Exophthalmos (also known as proptosis) is the protrusion of one or both eyes anteriorly outside the orbit. It occurs due to an increase in orbital content in the normal bony orbit anatomy. Depending on the underlying cause, exophthalmos may be accompanied by systemic symptoms.
Vision may be impaired if the optic nerve is compressed as a result of the underlying etiology of exophthalmos.
| Goals : |
• Identify the etiology.
• Summarize the evaluation of exophthalmos.
• Summarize management options for exophthalmos.
• Review multidisciplinary team strategies to improve care coordination and communication to achieve better patient care and outcomes.
| Etiology |
In adults, the most common cause of exophthalmos, both unilateral and bilateral, is thyroid-related eye disease, such as Graves’ disease ophthalmopathy. In children, the most common cause is orbital cellulitis, while bilateral exophthalmos is probably due to neuroblastoma and leukemia. In general, exophthalmos originates from four probable etiologies:
1. Extension of inflammation within the orbit, e.g., thyroid-related eye disease, orbital cellulitis, sarcoidosis, granulomatosis with polyangiitis, and IgG4-related disease.]
2. Invasion of the orbit by new growth, e.g. e.g., benign or malignant space-occupying orbital tumors, such as capillary hemangioma, neuroblastoma, neurofibromatosis, leukemia, lymphoma, mucocele, pseudotumors, and secondary metastatic deposits.
3. Interference with venous return from the orbit, e.g., orbital varices, carotid-cavernous fistula, cavernous sinus thrombosis.
4. Foreign matter forced into the orbit, e.g., by trauma.
| Epidemiology |
The incidence of exophthalmos may vary depending on the underlying cause. In unilateral exophthalmos, less than one-third of patients have thyrotoxic activity. Historically, 90% of bilateral exophthalmos were due to endocrine abnormalities. The mean position of the globe, measured with an exophthalmometer, is 16 mm but there is variation between sexes and races.
| Pathophysiology |
Exophthalmos usually arises from an increase in orbital contents, within the bony orbit, leading to displacement of the eyeball forward. The origin of the increased orbital content depends on the underlying cause.
In Graves’ ophthalmopathy, enlargement of the extraocular muscles and expansion of the orbital adipose tissue occurs due to the abnormal accumulation of hyaluronic acid and the accumulation of edema in the retro-orbital space. The mechanism of trauma and the pathogenesis of the neoplastic disease must also be taken into account.
| History and physical examination |
The presentation can be variable, depending on the underlying cause. Symptoms may include:
• Protruding eyes : can be measured with an exophthalmometer.
• Eyelid/periorbital swelling may be unilateral or bilateral and associated with conjunctival chemosis or orbital cellulitis.
• Diplopia : caused by restriction of extraocular muscles. They may be the inflammatory focus (myositis) or they may also be compressed by a growing tumor.
• Red eyes : conjunctival hyperemia increases with exophthalmos as a result of dilation. In severe cases, secondary exposure keratopathy may occur as a result of incomplete closure of the eyelid over the cornea.
• Ophthalmoplegia : typically in infectious conditions, inflammatory processes, or aggressive tumors.
• Reduced visual acuity
A complete history will help establish the underlying cause. Symptoms such as heat intolerance, weight loss, changes in bowel habits, and palpitations may support the diagnosis of thyrotoxicosis. There may be a history of trauma or constitutional symptoms, such as weight loss, that may suggest a cystic or tumor growth. The rate of occurrence can provide information about its etiology. Rapid onset may suggest inflammatory disease, malignant tumors, and carotid-cavernous fistula, while gradual onset implies benign pathology. The presence of pain usually indicates infection (eg, orbital cellulitis). Temporal exophthalmos, triggered by the Valsalva maneuver, may be compatible with orbital varicose veins.
The examination should include a general examination of the patient to identify any systemic disease such as Graves’ disease, leukemia, visceral neoplasia, or constitutional signs that may raise suspicion of malignancy. Doctors should perform a complete eye examination, evaluating the patient’s extraocular movements, visual acuity, visual field, accommodation, and pupillary reflexes. Intraocular and anterior segment pressures and fundoscopy should be performed.
Exophthalmos can be seen on examination and is quantified with an exophthalmometer, in which the extent is measured by the distance from the apex of the cornea to the midpoint of the anterior rim of the orbit. It may be accompanied by other extraocular and systemic signs related to systemic causes. The doctor must remain at the same level as the patient. In exophthalmos, the white of the sclera is usually exposed below the iris.
| Evaluation |
To establish the diagnosis, a complete study must be done, including a complete blood test, with complete blood count, thyroid function tests, detection of autoantibodies, kidney function tests, and C-reactive protein. If a serious infection is suspected (e.g., orbital cellulitis), nasal swabs and blood cultures are warranted.
