The Role of Non-surgical Management in Dysthyroid Orbitopathy

Dysthyroid orbitopathy (thyroid-associated orbitopathy or Graves’ ophthalmopathy) is the most common cause of both unilateral and bilateral proptosis in adults. This proptosis is usually accompanied by eyelid retraction, orbital congestion or motility disturbances. Each patient experiences a unique combination of symptoms and signs for an unpredictable duration and with varying severity. Although orbital manifestations typically improve within 2-5 years, visual loss due to optic nerve compression does occur. Careful observation and reassurance are helpful and often adequate, but judicious medical and surgical intervention is essential in some patients to prevent irreversible visual loss. Graves originally described a triad of hyperthyroidism, dermopathy, and eyelid retraction. While most patients with Graves ophthalmopathy have preexisting or simultaneously diagnosed hyperthyroidism, this is not universal. In at least 20%, the diagnosis of a thyroid disorder follows (often by years) the initial orbital manifestations. Furthermore, 3% never develop a clinically apparent thyroid imbalance, although they may demonstrate abnormalities when immune testing is performed. Finally, rather than being characteristically hyperactive, the thyroid may be hypoactive or involved in a neoplastic process. Conversely, only 20% with systemic Graves demonstrate symptomatic and clinically apparent orbital disease. Up to 90%, however, possess extraocular muscle enlargement on computed tomography (CT). Hyperthyroidism and the characteristic orbital signs of Graves disease are therefore definitively but inconstantly liked. Thus the term thyroid-associated orbitopathy is most descriptive and least confusing. Our understanding of the link between systemic thyroid disease and orbitopathy has expanded greatly over the last 20 years, although the precise pathogenesis remains a point of debate. Activation of the thyroid gland, as a result of inflammation, trauma, surgery, smoking and radiation appears to prompt release into the blood of a thyroid antigen that stimulates both the cellular and humoral arms of the immune system. Then, antibodies to the thyroid stimulating hormone (TSH) receptor and other antigens are produced, enhancing release of thyroid hormone and amplification of thyroid antigen production. Activated T lymphocytes invade the orbital connective tissue at the same time a local humoral immune reaction is initiated. Retrobulbar fibroblasts proliferate, resulting in increased synthesis and release of glycosaminoglycans. Locally produced lymphokines amplify the cascade. A shared orbit-thyroid antigen(s) is then presented and released into the circulation. This combination of cell-mediated and humoral activation promotes inflammatory cell migration and production of edema in the orbit. The result is thickening of extraocular muscle and an increase in orbital fat volume. The specifics of each step are currently the subject of intense investigation. Thyroid-associated orbitopathy (TAO) is five times more likely to affect women than men (4:1). There is a gender-specific bimodal presentation, with peak incidence between 40-44 and 60-64 in women and 45-49 and 65-69 in men (Mayo study). Although all races may be affected, Caucasians develop TAO much more commonly. Presentation in childhood is unusual but not rare. Genetic factors appear to play a role in development of TAO; 20-60% of affected patients has a family history of a thyroid disorder. Environmental factors are also important; cigarette smoking aggravates and prolongs the orbital inflammation. Thyroid-associated orbitopathy is a self-limited disease, but each orbital sign varies in prevalence and persistence. Soft tissue inflammation and congestion are common and nonspecific signs and typically resolve within 5 years. Eyelid retraction, either unilateral or bilateral, is common (90% prevalence) and the sign most likely to persist chronically. Although extraocular muscle function occurs in 40% of patients, intermittent diplopia usually resolves over time. One third of patients who develop constant diplopia will also improve spontaneously. Unilateral or bilateral proptosis occurs in 60% of patients. Improvement in proptosis is unusual with fewer than 10% of patients demonstrating significant improvement within 5 years. Vision loss occurs in fewer than 5% of those with orbital involvement. Compressive optic neuropathy is the most common cause of visual loss; corneal scarring or secondary glaucoma is more unusual.