Graves’ Orbitopathy, also known as Thyroid Eye Disease (TED), is an autoimmune condition that affects the tissues and muscles behind the eyes. This causes orbital structures to swell, which can lead to the eyes appearing to bulge forward. The condition is closely linked with Graves’ disease, an autoimmune disorder characterized by an overactive thyroid gland. Approximately one in three individuals with Graves’ disease will develop Graves’ orbitopathy, though it can also occur in people with normal or low thyroid function.
The Underlying Autoimmune Process
The condition arises when the body’s immune system mistakenly produces antibodies that attack healthy tissues. These autoantibodies, specifically thyroid-stimulating hormone receptor (TSH-R) antibodies, target the thyroid gland and similar proteins found in the fatty tissues and muscles within the eye socket. This misdirected attack triggers an inflammatory response in the orbital tissues, leading to their expansion and swelling. The accumulation of hydrophilic substances like glycosaminoglycans further contributes to the edema and increased orbital volume.
Several factors can influence the development or worsening of Graves’ orbitopathy. Smoking is a significant modifiable risk factor, greatly increasing the risk. Age and gender also play a role, with women being more commonly affected than men, often with an onset around 30 to 40 years of age.
Key Symptoms and Disease Phases
Graves’ orbitopathy manifests with a range of symptoms, from mild irritation to more severe changes impacting vision and appearance. A common sign is proptosis, characterized by the bulging or protrusion of one or both eyes. Another symptom is eyelid retraction, where the eyelids pull back, creating a wide-eyed or staring appearance. Patients may also experience pain or a feeling of pressure behind the eyes, along with sensations of dryness, grittiness, or excessive tearing.
Double vision, known as diplopia, can occur due to the swelling and dysfunction of the eye muscles. Redness and swelling of the eyes and eyelids are also frequent inflammatory signs. While less common, severe cases can lead to vision loss if the enlarged eye muscles compress the optic nerve. This complication affects about 3-5% of individuals with clinical disease.
The disease typically progresses through two distinct phases. The active phase is characterized by ongoing inflammation where symptoms like pain, swelling, and redness worsen. This inflammatory period usually lasts between six months and three years, during which early intervention can potentially help reverse symptoms. Following this, the condition enters an inactive phase, where the inflammation subsides. Although inflammation decreases, the physical changes, such as bulging eyes, eyelid retraction, or double vision, often persist due to scarring of orbital tissues.
How Graves’ Orbitopathy is Diagnosed
Diagnosing Graves’ orbitopathy typically involves a comprehensive evaluation by an ophthalmologist, a doctor specializing in eye care. This process begins with a detailed clinical eye examination, where the doctor assesses eye movement, checks for eyelid retraction, and measures the degree of eye protrusion using an exophthalmometer. The examination also includes checking for signs of inflammation, such as redness and swelling of the conjunctiva, the membrane lining the eyelids and covering the white part of the eye.
Blood tests are also performed to evaluate thyroid hormone levels, including thyroid-stimulating hormone (TSH), and to detect specific antibodies like thyroid-stimulating immunoglobulin (TSI) and TSH receptor antibodies (TRAb). While most patients with Graves’ orbitopathy have abnormal thyroid hormone levels, some may present with normal or even low levels. Imaging studies provide a visual assessment of the orbital structures. A computed tomography (CT) scan or magnetic resonance imaging (MRI) of the orbits can reveal enlarged eye muscles and expanded fatty tissues behind the eyes, helping to confirm the diagnosis and distinguish it from other orbital conditions.
Managing and Treating the Condition
Treatment for Graves’ orbitopathy is highly individualized and aims to alleviate symptoms, reduce inflammation, and correct residual physical changes. For mild symptoms, simple measures can provide relief, such as using artificial tears multiple times a day to combat dryness and grittiness. Applying cool compresses to the eyes and wearing sunglasses can also help with irritation and light sensitivity. Selenium supplements may offer benefits in mild cases.
In the active phase, when inflammation is present, medical interventions are used to reduce swelling and prevent further damage. Corticosteroids, such as prednisone, are often prescribed to suppress the immune response and decrease inflammation. A more targeted treatment, teprotumumab-trbw, is a biologic infusion therapy approved for moderate-to-severe thyroid eye disease. This monoclonal antibody works by inhibiting the insulin-like growth factor-1 receptor (IGF-1R), which is involved in the inflammatory processes within the eye orbit, thereby preventing the expansion of muscle and fat behind the eye.
Once the active inflammatory phase has passed and the condition has stabilized, typically after 3 to 6 months of inactivity, rehabilitative surgeries may be considered to address persistent physical changes. Orbital decompression surgery is performed to create more space within the eye socket by removing small amounts of bone between the orbits and sinuses. This procedure can reduce eye bulging and relieve pressure on the optic nerve. Strabismus surgery may be necessary to correct double vision by realigning the eye muscles. Lastly, eyelid surgery can be performed to address eyelid retraction and improve eye closure.