Proptosis

Proptosis (exophthalmos) is forward displacement of the globe, measured by exophthalmometry (over 21 mm, or a difference of 2 mm or more between eyes). It signals disease of the orbit, or occasionally the cavernous sinus or skull base.

Anatomy. The bony orbit contains the globe, extraocular muscles, optic nerve, fat, lacrimal gland, vessels and nerves, enclosed by the septum anteriorly and the superior orbital fissure and optic canal posteriorly. Increased orbital volume pushes the globe forward; direction of displacement points to the site of the lesion.

Classification. Unilateral or bilateral, acute (hours to days), subacute (weeks), chronic (months to years), and pulsatile or non-pulsatile. By cause: inflammatory (thyroid eye disease, idiopathic orbital inflammation), infective (orbital cellulitis), vascular (carotid cavernous fistula, varix, haemorrhage), neoplastic (primary and secondary), traumatic, and pseudoproptosis (axial myopia, lid retraction, contralateral enophthalmos).

Key distinctions. Bilateral progressive proptosis with lid retraction and lid lag indicates thyroid eye disease. Fever, pain and restricted movement indicate orbital cellulitis. Pulsatile proptosis with a bruit and red eye indicates carotid cavernous fistula. Axial displacement indicates a retrobulbar mass; inferomedial displacement indicates a lacrimal gland lesion.

History.

• Speed of onset, laterality, pain, redness, double vision, reduced vision, colour desaturation, eyelid swelling, headache and fever.
• Recent sinus or dental infection, trauma, and childhood onset.
• Thyroid symptoms (weight loss, palpitations, heat intolerance, tremor), previous thyroid disease, and smoking.
• Cancer history, weight loss, bruit or pulsation, and systemic disease.

Examination. Vital signs, visual acuity, colour vision (Ishihara), pupils (relative afferent defect), visual fields, eye movements (restriction, pain), exophthalmometry (Hertel), lid position (retraction, lag), chemosis and injection.

Cornea (exposure), intraocular pressure (rises on upgaze in restrictive myopathy), fundus (disc swelling, choroidal folds), globe displacement direction.

Orbital palpation (mass, thrill), auscultation (bruit), resistance to retropulsion, Valsalva effect, sinuses, nose and teeth, thyroid, skin (rash), and neurological examination.

Red flags

• Reduced vision, colour desaturation or relative afferent pupillary defect (optic neuropathy)
• Fever with painful restricted movement and lid swelling (orbital cellulitis)
• Sudden proptosis after trauma or with severe pain (retrobulbar haemorrhage, emergency)
• Pulsatile proptosis, bruit or red eye with dilated vessels (carotid cavernous fistula)
• Corneal exposure and ulceration
• Child with rapid proptosis (rhabdomyosarcoma, neuroblastoma, leukaemia, orbital cellulitis)
• Diabetes or immunosuppression with black necrotic mucosa (mucormycosis)
• Headache, cranial nerve palsies or neurological signs (cavernous sinus, skull base)
• Cancer history or weight loss

Special groups. Children: orbital cellulitis, capillary haemangioma, dermoid, rhabdomyosarcoma, leukaemia, neuroblastoma metastasis, and Langerhans cell histiocytosis. Pregnancy: thyroid eye disease and venous sinus thrombosis. Older adults: lymphoma, metastasis and thyroid disease. Region specific: Burkitt lymphoma, tuberculosis, mucormycosis and aspergillosis.

Inflammatory

• Thyroid eye disease (Graves), idiopathic orbital inflammatory syndrome (orbital pseudotumour), myositis, dacryoadenitis
• IgG4 related disease, sarcoidosis, granulomatosis with polyangiitis, giant cell arteritis, vasculitis
• Langerhans cell histiocytosis, Erdheim Chester disease, Rosai Dorfman disease

Infective

• Preseptal and orbital cellulitis, subperiosteal abscess, orbital abscess, cavernous sinus thrombosis
• Mucormycosis, aspergillosis, tuberculosis, actinomycosis, parasitic (cysticercosis, hydatid)

Vascular

• Carotid cavernous fistula (direct and dural), orbital varix, cavernous haemangioma, lymphatic malformation, arteriovenous malformation
• Retrobulbar haemorrhage, orbital haematoma, subperiosteal haematoma

