The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy

Graves' orbitopathy (GO) is the main extrathyroidal manifestati on of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and seve rity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smo king, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (seleni um-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. gluco corticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safe ty profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive coun seling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A c umulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, h igher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplop ia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylpredn isolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) te protumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v . methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.