AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Exophthalmos is defined in Dorland's Medical Dictionary as an "abnormal protrusion of the eyeball; also labeled as proptosis." Proptosis in the same reference is defined as exophthalmos.

Henderson reserves the use of the word exophthalmos for those cases of proptosis secondary to endocrinological dysfunction.⁶ Therefore, this dictum will be followed, and non–endocrine-mediated globe protrusion will be referred to as proptosis and exophthalmos will be reserved for protrusion secondary to endocrinopathies.

Pathophysiology

The etiological basis of proptosis can be inflammatory, vascular, or infectious. In adults, thyroid orbitopathy is the most common cause of unilateral and bilateral exophthalmos. Other causes include such neoplasms as cavernous hemangiomas, lymphangiomas, lymphomas, Wegener granulomatosis, and orbital cellulitis.

In children, unilateral proptosis is often due to an orbital cellulitis–type picture, and, in bilateral cases, neuroblastoma and leukemia are more likely.

For instance, lymphangiomas, by their histologic nature, can increase in size during viral illnesses and result in an increase in orbital volume. A ruptured lymph hemangioma can enlarge due to its rupture and sequestering of heme, which pathologically is described as a chocolate cyst. Orbital varices can result in proptosis with increased venous pressure in the orbit as seen with a Valsalva maneuver or change in postural position.

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. Lymphocytes, plasma, and mast cells are the cellular constituents in this process. The deposition of glycosaminoglycans and the influx of water increase the orbital contents. Obstruction of the superior ophthalmic vein with resultant diminished venous outflow also contributes to the orbital engorgement.

Nunery has segregated patients with thyroid-related orbitopathy into type I and type II.⁸ Those with type I do not have restrictive myopathy, whereas those with type II do. Type I was believed to be caused by a profundity of hyaluronic acid manufactured by the orbital fibroblasts, stimulating lipoid hyperplasia and edema. Patients with type II experience restrictive myopathy and have diplopia within 20° of fixation.

Orbital emphysema can be a significant cause of proptosis and requires emergency treatment.

No matter what the etiology may be, globular protrusion is secondary to the increase in volume within the fixed bony orbital confines. Since the orbit is widest at its anterior aspect, the orbital contents are displaced anteriorly, resulting in proptosis and exophthalmos.

Mortality/Morbidity

Proptosis due to any cause can compromise visual function and the integrity of the eye.

• A proptotic eye not adequately protected by the lids, as with lagophthalmos, can develop exposure punctuate keratopathy. Such disruption of the finely orchestrated homeostatic mechanism to protect the eye will result in corneal compromise, epithelial death, ulceration, and possible corneal perforation in severe cases. At a minimum, the disruption of the tear film layer and incomplete moisturizing of the eye will adversely affect vision and ocular comfort.
• Proptosis secondary to a space-occupying process can result in a compressive optic neuropathy. Impeded optic nerve blood flow results in irreversible neuronal death and diminished optic nerve function. Such manifestations as depression of visual and color acuities, pupillary dysfunction, and constriction of visual field can occur.
• Proptotic compressive effects are remedied initially by forward protrusion of the eye, thereby reducing the compressive effect within the orbit. However, the eye can extend only so far, and severe stretching can adversely affect the eye and compromise the optic nerve.

Race

• In adult Caucasian males, the average distance of globe protrusion is 21 mm, and, in adult African American males, it is 23 mm.
• Females also show racial variation. A difference of more than 2 mm between the 2 eyes of any given patient is considered abnormal.

Sex

Thyroid orbitopathy has a female preponderance with a female-to-male ratio of 5:1.

Age

Proptosis occurs in both adults and children at any age. Thyroid orbitopathy and the resultant exophthalmos show a predilection for females aged 30-50 years.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

A meticulous history of the patient's ocular and systemic systems is key in establishing a diagnosis.

• The ophthalmic history should address the duration and the rate of onset of the proptosis. The patient should be queried about pain, change in visual acuity or refraction, diplopia, and decreased fields of vision. Transient visual loss or blackout periods may signify optic nerve compromise and may call for rapid intervention.
• Complaints of foreign body sensation or dry gritty eyes are symptoms that may indicate corneal decompensation.
• In performing a thorough medical history and a review of systems, the ophthalmologist should consider orbital involvement secondary to systemic pathology.
• Past trauma and family history also may aid in the diagnosis.

Physical

Evaluation of the patient with exophthalmos begins with a thorough ophthalmic and medical history. When concomitant sinus disease or an intranasal source is suspected, a speculum or endoscopic intranasal examination is warranted. Special emphasis on the duration and rate of progression of the patient's signs and symptoms is essential. Pain, diplopia, pulsation, change in effect or size with position or Valsalva maneuver, and disturbance of visual acuity are symptoms that should be explored.

• A complete ophthalmic examination is paramount. Periorbital changes can be noted easily on gross examination in a well-illuminated examination room.
• • Hypertelorism, exorbitism, eyeball protrusion (proptosis), eyelid lesions or edema, chemosis, and engorged conjunctival vessels are several periorbital signs.

