Exophthalmos

Overview
Exophthalmos is a bulging of the eye anteriorly out of the orbit. Some sources define exophthalmos as a protrusion of the globe greater than 18 mm and proptosis as a protusion equal to or less than 18 mm. (Epstein et al, 2003). Others define "exophthalmos" as protusion secondary to endocrine dysfunction and "proptosis" as any non-endocrine-mediated protusion.

Exophthalmos can be either bilateral (as is often seen in Grave's Disease) or unilateral (as is often seen in an orbital tumor). Measurement of the degree of exophthalmos is performed using an exophthalmometer. Complete or partial dislocation from the orbit is also possible from trauma or swelling of surrounding tissue resulting from trauma.

In the case of Graves Disease, the displacement of the eye is due to abnormal connective tissue deposition in the orbit and extraocular muscles which can be visualized by CT or MRI.

If left untreated, exophthalmos can causes the eye lids to fail to close during sleep leading to corneal damage. The process that is causing the displacement of the eye may also compress the optic nerve or ophthalmic artery leading to blindness.

Epidemiology and Demographics
In adults, thyroid orbitopathy is the most common cause of unilateral and bilateral exophthalmos. Thyroid orbitopathy has a female preponderance with a female-to-male ratio of 5:1. In caucasian males, the average distance of globe protrusion is 21 mm, and, in african american males, it is 23 mm. Females also show racial variation but a difference of more than 2 mm between the 2 eyes of any given patient is considered abnormal.

Pathophysiology & Etiology
The etiological basis of proptosis can be inflammatory, vascular, or infectious. In adults, thyroid orbitopathy is the most common cause of exophthalmos. In children, unilateral proptosis is often due to an orbital cellulitis, and, in bilateral cases, neuroblastoma and leukemia are more likely.

The etiology of the thyroid-related orbitopathy is an autoimmune-mediated inflammatory process of the orbital tissues, predominantly affecting the fat and the extraocular muscles.

Genetics
See below regarding causes related to genetic diseases.

Natural History and Complications
Proptosis can compromise visual function and the integrity of the eye. A proptotic eye can develop exposure punctuate keratopathy. This will result in corneal compromise, epithelial death, ulceration, and possible corneal perforation. Proptosis secondary to a space-occupying process can result in a compressive optic neuropathy as well. Such manifestations as depression of visual and color acuities, pupillary dysfunction, and constriction of visual field can occur.

Complete Differential Diagnosis of the Causes of Exophthalmos:
(In alphabetical order)

ipsilateral lid retraction, axial myopia, contralateral blepharoptosis)
 * Arteriorvenous malformation
 * Aspergillosis (invasive, orbital)
 * Basedow syndrome (combination of hyperthyroidism, goitre, and exophthalmos )
 * Carotid-cavernous fistula
 * Cavernous Sinus Thrombosis
 * Churg-Strauss syndrome
 * Cloverleaf skull syndrome
 * Cole-Carpenter syndrome
 * Corneal ulcer
 * Crouzon craniofacial dysostosis (Crouzon syndrome)
 * Dalrymple's sign
 * Dermoid cyst
 * Endophthalmitis
 * Erdheim-Chester disease
 * Graves' disease
 * Hemangioma
 * Histiocytosis X
 * Hyperthyroidism
 * Infiltrative ophthalmopathy (hyperthyroidism)
 * Insulin receptor defect with insulin-resistant diabetes mellitus
 * Lowry-MacLean syndrome
 * Leukemia
 * Lymphoma
 * Meningioma
 * Mucormycosis
 * Nasal type natural killer/T-cell lymphoma
 * Neu-Laxova syndrome
 * Neuroblastoma
 * Neurofibromatosis
 * Optic glioma
 * Orbital cellulitis
 * Orbital emphysema: from fracture of a sinus or sneezing.
 * Orbital inflammatory pseudotumor: The term is used to describe any idiopathic inflammatory lesion that simulates a neoplasm within the orbit. It can be subdivided into different types: granulomatous, sclerosing, vasculitic and eosinophilic, depending upon the histological characteristics. There are strong similarities between OIP and the Tolosa-Hunt syndrome of painful ophthalmoplegia.
 * Orbital mass or tumors
 * Osteodysplasty (Melnick-Needles)
 * Polyarteritis nodosa
 * Pseudoproptosis (buphthalmos, contralateral enophthalmos
 * Raine syndrome
 * Relapsing polychondritis
 * Retinoblastoma
 * Schinzel-Giedion midface-retraction syndrome
 * Sinusitis
 * Sturge-Weber syndrome: a neurological disorder indicated at birth by seizures accompanied by a large port-wine stain birthmark on the forehead and upper eyelid of one side of the face.
 * TAO (Thyroid associated orbitopathy)
 * Tolosa-Hunt syndrome
 * Trauma
 * Von Recklinghausen's disease (Neurofibromatosis)
 * Varices, orbital
 * Wegener granulomatosis

Complete Differential Diagnosis of the Causes of Exophthalmos:
(By organ system)

History and Symptoms

 * Includes:
 * age
 * rate of onset
 * pain
 * fever
 * diplopia
 * thyroid disease
 * sinusitis
 * diabetes
 * cancer

Eyes

 * full optomologic exam
 * Boston's sign: spasmodic lowering of the upper eyelid on downward rotation of the eye, indicating exophthalmic goiter.
 * Stellwag's sign: infrequent or incomplete blinking associated with exophthalmos or Graves orbitopathy.
 * Von Graefe's sign: immobility or lagging of the upper eyelid on downward rotation of the eye, indicating exophthalmic goiter.

Ear Nose and Throat

 * full otolaryngologic exam

Neurologic

 * full neurologic exam

Laboratory Findings

 * Labs include
 * thyroid function tests
 * ESR
 * CRP
 * CBC
 * ANCA
 * ANA
 * Blood culture

MRI and CT

 * CT of orbits

Echocardiography or Ultrasound

 * Ultrasound if arteriovenous malformation is suspected

Acute Pharmacotherapies

 * Direct IV antibiotics -> if infectious
 * Systemic steroids -> if non infectious

Indications for Surgery

 * Surgical decompression

Primary Prevention

 * Prevent eye injury
 * Artificial tears
 * Eye protection (sunglasses)

Related Chapters

 * Boston's sign
 * Enophthalmos
 * Von Graefe's sign
 * Graves ophthalmopathy