ABSTRACT
Graves’ disease (GD) is an autoimmune syndrome characterized by hyperthyroidism and a diffusely enlarged thyroid gland. The most prominent extrathyroidal manifestation of this thyroid disease is thyroid-associated or Graves’ ophthalmopathy (GO), a medically incurable and chronic autoimmune process that affects all orbital tissue compartments and leads to various eye complications such as discomfort, lid edema and retraction, proptosis, extraocular muscle dysfunction, diplopia, and sight loss. Various degrees of GO occur in 80-90% of patients with GD. In most instances, the orbital problems appear within 18 months after diagnosis of thyroid disease. The close clinical association of GD with GO and pretibial dermopathy (PTD), a less frequent extrathyroidal manifestation, suggests a common antigen for these affected tissues (1,2). Enlargement of extraocular muscle bodies together with an increase of orbital connective/fatty tissue within the bony orbits is responsible for most of the orbital problems in patients with severe active GO. This enlargement is caused by marked infiltration of immunocompetent cells, such as macrophages, T lymphocytes and some B cells, and by abundant quantities of collagen and hydrophilic glycosaminoglycans (GAGs). The inflammatory process is likely to be driven by T cells, which access and infiltrate the retro-orbital space after interaction with several adhesion molecules. Once recruited, T cells release numerous cytokines capable of stimulating cell proliferation, GAG synthesis, recruitment of new fat cells from orbital adipose precursor cells, and expression of various immunomodulatory molecules by orbital preadipocyte fibroblasts (3). Although these mechanisms may sufficiently explain various aspects of how GO may evolve and be propagated, the primary antigen for this autoimmune process has remained elusive.
