PROPTOSIS (EXOPHTHALMOS)

Signs and Symptoms

Proptosis is a non-ocular term generically meaning “to push forward.” Ocularly, it is the forward projection or displacement of the eyeball.1 Exophthalmos is a term specific to the eye, connoting an abnormally protruding globe.2 The ophthalmic community uses the words interchangeably. Normal exophthalmometry measurements increase with age:4

Age Normal Exophthalmometry

≤4 13.2mm

5-8 14.4mm

9-12 15.2mm

≥13 16.2mm to 21.0mm

Asymmetry is common, estimated to occur in 14% of the population, with an average difference of 2.5mm between the two eyes.4,5 Normal values also vary by race, with patients of African origin measuring slightly larger.6

Proptosis is not a diagnosis but rather a finding. While the configuration of the orbital margins and position of the eyes relative to the facial plane varies considerably, pathologic proptosis/exophthalmos is generally a condition that evolves to produce symptoms in one or both eyes.5-8 In general, unilateral cases of ocular protrusion (>6mm) are more noticeable and of greater concern.9-16

A common initial symptom produced by globe protrusion is ocular discomfort caused by exposure, with ocular dryness due to evaporation and reduced coverage of the lacrimal lake.9-14 Dryness, burning, grittiness, foreign body sensation and paradoxical tearing with epiphora are all common. Pain may be reported and signify an acute onset rather than a chronic condition. Redness and swelling of the conjunctiva are visible accompanying features.

Visual function may be normal or profoundly reduced, depending upon the severity and nature of the exposure (corneal damage) and underlying etiology.14 Visual fields may also be compromised if the optic nerve has been affected by the entity producing the forward displacement.14,15 If the extraocular muscles are involved (entrapment, infiltration, myositis, tendonitis, tumor) diplopia is possible, though not uniformly present.9-13

Proptosis and exophthalmos are usually associated clinically with increased palpebral fissure width and lid retraction.9-15 This is measurable using the marginal reflex distance (MRD), where the distance from the lid margin to the central corneal reflex is increased.17

Extraocular muscle motilities may show restrictions and a positive forced duction test depending on the severity of underlying etiology.8-15 Other biomicroscopic signs include variable conjunctival hyperemia, conjunctival chemosis, epithelial keratopathy and corneal scarring in chronic cases. Exophthalmometry (Hertel or Ludde methods) is the diagnostic procedure of choice to measure the ocular protrusive value.5,13

Pathophysiology

Proptosis or exophthalmos is the clinical result of increased volume within the orbital cavity. Accumulation of extraorbital cellular material (blood, vasculature, fluid, new tissue) or enlargement of any of the orbital contents (extraocular muscles, optic nerve, lacrimal gland, displacement of orbital bones) may result in forward displacement of the globe.18-25 A wide range of etiologies may produce this phenomenon. Infiltrative disorders, infection, inflammatory disease, vascular conditions and neoplasm are the most common causes.7,8,10,12,13,18-26

Thyroid eye disease (i.e., Graves’ disease, Graves’ ophthalmopathy, thyroid ophthalmopathy) is among the most frequently encountered etiopathologies associated with proptosis/exophthalmos in adults.8,13,26 Infiltration of the extraocular muscles and orbital fat by the cells of a maladapted immune system (e.g., lymphocytes, macrophages and plasma cells) along with thyroglobin-stimulated complexing of glycosaminoglycan with the extraocular muscles (EOM) creates orbital congestion and tendon-sparing EOM thickening that causes anterior dislocation of the eye.26-30

Since thyroid disease is a systemic condition, bilateral ocular involvement is anticipated; however, some cases may display marked asymmetry, even to the point of unilateral proptosis.26-30 Other documented causes of exophthalmos/proptosis include infection (e.g., orbital cellulitis, phycomycosis), orbital inflammatory disease, lymphoid tumors (e.g., lymphoma), vascular disease (e.g., intraorbital and retrobulbar hemorrhage, vasculitis, venous varices, arteriovenous malformations, carotid cavernous fistula), orbital metastasis, lacrimal gland tumors, posterior scleritis, trauma and invasive sinus disease. 7,8,10,12,13,18-26

Axially myopic eyes and eyes with shallow orbits or greater than normal amounts of orbital fat may appear to be exophthalmic. This appearance may be verified by old photographs. When questioned, patients will confirm this appearance existing all their lives with no evidence of symptoms, loss of function or changes.

