Combined Systemic Steroids And Methotrexate In The Treatment Of Thyroid-associated Ophthalmopathy In Active Phase

Purpose:Thyroid-associated ophthalmopathy（TAO）is one of the most common orbital diseases in adults.While glucocorticoid pulse therapy is the first line of treatment for moderate to severe TAO in active phase,there are still some patients not responsive.The aims of this prospective randomized control study（RCT）is to study the efficacy and safety of these two protocol:intravenous corticosteroid combined with methotrexate and intravenous corticosteroid alone in the treatment of moderate to severe TAO in active phase,and to provide new clinical evidence.During the process of RCT,subfovea choroid thickness（SFCT）was measured to compare the difference between different activity and severity patient groups.The study may find an auxiliary evaluation system of TAO staging and possible follow-up indicators.Methods:This is a RCT among patients with moderate to severe active TAO.Patients were randomly signed into combined group（4.5g intravenous corticosteroid regimen plus oral methotrexate）and glucocorticoid alone group（4.5g intravenous corticosteroid regimen plus placebo）.Ophthalmic evaluation was done at the end of 6^th and 12^th week.Efficacy rate and incidence of adverse reactions were recorded.At the same time,enhanced depth imaging spectral domain optical coherence tomography（EDI-SD-OCT）was used to evaluate the SFCT of TAO patients and healthy controls.SFCT was measured before and after glucocorticoid treatment.Analysis of the possible influence factors of SFCT was done by multivariate regression.Results:A total of 125 patients with TAO from January 2016 to January2017 were enrolled in this study.53 patients with moderate to severe active TAO was included in the RCT study.Combined group had 22 patients.The overall efficiency at the end of 6^th and 12^th of were 68.2%and 81.8%.Systemic steroids alone group had 23 patients.The overall efficiency at the end of 6^th and 12^thof were 56.5%and 73.9%.There was no statistically significant difference on the overall efficiency rate（P=0.763 and P=0.722）.At the end of the 12^th week,combined group had higher incidence of ALT and AST increase compared to systemic steroids alone group（P=0.02 and P=0.009）.On the same time,the SFCT of 62 TAO patients and 63 healthy controls were measured by EDI-SD-OCT.The SFCT of patients with active TAO was 273.52±76.54μm,significantly higher than that of inactive TAO patients 234.83±47.49μm（P=0.013）and healthy control group 225.34±56.95μm（P=0.001）.The SFCT of moderate to severe TAO was 262.19±65.27μm,significantly higher than the healthy control group 225.34±56.95μm（P=0.003）and severe TAO 222.92±61.30μm（P=0.04）.20patients were treated with glucocorticoid.After treatment for 12 weeks the SFCT was 231.64±47.88μm,significantly lower than that before treatment（272.35±63.67μm,P=0.028）.SFCT was significantly correlated with age,CAS score and axis length,and the prediction model of choroidal thickness could be established.SFCT=513.97-1.09×Age+11.95×CAS-9.99×Axis Length,R²=0.40.Conclusions:Glucocorticoids combined with MTX is effective in the treatment of moderate and severe TAO patients effectively,which can effectively reduce CAS score,improve vision,improve the degree of exophthalmos,but there was no significant difference in efficiency compared to systemic steroids alone group.The combination of MTX may lead to higher liver toxicity in terms of safety evaluation.The thickness of foveal choroidal thyroid-associated ophthalmopathy patients with macular changes,and the thickness of patients increased significantly,SFCT is expected to become a staging index help determine the disease;the value and the age of patients,was significantly related to CAS score and axial length,choroidal thickening and young,active inflammation and slim shaft related;intravenous glucocorticoid before and after treatment in patients with SFCT was also changed,and EDI-SD-OCT is a noninvasive,eye doctor is expected to use the monitoring value of SFCT for the effect of intravenous glucocorticoid therapy and follow-up evaluation.