Role of Lysyl Oxidase-Like Protein 3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.

Purpose: The lysyl oxidase (LOX) family has been implicated in the pathogenesis of diseases caused by inflammation and fibrosis. Therefore, we aimed to examine the role of lysyl oxidase-like protein 3 (LOXL3) in Graves' orbitopathy (GO) pathogenesis and its potential as a treatment target.

Methods: Quantitative real-time polymerase chain reaction compared the transcript levels of the five LOX family subtypes in orbital tissue explants obtained from patients with GO (n = 18) and healthy controls (n = 15).

Therapeutic role of physalin A in the pathogenesis of Graves' orbitopathy.

Background: Graves' orbitopathy (GO) is an autoimmune condition that causes serious ocular symptoms; its treatment strategies are limited. Physalin A is a phytosterol that has shown various therapeutic properties, including anti-inflammatory and anti-fibrotic effects. In this study, we investigated whether physalin A could inhibit inflammation, fibrosis, hyaluronan (hyaluronic acid) production, and adipogenesis, which are crucial to the pathogenesis of GO.

Therapeutic role of histone deacetylase inhibition in an model of Graves' orbitopathy.

Graves' orbitopathy (GO), a manifestation of Graves' disease, is characterized by orbital fibroblast‑induced inflammation, leading to fibrosis or adipogenesis. Histone deacetylase (HDAC) serves a central role in autoimmune diseases and fibrosis. The present study investigated HDAC inhibition in orbital fibroblasts from patients with GO to evaluate its potential as a therapeutic agent.

Pentraxin 3 mediates inflammation and adipogenesis in Graves' orbitopathy pathogenesis.

Pentraxin 3 (PTX3) is a prototypic humoral soluble pattern-recognition molecule known to function in immunity-related inflammation. Given the lack of information on the precise functions of PTX3 in the pathogenesis of Graves' orbitopathy (GO), this study investigated the role of PTX3 in the inflammation and adipogenesis mechanisms of GO. We first compared the PTX3 expression between orbital tissues from patients with GO and normal controls using real-time PCR, which estimated significantly higher PTX3 transcript levels in the GO tissues than in the normal tissues.

Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy.

Purpose: Orbital fibroblasts play key roles in the pathogenesis of Graves' orbitopathy (GO), and previous findings have shown that endoplasmic reticulum (ER) stress and autophagy also contribute to GO. In this study, we investigated the presently unclear roles of inositol-requiring enzyme 1 (IRE1) and related autophagy processes in the pro-fibrotic mechanism of GO.

Materials And Methods: Orbital adipose/connective tissues were obtained from eight GO patients and six normal individuals during surgery.

Yes-Associated Protein Mediates the Transition from Inflammation to Fibrosis in Graves' Orbitopathy.

In Graves' orbitopathy (GO), localized orbital inflammation within the fixed orbit often leads to a fibrotic phenotype resulting in restrictive myopathy or refractory proptosis. However, the molecular pathways related to the transition from inflammation to fibrosis in GO are less understood. Yes-associated protein (YAP) and its homolog, transcriptional coactivator with PDZ-binding motif (TAZ; a Hippo pathway effector), are critical mechanosensors of mechanical stimuli and activate signaling cascades for cell proliferation, differentiation, and transformation.

The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves' Orbitopathy.

Purpose: Graves' orbitopathy (GO) is an orbital manifestation of autoimmune Graves' disease, and orbital fibroblast is considered a target cell, producing pro-inflammatory cytokines and/or differentiating into adipocytes. Adipose tissue has been focused on as an endocrine and inflammatory organ secreting adipokines. We investigated the pathogenic role of a specific adipokine, adipsin, known as complement factor D in Graves' orbital fibroblasts.

Preoperative Risk Factors for Proptosis Recurrence After Rehabilitative Orbital Decompression in Graves' Orbitopathy Patients.

Purpose: Rehabilitative orbital decompression treats disfiguring exophthalmos in patients with Graves' orbitopathy (GO). This study aimed to identify risk factors associated with the postoperative recurrence of proptosis after orbital decompression.

Design: Retrospective, case-control study.

Sarcopenia as a potential risk factor for senile blepharoptosis: Nationwide Surveys (KNHANES 2008-2011).

As the world's population is aging, sarcopenia is recognized as essential to assess people's lifelong condition and do appropriate early intervention. Senile blepharoptosis is also a problem in old age deteriorating visual function and causing a cosmetic decline. We investigated the association between sarcopenia and the prevalence of senile blepharoptosis, using a nationwide representative survey in Korea.

Therapeutic effect of ibrutinib, a selective Bruton's tyrosine kinase inhibitor, in orbital fibroblasts from patients with Graves' orbitopathy.

Purpose: Bruton's tyrosine kinase (BTK) is an essential protein in B-cell antigen receptor (BCR) signaling pathway and is known to be related to pathogenetic effect on B-cell related malignancies and various autoimmune diseases. In this study, we investigated the therapeutic effect of ibrutinib, an orally bioavailable BTK inhibitor in the pathogenesis of Graves' orbitopathy (GO) in in vitro model.

Methods: Expression of BTK in orbital tissues from GO and normal control subjects were evaluated by real-time polymerase chain reaction (PCR).

Endoscopic transorbital approach to the cavernous sinus: Cadaveric anatomy study and clinical application (SevEN-009).

Objective: Cavernous sinus (CS) invasion is frequently encountered in the management of skull base tumors. Surgical treatment of tumors in the CS is technically demanding, and selection of an optimal surgical approach is critical for maximal tumor removal and patient safety. We aimed to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the CS based on a cadaveric study.

Longitudinal association of thyroid-stimulating immunoglobulin levels with clinical characteristics in thyroid eye disease.

