The Clinicopathologic Basis of Graves' Ophthalmopathy: A Review

Abstract

Improved understanding of the pathogenic mechanisms of GO should hopefully lead to new diagnostic and therapeutic approaches to this problematic condition.

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

“…GO may be a most disabling condition with very unsatisfactory treatment approaches (30,39,40). The primary antigen appears to be the TSHR expressed on fibroblasts and adipocytes throughout the body, but they find themselves in a retroorbital environment that exacerbates the immune response to their presence (40)(41)(42).…”

“…GD was defined as the presence of chemical hyperthyroidism and a normal or increased diffuse thyroid radioiodine uptake and/or the presence of TSHR antibodies. GO (also known as thyroid eye disease and dysthyroid/ thyroid-associated orbitopathy) was defined clinically as a chronic autoimmune inflammatory disorder impacting the orbit around the eye, presenting various eye features as described (30). A group of Caucasian controls (n = 402) was available from commercial sources (Coriell Institute, Camden, NJ).…”

Study of Serum Antibodies Against Three Eye Muscle Antigens and the Connective Tissue Antigen Collagen XIII in Patients with Graves' Disease With and Without Ophthalmopathy: Correlation With Clinical Features

“…It has been proposed previously that the initial inflammatory reaction occurs in the orbital and adipose connective tissues leading to orbital fibroblast stimulation and congestive eye signs, with secondary damage to the eye muscle fibres (8,9). A good candidate for the connective tissue antigen is the thyrotropin receptor (TSH-r), which has been localized, in both orbital fat and eye muscle tissue (10).…”

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

“…In about 10% of cases, the eye changes occur in the apparent absence of thyroid autoimmunity, so-called "euthyroid Graves disease" [3]. The mechanism for autoimmune-mediated inflammation in the eye muscles and OCT and fat is unclear but a popular hypothesis is that autoimmunity against the TSH-Receptor (TSHR) expressed in the orbital pre adipocytes and fibroblasts [6][7][8], or eye muscle cell [9], may initiate the inflammatory changes. While the extra ocular muscle reaction, which can occur in the absence of OCT and fat inflammation, may be a separate TAO subtype [10,11], it has not been shown conclusively that the two types differ from Nunery types 1 (mainly involving the orbital fat without restrictive myopathy) and 2 (with diplopia and restrictive myopathy) [12].…”