Reclaiming the periphery: Automated kinetic perimetry for measuring peripheral visual fields in patients with glaucoma

Purpose: Peripheral vision is important for mobility, balance, and guidance of attention, but standard perimetry examines only <20% of the entire visual field. We report on the relation between central and peripheral visual field damage, and on retest variability, with a simple approach for automated kinetic perimetry (AKP) of the peripheral field. Methods: Thirty patients with glaucoma (median age 68, range 59–83 years; median Mean Deviation −8.0, range −16.3–0.1 dB) performed AKP and static automated perimetry (SAP) (German Adaptive Threshold Estimation strategy, 24-2 test). Automated kinetic perimetry consisted of a fully automated measurement of a single isopter (III.1.e). Central and peripheral visual fields were measured twice on the same day. Results: Peripheral and central visual fields were only moderately related (Spearman's ρ, 0.51). Approximately 90% of test-retest differences in mean isopter radius were < ±4 deg. Relative to the range of measurements in this sample, the retest variability of AKP was similar to that of SAP. Conclusions: Patients with similar central visual field loss can have strikingly different peripheral visual fields, and therefore measuring the peripheral visual field may add clinically valuable information

DynPeak : An algorithm for pulse detection and frequency analysis in hormonal time series

The endocrine control of the reproductive function is often studied from the analysis of luteinizing hormone (LH) pulsatile secretion by the pituitary gland. Whereas measurements in the cavernous sinus cumulate anatomical and technical difficulties, LH levels can be easily assessed from jugular blood. However, plasma levels result from a convolution process due to clearance effects when LH enters the general circulation. Simultaneous measurements comparing LH levels in the cavernous sinus and jugular blood have revealed clear differences in the pulse shape, the amplitude and the baseline. Besides, experimental sampling occurs at a relatively low frequency (typically every 10 min) with respect to LH highest frequency release (one pulse per hour) and the resulting LH measurements are noised by both experimental and assay errors. As a result, the pattern of plasma LH may be not so clearly pulsatile. Yet, reliable information on the InterPulse Intervals (IPI) is a prerequisite to study precisely the steroid feedback exerted on the pituitary level. Hence, there is a real need for robust IPI detection algorithms. In this article, we present an algorithm for the monitoring of LH pulse frequency, basing ourselves both on the available endocrinological knowledge on LH pulse (shape and duration with respect to the frequency regime) and synthetic LH data generated by a simple model. We make use of synthetic data to make clear some basic notions underlying our algorithmic choices. We focus on explaining how the process of sampling affects drastically the original pattern of secretion, and especially the amplitude of the detectable pulses. We then describe the algorithm in details and perform it on different sets of both synthetic and experimental LH time series. We further comment on how to diagnose possible outliers from the series of IPIs which is the main output of the algorithm.Comment: Nombre de pages : 35 ; Nombre de figures : 16 ; Nombre de tableaux :

Central aspects of systemic oestradiol negative‐ and positive‐feedback on the reproductive neuroendocrine system

The central nervous system regulates fertility via the release of gonadotrophin‐releasing hormone (GnRH). This control revolves around the hypothalamic‐pituitary‐gonadal axis, which operates under traditional homeostatic feedback by sex steroids from the gonads in males and most of the time in females. An exception is the late follicular phase in females, when homeostatic feedback is suspended and a positive‐feedback response to oestradiol initiates the preovulatory surges of GnRH and luteinising hormone. Here, we briefly review the history of how mechanisms underlying central control of ovulation by circulating steroids have been studied, discuss the relative merit of different model systems and integrate some of the more recent findings in this area into an overall picture of how this phenomenon occurs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153639/1/jne12724.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153639/2/jne12724_am.pd

