Corneal Confocal Microscopy Identifies and Differentiates Patients With Multiple Sclerosis and Epilepsy.

Purpose: To assess whether corneal nerve analysis can identify and differentiate patients with multiple sclerosis (MS) from those with epilepsy.

Methods: Participants with MS (n = 83), participants with epilepsy (n = 50), and healthy controls (HCs) (n = 20) underwent corneal confocal microscopy (CCM) and quantification of automated corneal nerve fiber length (ACNFL), automated corneal nerve fractal dimension (ACNFrD), and ACNFrD/ACNFL ratio of the subbasal nerve plexus.

Results: ACNFL (MS: P < 0.

Glucose-lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes.

Aim: Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN.

Methods: Participants with T2D were grouped based on whether their glucose lowering medications were associated with weight gain (WG) or weight loss (WL).

Corneal nerve loss in adolescents with obesity and acanthosis nigricans.

Background/aim: Obesity and related metabolic abnormalities in adults are associated with peripheral neuropathy. Acanthosis nigricans (AN) is associated with insulin resistance, fatty liver, hyperlipidemia and glucose intolerance, all of which are risk factors for neuropathy. The aim of this study was to investigate if obese adolescents with AN have evidence of small nerve fiber damage.

Sustained corneal nerve loss predicts the development of diabetic neuropathy in type 2 diabetes.

Introduction: This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D).

Methods: Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4-7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, <24 fibers/mm), corneal nerve branch density (CNBD, <21 branches/mm), and corneal nerve fiber length (CNFL, <16 mm/mm) persisting for ≥50% of the study duration.

Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis.

Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions.

Brain alterations in regions associated with end-organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study.

Background: Diabetes mellitus (DM) is associated with structural grey matter alterations in the brain, including changes in the somatosensory and pain processing regions seen in association with diabetic peripheral neuropathy. In this case-controlled biobank study, we aimed to ascertain differences in grey and white matter anatomy in people with DM compared with non-diabetic controls (NDC).

Methods: This study utilises the UK Biobank prospective, population-based, multicentre study of UK residents.

Corneal confocal microscopy demonstrates varying degrees of neurodegeneration in atypical parkinsonian disorders.

Objective: We have used corneal confocal microscopy (CCM) to identify corneal nerve loss as a potential marker of neurodegeneration in participants with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).

Methods: Patients with PD (n = 19), PSP (n = 11), MSA (n = 8) and healthy controls (n = 18) underwent neurological assessment and CCM.

Results: Corneal nerve fibre density was significantly lower in participants with PD (p = 0.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions.

Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment.

Design: Prospective observational study conducted between September 2016 and February 2020.

Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers.

Objective: In this study, we evaluate small and large nerve fibre pathology in relation to diabetic foot ulceration (DFU) and incident cardiovascular and cerebrovascular events in type 1 diabetes (T1D).

Methods: A prospective observational study was conducted on people with T1D without diabetic peripheral neuropathy (DPN) ( = 25), T1D with DPN ( = 28), T1D with DFU ( = 25) and 32 healthy volunteers. ROC analysis of parameters was conducted to diagnose DPN and DFU, and multivariate Cox regression analysis was performed to evaluate the predictive ability of corneal nerves for cardiac and cerebrovascular events over 3 years.

Where Art Thou O treatment for diabetic neuropathy: the sequel.

Introduction: Having lived through a pandemic and witnessed how regulatory approval processes can evolve rapidly; it is lamentable how we continue to rely on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN.

Areas Covered: Small (Aδ and C) fibers are key to the genesis of pain, regulate skin blood flow, and play an integral role in the development of diabetic foot ulceration but continue to be ignored. This article challenges the rationale for the FDA insisting on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN.

Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulty in communication and interaction with others. Postmortem studies have shown cerebral neuronal loss and neuroimaging studies show neuronal loss in the amygdala, cerebellum and inter-hemispheric regions of the brain. Recent studies have shown altered tactile discrimination and allodynia on the face, mouth, hands and feet and intraepidermal nerve fiber loss in the legs of subjects with ASD.

Corneal confocal microscopy identifies corneal nerve fiber loss in patients with migraine.

Background/hypothesis: Migraine affects >1 billion people but its pathophysiology remains poorly understood. Alterations in the trigeminovascular system play an important role. We have compared corneal nerve morphology in patients with migraine to healthy controls.

Cardiovascular autonomic neuropathy is associated with increased glycemic variability driven by hyperglycemia rather than hypoglycemia in patients with diabetes.

Aim: Cardiac autonomic neuropathy (CAN) has been suggested to be associated with hypoglycemia and impaired hypoglycemia unawareness. We have assessed the relationship between CAN and extensive measures of glucose variability (GV) in patients with type 1 and type 2 diabetes.

