Thyroid-associated ophthalmopathy (TAO) is a potentially sight-threatening ocular disease. About 3–5% of patients with TAO have severe disease with intense pain, inflammation, and sight-threatening corneal ulceration or compressive optic neuropathy. The current treatments of TAO are often suboptimal, mainly because the existing therapies do not target the pathogenesis of the disease. TAO mechanism is unclear. Ocular fibrocytes express relatively high levels of the functional TSH receptor (TSHR), and many indirect evidences support its participation. Over expression of insulin-like growth factor-1 receptor (IGF-IR) in fibroblasts, leading to inappropriate expression of inflammatory factors, production of hyaluronic acid and cell activation in orbital fibroblasts are also possible mechanisms. IGF-1R and TSHR form a physical and functional signaling complex. Inhibition of IGF-IR activity leads to the attenuation of signaling initiated at either receptor. Teprotumumab (TMB) is a human immunoglobulin G1 monoclonal antibody, binding to IGF-IR. Recently two TMB clinical trials had been implemented in TAO patients, indicating dramatic reductions in disease activity and severity, which approved its use for the treatment of TAO in the US. This review summarizes the treatments of TAO, focusing on the pathogenesis of IGF-1R in TAO and its application prospects.

中文翻译：

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Teprotumumab：中重度甲状腺相关眼病治疗的曙光

甲状腺相关眼病 (TAO) 是一种潜在威胁视力的眼病。大约 3-5% 的 TAO 患者患有严重的疾病，伴有剧烈疼痛、炎症和威胁视力的角膜溃疡或压迫性视神经病变。目前对 TAO 的治疗往往不是最理想的，主要是因为现有的治疗方法没有针对疾病的发病机制。TAO机制尚不清楚。眼部纤维细胞表达相对高水平的功能性 TSH 受体 (TSHR)，许多间接证据支持其参与。成纤维细胞中胰岛素样生长因子-1受体（IGF-IR）的过度表达，导致炎症因子的不适当表达、透明质酸的产生和眼眶成纤维细胞的细胞活化也是可能的机制。IGF-1R 和 TSHR 形成一个物理和功能信号复合体。IGF-IR 活性的抑制导致在任一受体上启动的信号传导减弱。Teprotumumab (TMB) 是一种人免疫球蛋白 G1 单克隆抗体，与 IGF-IR 结合。最近在 TAO 患者中实施了两项 TMB 临床试验，表明疾病活动度和严重程度显着降低，这在美国批准了其用于治疗 TAO。本文综述了TAO的治疗方法，重点阐述了IGF-1R在TAO中的发病机制及其应用前景。表明疾病活动度和严重程度显着降低，这在美国批准了其用于治疗 TAO。本文综述了TAO的治疗方法，重点阐述了IGF-1R在TAO中的发病机制及其应用前景。表明疾病活动度和严重程度显着降低，这在美国批准了其用于治疗 TAO。本文综述了TAO的治疗方法，重点阐述了IGF-1R在TAO中的发病机制及其应用前景。