Reclaiming the periphery: Kinetic perimetry in patients with glaucoma

Static automated perimetry of the central 30˚ is the most often used visual field test in glaucoma patients. Short test durations are achieved by focusing on a central region, which constitutes ~20% of the visual field. However, ignoring the periphery may sacrifice information on how patients are affected functionally. Peripheral vision is important for guiding attention, balance and mobility. An efficient standard automated examination for the peripheral visual field has not been established yet. This thesis aims to lay groundwork for the development of such a test. I introduce a kinetic automated test, which estimates an isopter with three repeated presentations per meridian. I ask whether measuring a peripheral isopter adds information to central visual field test results, investigate retest reliability and evaluate the efficiency of test procedures with repeated presentations through computer simulations. Moreover, I investigate how visual field thresholds obtained with static and kinetic stimuli relate to each other and examine the influence of stimulus sizes III and V on static threshold estimates. I also investigate the relationship between response variability and contrast sensitivity in the peripheral visual field. Based on the results, I suggest using repeated presentations in automated kinetic tests. I demonstrate that data driven computer simulations are useful for the development of efficient automated kinetic perimetry. The frequency-of-seeing results suggest that response variability to static stimuli in the far periphery is lower than suggested by previous data (Henson et al., 2000). This is relevant to future computer simulations of peripheral visual field tests with static automated perimetry. As a future avenue for examining the visual field periphery I propose a combined static kinetic automated visual field test, which combines a peripheral isopter as a region of interest with static stimuli inside this region. In a separate investigation, I examine the influence of visual field damage on reading performance and evaluate the relationship between reading performance and eye movements, using a within-patient between-eye study design in glaucoma patients with asymmetrical visual field loss. Between-eye reading performance was affected by visual field loss and co-occurred with specific eye movement patterns. The within-patient between-eye design appeared to be useful for investigating the relationship between visual field loss and functional disability

Using Eye Tracking to Assess Reading Performance in Patients with Glaucoma: A Within-Person Study

Reading is often cited as a demanding task for patients with glaucomatous visual field (VF) loss, yet reading speed varies widely between patients and does not appear to be predicted by standard visual function measures. This within-person study aimed to investigate reading duration and eye movements when reading short passages of text in a patient’s worse eye (most VF damage) when compared to their better eye (least VF damage). Reading duration and saccade rate were significantly different on average in the worse eye when compared to the better eye () in 14 patients with glaucoma that had median (interquartile range) between-eye difference in mean deviation (MD; a standard clinical measure for VF loss) of 9.8 (8.3 to 14.8) dB; differences were not related to the size of the difference in MD between eyes. Patients with a more pronounced effect of longer reading duration on their worse eye made a larger proportion of “regressions” (backward saccades) and “unknown” EMs (not adhering to expected reading patterns) when reading with the worse eye when compared to the better eye. A between-eye study in patients with asymmetric disease, coupled with eye tracking, provides a useful experimental design for exploring reading performance in glaucoma

To what extent are psychiatrists aware of the comorbid somatic illnesses of their patients with serious mental illnesses? – a cross-sectional secondary data analysis

Background Somatic comorbidities are a serious problem in patients with severe mental illnesses. These comorbidities often remain undiagnosed for a long time. In Germany, physicians are not allowed to access patients’ health insurance data and do not have routine access to documentation from other providers of health care. Against this background, the objective of this article was to investigate psychiatrists’ knowledge of relevant somatic comorbidities in their patients with severe mental illnesses. Methods Cross- sectional secondary data analysis was performed using primary data from a prospective study evaluating a model of integrated care of patients with serious mental illnesses. The primary data were linked with claims data from health insurers. Patients’ diagnoses were derived on the basis of the ICD-10 and the Anatomical Therapeutic Chemical (ATC) classification system. Diabetes, hypertension, coronary artery disease (CAD), hyperlipidaemia, glaucoma, osteoporosis, polyarthritis and chronic obstructive pulmonary disease (COPD) were selected for evaluation. We compared the number of diagnoses reported in the psychiatrists’ clinical report forms with those in the health insurance data. Results The study evaluated records from 1,195 patients with severe mental illnesses. The frequency of documentation of hypertension ranged from 21% in claims data to 4% in psychiatrists’ documentation, for COPD from 12 to 0%, respectively, and for diabetes from 7 to 2%, respectively. The percentage of diagnoses deduced from claims data but not documented by psychiatrists ranged from 68% for diabetes and 83% for hypertension, to 90% for CAD to 98% for COPD. Conclusions The majority of psychiatrists participating in the integrated care programme were insufficiently aware of the somatic comorbidities of their patients. We support allowing physicians to access patients’ entire medical records to increase their knowledge of patients’ medical histories and, consequently, to increase the safety and quality of care

