In the medical literature, Robert James Graves was the first to describe the association of goiter with protrusion of the eye (proptosis) in 1835. Graves' ophthalmopathy is a rare condition that occurs before the onset of overt thyroid disease. before, with it together or later may occur and is usually of slow onset over months
The disease affects people between the ages of 30 and 50. Women are four times more likely to develop Graves' disease than men. When men are affected, they tend to have a later onset and a poorer prognosis. At the time of diagnosis, patients with Graves' disease may have thyroid function tests that show hyperthyroidism in , Hashimoto's thyroiditis in %3, hypothyroidism in %1, and no abnormalities in %6.
Graves' ophthalmopathy, also known as thyroid-related eye disease (Graves' ophthalmopathy), is an autoimmune inflammatory disorder of the eye muscles and tissues surrounding the eye, characterized by upper eyelid retraction, delayed eyelid closure, swelling, redness, conjunctivitis, and bulging and protruding eyes (exophthalmos). Graves' disease is most commonly seen in individuals with hyperthyroidism and, less commonly, in individuals with Hashimoto's thyroiditis or those who are euthyroid.
Autoantibodies target fibroblasts in the eye muscles, and these fibroblasts can differentiate into fat cells (adipocytes). The fat cells and muscles become enlarged and inflamed. Veins become constricted and unable to drain fluid around the eye, causing edema.
The annual incidence is 16/100,000 in women and 3/100,000 in men. Approximately 1 in 100 cases of T3-T5 develops severe disease, with intense pain and vision-threatening corneal ulceration or optic nerve compression. This disease, which is associated with many autoimmune diseases, increases its incidence 7.7-fold with smoking. Therefore, smoking should be avoided.
Mild illness It usually resolves and requires only measures to reduce discomfort and dryness, such as artificial tears and, if possible, smoking cessation. Severe cases are a medical emergency and are treated with cortisone medications (steroids) and sometimes cyclosporine. In mild disease, patients present with eyelid tenseness and open eyes. In fact, upper eyelid retraction is the most common ocular sign of Graves' disease. This sign is associated with eyelid lag on infraduction gaze (Von Graefe's sign), globe lag on supraduction (Kocher's sign), widened palpebral fissure on fixation (Dalrymple's sign), and inability to fully close the eyelids (lagophthalmos, Stellwag's sign). The cornea is more prone to dryness because of proptosis, eyelid retraction, and lagophthalmos and may present with chemosis, punctate epithelial erosions, and upper limbic keratoconjunctivitis. Patients also have lacrimal gland dysfunction, with decreased tear production and composition. Nonspecific symptoms of these conditions include irritation, a gritty sensation in the eye, photophobia, stinging, and blurred vision. Pain is not typical, but patients often complain of orbital pressure. Periorbital swelling may also occur due to inflammation.
Moderate In active disease, signs and symptoms are persistent and progressive. Inflammation and edema of the extraocular muscles lead to gaze disturbances and strabismus. The inferior rectus muscle is the most commonly affected muscle, and patients may experience vertical diplopia and limited eye elevation during upward gaze due to muscle fibrosis. This can also increase intraocular pressure. The diplopia is initially intermittent but can become chronic. The medial rectus is the second most commonly affected muscle, but multiple muscles can be affected asymmetrically.
More severe and in active disease, mass effects and cicatricial changes occur in the orbit. This manifests as progressive exophthalmos, a restrictive myopathy that restricts eye movements, and optic neuropathy. The optic nerve is at risk of compression due to enlargement of the extraocular muscles at the orbital apex. Stretching of the nerve due to periocular fat accumulation or increased orbital volume can also lead to optic nerve damage. The patient presents with loss of visual acuity, visual field defects, afferent pupillary defects, and loss of color vision. This is an emergency and requires immediate surgery to prevent permanent blindness.
Magnetic resonance imaging of the periorbital region demonstrates narrowing of the retroorbital space and dilation of the eye muscles, supporting the diagnosis of Graves' ophthalmopathy. Graves' ophthalmopathy is an orbital autoimmune disease. The thyroid-stimulating hormone receptor (TSH-R), an antigen found in orbital fat and connective tissue, is a target of autoimmune attack.
