Dysregulated 24 h melatonin secretion associated with intrinsically photosensitive retinal ganglion cell function in diabetic retinopathy: a cross-sectional study.

Aims/hypothesis: The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function.

Methods: Participants with type 2 diabetes, with diabetic retinopathy (n=14) and without diabetic retinopathy (n=9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR).

Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes.

Sleep irregularity and variability have been shown to be detrimental to cardiometabolic health. The present pilot study explored if higher day-to-day sleep irregularity and variability were associated with systemic inflammation, as assessed by high-sensitivity C-reactive protein, in type 2 diabetes. Thirty-five patients with type 2 diabetes (mean age 54.

Improvement of retinal function in Alzheimer disease-associated retinopathy by dietary lysophosphatidylcholine-EPA/DHA.

Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD, abnormalities in visual functions often precede them, and are increasingly being used as diagnostic and prognostic markers for the disease. Retina contains the highest concentration of the essential fatty acid docosahexaenoic acid (DHA) in the body, and its deficiency is associated with several retinal diseases including diabetic retinopathy and age related macular degeneration.

Effects of normal aging on the mouse retina assessed by full-field flash and flicker electroretinography.

Changes in the full-field flash and flicker electroretinogram (ERG) that accompany normal aging were evaluated in mice. ERGs were recorded from a single cohort of C57BL/6J mice from 5 to 70 weeks of age using conventional techniques. Dark-adapted ERGs were recorded for flash luminances of - 3.

Rod photoreceptor activation and deactivation in early-stage diabetic eye disease.

Purpose: To infer rod phototransduction activation and deactivation characteristics in diabetics who have mild or no clinically-apparent retinopathy.

Methods: Fifteen non-diabetic controls, 15 diabetics with no clinically-apparent diabetic retinopathy (NDR), and 15 diabetics with mild non-proliferative diabetic retinopathy (MDR) participated. Dark-adapted flash electroretinograms (3.

Occult retinopathy following treatment of Hepatitis C with glecaprevir/pibrentasvir (Mavyret).

Background/purpose: Medication-induced ocular toxicity is an important consideration in the differential diagnosis of unexplained visual disturbance. We present a case of visual disturbance after starting treatment with glecaprevir/pibrentasvir (Mavyret), a therapy for Hepatitis C virus approved by the FDA in 2017.

Methods: A 50-year-old male with no significant ocular history experienced bilateral visual disturbance, including visual field and acuity loss, shortly after initiating treatment with Mavyret for Hepatitis C.

Visual Field Abnormalities in Early-Stage Diabetic Retinopathy Assessed by Chromatic Perimetry.

Purpose: The purpose of this study was to define the nature and extent of sensitivity loss using chromatic perimetry in diabetics who have mild or no retinopathy.

Methods: Thirty-four individuals with type II diabetes mellitus who have mild nonproliferative diabetic retinopathy (MDR; N = 17) or no diabetic retinopathy (NDR; N = 17) and 15 visually normal, non-diabetic controls participated. Sensitivity was assessed along the horizontal visual field meridian using an Octopus 900 perimeter.

Two-Color Dark-Adapted Perimetry Implemented With a Commercially Available Perimeter to Characterize Rod-Pathway Sensitivity.

Background And Objective: To characterize rod-pathway function across the visual field using 2-color dark-adapted perimetry (2cDAP) implemented with conventional Octopus 900 Pro perimeters.

Patients And Methods: Eighteen visually normal individuals and two retinitis pigmentosa (RP) patients participated. Thresholds were measured under dark-adapted conditions at 15 locations along the horizontal meridian using short (450 nm) and long (610 nm) wavelength stimuli.

Spatial and Temporal Integration Abnormalities in X-Linked Retinoschisis.

Purpose: To evaluate spatial and temporal integration across the visual field in individuals with juvenile X-linked retinoschisis (XLRS).

Methods: Nine subjects with XLRS and 10 visually normal individuals participated. Luminance thresholds were measured at 15 locations along the horizontal visual field meridian.

Contrast Sensitivity and Equivalent Intrinsic Noise in X-Linked Retinoschisis.

Purpose: To define relationships among contrast sensitivity (CS), equivalent intrinsic noise (Neq; a measure of noise within the visual pathway), and retinal thickness in X-linked retinoschisis (XLRS).

Methods: Nine XLRS and 10 visually-normal subjects participated. CS was measured in the presence and absence of luminance noise.

Effect of Pharmacological Pupil Dilation on Dark-Adapted Perimetric Sensitivity in Healthy Subjects Using an Octopus 900 Perimeter.

Purpose: To determine whether dilation status has a clinically meaningful effect on sensitivity in normal subjects undergoing two-color dark-adapted perimetry, which can be useful to assess rod function.

Methods: A perimeter measured naturally and pharmacologically dilated scotopic sensitivities using a test grid consisting of 16 points across the horizontal meridian ranging from 60° temporal to 45° nasal using cyan (500 nm wavelength) or red (650 nm wavelength) stimuli. The primary outcome was average overall sensitivity based on dilation status, which was compared using a linear mixed effect model for each color stimuli.

Cone pathway dysfunction in Jalili syndrome due to a novel familial variant of revealed by pupillometry and electrophysiologic investigations.

Purpose: To evaluate retinal function in a family presenting with Jalili syndrome due to a previously unreported variant in .

