Thyroid eye disease (Graves ophthalmopathy) is a syndrome of clinical and orbital imaging abnormalities caused by deposition of mucopolysaccharides and infiltration with chronic inflammatory cells of the orbital tissues, particularly the extraocular muscles. In patients with Graves disease, 20–40% have clinically apparent eye disease; about 5–10% of patients experience severe exophthalmos, with the eye being pushed forward by increased retro-orbital fat and eye muscles that have been thickened by lymphocytic infiltration. The severity of eye disease is not closely correlated with the severity of thyrotoxicosis; clinical or laboratory evidence of thyroid dysfunction and thyroid antibodies may not be detectable at presentation or even on long-term follow-up, but their absence requires consideration of other disease entities.
Thyroid eye disease has an early inflammatory stage, typically lasting 18–36 months, where there is active lymphocytic infiltration into retrobulbar tissues. The active inflammatory stage then tends to evolve to a chronic, fibrotic, “burned out” stage in which treatment of the exophthalmos is medically resistant to glucocorticoid treatment. Aggravation of thyroid eye disease has occurred after 131I treatment (see Radioactive iodine, above) or during therapy with thiazolidinediones (eg, pioglitazone); the presence of thyroid eye disease is a relative contraindication to 131I treatment. Cigarette smoking increases the severity of thyroid eye disease, and ethanol injection of thyroid nodules have been reported to be followed by severe disease.
The primary clinical features of thyroid eye disease of any etiology include upper eyelid retraction (Dalrymple sign), lid lag with downward gaze (von Graefe sign), and a staring appearance (Kocher sign) (eFigure 26–9). There can be proptosis, conjunctival chemosis, episcleral inflammation, and weakness of upward gaze (Stellwag sign) (eFigure 26–10)) (eFigure 26–11). Corneal drying may occur with inadequate lid closure. Eye changes may sometimes be asymmetric or unilateral. Resulting symptoms are cosmetic abnormalities and surface irritation. Patients with severe exophthalmos can experience diplopia from extraocular muscle entrapment and optic nerve compression, causing progressive loss of color vision, visual acuity, and visual fields (inferior especially).
Severe ophthalmopathy of Graves disease. Note marked periorbital edema, injection of corneal blood vessels, and proptosis. There was also striking limitation of upward and lateral eye movements and reduced visual acuity. (Reproduced, with permission, from Greenspan FS, Strewler GJ [editors]. Basic & Clinical Endocrinology, 5th ed. Copyright © 1997 by The McGraw-Hill Companies, Inc.)
Thyroid eye disease (Graves ophthalmopathy). Proptosis, lid retraction, and vertical and horizontal squint. (Used, with permission, from M R Vagefi.)
Thyroid eye disease. Inferior rectus fibrosis causing (A) downward deviation and (B) limitation of elevation of right eye. (Reproduced, with permission, from Riordan-Eva P, Augsburger JJ. Vaughan & Asbury's General Ophthalmology, 19th ed. ...