Thyroid Eye Disease in the Teprotumumab Era: A Narrative Review of Expanding the Therapeutic Window Beyond Disease Activity.

Thyroid eye disease (TED) is an autoimmune inflammatory disorder most commonly associated with Graves' disease and encompasses a broad clinical spectrum, ranging from mild eyelid and ocular surface changes to sight-threatening complications such as dysthyroid optic neuropathy (DON). This narrative review provides an updated, clinically oriented synthesis of TED, emphasizing the distinction between disease activity and severity, contemporary clinical assessment, established treatment strategies, and the evolving therapeutic window of targeted therapy. PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE) was searched, with the literature supplemented by targeted review of contemporary guidelines, consensus statements, pivotal clinical trials, prospective studies, systematic reviews, and reference lists of key publications. Particular emphasis was placed on disease activity and severity, conventional immunomodulatory treatment, teprotumumab, emerging insulin-like growth factor-1 receptor (IGF-1R)-directed therapies, and evidence addressing longstanding or less-active disease, delayed response, retreatment, durability, and reactivation. The Clinical Activity Score (CAS) and Vision, Inflammation, Strabismus, and Appearance (VISA) framework provide structured approaches to assessing disease activity and clinical manifestations. Management is guided by disease activity, severity, disease duration, phenotype, and treatment goals, ranging from supportive measures, risk-factor modification, and selenium supplementation in appropriate patients with mild disease to intravenous glucocorticoids, mycophenolate, targeted therapy, and selected orbital radiotherapy in active moderate-to-severe disease. Teprotumumab has broadened therapeutic options beyond the traditional paradigm of treating predominantly early, highly active TED, with emerging evidence supporting clinically meaningful responses in longstanding and less-active disease, including delayed responses and retreatment. Long-term studies also highlight variability in durability and the possibility of disease reactivation. Veligrotug and other targeted approaches are further expanding the therapeutic landscape. Sight-threatening disease requires urgent treatment, whereas rehabilitative orbital, strabismus, and eyelid surgery remain central for persistent structural sequelae. Overall, contemporary TED management is shifting from a predominantly phase-based model toward individualized treatment based on activity, severity, disease duration, phenotype, and the patient's principal therapeutic goal. Important questions regarding durability, retreatment, long-term safety, predictors of response, cost, and access remain unresolved.