Men Clara J, Kossler Andrea L, Wester Sara T
Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA, USA.
Byers Eye Institute, School of Medicine, Stanford University, 2452 Watson Ct, Palo Alto, CA 94303, USA.
Ther Adv Ophthalmol. 2021 Jun 30;13:25158414211027760. doi: 10.1177/25158414211027760. eCollection 2021 Jan-Dec.
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.
甲状腺眼病（TED）是一种复杂疾病，伴有多种临床表现，包括面部畸形、视力丧失和生活质量下降。传统上，类固醇疗法和/或放射疗法常用于治疗活动期TED。虽然这些疗法有助于减轻炎症，但它们通常对疾病结局，包括眼球突出和复视，没有可持续的、显著的长期效果。我们对TED病理生理学认识的最新进展已将治疗重点转向靶向生物疗法。生物制剂具有精确免疫调节的优势，与传统方法相比，其安全性更好、疗效更佳。例如，已发现胰岛素样生长因子-1受体（IGF-1R）在TED患者中上调，并与促甲状腺激素受体（TSHR）共定位，形成信号复合物。替普罗单抗是一种靶向IGF-1R的抗体。通过抑制IGF-1R/TSHR信号通路，替普罗单抗可能会减少TED患者促炎细胞因子的产生、透明质酸分泌和眼眶成纤维细胞活化。由于II期和III期临床试验结果令人鼓舞，替普罗单抗已成为美国食品药品监督管理局（FDA）批准的首个用于治疗TED的生物制剂。此外，目前正在进行多项研究，探讨在包括TED在内的各种自身免疫性疾病中使用靶向新生儿Fc受体（FcRn）的抗体。FcRn的功能是转运免疫球蛋白G（IgG）并防止其溶酶体降解。通过阻断IgG的再循环，这种方法可能会抑制机体的免疫反应，尤其是与某些自身免疫性疾病相关的致病性IgG。因此，我们对TED病理生理学认识的进展正带来更多靶向治疗选择，我们正进入TED管理的一个令人兴奋的新阶段。本综述将涵盖对TED病理生理学理解的最新见解、新型治疗选择以及TED新潜在治疗选择的正在进行的研究。