  • Blepharoptosis, lagophthalmos (incomplete lid closure), and interpalpebral fissure distance are additional signs to be considered during the examination.

• Palpation of the anterior orbit can assess the level of tenderness, texture, and mobility of the mass.
• • Tenderness may denote an inflammatory process or neural invasion by a neoplasm.

  • Attention should be paid to regional lymph nodes.

  • Tactile inspection of the globe may reveal pulsations secondary to arteriovenous communications or physiological intracranially pulsations transmitted through a bony defect of the orbit, such as an encephalocele.

• Protrusion of the eye is an important clinical manifestation of orbital disease. In addition to proptosis, one should note the displacement of the eye in planes other than the anteroposterior dimension (eg, downward, lateral).
• • Hertel exophthalmometry is a well-accepted tool to quantitate proptosis. The base is determined by the interlateral canthal space. The transection of the central cornea by the premarked millimeter ruler records the amount of anterior displacement of the globe. Its use requires intact lateral orbital rims. If the rim is not intact, a Luedde exophthalmometer can be used.
  • Relative protrusion can be observed by simply standing behind a seated patient and gazing downward toward the chin from the forehead to assess the displacement of one globe as compared to the contralateral side.

• Auscultation of the orbit may detect a high flow state in the orbit or intracranially. The bell is useful for this examination. If a high-flow lesion is suspected (eg, carotid cavernous fistula), arteriography should be sought to further qualify these lesions. It is important to have the contralateral eye remain fixated on a target while auscultating the orbit.
• Decreased visual acuity, change of refraction, and pupillary abnormalities should be noted.
• Extraocular motility dysfunction and diplopia should be carefully assessed and documented.
• Forced duction testing may qualify the dysfunction as restrictive or neurogenic in nature. Intraocular pressure may be elevated, and slit lamp examination can discern chemosis and engorged or sentinel vessels.
• Dilated funduscopic examination may reveal optic disc edema or pallor, retinal detachment, choroidal folds, vascular engorgement or shunt vessels, or indentation of the posterior pole.

Causes

Proptosis can be the result of a myriad of disease processes resulting from primary orbital pathology or systemic disease processes. The list below is not comprehensive but can help in forming a differential diagnosis. The list only consists of adult causes since a fair amount of overlap exists in the differential diagnosis of exophthalmos in adults and children.

• Proptosis in adults
• • Infectious
    • Orbital cellulitis

    • Mucormycosis

    • Concurrent sinus disease
  • Inflammatory
    • Orbital inflammatory syndrome (orbital pseudotumor, benign orbital inflammation)

    • Thyroidopathy
  • Vasculitis
    • Wegener granulomatosis

    • Churg-Strauss syndrome
  • Neoplastic
    • Lacrimal

    • Lymphoma

    • Leukemia

    • Meningioma

    • Glioma

    • Metastatic (breast in women, lung and prostate in men, gastrointestinal, kidney)
  • Orbital vascular disease
    • Orbital varix (venous malformation)

    • Orbital arteriovenous malformation (carotid-cavernous sinus fistula, arteriovenous malformation)
  • Trauma
    • Traumatic or iatrogenic orbital hemorrhage

    • Orbital fractures

    • Facial fractures
  • Pseudoproptosis (pseudoexophthalmos)
    • Buphthalmos

    • Contralateral enophthalmos

    • Ipsilateral lid retraction

    • Axial myopia

    • Contralateral blepharoptosis

DIFFERENTIALS

Section 4 of 11  

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• Differentials
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• Follow-up
• Miscellaneous
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Other Problems to be Considered

Pseudoproptosis can manifest itself in many ways. If the contralateral orbit is enophthalmic, then the ipsilateral side will be viewed erroneously as being proptotic. If there is contralateral blepharoptosis, there can be the appearance of ipsilateral proptosis. Axial myopia or buphthalmos can mimic proptosis as can asymmetrical bones of the orbital rims or midface. Pseudoproptosis also can be simulated by upper eyelid or lower eyelid retraction. The resultant scleral show creates the impression of the globe protruding forward. In patients with contralateral enophthalmos, the normal orbit, which is situated more anteriorly, may simulate proptosis when there is none.

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Patients with thyroidopathy should undergo the appropriate thyroid function studies, even though some patients are euthyroid at the time of presentation with exophthalmos. Approximately 80% of those with Graves disease manifest orbital signs within 18 months, supporting the need for ophthalmic evaluation.
• Any patient suspected of having a neoplasm as the cause of the proptosis should undergo imaging studies (see Imaging Studies). The imaging results should direct further laboratory studies. For example, in a patient with proptosis due to lymphoma, hematologic studies, further body imaging, and a bone marrow biopsy may be indicated.
• In patients with proptosis due to orbital cellulitis, complete blood counts, blood and nasal cultures, and sinus imaging studies may be warranted.

