Thyroid eye disease

Weissel M, Hauff W. Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient with severe thyroid eye disease. Thyroid 2000 10(6) 521. 

Starkey K, Heufelder A, Baker G, Joba W, Evans M, Davies S, Ludgate M. Peroxisome proliferator activated receptor-gamma in thyroid eye disease contraindication for thiazolidinedione use J Clin Endocrinol Metab 2003 88 55-9. 

Lid retraction can appear in the presence of chemical and clinical enthyroidism and is often unrelated to control of any existing thyroid dysfunction. EyeUd lag (von Graefe s sign) often accompanies Ud retraction (Fignre 32-2), bnt Ud lag by itself is not pathognomonic of thyroid eye disease. lid retraction disappears sponta-neonsly after 15 years in approximately 60% of patients. 

The incidence of optic neuropathy in thyroid eye disease is 5% to 10%. The class 6 patient usually has mild to moderate proptosis and relatively shallow orbits. Thyroid optic neuropathy may be evidenced by papilledema, papillitis, or retrobulbar neuritis and usually is characterized by a painless and gradual loss of visual acuity. Common visual field defects include central scotomas, arcuate or altitudinal defects, paracentral scotomas, or generalized depressions. Thus visual field and optic disc examinations are the best diagnostic tools for early optic neuropathy. Occasionally, vision loss can occur precipitously over 1 or 2 weeks. Other features of optic nerve dysfunction frequently associated with the decreased visual acuity are color vision disturbances, afferent pupillary defects in the less proptotic eye in patients with asymmetric involvement, and prolongation of the pupil cycle time. 

Plasmapheresis is primarily used in patients with muscular dystrophy and lately with parkinsonism. However, the use of plasmapheresis in thyroid eye disease has mirrored problems observed in assessing responses in other autoimmune disease. The concept of an immune complex involvement in the pathophysiology of thyroid eye disease is unproven. A study reported 11 patients who received multiple plasmapheresis sessions with systemic prednisone and azathioprine. It noted that this form of... 

Figure 32-12 Approaches for orbital decompression. (Modified from Char DH. Thyroid eye disease, ed. 2. New York Churchill Livingstone, 1990.)...

The natural history of Graves disease is of alternating remission and relapse. Progression to hypothyroidism can occur, especially after 1 treatment. Such patients should have long-term follow-up, and are likely to require thyroid hormone replacement therapy Severe forms of thyroid eye disease should be treated with steroids and immunosuppresants or low-dose radiotherapy. Urgent surgical decompression can be required for eyophthalmos. 

Figure 1 Schematic diagram of the eye in horizontal section indicating each ocular component, a, corneal epithelium b, keratocyte c, corneal endothelium d, aqueous humor e, conjunctiva /, sclera g, trabecular meshwork h, iris i, lens /, ciliary zonule and body k, vitreous /, retina m, interphotoreceptor matrix n, retinal pigment epithelium o, Bruch s membrane p, choroid q, optic nerve head r, lamina cribrosa extraocular muscles and tissues. The candidate glycosaminoglycans involved in the ocular components of each eye disease described in this chapter are as follows macular corneal dystrophy (b, c KS, CS/DS, HA), glaucoma (d HA g CS/DS, HS, HA q, r CS, HS, HA), cataract r. CS/DS, HS, HA), diabetic retinopathy (fc HA / HS), retinal detach-ment/proliferative vitreoretinopathy k, I, m, n CS/DS, HS, HA), myopia (f, p CS), thyroid eye disease (s CS, HA), pseudoexfoliation syndrome (c, d, g, h, i, j KS, CS/DS, HA). KS, keratan sulfate CS/DS, chondroitin sulfate/dermatan sulfate HS, heparan sulfate HA, hyaluronan.

CS/DS Macular corneal dystrophy, glaucoma, cataract, retinal detachment/proliferative vitreoretinopathy, myopia, thyroid eye disease, pseudoexfoliation syndrome HS Glaucoma, cataract, diabetic retinopathy, retinal detachment/proliferative... 

Thyroid eye disease is an immunological disorder that affects the orbital muscles and fat. Hyperthyroidism is observed with orbitopathy at some point in most patients, although the two are commonly synchronous. Histological examination of the retroocular connective tissues in thyroid eye disease reveals lymphocytic infiltration and accumulation of glycosaminoglycans produced locally by fibroblasts, which contribute to the pathogenesis of ophthalmopathy. 

Transmission electron microscopy analysis revealed a marked expansion of the endomysial space in thyroid eye disease extraocular muscle biopsies compared with that in control biopsies (69). An increased number of collagen fibers with hyaluronan were detected by immunogold staining, although the serum levels of hyaluronan and urinary glycosaminoglycans were not found to be sensitive indicators for the presence of these molecules within the extraocular muscles (69). Imai et al. further confirmed that the local accumulation of glycosaminoglycans in thyroid eye disease was not associated with the serum hyaluronan concentration (70). 

On the other hand, some molecules inhibit glycosaminoglycan synthesis. Pentoxifylline, an analogue of methylxanthine theobromine, inhibits the proliferation and biosynthetic activities of fibroblasts (81). Fibroblasts from the extraocular muscles of patients with thyroid eye disease and normal extraocular muscles were cultured in vitro in the presence or absence of pentoxifylline. In these fibroblast cultures, exposure to pentoxifylline resulted in a dose-dependent inhibition of glycosaminoglycan synthesis in all the fibroblasts. Therefore, pentoxifylline may be useful for the treatment of thyroid eye disease. In addition, treatment of fibroblasts with an IL-l-receptor antagonist or soluble IL-1 receptor significantly inhibited IL-l-stimulated glycosaminoglycan synthesis, indicating that such treatments may be useful for the prevention of thyroid eye disease (75). 

Interestingly, fibroblasts derived from retroocular connective tissue and skin in thyroid eye disease exhibited different hormonal regulation. Specifically, skin fibroblasts responded to T3 (100 nmol/liter) and dexamethasone (100 nmol/liter) with 27% and 55% inhibition of glycosaminoglycan accumulation, respectively, whereas retroocular fibroblasts responded to the two hormones with 12% and 8% inhibition, respectively (82). 

Kahaly G, Forster G, Hansen C. Glycosaminoglycans in thyroid eye disease. Thyroid 1998 8 429-432. 

Dysthyroid endocrine orbitopathy (EO) or thyroid eye disease is the most common disorder affecting the orbit, usually presents in middle-aged women, and represents the most frequent cause of unilateral or bilateral proptosis in adults (Mueller-Forell and Pitz 2004 Aviv and Miszkiel 2005). EO is predominantly associated with autoimmune hyperthyroidism, which is also referred to as Morbus Basedow or Grave s disease (Mueller-Forell and Pitz 2004), but the orbitopathy may precede thyroid disease or occur with euthyroid or hypothyroidism (Aviv and Miszkiel 2005). EO is associated with edema of all structures of the orbit. The hallmarks of EO, however, are spindle-shaped edema of the intra-orbital muscles, which leaves out the tendons, and enlargement of the intra-orbital fat tissue (Fig. 12.7) (Mueller-Forell and Pitz 2004 Aviv and Miszkiel 2005). Muscular edema usually is most pronounced in... 

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