Tapinarof, an Aryl Hydrocarbon Receptor Ligand, Mitigates Fibroblast Activation in Thyroid Eye Disease: Implications for Novel Therapy.

Purpose: In thyroid eye disease (TED), activation and proliferation of orbital fibroblasts (OFs) promotes remodeling and causes an increase in the volume of orbital tissue. Platelet-derived growth factors (PDGFs) are elevated in TED and promote OF activation. The aryl hydrocarbon receptor (AHR), a ligand activated nuclear receptor, is important in regulating OF activation.

Vision-related quality of life after unilateral occipital stroke.

Background/objectives: Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision-related quality of life (VR-QoL) is impacted by time since stroke.

Subjects/methods: We conducted a retrospective meta-analysis of 95 occipital stroke patients (female/male = 26/69, 27-78 years old, 0.

Training in Cortically Blinded Fields Appears to Confer Patient-Specific Benefit Against Retinal Thinning.

Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral hemifield, initiating a process of transsynaptic retrograde degeneration (TRD). Here, we examined retinal correlates of TRD using a new metric to account for global changes in inner retinal thickness and asked if perceptual training in the intact or blind field impacts its progression.

Methods: We performed a meta-analysis of optical coherence tomography data in 48 participants with unilateral V1 stroke and homonymous visual defects who completed clinical trial NCT03350919.

Training in cortically-blind fields confers patient-specific benefit against retinal thinning after occipital stroke.

Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral hemifield, initiating a process of trans-synaptic retrograde degeneration (TRD). Here, we examined retinal correlates of TRD using a new metric to account for global changes in inner retinal thickness, and asked if perceptual training in the intact or blind field impacts its progression.

Methods: We performed a meta-analysis of optical coherence tomography (OCT) data in 48 participants with unilateral V1 stroke and homonymous visual defects, who completed clinical trial NCT03350919.

Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease.

Context: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).

Objective: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.

Design: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials.

Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

Background: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort.

TNF-α and NF-κB signaling play a critical role in cigarette smoke-induced epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is characterized by the growth and contraction of cellular membranes within the vitreous cavity and on both surfaces of the retina, resulting in recurrent retinal detachments and poor visual outcomes. Proinflammatory cytokines like tumor necrosis factor alpha (TNFα) have been associated with PVR and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. Cigarette smoke is the only known modifiable risk factor for PVR, but the mechanisms are unclear.

More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor originally identified as an environmental sensor of xenobiotic chemicals. However, studies have revealed that the AHR regulates crucial aspects of cell growth and metabolism, development and the immune system. The importance of the AHR and AHR signaling in eye development, toxicology and disease is now being uncovered.

Variability of Retinal Vessel Tortuosity Measurements Using a Semiautomated Method Applied to Fundus Images in Subjects With Papilledema.

Purpose: To develop methods to quantitatively measure retinal vessel tortuosity from fundus images acquired in subjects with papilledema and assess sources of variability in these measurements.

Methods: Digital fundus images from 30 eyes of subjects with untreated idiopathic intracranial hypertension and papilledema were analyzed. Retinal vein and artery tortuosities for three to four vessels of each type were measured in a region of interest 1.

Thinking inside the box: Current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease.

Thyroid eye disease (TED) is an autoimmune disorder that manifests in the orbit. In TED, the connective tissue behind the eye becomes inflamed and remodels with increased fat accumulation and/or increased muscle and scar tissue. As orbital tissue expands, patients develop edema, exophthalmos, diplopia, and optic neuropathy.

MicroRNA-130a Is Elevated in Thyroid Eye Disease and Increases Lipid Accumulation in Fibroblasts Through the Suppression of AMPK.

Purpose: Thyroid eye disease (TED) is a condition that causes the tissue behind the eye to become inflamed and can result in excessive fatty tissue accumulation in the orbit. Two subpopulations of fibroblasts reside in the orbit: those that highly express Thy1 (Thy1+) and those with little or no Thy1 (Thy1-). Thy1- orbital fibroblasts (OFs) are more prone to lipid accumulation than Thy1+ OFs.

Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model.

Proliferative vitreoretinopathy (PVR) is a progressive disease that develops in a subset of patients who undergo surgery for retinal detachment repair, and results in significant vision loss. PVR is characterized by the migration of retinal pigment epithelial (RPE) cells into the vitreous cavity, where they undergo epithelial-to-mesenchymal transition and form contractile membranes within the vitreous and along the retina, resulting in recurrent retinal detachments. Currently, surgical intervention is the only treatment for PVR and there are no pharmacological agents that effectively inhibit or prevent PVR formation.

