Unilateral proptosis in a 40 year old lady is commonly due to: March 2011
Ans. C: Graves ophthalmopathy Graves ophthalmopathy (dysthyroid eye disease) is the most common cause of unilateral or bilateral proptosis in adults between the ages of 25-50 years Graves' ophthalmopathy/ Thyroid eye disease (TED)/ dysthyroid/thyroid-associated orbitopathy (TAO), Graves' orbitopathy It is an autoimmune inflammatory disorder affecting the orbit around the eye, characterized by upper eyelid retraction, swelling (edema), redness (erythema), conjunctivitis, and bulging eyes (proptosis). It is pa of a systemic process with variable expression in the eyes, thyroid, and skin, caused by autoantibodies that bind to tissues in those organs, and, in general, occurs with hypehyroidism. The most common form of hypehyroidism is Graves' disease. The autoantibodies target the fibroblasts in the eye muscles, and those fibroblasts can differentiate into fat cells (adipocytes). Fat cells and muscles expand and become inflamed. Veins become compressed, and are unable to drain fluid, causing edema. Cigarette smoking, which is associated with many autoimmune diseases, raises the incidence 7.7-fold. Epidemiology The pathology mostly affects persons of 30 to 50 years of age. Females are four times more likely to develop TAO than males. When males are affected, they tend to have a later onset and a poor prognosis. Pathophysiology In mild disease, patients present with eyelid retraction. In fact, upper eyelid retraction is the most common ocular sign of Graves' orbitopathy. This finding is associated with lid lag on infraduction (Von Graefe's sign), eye globe lag on supraduction (Kocher's sign), a widened palpebral fissure during fixation (Dalrymple's sign) and an incapacity of closing the eyelids completely (lagophthalmos). Due to the proptosis, eyelid retraction and lagophthalmos, the cornea is more prone to dryness and may present with chemosis, punctate epithelial erosions and superior limbic keratoconjunctivitis. The patients also have a dysfunction of the lacrimal gland with a decrease of the quantity and composition of tears produced. In moderate active disease, the signs and symptoms are persistent and increasing and include myopathy. The inflammation and edema of the extraocular muscles lead to gaze abnormalities. The inferior rectus muscle is the most commonly affected muscle and patient may experience veical diplopia on upgaze and limitation of elevation of the eyes due to fibrosis of the muscle. This may also increase the intraocular pressure of the eyes. The double vision is initially intermittent but can gradually become chronic. The medial rectus is the second-most-commonly-affected muscle, but multiple muscles may be affected, in an asymmetric fashion. In more severe and active disease, mass effects and cicatricial changes occur within the orbit. This is manifested by a progressive exophthalmos, a restrictive myopathy that restricts eye movements and an optic neuropathy. With enlargement of the extraocular muscle at the orbital apex, the optic nerve is at risk of compression. The orbital fat or the stretching of the nerve due to increased orbital volume may also lead to optic nerve damage. The patient experiences a loss of visual acuity, visual field defect, afferent pupillary defect, and loss of color vision. Diagnostic Graves' ophthalmopathy is diagnosed clinically by the presenting ocular signs and symptoms, but positive tests for antibodies (anti-thyroglobulin, anti-microsomal and anti-thyrotropin receptor) and abnormalities in thyroid hormones level (T3, T4, and TSH) help in suppoing the diagnosis. Orbital imaging is an interesting tool for the diagnosis of Graves' ophthalmopathy and is useful in monitoring patients for progression of the disease. Ultrasonography may detect early Graves' orbitopathy in patients without clinical orbital findings. It is less reliable than the CT scan and magnetic resonance imaging (MRI), Thus, CT scan or MRI is necessary when optic nerve involvement is suspected. On neuroimaging, the most characteristic findings are thick extraocular muscles with tendon sparing, usually bilateral, and proptosis. Classification of Graves' eye disease Mnemonic: "NO SPECS": Class 0: No signs or symptoms Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag) Class 2: Soft tissue involvement (oedema of conjunctivae and lids, conjunctival injection, etc.) Class 3: Proptosis Class 4: Extraocular muscle involvement (usually with diplopia) Class 5: Corneal involvement (primarily due to lagophthalmos) Class 6: Sight loss (due to optic nerve involvement) Treatment The first step is the regulation of thyroid hormone levels by a physician. Topical lubrication of the ocular surface is used to avoid corneal damage caused by exposure. Tarsorrhaphy is an alternative option when the complications of ocular exposure can't be avoided solely with the drops. Coicosteroids are efficient in reducing orbital inflammation, but the benefits cease after discontinuation. Radiotherapy is an alternative option to reduce acute orbital inflammation. A simple way of reducing inflammation is smoking cessation, as pro-inflammatory substances are found in cigarettes. Surgery may be done to decompress the orbit, to improve the proptosis, and to address the strabismus causing diplopia. Surgery is performed once the patient's disease has been stable for at least six months. Eyelid surgery is the most common surgery performed on Graves ophthalmopathy patients. TAO is an orbital autoimmune disease. The thyroid-stimulating hormone receptor (TSH-R) is an antigen found in orbital fat and connective tissue, and is a target for autoimmune assault. On histological examination, there is an infiltration of the orbital connective tissue by lymphocytes, plasmocytes, and mastocytes. The inflammation results in a deposition of collagen and glycosaminoglycans in the muscles, which leads to subsequent enlargement and fibrosis. There is also an induction of the lipogenesis by fibroblasts and preadipocytes, which causes orbital volume enlargement due to fat deposition. Poor prognostic indicators Age greater than 50 years Rapid onset of symptoms under 3 months Cigarette smoking Diabetes Severe or uncontrolled hypehyroidism Presence of pretibial myxedema High cholesterol levels (hyperlipidemia) Peripheral vascular disease
Cavernous hemangioma
Orbital cellulitis
Graves ophthalmopathy
Metastasis