What are the causes and treatment options for a unilateral protruding eye, also known as proptosis or exophthalmos?

Unilateral Protruding Eye: Diagnostic and Treatment Approach

Immediate Diagnostic Action

For unilateral proptosis, obtain MRI of the orbits without and with contrast as the initial imaging study to identify the underlying mass or pathologic process. 1

Differential Diagnosis Framework

Unilateral proptosis is concerning for several distinct pathologic processes that require systematic evaluation:

Primary Considerations by Location

Intraorbital masses affecting the globe, optic nerve, extraocular muscles, lacrimal glands, or orbital soft tissues are the most common causes of unilateral proptosis 1:

• Orbital tumors (benign or malignant)
• Lymphoma (diffusion-weighted MRI sequences are particularly useful for this diagnosis) 1
• Plexiform neurofibromas in children with neurofibromatosis type 1 1

Vascular abnormalities can present with isolated proptosis 1, 2:

• Carotid-cavernous fistula (CCF) presents with proptosis, orbital congestion, and chemosis in anterior-draining fistulas, or diplopia and pain in posterior-draining fistulas 1
• If standard MRI appears normal but clinical suspicion remains high, immediately obtain MRA or CTA to evaluate for CCF, as this can have devastating consequences if missed 2
• Vascular malformations anywhere within the orbit 1

Inflammatory conditions presenting unilaterally 1, 2:

• Thyroid eye disease (though typically bilateral, can be asymmetric or unilateral) 1, 3
• IgG4-related orbital disease 1, 2
• Idiopathic orbital inflammatory syndrome (IOIS) 1, 2

Skull base and cavernous sinus pathology extending into the orbit 1

Critical Clinical Features to Assess

Red Flags Requiring Urgent Evaluation

Pupillary involvement with ptosis indicates third nerve palsy and requires immediate neuroimaging with MRI or CTA to rule out posterior communicating artery aneurysm 4

Leukocoria (white pupillary reflex) indicates globe pathology including tumors, developmental processes, or infection, requiring urgent ophthalmology evaluation 1

Pulsatile exophthalmos suggests carotid-cavernous fistula or sphenoid wing dysplasia with temporal lobe herniation 1, 2

Associated Findings to Document

• Proptosis with inferior dystopia: Even with normal initial imaging, this demands vascular imaging (MRA/CTA) to exclude CCF 2
• Diplopia or strabismus: Suggests extraocular muscle involvement or neurological deficit 1
• Elevated intraocular pressure: Common with orbital masses or inflammatory conditions 1
• Eyelid edema or "bag of worms" texture: Characteristic of plexiform neurofibroma 1

Imaging Algorithm

First-Line Imaging

MRI orbits without and with contrast is the optimal initial study for nontraumatic unilateral proptosis 1:

• Superior soft tissue characterization
• Localizes and characterizes primary lesions
• Diffusion-weighted imaging useful for lymphoma 1
• Can extend to MRI head without and with contrast to assess intracranial extension or metastasis 1

Complementary Imaging

CT orbits with contrast provides complementary information 1, 2:

• Assesses orbital volumes and osseous anatomy
• Identifies calcifications missed on MRI
• Evaluates bony integrity and fractures

Vascular Imaging When Indicated

MRA or CTA urgently if CCF suspected (proptosis with orbital congestion, chemosis, or inferior dystopia) 1, 2

Digital subtraction angiography (DSA) is the gold standard if MRA/CTA negative but clinical suspicion remains high 2

Laboratory Evaluation

When inflammatory etiology suspected 2:

• Serum IgG4 levels for IgG4-related disease
• ESR and CRP
• Thyroid function tests if thyroid eye disease considered
• Consider infectious workup (syphilis, Lyme serology) based on clinical context

Treatment Approach by Etiology

Thyroid Eye Disease

• Endocrinology referral for thyroid management 5
• Timely therapy is crucial for reversing ocular manifestations 3
• Orbital decompression surgery can reduce proptosis up to 12mm in severe cases 6, 5

Orbital Tumors

• Surgical excision or biopsy based on imaging characteristics
• In children with suspected plexiform neurofibroma and known NF1, do not biopsy—confirm with MRI 1

Carotid-Cavernous Fistula

• Urgent referral to interventional neuroradiology for endovascular treatment 2

Inflammatory Conditions

• Do not start steroids without adequate workup, as this can mask diagnoses and worsen outcomes 2
• Consider corticosteroids after infectious and neoplastic causes excluded

Critical Pitfalls to Avoid

Never assume unilateral proptosis is benign—significant proptosis with or without inferior dystopia demands explanation 2

Standard brain MRI protocols may miss orbital pathology—ensure dedicated orbital imaging with thin sections was performed 2

Do not delay vascular imaging when CCF is in the differential, as delayed diagnosis can have devastating consequences 2

Failing to recognize pupil-involving third nerve palsy as a neurosurgical emergency can result in catastrophic outcomes 4

In children presenting with periorbital asymmetry or unilateral proptosis before age 5, evaluate for plexiform neurofibroma even without confirmed NF1 diagnosis 1

Monitoring Requirements

For patients with confirmed diagnosis on treatment 2:

• Serial visual acuity, color vision, and pupillary examination
• Visual field testing to monitor for compressive optic neuropathy
• Repeat imaging in 2-4 weeks if initial workup negative and empiric treatment initiated

Close cooperation between otolaryngology, endocrinology, and ophthalmology is essential for optimal management 6, 5