Exophthalmos (protruding eyes)

Generality

The exophthalmos consists in the protrusion of the eyeball, anteriorly out of the orbit; due to this anomaly the eyes become visually "protruding" or prominent.

The terms exophthalmos and proptosis are often used interchangeably, but with some reservations:

Esophthalmos is used to indicate bulging eyes in endocrine-related conditions;
The proptosis indicates, more precisely, the protrusion of the eyeballs caused by other causes (orbital tumor, vascular pathologies, retrobulbar hemorrhage, etc.)

The exophthalmos can be bilateral or unilateral, that is to hit both eyes or one.

The protrusion of the eye is secondary to the increase in the orbital volume within the bony boundaries, which instead remain fixed. The orbit is in fact closed at the posterior, medial and lateral walls; therefore, any extension of the structures located inside it will cause the anterior displacement of the eyeball, with consequent exophthalmos.

Causes

Exophthalmos can be the result of many processes deriving from primary orbital pathology (isolated or proximal) or from systemic diseases. The etiological basis can be mainly inflammatory, vascular, neoplastic or infectious. In adults, thyroid orbitopathy (that is, the pathology of the eye orbit of thyroid origin) is the most common cause of unilateral and bilateral exophthalmos. In particular, Graves' disease - an autoimmune disease that causes hyperthyroidism - is often associated with exophthalmos: protruding eyes are due to the anomalous infiltration of lymphocytes, plasma cells and mast cells at orbital connective tissue level; this causes a deposition of collagen and glycosaminoglycans in the extrinsic muscles of the eye, which in turn leads to fibrosis and to a further enlargement of the orbital volume.

Proptosis is sometimes associated with the development of tumors that develop in the eye cavity. Complete or partial orbit dislocation is also possible due to direct trauma or swelling of the surrounding tissue. In children, unilateral exophthalmos is commonly caused by orbital cellulitis, while neuroblastoma and leukemia are likely if the condition is bilateral.

The main causes of exophthalmos and proptosis are shown in the table.

Inflammatory / Infectious	Neoplastic
Graves ophthalmopathy Orbital cellulite dacryocystitis mucormycosis Orbital inflammatory syndrome Wegener's granulomatosis	Leukemia Meningioma Nasopharyngeal angiofibroma hemangioma Adenoma of the lacrimal gland glioma
Vascular	Other causes
Carotid-cavernous fistula Aortic insufficiency Cavernous sinus thrombosis	Hyperthyroidism Neuroblastoma Dermoid cysts Mucocele of the frontal sinus Orbital and facial fracture Retrobulbar hemorrhage Progeria

Symptoms

The most obvious clinical sign is the anterior displacement of the eye from the orbit.

Exophthalmos may be accompanied by other symptoms:

Eyelid swelling: may be associated with conjunctival chemosis (bulbar conjunctiva protrusion with respect to underlying tissues) and blepharoptosis.
Difficult to completely close the eyelids during blinking or night rest;
Double vision: caused by the limitation of the movement of the extrinsic muscles of the eyeball, which can be the source of inflammation (myositis) or be compressed by a growing tumor.
Redness and pain: they tend to occur in the presence of inflammation, infection or a rapidly progressing tumor. In more severe cases, there may be secondary exposure keratopathy, as a result of incomplete closure of the eyelid on the cornea. Corneal surface compromise can cause pain and affect visual acuity.
Reduced vision: the patient may experience reduced vision. Visual acuity can be compromised due to the direct involvement of the optic nerve in the pathophysiology of exophthalmos or if the macula is distorted by a lesion that pushes behind the globe (tumor or hemorrhage).

Depending on the cause, other ocular symptoms may be present. If exophthalmos is caused by a thyroid-related condition, such as Graves' disease, in addition to protruding eyes they can also manifest:

Inflammation, redness and eye pain;
Eye dryness;
Excessive tearing;
Sensitivity to light (photophobia).

Complications

A particularly severe proptosis can cause lagophthalmos (failure to close the eyelids). Continuous exposure of the eye can cause dryness and possible corneal damage (infections or ulcers), due to the increased friction during blinking. The pathological process that causes the displacement of the eyeball may also compress the optic nerve or the ophthalmic artery, causing blindness. Other possible complications include conjunctivitis and optic atrophy. Exophthalmos can increase the pressure behind and within the eye (intraocular pressure). Excessive intraocular pressure increases the risk for other eye diseases, such as glaucoma. If a person suddenly develops proptosis, especially in one eye, a very serious problem may be present, which should always be evaluated immediately by an eye specialist.

Diagnosis

Exophthalmos is often easy to recognize due to the obvious protrusion of the eyeballs.

A thorough patient history is the key to establishing a diagnosis. In fact, the clinical presentation varies according to the underlying cause. However, the very nature of exophthalmos translates into some common features. The direction of the ledge, severity, speed of onset and associated symptoms often give a good indication regarding the underlying cause, but this usually needs to be confirmed with further investigation. The ophthalmologist will monitor the range of eye movements, visual acuity, pupillary function, visual field defects and the interpalpebral fissure width. Measurement of exophthalmos is performed using an instrument called exophthalmometer. Most sources define proptosis as a protrusion of the eyeball greater than 18 mm. Blepharoptosis and lagophthalmos (incomplete eyelid closure) are additional signs to be considered during the examination.

Palpation of the anterior orbit allows assessment of the level of swelling, consistency and mass mobility. Edema may denote an inflammatory process or neural invasion from neoplasia. The tactile inspection of the globe can reveal secondary pulsations to the arteriovenous communications. If neoplasia is suspected as a cause of proptosis, a computed tomography (CT) or magnetic resonance imaging (MRI) can be performed to examine the eye cavity in more detail. The results should be directed to further laboratory studies. For example, in the case of lymphoma, hematological studies, body imaging and a bone marrow biopsy may be indicated. In patients with orbital cellulitis, cultures of blood and nasal samples and a complete blood count can be performed. Blood tests or a thyroid function test check whether the thyroid gland is functioning properly.

Treatment

Treatment depends on the underlying cause. Once the etiology of exophthalmos or proptosis has been established, medical therapies will be directed at reversing the basic problem and minimizing eye complications. Meanwhile, artificial tears can be used to provide symptomatic relief and protect the exposed cornea. For more severe cases, surgery may be required. Patients should be monitored regularly to assess the degree of exophthalmos and the complications resulting from this eye disease. Furthermore, any corneal damage should be identified early and resolved.