach to illustrate how different features of the waveform based on location and scale derived from raw and registered time series can reveal subtle differences between the groups. Results Analysis of the raw time trajectories confirmed findings of previous studies with a reduced and delayed b-wave amplitude in ASD. However, when the individual time trajectories were registered then group differences were visible in the mean amplitude at registered time ~ 0.6 suggesting a novel method to differentiate groups using registration of the ERG waveform.
Global motion coherent deficits in individuals with autism spectrum disorder and their family members are associated with retinal function
This study aims to evaluate if the reduced sensitivity to global motion observed in some individuals with autism spectrum disorder (ASD) is associated with altered retinal processing. Motion coherence thresholds were measured from individuals with ASD and their family members and compared to the test reference limits derived from control participants. The light adapted electroretinogram (ERG) a- and b-wave amplitudes and peak-times, and photopic negative response (PhNR) parameters were measured from the ASD individuals and their families and compared to those of controls. Abnormally high motion coherence thresholds were found in ASD probands and their family members compared to that in controls, particularly mothers. Altered retinal functions were found in ASD probands and their parents. The PhNR, a- and b-wave time-to-peak were significantly correlated with motion coherence thresholds. The altered retinal function was associated with the age, intelligence and autism severity of the ASD family members. There were associations between the motion coherence and ERG parameters, including smaller amplitudes of the PhNR, and longer time-to-peak of the a- and b-waves and time to the PhNR, compared to those with abnormal motion coherence thresholds. The results showed that global motion coherence deficits were associated with altered retinal function in ASD and their family members. The findings suggest that motion perception deficits follow a familial pattern and that affected mothers may have an increased risk of a child with ASD.
Discrete Wavelet Transform Analysis of the Electroretinogram in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder
Background To evaluate the electroretinogram waveform in autism spectrum disorder and attention deficit hyperactivity disorder using a discrete wavelet transform (DWT) approach. Methods A total of 55 autism spectrum disorder (ASD), 15 attention deficit hyperactivity disorder (ADHD) and 156 control individuals took part in this study. Full field light-adapted electroretinograms (ERGs) were recorded using a Troland protocol, accounting for pupil size, with five flash strengths ranging from -0.12 to 1.20 log photopic cd.s.m-2. A DWT analysis was performed using the Haar wavelet on the waveforms to examine the energy within the time windows of the a- and b-waves and the oscillatory potentials (OPs) which yielded six DWT coefficients related to these parameters. The central frequency bands were from 20-160 Hz relating to the a-wave, b-wave and OPs represented by the coefficients: a20, a40, b20, b40, op80 and op160 respectively. In addition, the b-wave amplitude and percentage energy contribution of the OPs (%OPs) in the total ERG broadband energy was evaluated. Results There were significant group differences (p<.001) in the coefficients corresponding to energies in the b-wave (b20, b40) and OPs (op80 and op160) as well as the b-wave amplitude. Notable differences between the ADHD and control groups were found in the b20 and b40 coefficients. In contrast, the greatest differences between the ASD and control group were found in the op80 and op160 coefficients. The b-wave amplitude showed both ASD and ADHD significant group differences from the control participants, for flash strengths greater than 0.4 log photopic cd.s.m-2 (p<.001). Conclusions This methodological approach may provide insights about neuronal activity in studies investigating group differences where retinal signaling may be altered through neurodevelopment or neurodegenerative conditions. However, further work will be required to determine if retinal signal analysis can offer a classification model for neurodevelopmental conditions in which there is a co-occurrence such as ASD and ADHD,
The electroretinogram b-wave amplitude: a differential physiological measure for Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder
