Updates on the understanding and management of thyroid eye disease

Abstract

Thyroid eye disease (TED) is a complex disease associated with myriad clinical presentations, including facial disfigurement, vision loss, and decreased quality of life. Traditionally, steroid therapy and/or radiation therapy were commonly used in the treatment of active TED. While these therapies can help reduce inflammation, they often do not have a sustainable, significant long-term effect on disease outcomes, including proptosis and diplopia. Recent advances in our understanding of the pathophysiology of TED have shifted the focus of treatment toward targeted biologic therapies. Biologics have the advantage of precise immune modulation, which can have better safety profiles and greater efficacy compared to traditional approaches. For instance, the insulin-like growth factor-1 receptor (IGF-1R) has been found to be upregulated in TED patients and to colocalize with the thyroid-stimulating hormone receptor (TSHR), forming a signaling complex. Teprotumumab is an antibody targeted against IGF-1R. By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED. Due to promising phase II and III clinical trial results, teprotumumab has become the first biologic US Food and Drug Administration (FDA)-approved for the treatment of TED. In addition, there are currently ongoing studies looking at the use of antibodies targeting the neonatal Fc receptor (FcRn) in various autoimmune diseases, including TED. FcRn functions to transport immunoglobulin G (IgG) and prevent their lysosomal degradation. By blocking the recycling of IgG, this approach may dampen the body’s immune response, in particular the pathogenic IgG implicated in some autoimmune diseases. Advances in our understanding of the pathophysiology of TED, therefore, are leading to more targeted therapeutic options, and we are entering an exciting new phase in the management of TED. This review will cover recent insights into the understanding of TED pathophysiology and novel treatment options as well as ongoing studies of new potential treatment options for TED.

Diffusion Tensor Imaging Technology to Quantitatively Assess Abnormal Changes in Patients With Thyroid-Associated Ophthalmopathy

“…Since MD reflects the magnitude of water diffusion, an escalating trend of MD values can be acquired. The acute inflammation stage is also associated with cell lysis and fibrous disruption (Men et al, 2021). FA can reflect integrity of microstructural architectures, as mentioned.…”

Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders

“…26% with 6 weekly SC doses of 680 mg (89). A phase 2b clinical trial of batoclimab as treatment for thyroid eye disease was paused when a 12-week assessment showed elevated total and LDL cholesterol levels in active-treatment patients (89,101). Efgartigimod alfa (argenx), recently approved by the FDA for treatment of gMG (105), is an engineered Fc fragment derived from human IgG1 that blocks FcRn recycling of IgG by binding naturally via its Fc domain to FcRn (97,106).…”

Management of eyelid retraction related to thyroid eye disease

“…These treatments have the advantage of targeting key receptors implicated in the pathogenesis and immune dysregulation involved in TED, with potentially better safety profile and greater efficacy compared to traditional approaches. [ 103 ] Table 2 summarizes the main therapies.…”

“…The IGF-1Rs have been found to be upregulated in TED patients and to colocalize with the thyroid-stimulating hormone receptor (TSHR), forming a signaling complex. [ 103 110 ] Teprotumumab is a recombinant, human immunoglobulin G1 κ monoclonal antibody, targeted against the IGF-1 receptor, generated in genetically engineered Chinese hamster ovary cells. [ 78 ] By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED.…”

“…[ 78 ] By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED. [ 103 ]…”