Novel Approaches to the Management of Graves` Ophthalmopathy

Abstract

Severe Graves' ophthalmopathy constitutes a complex therapeutic challenge and treatment outcome often is not satisfactory. Established methods of treatment include high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Recently, the use of intravenous glucocorticoids has been shown to provide more favorable results than oral glucocorticoids. Novel treatments under investigation include somatostatin analogues, intravenous immunoglobulins and antioxidants. Low-dose immunosuppressive drugs (namely cyclosporine and, possibly, methotrexate) might be useful as an adjunct to established methods, particularly in view of a glucocorticoid-sparing action. Because cytokines play an important role in the pathogenesis of the disease, cytokine antagonists, which are currently evaluated in rheumatoid arthritis and other autoimmune conditions, might constitute in the future a valuable tool for the management of eye disease. Prevention of Graves' ophthalmopathy would be desirable, but so far it is limited to secondary prevention (arrest of progression of subclinical disease to clinical disease) and tertiary prevention (avoidance of deterioration or complications of clinical disease): among preventive measures smoking withdrawal is probably the most important one. Primary prevention (in the absence of disease) is only speculative, but oral tolerance induction or vaccination with the offending antigen(s) might prove beneficial for prevention of Graves' ophthalmopathy in genetically susceptible individuals.

Methotrexate for the Treatment of Thyroid Eye Disease

“…Many alternative therapies have been reported for such patients, although their efficacy is still under debate [12, 14, 15]. The efficacy of methotrexate has been reported for many autoimmune diseases requiring a long-term maintenance therapy such as rheumatoid arthritis, inflammatory bowel disease, and Wegener's granulomatosis [21].…”

“…The efficacy of methotrexate has been reported for many autoimmune diseases requiring a long-term maintenance therapy such as rheumatoid arthritis, inflammatory bowel disease, and Wegener's granulomatosis [21]. Methotrexate is an immunosuppressive drug that inhibits dihydrofolate reductase enzyme, leading to the inhibition of the DNA, RNA, and protein synthesis [15, 22]. Cytotoxic and antiproliferative effects can be seen at high doses, while anti-inflammatory and immunomodulatory effects can be observed with chronic low-dose treatment [23, 24].…”

“…Cytotoxic and antiproliferative effects can be seen at high doses, while anti-inflammatory and immunomodulatory effects can be observed with chronic low-dose treatment [23, 24]. The use of methotrexate is proposed on the basis of the autoimmune nature of TED [11, 15, 25, 26]. …”

“…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 Diagnosis and Treatment of Thyroid-Associated Ophthalmopathy

“…It works only on the active phase and its effects are often less dramatic; however, it lasts longer than steroids, and in combination with steroids it works better than does either treatment alone [1,6]. A dose of 20 Gy in ten fractions over 2 weeks is a standard treatment [1].…”