Efficacy of Visual Retraining in the Hemianopic Field after Stroke: Results of a Randomized Clinical Trial.

Purpose: To evaluate the efficacy of motion discrimination training as a potential therapy for stroke-induced hemianopic visual field defects.

Design: Clinical trial.

Participants: Forty-eight patients with stroke-induced homonymous hemianopia (HH) were randomized into 2 training arms: intervention and control.

Rehabilitation of cortically induced visual field loss.

Purpose Of Review: Homonymous visual field defects are a common sequela of stroke, and are assumed to be permanent within a few weeks of the event. Because consensus about the efficacy of rehabilitation is lacking, visual therapy is rarely prescribed. Here, we review current rehabilitation options and strategies in the translational pipeline that could change these perspectives.

A Mouse Model of Proliferative Vitreoretinopathy Induced by Intravitreal Injection of Gas and RPE Cells.

Purpose: Develop a reproducible proliferative vitreoretinopathy (PVR) mouse model that mimics human PVR pathology.

Methods: Mice received intravitreal injections of SF gas, followed by retinal pigment epithelial cells 1 week later. PVR progression was monitored using fundus photography and optical coherence tomography imaging, and histologic analysis of the retina as an endpoint.

The aryl hydrocarbon receptor pathway controls matrix metalloproteinase-1 and collagen levels in human orbital fibroblasts.

Thyroid eye disease (TED) affects 25-50% of patients with Graves' Disease. In TED, collagen accumulation leads to an expansion of the extracellular matrix (ECM) which causes destructive tissue remodeling. The purpose of this study was to investigate the therapeutic potential of activating the aryl hydrocarbon receptor (AHR) to limit ECM accumulation in vitro.

Retinal vessel diameter changes after 6 months of treatment in the Idiopathic Intracranial Hypertension Treatment Trial.

Background/aims: Prior studies support an association between increased retinal venule diameter and elevated intracranial pressure (ICP). The purpose of this study was to test the hypothesis that retinal venule diameters decrease in association with long-term therapy for high ICP in subjects with idiopathic intracranial hypertension (IIH).

Methods: This is a retrospective analysis of multicentre randomised controlled trial data.

TSHR Signaling Stimulates Proliferation Through PI3K/Akt and Induction of miR-146a and miR-155 in Thyroid Eye Disease Orbital Fibroblasts.

Purpose: To investigate the molecular pathways that drive thyroid stimulating hormone receptor (TSHR)-induced cellular proliferation in orbital fibroblasts (OFs) from thyroid eye disease (TED) patients.

Methods: Orbital fibroblasts from TED and non-TED patients were treated with TSH and changes in gene expression and proliferation were measured. To determine the role of TSHR, TSHR-specific siRNA was used to deplete TSHR levels.

Proton pump inhibitors attenuate myofibroblast formation associated with thyroid eye disease through the aryl hydrocarbon receptor.

Thyroid eye disease (TED) can lead to scar formation and tissue remodeling in the orbital space. In severe cases, the scarring process leads to sight-threatening pathophysiology. There is no known effective way to prevent scar formation in TED patients, or to reverse scarring once it occurs.

The polyether ionophore salinomycin targets multiple cellular pathways to block proliferative vitreoretinopathy pathology.

Proliferative vitreoretinopathy (PVR) is characterized by membranes that form in the vitreous cavity and on both surfaces of the retina, which results in the formation of tractional membranes that can cause retinal detachment and intrinsic fibrosis of the retina, leading to retina foreshortening. Currently, there are no pharmacologic therapies that are effective in inhibiting or preventing PVR formation. One of the key aspects of PVR pathogenesis is retinal pigment epithelial (RPE) cell epithelial mesenchymal transition (EMT).

Probability of Success in the Ophthalmology Residency Match: Three-Year Outcomes Analysis of San Francisco Matching Program Data.

Objective: To develop a probability model of matching into a US ophthalmology residency program using San Francisco Matching Program (SF Match) data.

Design: Retrospective data analysis of de-identified application and matching data.

Participants: Registrants for the 2013, 2014, and 2015 ophthalmology residency matches conducted by the SF Match.

The Relationship Between Optic Disc Volume, Area, and Frisén Score in Patients With Idiopathic Intracranial Hypertension.

Purpose: To compare measurements of papilledema using fundus photography, optical coherence tomography (OCT), and Frisén score in patients with idiopathic intracranial hypertension (IIH).

Design: Retrospective, noncomparative analysis of randomized controlled trial data.

Methods: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) evaluated weight management and treatment with acetazolamide compared with placebo in patients with IIH and mild visual loss.