Objectives: The clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the longitudinal association between changes in serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb) levels and course of disease activity and severity over time.

Design: This was a multicentre, prospective, observational study.

Potential Therapeutic Role of Bone Morphogenic Protein 7 (BMP7) in the Pathogenesis of Graves' Orbitopathy.

Purpose: We investigated a role of bone morphogenic protein 7 (BMP7), a member of the TGF-β superfamily on pathogenic mechanism of Graves' orbitopathy (GO). The therapeutic effects of BMP7 on inflammation and fibrosis were evaluated in cultured Graves' orbital fibroblasts.

Methods: Expression of BMP7 was compared in cultured orbital tissue explants from GO (n = 12) and normal control (n = 12) subjects using real-time PCR.

Quantitative assessment of increase in orbital volume after orbital floor fracture reconstruction using a bioabsorbable implant.

Purpose: To assess the postoperative changes in the orbital volume and the degree of enophthalmos after orbital floor fracture reconstruction using a bioabsorbable implant and to determine the predictors of postoperative orbital volume change.

Methods: Single-center, retrospective case series of 16 patients who underwent orbital floor fracture reconstruction using a bioabsorbable implant [poly(L-lactic acid)-poly(glycolic acid)/β-tricalcium phosphate; Biobsorb β] were included. Three-dimensional volumetric calculations of orbit were determined using computed tomography scans and the degree of enophthalmos was assessed via Hertel exophthalmometry.

Serum Selenium Levels in Patients with Graves Disease: Associations with Clinical Activity and Severity in a Retrospective Case-control Study.

Purpose: To compare serum selenium levels in Graves patients and non-Graves control participants and to evaluate associations between serum selenium levels and clinical features of Graves orbitopathy (GO).

Methods: We conducted a single-center, retrospective case-control study among 33 patients with Graves disease without GO (GD), 31 patients with diagnosed GO, and 27 unaffected healthy participants enrolled between 2013 and 2020 at Severance Hospital. We compared serum selenium concentrations between the GD, GO, and healthy control groups, and analyzed associations between serum selenium and GO patients' clinical activity scores, severity (assessed through modified NOSPECS scores), and other clinical features using multivariate linear regression analysis.

Signal transducer and activator of transcription 3 as a potential therapeutic target for Graves' orbitopathy.

The roles of signal transducer and activator of transcription 3 (STAT3) in inflammation, oxidative stress, and adipogenesis during Graves' orbitopathy (GO) are incompletely understood. Here, STAT3 expression in orbital tissues (from individuals with GO and healthy control subjects) was studied, and the role of STAT3 in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in primary orbital fibroblasts. STAT3 mRNA expression was higher in GO orbital tissues than in non-GO tissues.

The underestimated incidence of an orbital angioleiomyoma is possibly associated with an orbital cavernous hemangioma: illustrative case.

Background: Orbital angioleiomyoma is generally considered a rare tumor; approximately 40 cases have been reported. However, after their experience with 6 consecutive cases in their single institution during 3 years, the authors speculate that the incidence of orbital angioleiomyomas is possibly underestimated.

Observations: A 34-year-old female presented with progressive exophthalmos of 2 years' duration.

PERK mediates oxidative stress and adipogenesis in Graves' orbitopathy pathogenesis.

We examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves' orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress-related genes in orbital tissue harvested from individuals with or without GO was studied using real-time PCR. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts.

Role of Proprotein Convertase Subtilisin/Kexin Type 9 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in the pathogenesis of inflammatory diseases. We sought to investigate the role of PCSK9 in the pathogenesis of Graves' orbitopathy (GO) and whether it may be a legitimate target for treatment.

Methods: The was compared between GO (n=11) and normal subjects (n=7) in orbital tissue explants using quantitative real-time PCR, and in cultured interleukin-1β (IL-1β)-treated fibroblasts using western blot.

A Pilot Clinical Study of Ocular Prosthesis Fabricated by Three-dimensional Printing and Sublimation Technique.

Purpose: We sought to evaluate the safety and effectiveness of patient-specific ocular prostheses produced by three-dimensional (3D) printing and the sublimation technique. A comparison with prostheses produced using manual manufacturing methods was then performed.

Methods: To confirm the biological and physiochemical safety, cytotoxicity, systemic acute toxicity, intradermal reaction, and skin sensitization tests were conducted according to the International Organization for Standardization guidelines.

Role of binding immunoglobulin protein (BiP) in Graves' orbitopathy pathogenesis.

Inflammation and adipogenesis represent the main pathogenic mechanisms of Graves' orbitopathy (GO), and oxidative stress is a well-known inducer of GO pathology. Endoplasmic reticulum (ER) stress has been suggested as a major contributor to inflammation and reactive oxygen species (ROS) generation. In this study, we investigated the role of the ER-stress chaperone protein, binding immunoglobulin protein (BiP), in GO pathogenesis.

Protein tyrosine phosphatase 1B as a therapeutic target for Graves' orbitopathy in an in vitro model.

Graves' orbitopathy (GO) is characterised in early stages by orbital fibroblast inflammation, which can be aggravated by oxidative stress and often leads to fibrosis. Protein tyrosine protein 1B (PTP1B) is a regulator of inflammation and a therapeutic target in diabetes. We investigated the role of PTP1B in the GO mechanism using orbital fibroblasts from GO and healthy non-GO subjects.

Anti-oxidative and anti-adipogenic effects of caffeine in an in vitro model of Graves' orbitopathy.

Oxidative stress and adipogenesis play key roles in the pathogenesis of Graves' orbitopathy (GO). In this study, the therapeutic effects of caffeine on the reduction of oxidative stress and adipogenesis were evaluated in primary cultured GO orbital fibroblasts in vitro. Orbital fibroblasts were cultured from orbital connective tissues obtained from individuals with GO.