Thyroid eye disease

Abstract

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of autoimmune Graves’ hyperthyroidism. TED is a debilitating and potentially blinding disease with unclear pathogenesis. Autoreactive inflammatory reactions targeting orbital fibroblasts (OFs) lead to the expansion of orbital adipose tissues and extraocular muscle swelling within the fixed bony orbit. There are many recent advances in the understating of molecular pathogenesis of TED. The production of autoantibodies to cross-linked thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) activates OFs to produce significant cytokines and chemokines and hyaluronan production and to induce adipocyte differentiation. In moderately severe active TED patients, multicenter clinical trials showed that inhibition of IGF-1R with teprotumumab was unprecedentedly effective with minimal side effects. The emergence of novel biologics resulted in a paradigm shift in the treatment of TED. We here review the literature on advances of pathogenesis of TED and promising therapeutic targets and drugs.

TMEM2 inhibits the development of Graves’ orbitopathy through the JAK-STAT signaling pathway

“…GO is an autoimmune disease that is characterized by the inflammation, expansion, remodeling and fibrosis of the orbital tissue ( 2 , 26 ). Elevated levels of several proteins, including human TSH receptor (hTSHR) and HA mediate fibrosis of orbital muscle tissue and tissue edema that potentiates inflammatory cell infiltration, respectively ( 27 , 28 ).…”

“…Graves’ orbitopathy (GO), also named Graves' orbitopathy, thyroid-associated ophthalmopathy, or thyroid eye disease, is the most common complication of Graves’ disease, an autoimmune disorder that negatively impacts the quality of life of patients by impairing visual function and causing cosmetic disfigurement ( 1 ). GO is characterized by inflammation, expansion, remodeling and fibrosis of the orbital tissue, and orbital fibroblasts (OFs) have been shown to be key target and effector cells that contribute to its pathogenesis ( 2 ). During GO progression, immune cells infiltrate the orbital tissue leading to activation of OFs.…”

A Review of Novel Medical Treatments for Thyroid Eye Disease

“…Additionally, statin possesses antifibrotic and anti-inflammatory properties [ 68 , 69 ]. More specifically, statins are known to decrease tumor necrosis factor-α and IL-6, which are involved in the pathogenesis of TED [ 16 , 70 , 71 ]. Recent studies have focused on the role of cholesterol in TED and medications that reduce cholesterol.…”

“…Furthermore, both T cells and B cells play integral roles in the pathophysiology of TED. T cells activate B cells via CD40/CD40L binding, promoting the production of autoantibodies and orbital fibroblasts [ 16 ]. These processes can be repetitive, leading to orbital congestion, and can result in fibrosis of the extraocular muscles (EOM) if sustained over a longer period, potentially causing restrictive strabismus.…”

Emerging therapies in the medical management of thyroid eye disease

“…Emerging immunologic therapies for the management of thyroid eye disease have diverse mechanisms of actions and routes of administration (3)(4)(5). Different conventional and biological immunosuppressive agents, such as cyclosporine, mycophenolate mofetil, rituximab, have been studied as a mediator of the autoimmune and autoinflammatory pathways in thyroid eye disease.…”