What has changed in thyroid eye disease in the last five years (2020-2025).

Background: Significant progress has been made in the management of thyroid eye disease (TED), based on the elucidation of important pathogenic mechanisms. This has led to novel therapeutics validated in randomized clinical trials. Autoreactive antigens that elicit specific orbital immune reactions have not yet been identified, although it has been shown that fibrocytes, circulating stem cells that differentiate into fibroblasts, are expressing the thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) and may be stimulated in the orbit by a cascade of inflammatory reactions inducing adipogenesis. TED clinical assessment: Moderate-severe forms of TED are the target for immunosuppressive therapy. Improvement in the assessment of the active and progressive phase of disease is becoming compelling, as the outcome of a treatment depends on how early during the progressive phase the disease is treated. The clinical activity score may not always help define the right time for treating. Therapy: In 2020, teprotumumab, an anti-IGF-1 receptor blocker, has been approved by FDA for the treatment of TED. Since then, other drugs were studied or are under investigation and will seek regulatory approval. Microbiome and TED: A series of studies have investigated the role of microbiome in thyroid autoimmunity and TED more in detail, based on the observation that treatment with antibiotics may modify the disease phenotype in a murine model of TED. Artificial intelligence: This approach is being studied for the assessment of TED, especially trying to standardize the use of orbital and facial images for improving the diagnosis of the disease in the early, progressive phase. In the future, these applications will allow the use of synthetic data, in addition to training on real patient images and data.