Methods: A family of three sisters with a novel variant, c.482 T > C p.

Luminance Thresholds and Their Correlation With Retinal Structure in X-Linked Retinoschisis.

Purpose: To provide a comprehensive analysis of light- and dark-adapted luminance thresholds and their associations with retinal structure in X-linked retinoschisis (XLRS).

Methods: Nine subjects with XLRS and 10 visually-normal individuals participated. Threshold was measured at 15 locations along the horizontal meridian of the visual field at several adaptation levels (5 × 10-5 to 50 cd/m2) after dark-adaptation.

Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behavior Disorder.

Background: Melanopsin retinal ganglion cell (mRGC)-mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α-synucleinopathies.

Objectives: To quantitatively compare PLR and mRGC-mediated contribution to PLR in 16 iRBD patients and 16 healthy controls.

Clinical electroretinography in diabetic retinopathy: a review.

The electroretinogram (ERG) is a noninvasive, objective technique to evaluate retinal function that has become increasingly important in the study of diabetic retinopathy. We summarize the principles and rationale of the ERG, present findings from recent clinical studies that have used the full-field ERG, multifocal ERG, and pattern ERG to evaluate neural dysfunction in patients with diabetes, and weigh the strengths and limitations of the technique as it applies to clinical studies and management of patients with diabetic retinopathy. Taken together, ERG studies have provided convincing evidence for dysfunction of the neural retina in patients with diabetes, including those who have no clinically-apparent retinal vascular abnormalities.

Rod pathway and cone pathway retinal dysfunction in the 5xFAD mouse model of Alzheimer's disease.

To characterize rod- and cone-pathway function in the 5xFAD mouse model of Alzheimer's disease (AD) using the full-field electroretinogram (ERG). Dark-adapted (DA; rod-pathway) and light-adapted (LA; cone-pathway) ERGs were recorded from three-month-old 5xFAD and wild type (WT) mice. ERGs were elicited by achromatic flashes (0.

Electrophysiological and Pupillometric Abnormalities in PROM1 Cone-Rod Dystrophy.

Purpose: To compare electrophysiological and pupillometric responses in subjects with cone-rod dystrophy due to autosomal recessive (AR) mutations.

Methods: Four subjects with AR dystrophy and 10 visually normal, age-similar controls participated in this study. Full-field, light- and dark-adapted electroretinograms (ERGs) were obtained using conventional techniques.

Chromatic Pupillometry Findings in Alzheimer's Disease.

Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribution of rods, cones, and mRGCs to the PLR. In particular, post-illumination pupil response (PIPR) is the most reliable pupil metric of mRGC function.

Full-Field Electroretinography, Pupillometry, and Luminance Thresholds in X-Linked Retinoschisis.

Purpose: To evaluate the nature and extent of functional abnormality in X-linked retinoschisis (XLRS) by comparing three dark-adapted, full-field measures: the electroretinogram (ERG), pupillary light reflex (PLR), and luminance threshold.

Methods: ERGs, PLRs (pupil constriction due to light stimulation), and luminance thresholds were measured from seven XLRS subjects and from 10 normally sighted, age-similar controls. ERGs and PLRs were obtained for a range of flash strengths, and these data were fit with Naka-Rushton functions to derive the maximum saturated b-wave (Vmax) and PLR (Pmax) amplitudes.

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

[This corrects the article DOI: 10.1371/journal.pone.

Relationship between Intrinsically Photosensitive Ganglion Cell Function and Circadian Regulation in Diabetic Retinopathy.

Background: Intrinsically photosensitive retinal ganglion cells (ipRGCs) control non-visual light responses (e.g. pupillary light reflex and circadian entrainment).

Structural and Functional Abnormalities in Early-stage Diabetic Retinopathy.

Purpose: To evaluate the relationship between microperimetric (MP) sensitivity and retinal thickness measured at co-registered retinal locations in individuals who have mild or no diabetic retinopathy.

Methods: Fifty non-diabetic control subjects and 50 type-2 diabetic subjects participated (25 had no clinically apparent DR [NDR] and 25 had mild nonproliferative DR [MDR]). MP sensitivity was measured at 36 retinal locations that were arranged in three concentric rings centered on the fovea (radii of 3°, 6°, and 12°).

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

Background: 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.

Contrast sensitivity is associated with outer-retina thickness in early-stage diabetic retinopathy.

Purpose: To determine the relationship between contrast sensitivity (CS) and outer-retina thickness (ORT) in diabetics who have minimal or no diabetic retinopathy (DR).

Methods: Twenty non-diabetic control subjects and 40 type-2 diabetic subjects participated (20 had no clinically apparent DR [NDR] and 20 had mild non-proliferative DR [NPDR]). No subject had a history of treatment for macular oedema.

Electrophysiological measures of dysfunction in early-stage diabetic retinopathy: No correlation between cone phototransduction and oscillatory potential abnormalities.

Purpose: To define the relationship between abnormalities in the activation phase of cone phototransduction and the oscillatory potentials (OPs) of the light-adapted electroretinogram in diabetics who have mild or no retinopathy.

Methods: Subjects included 20 non-diabetic controls and 40 type-2 diabetics (20 had no clinically apparent diabetic retinopathy [NDR] and 20 had mild nonproliferative DR). Single flash responses for a series of stimulus retinal illuminances were measured under light-adapted conditions using conventional techniques.