Background/Aim. To evaluate the efficacy of methotrexate for the treatment of thyroid eye disease (TED). Methods. 36 consecutive patients with active TED, previously treated with corticosteroids but stopped due to the occurrence of side effects, were commenced on methotrexate therapy. Two different weekly doses were administered depending on the weight of the patient (7.5？mg or 10？mg). Clinical activity score (7-CAS), visual acuity (VA), ocular motility, exophthalmos, and eyelid position were retrospectively evaluated at 3, 6, and 12 months and compared with baseline data. Results. There was a statistically significant improvement in 7-CAS at 3, 6, and 12 months after treatment ( ). There was no significant change in visual acuity. Ocular motility disturbances improved at 6 and 12 months ( ). There was no significant change in exophthalmos (mean 24？mm, SD 3？mm) or eyelid position (marginal reflex distance mean 6？mm, SD 1.5？mm) during the follow-up period. No side effects were registered. Conclusions. Methotrexate therapy is effective in reducing CAS and ocular motility disturbances. No significant improvement in proptosis or eyelid retraction should be expected from this treatment. Eventually, it might be considered a suitable alternative treatment in TED for patients who cannot tolerate steroids. 1. Introduction Thyroid eye disease (TED) is an autoimmune disease involving the retroocular tissues associated with Graves’ disease [1, 2]. Typical signs and symptoms include proptosis, retroorbital pain, tearing, conjunctival redness and edema, corneal lesions, impaired extraocular motility with or without diplopia, periorbital edema, visual impairment, and, rarely, blindness. Treatment options for TED include immunosuppressive agents, radiotherapy, and various surgical procedures such as orbital decompression, squint surgery, and correction of eyelid retraction [3–5]. Glucocorticoids are still the most widely used immunosuppressive agents for the treatment of TED and appear to be the most effective for associated soft tissue inflammation, optic neuropathy, and extraocular muscle impairment [6, 7]. The main disadvantages of glucocorticoid therapy are the potential recurrence of the disease after discontinuation and the side effects in long-term treatment [7]. Several alternative therapies have been proposed to manage resistant TED such as orbital radiation therapy, several other immunosuppressive agents, and biological drugs. However, the effectiveness of these treatments is still widely debated in the literature [8–15]. The aim of this study is to evaluate
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