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Alan Chun Hong Lee Division of Endocrinology and Metabolism, Department of Medicine, Queen Mary Hospital, Hong Kong, China
Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

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George J. Kahaly Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

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Background: Both Graves’ hyperthyroidism (GH) and Graves’ orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders. Summary: Immunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin receptor; iscalimab, an anti-CD40 monoclonal antibody which blocks the CD40-CD154 costimulatory pathway in B-T cell interaction; and K1-70, a thyrotropin receptor-blocking monoclonal antibody. Novel treatment strategies have also become available in GO. Mycophenolate significantly increased the overall response rate combined with standard glucocorticoid (GC) treatment compared to GC monotherapy. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, displayed strong anti-inflammatory action in GC-resistant cases. Teprotumumab, an anti-insulin-like growth factor 1 receptor monoclonal antibody, resulted in remarkable improvement in terms of disease activity, proptosis, and diplopia. Further, rituximab appears to be useful in active disease of recent onset without impending dysthyroid optic neuropathy. Key Messages: Therapeutic advances will continue to optimize our management of GH and associated orbitopathy in an effective and safe manner.

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Elena Hoppe Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany
Department of Paediatrics, Johannes Gutenberg University Medical Center, Mainz, Germany

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Alan Chun Hong Lee Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

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David Hoppe Department of Psychology, Technical University of Darmstadt, Darmstadt, Germany

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George J. Kahaly Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

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Objectives: To investigate the predictive factors for changes in the quality of life (GO-QoL) of patients with Graves’ orbitopathy (GO) prior to and after specific treatment. Methods: A prospective follow-up study was conducted at an academic tertiary referral orbital center with a joint thyroid-eye clinic on 100 consecutive patients with GO. Before and after the standard 12-week course of weekly intravenous methylprednisolone (cumulative dose 4.5 g), the GO-QoL questionnaire provided by the European Group on Graves’ Orbitopathy (EUGOGO) was completed. Endocrine and ophthalmic assessments were performed at each visit. Results: All patients were biochemically euthyroid and untreated for GO at baseline and presented with active and moderate-to-severe disease. Both GO-QoL subscales (visual functioning [VF] and appearance [AP]) significantly increased after immunosuppressive therapy and showed a sustained improvement for 6 months. At baseline, demographic variables (sex, age, and smoking) influenced QoL in the stepwise linear regression (p < 0.01, adjusted R<sup>2</sup> = 0.24 for VF and p < 0.01, adjusted R<sup>2</sup> = 0.21 for AP). In contrast, 6 months after treatment, the improved QoL was now exclusively associated with ophthalmic parameters (p < 0.01, adjusted R<sup>2</sup> = 0.47 for VF; p < 0.01, adjusted R<sup>2</sup> = 0.23 for AP). Conclusions: Predictive factors for GO-QoL differed not only between the 2 subscales but also before and after the first treatment of GO.

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Kenneth Ka Hei Lai K Lai, Department of Ophthalmology and Visual Sciences, PWH, Hong Kong, Hong Kong

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Fatema Mohamed Ali Abdulla Aljufairi F Aljufairi , Hong Kong, Hong Kong

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Jake Uy Sebastian J Sebastian , Department of Ophthalmology and Visual Sciences, PWH, Hong Kong, Hong Kong

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Yingying Wei Y Wei, Statistics, CUHK, Hong Kong, Hong Kong

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Ruofan Jia R Jia, Statistics, CUHK, Hong Kong, Hong Kong

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Karen Kar Wun Chan K Chan, Hong Kong, Hong Kong

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Elaine Yuen Ling Au E Au , Pathology, Queen Mary Hospital, Hong Kong, Hong Kong

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Alan Chun Hong Lee A Lee, Medicine , The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

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Chiu Ming Ng C Ng, Medicine , Queen Elizabeth Hospital, Hong Kong, Hong Kong, Hong Kong

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Hunter Kwok Lai Yuen H Yuen , Department of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital, Hong Kong, Hong Kong

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Wilson Wai Kuen Yip W Yip, Department of Ophthalmology and Visual Sciences, PWH, Hong Kong, Hong Kong

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Alvin Lerrmann Young A Young, Department of Ophthalmology and Visual Sciences, PWH, Hong Kong, Hong Kong

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George Pak Man Cheng G Cheng, Department of Ophthalmology and Visual Sciences, CUHK, Hong Kong, Hong Kong

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Clement Chee Yung Tham C Tham, Department of Ophthalmology and Visual Sciences, CUHK, Hong Kong, Hong Kong

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Chi Pui Pang C Pang, Department of Ophthalmology and Visual Sciences, CUHK, Hong Kong, Hong Kong

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Kelvin Kam Lung Chong K Chong, Department of Ophthalmology and Visual Sciences, CUHK, Hong Kong, Hong Kong

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Purpose:

This study aims to report correlations between thyroid-stimulating immunoglobulin(TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease(TED) patients.

Methods:

A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the clinical activity score(CAS), marginal reflex distance1(MRD1), extraocular muscle motility restriction(EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI.

Results:

A total of 255(197female) treatment-naïve patients, with an average onset age of 50±14 years, were included. Elevated pre-treatment TSI level was observed in 223(88%) patients. There was a weak positive correlation between TSI and CAS(r=0.28, P=0.000031), MRD1(r=0.17, P=0.0080), and the size of the levator palpebrae superioris/superior rectus complex(r=0.25, P=0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67(95% confidence interval:0.60-0.75) and 284%(Specificity:50%, sensitivity:85%). 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP(P=0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level(P<0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and non-responded to the first course of IVMP.

Conclusion:

TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be further warranted.

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