METHODS: A randomized controlled double-masked crossover trial was conducted in a single tertiary care academic medical center. Patients with long-standing, inactive GO but persistent proptosis (>20 mm in at least one eye) were recruited. Allowing for a 15% dropout rate, 31 patients (26 females) were randomized in order to identify a treatment effect of 2.0 mm (p = 0.05; power 0.88). Following informed consent, participants were randomized to receive bimatoprost or placebo for three months, after which they underwent a two-month washout before switching to the opposite treatment. The primary outcome was the change in exophthalmometry readings over the two three-month treatment periods.
RESULTS: The mean exophthalmometer at baseline was 23.6 mm (range 20.0-30.5 mm), and the mean age of the patients was 55 years (range 28-74 years). The median duration of GO was 7.6 years (interquartile range 3.6-12.3 years). The majority were still suffering from diplopia (61.3%) with bilateral involvement (61.3%). Using multi-level modeling adjusted for baseline, period, and carry-over, bimatoprost resulted in a -0.17 mm (reduction) exophthalmometry change ([confidence interval -0.67 to +0.32]; p = 0.490). There was a mean change in intraocular pressure of -2.7 mmHg ([confidence interval -4.0 to -1.4]; p = 0.0070). One patient showed periorbital fat atrophy on treatment, which resolved on stopping treatment. Independent analysis of proptosis by photographic images (all subjects) and subgroup analysis on monocular disease (n = 12) did not show any apparent benefit.
CONCLUSIONS: In inactive GO, bimatoprost treatment over a three-month period does not result in an improvement in proptosis.
OBJECTIVE: This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs).
METHODS: Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components.
RESULTS: At recruitment, when patients were hyperthyroid and TRAb positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HCs. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HCs. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and free thyroxine, respectively, and was also significantly associated with smoking in GO; smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAb more than 200 days after commencing antithyroid drug treatment.
CONCLUSION: The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAb is predictive of relapse; identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales.