Graves Orbitopathy: Update on Diagnosis and Therapy

Abstract

Graves orbitopathy (GO) is an autoimmune disorder representing the most frequent extrathyroidal manifestation of Graves disease. It is rare, with an age-adjusted incidence of approximately 16.0 cases per 100,000 population per year in women and 2.9 cases per 100,000 population per year in men. GO is an inflammatory process characterized by edema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease activity at initial presentation. A Hertel exophthalmometer measurement of >2 mm above normal for race usually categorizes a patient as having moderate-to-severe GO. Encouraging smoking cessation and achieving euthyroidism in the individual patient are important. Simple treatment measures such as lubricants for lid retraction, nocturnal ointments for incomplete eye closure, prisms in diplopia, or botulinum toxin injections for upper-lid retraction can be effective in mild cases of GO. Glucocorticoids, orbital radiotherapy, and decompression/rehabilitative surgery are generally indicated for moderate-to-severe GO and for sight-threatening optic neuropathy. Future therapies, including rituximab aimed at treating the molecular and immunological basis of GO, are under investigation and hold promise for the future.

Clinical and immunological changes in patients with active moderate-to-severe Graves̕ orbitopathy treated with very low-dose rituximab

“…More recent studies suggest that pulsed intravenous methylprednisolone is more effective and has an improved side-effect profile compared to high-dose oral prednisone [7,8]. This therapy is effective in 70-80% of patients, compared to 50% in those treated orally [2,4,7]. However, a significant proportion of them (20-30%) do not respond to glucocorticoids, and furthermore approximately 10-20% of all treated patients relapse after therapy withdrawal [8].…”

“…It may also occur in patients without any current or prior hyperthyroidism (euthyroid or ophthalmic Graves' disease) or in hypothyroid patients due to chronic autoimmune thyroiditis [3]. GO is an inflammatory process characterised by oedema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat resulting in periorbital and conjunctival oedema, chemosis, lid retraction, exophthalmos, and dysmotility of eye muscles, accompanied by spontaneous retrobulbar pain, pain on eye movement, watery and burning eyes, and/or diplopia [1,2,4]. Severe GO leads to exposure keratopathy and compressive optic neuropathy (dysthyroid optic neuropathy -DON), which may cause visual loss [1,4,5].…”

Radiotherapy for Graves’ disease. The possible role of low-dose radiotherapy

“…16,17 Treatment of moderate or severe active disease has been limited to steroids and retrobulbar RT, particularly in the case of eye muscle involvement. 9,[18][19][20] In the relatively rare case where vision is threatened, emergency decompression surgery can be performed. The proptosis, motility, or cosmetic concerns associated with stable GO are commonly remedied with surgical intervention.…”

Euthyroid Graves’ orbitopathy and incidental papillary thyroid microcarcinoma

“…[1][2][3][4][5] As a multifactorial disorder, GO is influenced by non-preventable factors (age, sex, genetic factors) and exogenous factors (cigarette smoking, thyroid dysfunction, radioiodine treatment). 5,6 The pathogenesis of GO includes the TSH-receptor as an antigen, fibroblasts, and adipocytes as the main cell contributors, and a specific cytokine-mediated immunologic response.…”