Biochem Med (Zagreb). in the study. The mean duration of TED was 29 months (38). Following teprotumumab therapy, the mean (SD) decrease in volume for each region was 0.75?mL (0.84) in the upper face, 1.8?mL (1.3) in the periorbital region, 0.17?mL (0.5) in the temples, 1.62?mL (3.16) in the midface, and 2.67?mL (4.6) in the lower face. The mean (SD) decrease in the volume of the full face was 8.9?mL (8.7). There was also a significant reduction in MRD1, MRD2, and the intercanthal space following treatment. There was no relationship between previous steroid use and total body weight reduction and changes in facial volume. Conclusion: TED may cause significant tissue expansion across the entire face and this may be reduced following teprotumumab therapy. INTRODUCTION Thyroid eye disease (TED) is usually IKK-gamma (phospho-Ser85) antibody a complex autoimmune condition that manifests acutely with signs of inflammation affecting orbital and periorbital soft tissues. At this stage, patients may present with disfiguring proptosis, diplopia, and eyelid retraction. In the chronic stages, inflammation decreases, but changes to orbital tissues typically become permanent. Soft-tissue changes are not restricted to the orbit; several studies have exhibited increased retro-orbicularis fat volume and eyebrow volume in patients with TED.1,2 Orbital imaging studies have shown brow changes unique to TED patients and distinct from those caused by aging.3 Hwang et al demonstrated increased soft-tissue volume and fat within the temporal fossa in patients with TED, suggesting that this facial changes occurring in TED may not be limited to the periorbital region.4 Changes to appearance and vision have been shown to impact patients self-confidence and ability to carry out daily tasks and, therefore, quality of life.5 Soft-tissue expansion in TED may be explained by overexpression of the insulin-like growth factor 1 receptor (IGF-1R) and its interaction with GABOB (beta-hydroxy-GABA) the thyrotropin receptor (TSHR), a key pathogenic feature of this condition.6 These receptors form a physical and functional complex around the cell membrane of orbital fibroblasts (OFs), and professional immune cells (B cells and T cells7). Binding of autoantibodies to this receptor complex leads to increased production of proinflammatory cytokines,8 hyaluronan, and the differentiation of OFs into myofibroblasts or adipocytes causing soft-tissue expansion.9 Teprotumumab, a fully human monoclonal immunoglobulin to the IGF-1R, has recently been approved for the treatment of TED in the United States.10 Teprotumumab binds to the IGF-1R and inhibits downstream pathways.11 Recent phase 2 and 3 randomized, double-masked clinical trials (“type”:”clinical-trial”,”attrs”:”text”:”NCT01868997″,”term_id”:”NCT01868997″NCT01868997 and “type”:”clinical-trial”,”attrs”:”text”:”NCT03298867″,”term_id”:”NCT03298867″NCT03298867)12,13 have GABOB (beta-hydroxy-GABA) demonstrated marked reduction in proptosis in patients with active TED. Further work has quantified a significant decrease in orbital soft-tissue volume in patients with TED.14 Given the potential for TED to affect the extraorbital tissue on the face, and the impact of teprotumumab on orbital soft-tissue volume, we hypothesize that treatment with teprotumumab may have a similar impact on the soft tissue of other regions of the face. The primary aim of this study was to quantify facial soft-tissue changes following treatment with teprotumumab in patients with TED. Secondary outcomes included characterization of eyelid changes. METHODS This study adhered to the tenets of the Declaration of Helsinki, was performed in accordance with the Health Insurance Portability and Accountability Act, and was approved by the institutional review board at our institution. All patients provided written consent for participation. PATIENTS AND STUDIES In this prospective study, all patients presenting at our institution for the treatment of TED were considered for study eligibility. Patients who were currently GABOB (beta-hydroxy-GABA) on any other medical therapy for GABOB (beta-hydroxy-GABA) TED or had received rituximab or tocilizumab in the past were excluded. Furthermore, patients who had any plans to embark on a weight loss regime, or medications that might cause weight loss were excluded. Patients received infusions of teprotumumab (10?mg/kg for the first infusion and 20?mg/kg for subsequent infusions) every 3 weeks with the intention to complete 8 infusions over 24 weeks. Measurement of Clinical Outcomes The primary outcome measure was a change in soft-tissue volume of the face, from baseline (preinfusion) to within 3 weeks of the final infusion. Secondary outcome measures included eyelid position: marginal reflex distance (MRD) 1, MRD2, and the intercanthal distance of the same orbit. Other secondary outcomes included the mean change in proptosis, a change in the clinical activity score (CAS) and changes in body weight. Proptosis was assessed using the same Hertel exophthalmometer by the same person at each visit..