Management

For individuals presenting with new-onset ocular asymmetry or bilateral exophthalmos, management begins with a thorough history.6,16 The correlation of signs with symptoms while cross-referencing epidemiologic characteristics like race, age, sex and genetics can help to shorten the list of possibilities.6-8,10,12,13,18-30 Constitutional complaints should also be scrutinized, as these are often indicative of specific systemic conditions.6,16

Initial management for patients with new-onset ocular proptosis concentrates on corneal lubrication and reduction of local inflammation. Therapy includes frequent topical artificial tear drops and ointments as needed. Patients must be educated that thicker tear products (both drops and ointments) will increase contact time but temporarily blur vision. The use of protective topical antibiotic drops and ointments can protect damaged corneas. Topical non-steroidal and steroidal anti-inflammatory drops can improve comfort if inflammation is severe. Cycloplegia is usually not necessary. A moisture chamber by day and lid taping at night may be helpful. Punctal plugs can be considered to enhance natural tear volume in chronic cases. Diplopia, if present, can be eliminated by Fresnel press-on prisms in the best scenarios and by alternate eye patching when that fails.

The secondary concern is the underlying cause. The critical diagnostic test in cases demonstrating proptosis/exophthalmos of unknown etiology is orbital imaging.31,32 Computed tomography (CT) and magnetic resonance imaging (MRI), with and without contrast, may be used.31,32 Orbital ultrasonography can also help in the differential of proptosis or exophthalmos.31,32 The advantage of this technique is that it can be completed in the office and interpreted immediately; the test is rapid and far less expensive than its imaging counterparts. Unfortunately, the principle disadvantage is that it can only image the anterior aspects of the orbit.

Laboratory testing is indicated when a systemic disorder is presumed. A thyroid function panel—including thyroid stimulating hormone (TSH), serum triiodothyronine (T3), serum thyroxine (T4), thyroglobin antibodies, thyrotropin receptor antibodies and thyroid stimulating immunoglobulins—is appropriate.25-32 In cases where orbital inflammatory disease is suspected secondary to sarcoidosis, pulmonary function tests, chest X-ray and angiotensin-converting enzyme level may be diagnostic.10 A complete blood count (CBC) is always helpful in identifying general health status, though it is non-specific. CBC is particularly useful for uncovering malignancies such as leukemia and lymphoma. Adjunctive testing for orbital neoplasms may involve fine-needle aspiration biopsy (FNAB) or open conjunctival biopsy.10

Clinical Pearls

Bilateral evolving proptosis/exophthalmos is highly suggestive of thyroid disease, especially if ophthalmoplegia and diploia are concurrent.

Slowly progressive or new-onset unilateral proptosis/exophthalmos has a more ominous etiology.

The common signs and symptoms of hyperthyroidism include eyelid retraction, nervousness, irritability or panic attacks; insomnia; heat sensitivity or increased perspiration; weight loss (despite a normal appetite and diet); tachycardia; hand tremors; muscular weakness in the extremities; thinning of the hair and/or skin; frequent bowel movements; or lighter or less frequent menstrual periods.

MRI is the preferred orbital imaging technique in most cases of acute proptosis. CT may be preferable in conditions that display bony erosion (e.g., sinus abscess, mucocele); the evaluation of osseous and cartilaginous lesions and in cases involving recent trauma.

CT is necessary for patients with medical contraindications to MRI, such as patients with pacemakers, implanted cardiac defibrillator, aneurysm clips or claustrophobia.

1. Merriam Webster Online Dictionary. Available at: www.merriam-webster.com/dictionary/proptosis. Accessed 2-18-14.

2. Merriam Webster Online Dictionary. Available at: www.merriam-webster.com/dictionary/exophthalmos. Accessed 2-18-14

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