Background Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent childhood neurodevelopmental disorder. It shares some genetic risk with Autism Spectrum Disorder (ASD), and the conditions often occur together. Both are potentially associated with abnormal glutamate and GABA neurotransmission, which can be modelled by measuring the synaptic activity in the retina with an electroretinogram (ERG). Reduction of retinal responses in ASD has been reported, but little is known about retinal activity in ADHD. In this study, we compared the light-adapted ERGs of individuals with ADHD, ASD and controls to investigate whether retinal responses differ between these neurodevelopmental conditions. Methods Full field light-adapted ERGs were recorded from 15 ADHD, 57 ASD (without ADHD) and 59 control participants, aged from 5.4 to 27.3 years old. A Troland protocol was used with a random series of nine flash strengths from −0.367 to 1.204 log photopic cd.s.m −2 . The time-to-peak and amplitude of the a- and b-waves and the parameters of the Photopic Negative Response (PhNR) were compared amongst the three groups of participants, using generalised estimating equations. Results Statistically significant elevations of the ERG b-wave amplitudes, PhNR responses and faster timings of the b-wave time-to-peak were found in those with ADHD compared with both the control and ASD groups. The greatest elevation in the b-wave amplitudes associated with ADHD were observed at 1.204 log phot cd.s.m −2 flash strength ( p < .0001), at which the b-wave amplitude in ASD was significantly lower than that in the controls. Using this measure, ADHD could be distinguished from ASD with an area under the curve of 0.88. Conclusions The ERG b-wave amplitude appears to be a distinctive differential feature for both ADHD and ASD, which produced a reversed pattern of b-wave responses. These findings imply imbalances between glutamate and GABA neurotransmission which primarily regulate the b-wave formation. Abnormalities in the b-wave amplitude could provisionally serve as a biomarker for both neurodevelopmental conditions.
A Review of Ocular Complications Associated with Medications Used for Anxiety, Depression, and Stress
This review of commonly prescribed psychotropic drugs aims to update the clinician on possible ophthalmic side effects that may include dry eye, diplopia, mydriasis, and cataracts. This review summarizes our current knowledge of known ocular side effects of psychotropic drugs based on reviews, case reports, case-control studies, a case series, and cross-sectional observational studies reported in the recent literature. The review covers disorders related to depression, anxiety, and stress which are commonly encountered within society and can have debilitating impacts on an individual's quality of life that may require chronic therapeutic management. The main medications used in the treatment and management of these conditions typically target receptors, metabolic enzymes, or transport pumps that alter the pre- and/or post-synaptic levels of neurotransmitters such as serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, and opioids to improve mood and/or relieve pain and anxiety. Novel non-therapeutic options are undergoing clinical trials, and some patients may seek alternative therapies or have associated substance abuse issues to alleviate their symptoms. This review summarizes some of the clinical signs of depression and the main therapeutic options and their reported ocular side effects which may be pertinent today given the rise in use of psychotropic medications used to manage depression, anxiety, and stress.
Remodeling the light-adapted electroretinogram using a bayesian statistical approach
Objective To present a remodeling of the electroretinogram waveform using a covariance matrix to identify regions of interest and distinction between a control and attention deficit/hyperactivity disorder (ADHD) group. Electroretinograms were recorded in n  = 25 ADHD (16 male; age 11.9 ± 2.7 years) and n  = 38 (8 male; age 10.4 ± 2.8 years neurotypical control participants as part of a broad study into the determining if the electroretinogram could be a biomarker for ADHD. Flash strengths of 0.6 and 1.2 log cd.s.m − 2 on a white 40 cd.m − 2 background were used. Averaged waveforms from each eye and flash strength were analyzed with Bayesian regularization of the covariance matrices using 100 equal length time intervals. The eigenvalues of the covariance matrices were ranked for each group to indicate the degree of complexity within the regularized waveforms. Results The correlation matrices indicated less correlation within the waveforms for the ADHD group in time intervals beyond 70 msec. The eigenvalue plots suggest more complexity within the ADHD group compared to the control group. Consideration of the correlation structure between ERG waveforms from different populations may reveal additional features for identifying group differences in clinical populations.