替妥木单抗治疗甲状腺功能障碍性视神经病变：一项回顾性病例系列中的早期功能与结构改善

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中文摘要

甲状腺功能障碍性视神经病变（DON）是甲状腺眼病的一种严重且威胁视力的表现。我们开展了一项回顾性描述性病例系列研究，纳入单中心连续接受替妥木单抗治疗的DON患者，以评估功能性、结构性、基于磁共振成像（MRI）的炎症性及安全性结局。共纳入6例患者（10只眼）。在基线和随访期间评估眼水平结局，使用广义估计方程以考虑同一患者内的相关性。主要结局为最佳矫正视力（BCVA，以最小分辨角对数logMAR表示）和四条直肌横截面积之和（CSA）。次要结局为眼球突出度和四条直肌的平均T2信号强度比（T2-SIR）。估计边际平均BCVA从基线的0.35 logMAR改善至3周时的0.04、12周时的0.05和24周时的-0.08。直肌CSA之和从基线的2.11 cm2降至12周时的1.48 cm2和24周时的1.41 cm2。随访期间眼球突出度和平均T2-SIR也下降。大多数非听力相关不良事件为轻度；然而，1例患者因腹泻停药，另1例因疲劳和耳鸣停药。所有6例患者中至少1只耳发现美国言语-语言-听力协会（ASHA）定义的听力阈值偏移。这些发现提示，替妥木单抗与DON患者在功能性、解剖学和基于MRI的炎症性终点上的早期一致改善相关。仔细监测，尤其是听力学评估，仍然至关重要。

英文摘要

Dysthyroid optic neuropathy (DON) is a severe, vision-threatening manifestation of thyroid eye disease. We conducted a retrospective descriptive case series of consecutive patients with DON treated with teprotumumab at a single center to evaluate functional, structural, magnetic resonance imaging (MRI)-based inflammatory, and safety outcomes. Six patients (10 eyes) were included. Eye-level outcomes were assessed at baseline and during follow-up using generalized estimating equations to account for within-patient correlation. The primary outcomes were best-corrected visual acuity (BCVA), expressed as logarithm of the minimum angle of resolution (logMAR) and summed cross-sectional area of the four rectus muscles (CSA). Secondary outcomes were proptosis and mean T2 signal intensity ratio (T2-SIR) of the four rectus muscles. Estimated marginal mean BCVA improved from 0.35 logMAR at baseline to 0.04 at 3 weeks, 0.05 at 12 weeks, and -0.08 at 24 weeks. Summed rectus CSA decreased from 2.11 cm2 at baseline to 1.48 cm2 at 12 weeks and 1.41 cm2 at 24 weeks. Proptosis and mean T2-SIR also decreased during follow-up. Most non-hearing-related adverse events were mild; however, treatment was discontinued in one patient because of diarrhea and in another because of fatigue and tinnitus. American Speech-Language-Hearing Association (ASHA)-defined hearing threshold shifts were identified in at least one ear in all six patients. These findings suggest that teprotumumab was associated with early concordant improvement across functional, anatomic, and MRI-based inflammatory endpoints in patients with DON. Careful monitoring, particularly audiologic assessment, remains essential.