How to manage unilateral proptosis with inferior dystopia and normal MRI and fundus exam?

Management of Unilateral Proptosis with Inferior Dystopia and Normal Initial Imaging

Despite normal MRI findings, this patient requires urgent vascular imaging with MRA or CTA to rule out a carotid-cavernous fistula (CCF), followed by consideration of idiopathic orbital inflammatory syndrome (IOIS) or IgG4-related disease if vascular pathology is excluded. 1

Immediate Diagnostic Priorities

Vascular Imaging is Critical

• Perform MRA or CTA urgently to evaluate for CCF, which can present with proptosis and inferior dystopia (from orbital congestion and extraocular muscle dysfunction) even when standard MRI appears normal 1
• CCFs may show secondary findings including vascular congestion within the orbit, extraocular muscle enlargement, and enlarged superior ophthalmic veins that may not be apparent on routine MRI sequences 1
• If MRA/CTA is negative but clinical suspicion remains high, proceed to digital subtraction angiography (DSA), which is the gold standard for CCF diagnosis 1

Reassess MRI Quality and Sequences

• Verify that the original MRI included contrast-enhanced sequences and dedicated orbital protocols, as MRI orbits without and with contrast is the optimal modality for orbital pathology 1
• Consider repeat MRI with specific attention to:
  • Diffusion-weighted imaging if lymphoma is a consideration 1
  • Fat-suppressed sequences to evaluate for subtle inflammatory changes 2
  • Assessment of extraocular muscles for enlargement or enhancement patterns 2

Differential Diagnosis Framework

Inflammatory Conditions (Most Likely Given Normal Initial MRI)

• IOIS and IgG4-related orbital disease are primary considerations when standard imaging appears normal but significant proptosis exists 1
• These conditions may present with unilateral proptosis and can have subtle imaging findings that require careful review 1, 2
• Obtain serum IgG4 levels to evaluate for IgG4-related disease 2
• Consider orbital biopsy if imaging and serologic workup are inconclusive, as this may be necessary to rule out lymphoma or establish definitive diagnosis 2

Vascular Malformations

• Vascular malformations can occur anywhere within the orbit and may result in proptosis, sometimes with subtle imaging findings 1
• Time-resolved MRA can characterize flow patterns and distinguish high-flow from low-flow lesions 1

Occult Mass Lesions

• Despite "normal" MRI, consider atypical lipomatous tumors or other infiltrative lesions that may be difficult to distinguish from normal orbital fat 3
• Meningiomas involving the orbital apex or sphenoid wing can present with proptosis and may be subtle on initial imaging 4

Management Algorithm

Step 1: Complete Vascular Evaluation

• Order MRA or CTA immediately 1
• If positive for CCF, refer urgently to interventional neuroradiology for potential endovascular treatment 1

Step 2: Enhanced Inflammatory Workup

• Obtain CT orbits with contrast as complementary imaging, which provides information about orbital volumes, osseous anatomy, and may reveal calcifications missed on MRI 1
• Check inflammatory markers: ESR, CRP, serum IgG4 levels 2
• Consider infectious workup including syphilis and Lyme serology if clinical context suggests 1

Step 3: Consider Biopsy

• If imaging and serologic workup remain inconclusive after steps 1-2, orbital biopsy is indicated to rule out lymphoma, IgG4-related disease, or atypical neoplasms 2, 3
• Biopsy should include tissue for histopathology, immunohistochemistry (including IgG4 staining), and flow cytometry 2

Step 4: Empiric Treatment Consideration

• If inflammatory disease is strongly suspected clinically and malignancy has been reasonably excluded, consider trial of corticosteroids as first-line treatment for IOIS 2
• Monitor closely for response; lack of improvement within 1-2 weeks should prompt biopsy 2

Critical Pitfalls to Avoid

Do Not Accept "Normal MRI" at Face Value

• A 22mm proptosis with inferior dystopia is never normal and demands explanation 1
• Standard brain MRI protocols may miss orbital pathology; ensure dedicated orbital imaging was performed 1
• Subtle findings like mild extraocular muscle enlargement or orbital fat infiltration may be overlooked on initial read 2

Do Not Delay Vascular Imaging

• CCFs can present with isolated proptosis and may have devastating consequences if missed, including vision loss from elevated intraocular pressure or compressive optic neuropathy 1
• Posterior-draining CCFs may have subtle clinical findings but still cause significant orbital pathology 1

Do Not Start Steroids Without Adequate Workup

• While corticosteroids are first-line for IOIS, starting them before ruling out infection, malignancy (especially lymphoma), or vascular pathology can mask diagnoses and worsen outcomes 2
• Lymphoma can mimic inflammatory disease and may initially respond to steroids, delaying definitive diagnosis 1, 2

Consider Orbital Hemorrhage

• Spontaneous orbital hemorrhage, particularly involving the inferior rectus muscle or its sheath, can cause acute proptosis with inferior dystopia and may resolve spontaneously 5
• This diagnosis requires careful review of imaging for blood products and clinical correlation with timing of symptom onset 5

Monitoring and Follow-up

• Repeat imaging in 2-4 weeks if initial additional workup is negative and empiric treatment is initiated 2
• Monitor for development of compressive optic neuropathy with serial visual acuity, color vision, pupillary examination, and visual field testing 1, 2
• If proptosis worsens or vision deteriorates, urgent ophthalmology and orbital surgery consultation is mandatory 1, 2