ABSTRACT
Objective@#To evaluate the performance of baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping of the extraocular muscles (EOMs) in the prediction of treatment response to intravenous glucocorticoid (IVGC) therapy for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO) and to investigate the effect of fat-suppression (FS) in T2 mapping in this prediction. @*Materials and Methods@#A total of 79 patients clinically diagnosed with active, moderate-to-severe TAO (47 female, 32 male;mean age ± standard deviation, 46.1 ± 10 years), including 43 patients with a total of 86 orbits in the responsive group and 36 patients with a total of 72 orbits in the unresponsive group, were enrolled. Baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping with FS (i.e., FS T2 mapping) or without FS (i.e., conventional T2 mapping) of EOMs were compared between the two groups. Independent predictors of treatment response to IVGC were identified using multivariable analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the prediction models. Differences between the models were examined using the DeLong test. @*Results@#Compared to the unresponsive group, the responsive group had a shorter disease duration, lower kurtosis (FSkurtosis), lower standard deviation, larger 75th, 90th, and 95th (FS-95th) T2 relaxation times in FS mapping and lower kurtosis in conventional T2 mapping. Multivariable analysis revealed that disease duration, FS-95th percentile, and FS-kurtosis were independent predictors of treatment response. The combined model, integrating all identified predictors, had an optimized area under the ROC curve of 0.797, 88.4% sensitivity, and 62.5% specificity, which were significantly superior to those of the imaging model (p = 0.013). @*Conclusion@#An integrated combination of disease duration, FS-95th percentile, and FS-kurtosis was a potential predictor of treatment response to IVGC in patients with active and moderate-to-severe TAO. FS T2 mapping was superior to conventional T2 mapping in terms of prediction.
ABSTRACT
Objective To observe the expression change of phosphorylation glogyen synthase kinase 3β at Ser9 [p-GSK3β (Ser9)] and investigate whether GSK3β involved in the retinal ganglion cell (RGC) and optic nerve in rat ocular hypertension model.Methods Thirty health Sprague Dawley (SD) rats with normal intraocular pressure (IOP) were randomly divided into 3 groups(10 cases in each group):control group,2 weeks ocular hypertension(OHT) group and 4 weeks OHT group.The ocular hypertension model was established by using episcleral veins ligation and cauterization.5 eyes from each group were taken for frozen section at week 2 and week 4 after establishing ocular hypertension model.The number of RGC was counted with Nissl's staining.The expression and distribution of p-GSK3β (Ser9) in RGC and optic nerve were detected by immunofluorescence staining.The retinal sample of other 5 rats was harvested for detecting the expression of total glogyen synthase kinase 3 β (total GSK3β) and p-GSK3β (Ser9) by Western blot.Results There was no statistical difference in IOP before modeling among three groups (P =0.89),but there was statistical difference after modeling (P ＜0.01),compared with the control group,the increased rate of IOP in 2 weeks OHT group and 4 weeks OHT group were 59.13％ and 26.93％ (all P ＜ 0.05).The average RGC numbers of 2 weeks OHT group and 4 weeks OHT group were 120 ± 10 per eye and 86 ± 7 per eye,which were both less than the number 149 ± 12 per eye in control rats,there were statistical differences (all P ＜ 0.05).Furthermore,the number of RGC in 4 weeks OHT group was less than 2 weeks OHT group (P ＜0.01).The expression of p-GSK3 β (Ser9) in the retina and optic nerve were positive detected by immunofluorescence,and the intensity of p-GSK3β (Ser9) immunofluorescence staining in RGC and optic nerve of OHT rats were less than model control eyes.The amount of p-GSK3β (Ser9) in retina of 2 weeks OHT rats decreased 19.89％ compared with control group rats (P ＜ 0.05),and the amount of p-GSK3β (Ser9) in retina of 4 weeks OHT rats was significantly decreased 36.46％ compared with control group rats(all P ＜ 0.05).While the total GSK3β did not change(P ＞ 0.05).Conclusion The number of RGC and the expression of p-GSK3β (Ser9) in RGC and optic nerve of OHT rat eyes decreased significantly.The change expression of the p-GSK3β (Ser9) in the RGCs and optic nerve may be correlated with RGC neurodegeneration in glaucomatous disorders.