Pathogenesis of Graves’ Ophthalmopathy

The pathogenesis of Graves’ ophthalmopathy remains unknown. While we clearly recognize the central importance of thyroid stimulating immunoglobulin (TSI) in causing thyroid gland overactivity, we have no corresponding clearly responsible agent for Graves’ ophthalmopathy. In a proximate sense, we know that the clinical expressions of Graves’ ophthalmopathy are caused by either swelling in the retrobulbar space or by restriction in the range of extraocular muscle motion. We understand that swelling occurs due to accumulation of inflammatory cells and of glycosaminoglycans (GAG), which bind water in the retrobulbar space. A variety of inflammatory cytokines stimulate GAG secretion from orbital

fibroblasts. Although there is substantial evidence for an autoimmune process being responsible for Graves’ ophthalmopathy, the case remains unproven and there is weak evidence in favor of an infectious etiology.