Thyroid‐associated ophthalmopathy: a practical guide to classification, natural history and management

Abstract

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder that can be divided into three clinical subtypes: congestive, myopathic and mixed ophthalmopathy. It is probably caused by immune cross-reactivity between orbital and thyroid antigens. The best candidate antigens are the thyrotropin receptor and the novel protein, G2s, which is now identified as a fragment of the winged helix transcription factor, FOXP1. The relationship between radioiodine therapy and TAO is controversial, with two randomised controlled trials showing a transient worsening of the eye disease after treatment. The diagnosis of TAO is a clinical one, based on the presence of specific symptoms and signs. Orbital imaging, preferably magnetic resonance imaging, is useful when the diagnosis is in doubt and in patients with suspected optic neuropathy who may benefit from early intervention. Despite their lack of specificity, orbital antibodies may add weight to the diagnosis and may potentially be a useful tool in classifying the different subtypes of TAO and in monitoring disease activity. While antibodies against G2s and the thyrotropin receptor are seen in all subtypes, those against Fp and collagen XIII may be associated with the myopathic and congestive subtypes, respectively, where Fp is the flavoprotein subunit of the mitochondrial enzyme, succinate dehydrogenase. In most patients, TAO is self-limiting and no specific treatment is required. When treatment is indicated, glucocorticoids are the mainstay of therapy. Orbital radiotherapy improves the efficacy of glucocorticoids, but is probably less beneficial as monotherapy. Orbital surgery is best reserved for patients with 'burnt out' inactive disease, but urgent orbital decompression may be required for optic neuropathy. The severity and clinical activity of TAO are important in determining the need for specific treatment and the likelihood of success with medical therapy, respectively.

Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy

“…These studies were approved by the Mount Sinai Institutional Review Board. A total of 199 patients with severe GO had undergone orbital decompression cosmetic surgery for their disease, and 57 had less critical GO but all had Werner class IIIa or higher GO (4,29), as well as 90 patients who had no clinical signs of eye disease (non-GO, or GD without GO). All patients had over a 2-year history of AITD.…”

“…TSHR antibodies act as TSH agonists and induce thyroid overactivity. It has been estimated that 25%-50% of GD patients have clinical signs of Graves' ophthalmopathy or orbitopathy (GO), with the vast majority having relatively mild disease (3,4). As with all autoimmune disorders, it is thought that GD is caused by the interaction of genetic, epigenetic, and environmental factors in a stochastic manner.…”

Infraorbital groove localisation for the endoscopic decompression of the orbit in Graves’ disease

“…Karakas et al [21] measured 62 orbits of 31 male Caucasian adults. They described the distances from the infraorbital foramen to the midpoint of the lateral margin of the lacrimal fossa -23.8 ± 7.2 mm; to the inferior orbital fissure -31.9 ± 3.9 mm and to the inferior orbital rim -6.7 ± 1.9 mm and to the inferior aspect of the optic canal -50.3 ± 3.2 mm [15,19]. Those data are difficult to compare with data of our study as authors choose different landmarks.…”

“…Thyroid ophthalmopathy is the most frequent cause of orbital disease in the adult population, responsible for 15% to 28% of cases of unilateral and 80% of cases of bilateral exophthalmia [8,15,29]. Optic neuropathy is an uncommon manifestation which occurs with rate of incidence ranging from 2% to 8.6% of patients with Graves' ophthalmopathy but causes severe complications [7,38,47].…”

Thyroid Peroxidase and Thyroglobulin Antibodies and Ophthalmopathy in Patients with Graves’ Disease, Hashimoto Thyroiditis and Transient Thyroiditis

“…Inflammation of the Orbital Connective Tissue (OCT) and fat, extraocular muscles and the levator palpebrae superioris muscle in the upper eyelids occurs in about 40% of patients with Graves hyperthyroidism [1][2][3] while generally mild eye signs or isolated Upper Eyelid Retraction (UER) occurs in about 25% of patients with Hashimoto thyroiditis [4] and, occasionally, in patients with transient thyroiditis [5]. The best name for this disorder is "Thyroid-Associated Ophthalmopathy (TAO)".…”