Euthyroid graves' ophthalmopathy in a Chinese population: A cross-sectional follow-up study.

OBJECTIVES: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. METHODS: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. RESULTS: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. CONCLUSIONS: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

Rapamycin improves Graves' orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by the reduction of both CD4+ CTLs and the reduction of orbital inflammation, adipogenesis, and fibrosis. CD4+ CTLs from patients with active GO showed upregulation of the mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and the clinical activity score in steroid-refractory patients with GO. Single-cell RNA-Seq revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

The good toxin: 10 years of experience with botulinum toxin A in the treatment of benign essential blepharospasm.

PURPOSE: To describe the efficacy and safety of botulinum toxin A (Botox) in patients with benign essential blepharospasm. METHODS: Retrospective review of operation, injection, and medical records. RESULTS: Information of 29 patients (nine males) was reviewed, and the average age of benign essential blepharospasm onset was 59.1 years. The average number of injections per patient was 14.2 ± 8.2 (5-44) and the average follow-up was 75.8 ± 47.3 months (15-180). The average unit dose was 14.2 ± 8.2 (10-30) ipsilaterally in the patient's first year and was 21.4 ± 5.0 (12.5-30) ipsilaterally in their last year (p = 0.00458). The average onset time was 3.8 ± 1.9 (1-7) days in a patient's first year and was 3.6 ± 1.7 (2-7) days in their last year (p = 0.549). The average effective duration was 2.86 ± 1.1 months in a patient's first year and was 2.53 ± 0.9 in their final year (p = 0.187). The Subjective Spasm Alleviation Scale was 1.72 ± 0.4 at the first year and was 1.79 ± 0.5 in the last year (p = 0.187). Ten (34.5%) patients with eyelid disease had surgical correction. The Subjective Spasm Alleviation Scale was 1.50 ± 0.5 before and was 2.0 ± 0 six months after the operation (p = 0.0268). Post-injection complications were experienced in eight (27.6%) patients. The most common complication was ptosis (n = 7), followed by diplopia (n = 1), dry eye (n = 1), and tearing (n = 1). No life-threatening complication was reported. CONCLUSION: Botox was a safe and effective treatment in benign essential blepharospasm which required an increased dosage over time. Ptosis was the most common complication and no life-threatening condition was reported. Surgical correction of those with eyelid diseases showed subjective improvement of subsequent Botox treatment.