Radiological images are essential for diagnosis and treatment. Computed tomography and magnetic resonance imaging are the gold standard modalities for evaluating the orbit or skull for causes of severe infection, mass growth, and foreign bodies related to exophthalmos. Positron emission tomography (PET) allows the evaluation of metastatic diseases, including leukemia, lymphoma, and cancer metastases. Many cases may present with overlapping clinical features making the diagnosis difficult to confirm, and a tissue biopsy may be necessary for a definitive answer.
Proptosis or exophthalmos may be associated with other deviations of the eyeball, namely hyperglobus, hypoglobus, esoglobus or exoglobus.
| Treatment and management |
> General
To control exophthalmos and maintain ocular function, it is necessary to treat the underlying cause. For thyroid-related orbitopathy and other secondary causes, effective management requires a multidisciplinary approach with ophthalmologists, primary care clinicians, and endocrinologists.
> Lifestyle modifications
To prevent and avoid the progression of thyroid eye disease, it is essential to stop smoking.
> Conservative management
Supportive therapies will provide appropriate symptomatic relief for patients while treatment of the underlying cause is initiated. Preservative-free topical ocular lubricants should be administered and the eyelids covered if the patient has dry eyes. About 66% of mild cases resolve within 6 months, so supportive therapy may be sufficient. Sunglasses and protective glasses may be recommended to reduce photosensitivity and glare. Diplopia can be managed with Fresnel prism or monocular occlusion. Finally, upper eyelid retraction can be corrected with an injection of botulinum toxin directly into the upper eyelid levator.
> Medical management
Moderate to severe thyroid orbitopathy is treated with oral and intravenous corticosteroids. Inflammatory and autoimmune causes will benefit from reduced orbital edema and congestion. To reduce tumor volume and burden, one option is the administration of chemotherapy agents.
> Surgical management
Surgery is indicated to remove offending tissue, a tumor, or malignant disease. For decades, orbital decompression and extraocular muscle repair have served to protect vision in severe cases of exophthalmos, particularly when patients do not respond to medical treatment. Visual function has reportedly improved in up to 82% of cases.
| Differential diagnosis |
The most common differential diagnoses that should be considered in patients with exophthalmos are autoimmune, inflammatory, traumatic and neoplastic diseases. They include thyroid-associated orbitopathy, related to Graves’ disease.
Infectious conditions, such as orbital cellulitis and preseptal cellulitis, as well as vascular malformations, including carotid-cavernous fistula; Benign and malignant tumors including malignant neoplasms (eg, capillary hemangioma, neuroblastoma, leukemia, lymphoma, mucocele, pseudotumors, and secondary metastatic tumors) can give rise to metastatic deposits in the orbit.
Other rare differential diagnoses may include Crouzon syndrome and Apert syndrome. Periorbital fractures due to trauma can cause periorbital hemorrhage that can potentially protrude the eyeball.
| Forecast |
Early detection of the underlying cause of exophthalmos is vital for its resolution. Generally, any associated swelling, pain or erythema self-limits after 2-3 months, although this may vary from patient to patient.
Thyroid-related exophthalmos may take much longer or may not return to normal, and in up to 5% of cases the diplopia is permanent and worsens or maintains permanent visual impairment.
| Complications |
In general, they are related to the underlying disease. Prolonged exposure of the cornea can cause secondary exposure keratopathy if the cornea becomes very dry, especially at night, if eyelid closure is incomplete. This condition can lead to chemosis and conjunctivitis.
Corneal ulceration and keratitis may follow as additional complications. If the underlying etiology is treated early and promptly, permanent visual disturbances, such as diplopia, are rare. Other rare complications also include superior limbic keratoconjunctivitis and optic atrophy.
| Patient deterrence and education |
Patients should be aware that regular monitoring and supportive strategies will provide symptomatic relief in addition to medical or surgical treatment of the underlying cause. As such, regular lubrication of the eyes, monitoring, and commitment to the therapeutic plan established by the ophthalmologist, primary care physician, and inpatient physician will ensure that patients receive appropriate treatment.
| Improving healthcare team outcomes |
To coordinate the best outcomes for patients with thyroid-related exophthalmos, the involvement of an interdisciplinary team (ophthalmologist, primary care physicians, and endocrinologist) is important.
For a better prognosis, regular monitoring of visual function is necessary. Shared decision making for patient care management planning provides maximum benefit, taking into account the patient’s ideas, concerns and expectations.
Synergistic collaboration with the patient on their health will lead to more favorable outcomes.
