Abstract
Thyroid-associated orbitopathy (TAO) is an autoimmune condition of the orbit which is closely associated with Graves' hyperthyroidism, although either condition may exist without the other. It may antedate, coincide with or follow hyperthyroidism (1±10). Assessment of the frequency of the association depends on the method used for detecting TAO; with sensitive methods subclinical TAO can be demonstrated in 70% of patients with hyperthyroidism. The clinical features of the disorder vary from a mild grittiness of the eyes to severe diplopia, loss of vision and dis®guring proptosis. The most obvious pathological change within the orbit is the enlargement of extraocular muscles (11±13). In most cases microscopy reveals that the muscle ®bres are preserved and the increase in muscle bulk re ects changes in the connective tissue: ®broblasts are very numerous, there is lymphocyte in®ltration, an excessive deposition of collagen and of glycosaminoglycans (gag) which lead to interstitial oedema (14±22). A role for cytokines in TAO (23) seems likely: it may be that the autoimmune response evokes the local production within the orbit of cytokines which cause ®broblast stimulation and hence the production of collagen and gag (24±28). The muscles most frequently affected are the medial and inferior recti. Functionally, the effect is of tightness or contraction of the muscles, and thus the patient may experience dif®culty with upward or lateral gaze. The increased bulk of the muscles and of orbital connective tissue leads to an increase in pressure within the orbit, which results in some cases in proptosis, and in other cases, where the tissues at the apex of the orbit are involved, in optic neuropathy and disc oedema. There is a natural tendency towards spontaneous improvement: the spontaneous course depicts an active phase which slowly abates, after which an inactive phase ensues (29), which may still be associated with ophthalmic abnormalities. Although sparse, there are histology data to support this idea of active and inactive disease phases (30, 31). The orbital tissues are oedematous in patients with early disease, whereas patients with longstanding TAO have ®brous tissues. On histological examination, early disease was associated with a mononuclear cell in®ltrate, while in the late stages only dense collagen scar tissue was found. In addition to macrophages and Tand B-lymphocytes, granulated mast cells may be present. Thus, there seems to be consensus that oedema with a lymphocyte in®ltrate of the orbital tissues characterizes the active stage, whereas ®brosis can be seen during all stages but is much more abundant in inactive TAO. This natural course has been the basis for the initiation of immunomodulatory therapies (32±36). They are aimed at the oedematous, lymphocyte in®ltration and the activated ®broblasts. Medical treatment will only be effective during the active phase and should not be given to patients with inactive TAO. In contrast, it is generally recommended that rehabilitative surgery should only be done on patients with inactive TAO (37, 38).
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