Prospective molecular targets for the future of thyroid eye disease treatment

INTRODUCTION: Thyroid eye disease (TED) is the most common orbital inflammatory disorder associated with autoimmune thyroid disease. Conventional anti-inflammatory treatment fails to address the heterogeneous clinical manifestations and are frequently associated with adverse events. These limitations underscore the need to identify robust molecular targets and develop mechanism-based precise treatment for TED. AREAS COVERED: This review summarized the landscape of prospective molecular targets for TED treatment. We provided a concise overview of the molecular mechanisms in TED, which is initiated by abnormal activation of insulin-like growth factor-1 receptor and thyroid-stimulating hormone receptor, and amplified by downstream inflammatory signaling. The discussion of emerging therapeutic molecular targets was then presented, which can be divided into four categories: blockade of disease-specific autoantibody response, modulation of pathogenic humoral immunity, inhibition of cytokine-mediated inflammatory pathway and mitigation of fibroblast-centered tissue remodeling. We elaborated on current major molecular targets, and highlighted promising candidates that may facilitate the development of next-generation precision therapies. EXPERT OPINION: Advances in understanding TED pathogenesis have expanded the repertoire of promising molecular targets. Future therapeutic development should extend beyond the validation of novel molecular targets to incorporate biomarker-guided patient stratification, rational combination therapies, and optimized drug delivery systems, thereby improving the treatment efficacy.