Intravenous Glucocorticoids And Orbital Radiation Therapy In The Treatment Of Moderate To Severe And Active Thyroid-Associated Ophthalmopathy

Objective: Intravenous glucocorticoids(iv GC)have been recommended as a first-line treatment of moderate-to-severe and active thyroid-associated ophthalmopathy(TAO).However,not all patients are responsive to iv GC.The identification of potential factors used to predict their efficacy and the selection of suitable patients have both been lacking.Patients who were not responsive to iv GC or iv GC intolerant are collectively referred to as refractory TAO.Orbital radiation therapy has been recommended for refractory TAO.But it still has several side effects.Oral glucocorticoids is another kind of treatment for TAO.We will compare the efficacy and safety of orbital radiation therapy combined with low-dose oral glucocorticoids and orbital radiation therapy alone for refractory TAO.Methods: It was a single center retrospective study including 96 patients with moderateto-severe and active TAO.Potential factors related to the effects of iv GC were analyzed using logistic regression in 90 patients,who received 4.5 g iv GC therapy.Response was defined as the achievement of at least three points of the overall response.Among them,47 patients received orbital radiation therapy.Twenty-five patients were using orbital radiation therapy combined with low-dose oral glucocorticoids,while 22 patients were using orbital radiation therapy alone.The efficacy and safety of these two groups have been compared.Results: Fifty-two(57.8%)patients showed a positive response to iv GC therapy.Significant correlations were observed between the effects of iv GC and pretreatment clinical activity score(CAS),duration of eye symptoms,and restoration of euthyroidism.The two latter factors were both independent.The duration of eye symptoms was negatively correlated with the effects of iv GC,with an odds ratio(OR)of 0.984(p=0.012).Restoration of euthyroidism(OR=3.282,p=0.039)and pretreatment CAS(OR=1.653,p=0.000)were both positively correlated with the effects of iv GC.The diagnostic accuracy of the duration of eye symptoms was ≤13 months(p=0.000),with a specificity of 76.9%,and sensitivity of 65.8%.The diagnostic accuracy of the pretreatment CAS was more than 2.5(p=0.000),with a specificity of 61.5% and sensitivity of 80.5%.Besides,a multi-variables prediction model were established as well,which was better in the forecasting aspect with an area under curve of 0.784(p=0.000).For refractory TAO,both two groups presented improvement in CAS,diplopia and eye ball movement.But not in exophthalmos,palpebral fissure height or intraocular pressure.There is no significant difference between two groups.However,orbital radiation therapy combined with low-dose oral glucocorticoids group shows more safety,especially in chemosis(p=0.031).Conclusions: The duration of eye symptoms and restoration of euthyroidism are independent factors that are associated with the effects of iv GC.The following practical implications were inferred: firstly,the shorter the duration of eye symptoms,the more favorable the effects of iv GC therapy.Thus,prompt diagnosis and treatment(within 13 months)is important.Secondly,the restoration of euthyroidism improves the efficacy of iv GC.Thirdly,hope the multi-variables prediction model can be applied to clinical therapy in the future.Orbital radiation therapy combined with low-dose oral glucocorticoids was recommended for refractory TAO.