Novel Immunomodulatory Treatment Modalities for Thyroid-Associated Orbitopathy

Thyroid Associated Orbitopathy (TAO) is one of the challenging inflammatory orbital conditions to treat. In the past three decades, immunotherapy and biological agents were introduced into the armamentarium of treatment of TAO. Intravenous glucocorticoids (GCs) are considered the cornerstone treatment of active TAO alleviating inflammatory signs and compressive optic neuropathy (CON). Periorbital steroids appear to significantly improve upper lid retraction. Radiotherapy, preferably combined with steroids, should be considered early in patients with diplopia. This combination can also be used in patients presenting with CON. Definite evidence supporting the use of cyclosporine and methotrexate as first line agents is still lacking; however, they are generally effective in improving inflammatory signs when combined with GCs. Eventually they can be considered as second-line treatment in steroid intolerant/dependent patients. Mycophenolate Mofetil seems to be a suitable alternative to radiotherapy in patients with motility disturbances. Rituximab and tocilizumab are effective second-line agents, with the first used with caution in patients with CON. By far, Teprotumumab, seems to be a very effective agent for proptosis reduction along with a remarkable control of the inflammatory signs and motility disturbance. No single agent can be currently considered the best therapeutic option to address all the clinical manifestations of active moderate-to-severe TAO, besides many gaps in the literature still exist to trace straightforward guidelines. Clinicians should tailor management combining the latest evidence-based information with their own experience and clinical setting.