Imaging Studies

• CT scan, first used in the 1970s, is the product of tissue density calculations. X-rays with different vectors are emitted, penetrating through target tissues with resulting radioabsorbencies. These differences in radioabsorbencies are assigned value-specific gray shades to create the 2-dimensional image. CT scan can produce detailed axial and coronal views of soft tissue and bony structures. Image windows from 1.0-3.0 mm in thickness allow for detailed evaluation of orbital masses. Contrast-enhanced images may be obtained and can help in identifying inflammatory processes, vascular tumors, and engorged vessels. Calcified lesions are discernible without the addition of contrast.
• Magnetic resonance imaging (MRI) excites protons by applying a radio frequency with a strong magnetic field. Hydrogen nuclei emit signal intensities that are assigned specific gray tones to create an anatomical reproduction. Three-dimensional views can be gained directly, in any anatomical plane, offering excellent spatial resolution of orbital masses and soft-tissue enhancement. MRI may provide excellent soft-tissue resolution, but CT scan is superior for gleaning details about orbital bony structures.
• Ocular ultrasonography can be used to visualize anterior and middle orbital lesions. Sound waves of 5-15 MHz breech orbital tissues that reflect echogenic energy captured by an oscilloscope. A-scan ultrasonography allows for a 1-dimensional description of echoes, while B-scan ultrasonography provides a 2-dimensional image. C-scan ultrasonography affords coronal views, and D-scan ultrasonography creates 3-dimensional orbital views. With the advent of CT scan, C- and D-scan ultrasonography remains unpopular. Doppler ultrasonography may be used to evaluate orbital vasculature and blood flow.

TREATMENT

Section 6 of 11  

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Medical Care

Medical care for patients with exophthalmos is directed at reversing the problem and minimizing ocular complications.

Consultations

Once the etiology of exophthalmos or proptosis is established, the appropriate specialists should partake in the patient's care.

MEDICATION

Section 7 of 11  

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Ocular lubricants

Keep adequate moisture in eye and prevent dryness.

FOLLOW-UP

Section 8 of 11  

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• Follow-up
• Miscellaneous
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Further Outpatient Care

• Patients should be monitored in intervals tailored to the degree of exophthalmos and complications arising from this ocular malady. Measurement of exophthalmos, visual and color acuities, pupillary function, extraocular motilities, and visual fields should be obtained. In addition, any corneal breakdown should be assessed and remedied.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• The patient who presents with proptosis or exophthalmos must be evaluated, and ancillary testing using imaging studies and corresponding laboratory investigations to ascertain the causation must be obtained. The failure to address these findings can lead to unintended sequelae. The clinician must be alert to frequently subtle asymmetries between the 2 sides. Certain symptoms, such as pain or a sudden diminution in vision, indicate a more rapid course and impose a more rapid response to obtain the diagnosis and treatment. Preservation of vision and function of the globe and orbit is of paramount importance.

MULTIMEDIA

Section 10 of 11  

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• Multimedia
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Media file 1:  Bilateral exophthalmos and upper lid retraction secondary to Graves disease.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
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1. Bastion ML, Wong YC. A case of sneezing-related orbital emphysema treated by aspiration-decompression in the office. Ophthal Plast Reconstr Surg. Nov-Dec 2006;22(6):500-1. [Medline].
2. Burde RM, Savino PJ, Trobe JD. Proptosis and adnexal masses. In: Clinical Decisions in Neuro-ophthalmology. 2^nd ed. St. Louis: Mosby; 1992:379-416.
3. Christiansen E, Kofoed-Enevoldsen A. Graves' ophthalmopathy. J Clin Endocrinol Metab. May 2001;86(5):2327-8. [Medline].
4. Cohen AJ, Mercandetti M, Weinberg DA. Cavernous hemangioma. eMedicine Journal [serial online]. August 2, 2006;Available at www.emedicine.com/oph/topic216.htm.
5. Devi B, Bhat D, Madhusudhan H, et al. Primary intraosseous meningioma of orbit and anterior cranial fossa: a case report and literature review. Australas Radiol. May 2001;45(2):211-4. [Medline].
6. Henderson JW. Orbital Tumors. 3^rd ed. New York: Raven Press; 1994.
7. Mercandetti M, Cohen AJ. Tumors, orbital. eMedicine Journal [serial online]. February 7, 2007;Available at http://www.emedicine.com/oph/topic758.htm.
8. Nunery WR. Ophthalmic Graves' disease: a dual theory of pathogenesis. Oph Clin N Amer. 1991;4.
9. Nunery WR, Martin RT, Heinz GW, Gavin TJ. The association of cigarette smoking with clinical subtypes of ophthalmic Graves' disease. Ophthal Plast Reconstr Surg. Jun 1993;9(2):77-82. [Medline].
10. Philips PH. The orbit. Oph Clin N Amer. 2001;14:109-27.
11. Piest K. Exophthalmos. In: Decision Making in Ophthalmology. 2^nd ed. St. Louis: Mosby; 2000:132-3.
12. Spence CA, Duong DH, Monsein L, Dennis MW. Ophthalmoplegia resulting from an intraorbital hematoma. Surg Neurol. Dec 2000;54(6):447-51. [Medline].
13. Vardizer Y, Berendschot TT, Mourits MP. Effect of exophthalmometer design on its accuracy. Ophthal Plast Reconstr Surg. Nov 2005;21(6):427-30. [Medline].

Article Last Updated: Feb 7, 2007