Histological examination reveals involvement of the orbital connective tissue by lymphocytes, plasmocytes, and mastocytes. Inflammation causes the deposition of collagen and glycosaminoglycans in the muscles, which subsequently leads to expansion and tissue stiffening. There is also increased lipogenesis by fibroblasts and adipose precursor cells, resulting in expansion of the orbital fat and extraocular muscles. This increase in the volume of intraorbital contents within the bony orbital margins can lead to dysthyroid optic neuropathy (DON), increased intraocular pressure, eye dislocation, and venous engorgement leading to chemosis (conjunctival edema) and periorbital edema. Additionally, the expansion of intraorbital soft tissue volume can remodel and expand the bony orbit, a form of autodecompression.
Graves' ophthalmopathy is diagnosed clinically by the presenting eye signs and symptoms, but positive tests for antibodies (anti-thyroglobulin, anti-microsomal, and anti-thyrotropin receptor) and abnormalities in thyroid hormone levels (T3, T4, and TSH) help support the diagnosis.
Orbital imaging is a complementary tool for the diagnosis of Graves' ophthalmopathy and is useful in monitoring patients for disease progression. However, computed tomography and magnetic resonance imaging can be used to assess extraocular muscle involvement at the orbital apex, which can lead to blindness. Therefore, CT scanning or MRI is necessary when optic nerve involvement is suspected. The most characteristic neuroimaging finding is proptosis, usually bilateral, with thick extraocular muscles with preservation of tendon dimensions.
- Being over 50 years of age
Rapid onset of symptoms in less than 3 months
-Smoking
-Presence of diabetes
Severe or uncontrolled hyperthyroidism
-Presence of pretibial myxedema
-High cholesterol levels (hyperlipidemia)
-Peripheral vascular disease
Not smoking or quitting smoking is the most common recommendation in the literature. Selenium supplementation and some recent research suggest that statin use may also be helpful.
While some people experience spontaneous resolution of symptoms within a year, many require treatment. The first step is to regulate thyroid hormone levels. Artificial tears should be used to prevent corneal damage due to dry eyes. Corticosteroids are effective in reducing orbital inflammation, but their benefits end with discontinuation of treatment. Corticosteroid treatment is also limited by numerous side effects. Radiotherapy is an alternative option for reducing acute orbital inflammation. However, its effectiveness remains controversial. Because cigarettes contain proinflammatory substances, quitting smoking is a simple way to reduce inflammation. Teprotumumab-trbw may also be used. There is tentative evidence that selenium is effective in mild disease. In January 2020, the U.S. Food and Drug Administration approved teprotumumab-trbw for the treatment of Graves' ophthalmopathy.
Although there are some reports that total or subtotal thyroidectomy, perhaps after a 12-month delay, may help reduce TSH receptor antibody (TRAb) levels and consequently alleviate ocular symptoms, the impact of thyroid surgery on Graves' disease remains unclear. Therefore, it would be more accurate to consider Graves' disease separately from thyroid disease after the disease has begun.
Surgery can be performed to decompress the orbit, improve proptosis, and correct the strabismus that causes diplopia. Surgery is performed after the patient's condition has been stable for at least six months. However, in severe cases, surgery becomes urgent to prevent blindness from optic nerve compression. Because the eye socket is made of bone, there is nowhere for the swelling of the eye muscles to accommodate, and as a result, the eye is pushed forward into a protruding position. Orbital decompression involves removing some bone from the eye socket to open one or more sinuses, making room for the swollen tissue and allowing the eye to return to its normal position, and also to relieve compression of the optic nerve, which can threaten vision.
Eyelid surgery is the most common procedure performed for patients with Graves' ophthalmopathy. Lid lengthening surgeries can be performed on the upper and lower eyelids to improve the patient's appearance and ocular surface exposure symptoms. Marginal myotomy of the levator palpebrae muscle can reduce the height of the palpebral fissure by 2-3 mm. In cases of more severe upper eyelid retraction or exposed keratitis, marginal myotomy of the levator palpebrae with lateral tarsal canthoplasty is recommended. This procedure can lower the upper eyelid by up to 8 mm. Other approaches include mullerectomy (resection of the Müller muscle), eyelid spacer grafts, and retraction of the lower eyelid retractors. Blepharoplasty can also be performed to remove excess fat from the lower eyelid.
