替妥木单抗时代的甲状腺眼病：病理生理学、临床活动度评估及更新的治疗格局

文献信息

中文摘要

甲状腺眼病（TED）是Graves病最主要的甲状腺外表现，是一种自身免疫性眼眶病。其病理生理涉及眼眶成纤维细胞上异常的促甲状腺激素受体（TSHR）和胰岛素样生长因子1受体（IGF-1R）信号传导，导致糖胺聚糖蓄积、脂肪生成、炎性水肿及眼外肌增大。活动期通常具有自限性，但可经医学干预改变，主要以炎症、水肿和组织扩张为特征；而慢性非活动性疾病则以纤维化和固定的结构改变为主。这篇面向美国的综述旨在提供截至2026年该领域的更新：（1）总结将甲状腺自身免疫与眼眶重塑联系起来的分子病理生理学及当前药物靶点；（2）讨论活动度与严重度的评估，并对临床活动度评分（CAS）进行评价；（3）解释不同结构和功能影像学模式在TED评估和管理中的互补作用。随后我们沿治疗阶梯展开，从保守措施到使用糖皮质激素和保类固醇的免疫抑制，再到靶向生物制剂的使用。我们特别关注IGF-1R抑制，包括替妥木单抗和veligrotug的使用，以及上市后结果，包括耳科和代谢不良事件负担、复发、治疗序贯，以及治疗慢性和低活动度疾病的新兴疗效。CAS的观察者间信度有限，这提示需要额外的可重复活动度指标。

英文摘要

Thyroid eye disease (TED), the principal extrathyroidal manifestation of Graves' disease, is an autoimmune orbitopathy. The pathophysiology involves aberrant thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) signaling on orbital fibroblasts, leading to glycosaminoglycan accumulation, adipogenesis, inflammatory edema, and extraocular-muscle enlargement. The active phase is typically self-limited yet medically modifiable, characterized primarily by inflammation, edema, and tissue expansion, whereas chronic inactive disease is dominated by fibrosis and fixed structural change. This US-oriented review aims to provide updates in the field through 2026: (1) summarizing the molecular pathophysiology linking thyroid autoimmunity to orbital remodeling and current drug targets; (2) discussing activity-versus-severity assessment, with appraisal of the Clinical Activity Score (CAS); and (3) explaining the complementary roles of different structural and functional imaging modalities in the evaluation and management of TED. We then follow the therapeutic ladder, from conservative measures through the employment of glucocorticoids and steroid-sparing immunosuppression to the use of targeted biologics. We give particular attention to IGF-1R inhibition, including the use of teprotumumab and veligrotug, and to post-approval results, including otologic and metabolic adverse-event burden, recurrence, treatment sequencing, and the emerging efficacy of the treatment of chronic and low-activity disease. The CAS's limited inter-observer reliability identifies additional reproducible activity measures as an open need.