Methods: Participants with diabetes underwent continuous glucose monitoring (CGM) to obtain measures of GV and the extent of hyperglycemia and hypoglycemia and cardiovascular autonomic reflex testing.

Corneal nerve loss predicts dementia in patients with mild cognitive impairment.

Objectives: This study compared the utility of corneal nerve measures with brain volumetry for predicting progression to dementia in individuals with mild cognitive impairment (MCI).

Methods: Participants with no cognitive impairment (NCI) and MCI underwent assessment of cognitive function, brain volumetry of thirteen brain structures, including the hippocampus and corneal confocal microscopy (CCM). Participants with MCI were followed up in the clinic to identify progression to dementia.

Artificial Intelligence Based Analysis of Corneal Confocal Microscopy Images for Diagnosing Peripheral Neuropathy: A Binary Classification Model.

Diabetic peripheral neuropathy (DPN) is the leading cause of neuropathy worldwide resulting in excess morbidity and mortality. We aimed to develop an artificial intelligence deep learning algorithm to classify the presence or absence of peripheral neuropathy (PN) in participants with diabetes or pre-diabetes using corneal confocal microscopy (CCM) images of the sub-basal nerve plexus. A modified ResNet-50 model was trained to perform the binary classification of PN (PN+) versus no PN (PN-) based on the Toronto consensus criteria.

Diagnostic Accuracy of Perception Threshold Tracking in the Detection of Small Fiber Damage in Type 1 Diabetes.

Aim: An objective assessment of small nerve fibers is key to the early detection of diabetic peripheral neuropathy (DPN). This study investigates the diagnostic accuracy of a novel perception threshold tracking technique in detecting small nerve fiber damage.

Methods: Participants with type 1 diabetes (T1DM) without DPN (n = 20), with DPN (n = 20), with painful DPN (n = 20) and 20 healthy controls (HCs) underwent perception threshold tracking on the foot and corneal confocal microscopy.

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability.

Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS.

Corneal Langerhans cells in children with celiac disease.

Celiac disease (CeD) is a common small bowel enteropathy characterized by an altered adaptive immune system and increased mucosal antigen presenting cells. This study aims to establish if quantification of corneal Langerhans cells (LCs) using corneal confocal microscopy (CCM) could act as a surrogate marker for antigen presenting cell status and hence disease activity in children with CeD. Twenty children with stable CeD and 20 age-matched controls underwent CCM and quantification of central corneal total, mature and immature LC density.

Artificial Intelligence and Corneal Confocal Microscopy: The Start of a Beautiful Relationship.

Corneal confocal microscopy (CCM) is a rapid non-invasive in vivo ophthalmic imaging technique that images the cornea. Historically, it was utilised in the diagnosis and clinical management of corneal epithelial and stromal disorders. However, over the past 20 years, CCM has been increasingly used to image sub-basal small nerve fibres in a variety of peripheral neuropathies and central neurodegenerative diseases.

Continuous glucose monitoring reveals a novel association between duration and severity of hypoglycemia, and small nerve fiber injury in patients with diabetes.

Objective: Continuous glucose monitoring (CGM) has revealed that glycemic variability and low time in range are associated with albuminuria and retinopathy. We have investigated the relationship between glucose metrics derived from CGM and a highly sensitive measure of neuropathy using corneal confocal microscopy in participants with type 1 and type 2 diabetes.

Methods: A total of 40 participants with diabetes and 28 healthy controls underwent quantification of corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and inferior whorl length (IWL) and those with diabetes underwent CGM for four consecutive days.

Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes.

Aim: To explore if novel non-invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes.

Methods: Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross-sectional analysis with optical coherence tomography angiography (OCT-A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC).

Results: Seventy-five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied.

Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes.

Aims/introduction: Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years.

Materials And Methods: Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow-up.

Corneal confocal microscopy identifies small nerve fibre damage in patients with hypertriglyceridemia.

Background: Hypertriglyceridemia has been identified as a risk factor for diabetic neuropathy.

Objective: Patients with hypertriglyceridemia underwent assessment of neuropathy and corneal confocal microscopy.

Methods: 24 patients with severe hypertriglyceridemia defined as a triglyceride level more than 5.

Retinal vessel multifractals predict pial collateral status in patients with acute ischemic stroke.

Objectives: Pial collateral blood flow is a major determinant of the outcomes of acute ischemic stroke. This study was undertaken to determine whether retinal vessel metrics can predict the pial collateral status and stroke outcomes in patients.

Methods: Thirty-five patients with acute stroke secondary to middle cerebral artery (MCA) occlusion underwent grading of their pial collateral status from computed tomography angiography and retinal vessel analysis from retinal fundus images.