Circannual Alterations in the Circadian Rhythm of Melatonin Secretion

To determine if a circadian rhythm known to be functionally related to the reproductive axis varies on a circannual basis, we monitored the circadian secretion of melatonin at monthly intervals for 2 years in four ovariectomized, estradiol-implanted ewes held in a constant short-day photoperiod. Prior to the study, ewes had been housed in a short-day (8L:16D) photoperiod for 4 years and were exhibiting circannual reproductive rhythms as assessed by serum luteinizing hormone (LH) levels. Three of the four sheep showed unambiguous deviations from the expected nocturnal melatonin secretion at two different times approximately 1 year apart. Nocturnal rises in melatonin, which usually last the duration of the dark phase, were delayed by 3-14 h or were missing. Altogether, five of the seven melatonin alterations observed in these three ewes occurred during the nadir of the circannual LH cycle. In the remaining ewe, we did not observe an altered melatonin secretory pattern during this period, and this ewe also failed to show a high amplitude circannual cycle of LH. The results provide evidence for a circannual change in the circadian rhythm of melatonin secretion. This alteration in melatonin secretion may serve as a "functional" change in daylength, and thereby may influence the expression of the circannual reproductive rhythm of sheep held in a fixed photoperiod for an extended time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68029/2/10.1177_074873049501000104.pd

Rapid Nongenomic Effects of Oestradiol on Gonadotrophin‐Releasing Hormone Neurones

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89550/1/j.1365-2826.2011.02135.x.pd

Pulsatile Hormonal Signaling to Extracellular Signal-Regulated Kinase: Exploring System Sensitivity to Gonadotropin-Releasing Hormone Pulse Frequency and Width

Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses that stimulate synthesis and secretion of pituitary gonadotropin hormones and thereby mediate control of reproduction. It acts via G-protein-coupled receptors to stimulate effectors, including ERK. Information could be encoded in GnRH pulse frequency, width, amplitude, or other features of pulse shape, but the relative importance of these features is unknown. Here we examine this using automated fluorescence microscopy and mathematical modeling, focusing on ERK signaling. The simplest scenario is one in which the system is linear, and response dynamics are relatively fast (compared with the signal dynamics). In this case integrated system output (ERK activation or ERK-driven transcription) will be roughly proportional to integrated input, but we find that this is not the case. Notably, we find that relatively slow response kinetics lead to ERK activity beyond the GnRH pulse, and this reduces sensitivity to pulse width. More generally, we show that the slowing of response kinetics through the signaling cascade creates a system that is robust to pulse width. We, therefore, show how various levels of response kinetics synergize to dictate system sensitivity to different features of pulsatile hormone input. We reveal the mathematical and biochemical basis of a dynamic GnRH signaling system that is robust to changes in pulse amplitude and width but is sensitive to changes in receptor occupancy and frequency, precisely the features that are tightly regulated and exploited to exert physiological control in vivo

Live view of gonadotropin-releasing hormone containing neuron migration

Neurons that synthesize GnRH control the reproductive axis and migrate over long distances and through different environments during development. Prior studies provided strong clues for the types of molecules encountered and movements expected along the migratory route. However, our studies provide the first real-time views of the behavior of GnRH neurons in the context of an in vitro preparation that maintains conditions comparable to those in vivo. The live views provide direct evidence of the changing behavior of GnRH neurons in their different environments, showing that GnRH neurons move with greater frequency and with more changes in direction after they enter the brain. Perturbations of guiding fibers distal to moving GnRH neurons in the nasal compartment influenced movement without detectable changes in the fibers in the immediate vicinity of moving GnRH neurons. This suggests that the use of fibers by GnRH neurons for guidance may entail selective signaling in addition to mechanical guidance. These studies establish a model to evaluate the influences of specific molecules that are important for their migration