The Rate of Retreatment in Patients treated with teprotumumab: A Multicenter Study of 119 Patients with 1 year Follow Up.

OBJECTIVE OR PURPOSE: To determine the rate of retreatment in patients who receive a full course of teprotumumab therapy for Thyroid Eye Disease (TED) and drivers of retreatment. DESIGN: Multi center, retrospective study SUBJECTS: All patients who received a full course of treatment and had available data at 1 year post initial treatment were included. METHODS: Charts were reviewed for the following information: age, gender, months since diagnosis of TED, smoking status, prior treatments. Further, the clinical activity score (CAS), proptosis and the Gorman diplopia score were reviewed at baseline, at the end of the first course and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of retreatment. MAIN OUTCOME MEASURES: Rate of retreatment and the drivers of retreatment. RESULTS: 119 patients were included from 3 centers across the US. The overall retreatment rate was 24% (29/119). There was no difference between the 3 sites (p = 0.6). In univariate analyses, at baseline, there was no difference in proptosis (p = 0.07), diplopia score (p = 0.4) or duration of TED (p = 0.4), between retreated and non-retreated patients. From the retreated group, 82% had a significant proptosis response (≥ 2 mms reduction from baseline) following their initial course, while 68% of patients had a clinically significant proptosis response in the non-retreated group (p = 0.16). The use of other treatments prior to the first infusion of teprotumumab and baseline thyroid dysfunction, were not significantly different between the retreated and non-retreated groups (p = 0.06 and 0.09, respectively). The mean (SD) difference between the end of first treatment and at baseline prior to second treatment (in those who received it) was 2 (2) for CAS, 2 mms (4) for proptosis and 1 (1) for diplopia. Age as the only significant driver of retreatment (p < 0.05). Retreated patients were 7 years older than their non retreated counterparts (age 60 vs 53 (p < 0.05). CONCLUSIONS: In patients receiving a full course of teprotumumab therapy, the rate of retreatment is 24%. Age is the only driver of retreatment.

Erdheim-Chester Disease With Eyelid and Orbital Involvement: A Review of Treatment Modalities at One Institution From 2014 to 2022.

PURPOSE: To review all cases of Erdheim-Chester disease (ECD) with orbital involvement treated at Bascom Palmer Eye Institute in Miami, Florida from 2014 to 2022 and compare presentations, treatment modalities, and outcomes. METHODS: A retrospective chart review of all patients diagnosed with ECD who presented to Bascom Palmer Eye Institute from 2014 to 2022 was performed. Data collected included demographics, pretreatment history and ophthalmic examination, pathology report, treatment, subsequent examination, and relevant laboratory results. Histopathology, treatments, and outcomes were reviewed and compared between patients. RESULTS: Four cases were included. Primary treatments included vemurafenib (n = 2), cobimetinib (n = 1), and prednisone (n = 1). All patients demonstrated improvement of ophthalmic symptoms. Vemurafenib was the only medical treatment that was tolerated well and resulted in significant improvement in proptosis despite some reported dry eye; all other medications were discontinued due to intolerable side effects. CONCLUSIONS: BRAF inhibitors such as vemurafenib have been used as novel therapy in the treatment of ECD. Vemurafenib demonstrated its utility in reducing proptosis in ECD patients at one ophthalmic institution. Vemurafenib may be a favorable treatment option for BRAF-positive ECD patients presenting with orbital disease.

A Novel Association Between Human Papillomavirus and Thyroid Eye Disease.

Context: Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R). Objective: To explore the potential involvement of viral infections in TED pathogenesis. Methods: Using NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, including Papillomaviridae , Paramyxoviridae , Herpesviridae , Enterovirus , Polyomaviridae , and Rhabdoviridae . Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 22 TED patients and controls to quantify antiviral antibody titers. Demographics and clinical data were reviewed. Results: Homology analysis revealed conserved motifs between TSHR and IGF-1R with several viral proteins, particularly the human papillomavirus 18 (HPV18) L1 capsid protein. Basic demographic and clinical information between the cohorts were comparable. ELISAs showed statistically significant differences in the average HPV18 L1 IgG normalized optical density levels among tissues of control ( M = 0.9387, SD = 0.3548), chronic TED ( M = 2.305, SD = 1.064), and active acute TED ( M = 4.087, SD = 2.034) patients. These elevated HPV18 L1 IgG titers did not statistically correlate with TSH, T4, or TSI levels, and were elevated in TED patients irrespective of treatment with teprotumumab, indicating a direct immunological response to HPV. Conclusions: This study presents the first molecular evidence linking HPV and TED, highlighting molecular mimicry between HPV capsid protein and key autoimmunity targets in TED. This suggests an immunological link contributing to TED's pathogenesis, opening new avenues for understanding and managing the disease.