Posts in category: Disease & Drugs

Thyroid Eye Disease (TED), also known as Graves’ ophthalmopathy, is a rare autoimmune disorder in which the immune system mistakenly attacks the muscles and fat surrounding the eyes. This immune response leads to inflammation and swelling, causing symptoms such as double vision, eye pain, and eye bulging (proptosis). In severe cases, TED can result in vision loss and facial disfigurement.

According to the American Academy of Ophthalmology and the National Organization for Rare Disorders, TED is classified as a rare disease. Notably, only about 3% to 5% of cases progress to severe disease, making such presentations especially uncommon. 30 to 50% of all Graves’ disease patients are affected by this condition. Some reports show that it increases suicidal risk in patients with TED. The disease typically begins with an active inflammatory phase, characterized by redness of the eyes, pain around and behind the eyes, and swelling of the tissues surrounding the orbits. If inflammation persists, it can lead to structural changes in the retroorbital fat and muscles, resulting in proptosis, diplopia (double vision), and, in advanced cases, corneal damage or optic nerve compression.

The pathophysiological basis of typical orbital inflammation and tissue expansion in thyroid eye disease (TED) is well established. Orbital fibroblasts in TED patients overexpress thyroid-stimulating hormone receptors (TSHR). These receptors can be activated either by excess thyroid hormone or by thyroid-stimulating antibodies (TSAb), leading to the transformation of orbital preadipocytes, a subset of fibroblasts, into fat cells. This contributes to an increase in orbital adipose tissue volume.

Another alternate pathway that plays a key role is the Insulin-like growth factor-1 (IGF-1) pathway. In patients with Graves’ disease, IGF-1 and its receptors are overexpressed on T and B lymphocytes. Graves’ IgG autoantibodies targeting the IGF-1 receptor stimulate orbital fibroblasts, triggering their proliferation, the release of inflammatory cytokines, and the production of hyaluronan, a molecule that draws in water and causes further tissue swelling.

Decisively, TSH receptors (TSHR) and IGF-1 receptors (IGF-1R) are co-expressed on the surface of orbital fibroblasts and are believed to function synergistically. Evidence suggests significant cross-talk between these signaling pathways, which enhances the inflammatory response and tissue remodeling that are hallmarks of thyroid eye disease (TED).

Conventional treatments for Thyroid Eye Disease (TED) such as corticosteroids, radiation therapy, and surgical procedures come with considerable limitations. Corticosteroids can effectively reduce inflammation, their benefits are often short-lived, with symptoms normally recurring once the treatment is tapered. Also they are associated with a range of systemic side effects, including weight gain, high blood pressure, elevated blood sugar levels, mood disturbances, and a increased risk of infections. Surgical interventions like orbital decompression and strabismus correction are invasive, irreversible, and often require multiple procedures to manage the full spectrum of TED manifestations. These traditional therapies primarily focus on symptom relief rather than addressing the root autoimmune cause of the disease, emphasizing the need for more targeted, disease-modifying treatment options.