Neoplastic

• Primary: cavernous haemangioma, capillary haemangioma, schwannoma, neurofibroma, optic nerve glioma, optic nerve sheath meningioma, lacrimal gland tumours (pleomorphic adenoma, adenoid cystic carcinoma), lymphoma, dermoid cyst, rhabdomyosarcoma
• Secondary: sinonasal, nasopharyngeal and skull base tumours, meningioma (sphenoid wing), pituitary adenoma
• Metastasis: breast, lung, prostate, melanoma, neuroblastoma, leukaemia

Traumatic and structural

• Orbital fracture with emphysema or haematoma, foreign body, mucocoele (sinus), encephalocele

Pseudoproptosis

• Axial myopia, buphthalmos (congenital glaucoma), lid retraction, contralateral enophthalmos, facial asymmetry and shallow orbits (craniosynostosis)

Reasoning. Quantify proptosis and look for optic nerve compromise. Image the orbit in nearly all cases and use the pattern of enlargement (muscle, lacrimal gland, retrobulbar, optic nerve) to narrow the diagnosis.

First line. Visual acuity, colour vision, pupils, fields, exophthalmometry, motility, fundus and intraocular pressure.

Targeted tests.

• CT orbits with contrast for bone, sinus disease, trauma and abscess; MRI orbits with gadolinium and fat suppression for soft tissue, optic nerve, cavernous sinus and intracranial extension; MR or CT venography and digital subtraction angiography for carotid cavernous fistula; ultrasonography with Doppler for vascular lesions.
• Thyroid stimulating hormone, free thyroxine and thyroid receptor antibodies for thyroid eye disease.
• Full blood count, ESR, C reactive protein, blood cultures and glucose for infection; ANCA, antinuclear antibody, angiotensin converting enzyme, serum IgG4 and immunoglobulins; chest radiograph or CT.
• Biopsy (incisional or excisional) for undiagnosed masses and for inflammation not responding to treatment; fine needle aspiration for selected lesions; lymphoma staging and bone marrow when indicated.
• Fungal stains and cultures and urgent nasal endoscopy with biopsy for suspected mucormycosis.
• Urine catecholamines and MIBG for suspected neuroblastoma.

Limitations. Exophthalmometry varies between observers and instruments. Imaging may not separate inflammation from lymphoma without biopsy.

Emergencies.

• Retrobulbar haemorrhage with vision loss or high pressure: emergency lateral canthotomy and cantholysis (do not delay for imaging), then IV acetazolamide 500 mg, IV mannitol 20 percent 1 to 2 g/kg over 30 minutes, and methylprednisolone 500 mg to 1 g IV, with ophthalmology.
• Orbital cellulitis: admit.
• Ceftriaxone 2 g IV every 12 hours (children 50 mg/kg every 12 hours, maximum 2 g) plus metronidazole 500 mg IV every 8 hours (children 7.5 mg/kg every 8 hours).
• Add vancomycin when meticillin resistant Staphylococcus aureus is possible (25 to 30 mg/kg IV loading dose, maximum 3 g, then 15 to 20 mg/kg every 8 to 12 hours adjusted to creatinine clearance and levels).
• Urgent CT, ENT and ophthalmology, and drainage for abscess or failure to improve in 24 to 48 hours.
• Mucormycosis: immediate ENT, ophthalmology and infectious disease referral; liposomal amphotericin B 5 mg/kg IV daily (up to 10 mg/kg with CNS disease), glycaemic control, and urgent surgical debridement.
• Cavernous sinus thrombosis: IV antibiotics (ceftriaxone 2 g IV every 12 hours plus metronidazole 500 mg IV every 8 hours) and anticoagulation by specialist decision (enoxaparin 1 mg/kg subcutaneously every 12 hours, adjusted when creatinine clearance is under 30 mL/min).

Thyroid eye disease. Restore and maintain a euthyroid state (carbimazole 15 to 40 mg orally daily then titrate, or block and replace; monitor blood count). Radioiodine can worsen disease and requires prednisolone cover, 0.3 to 0.5 mg/kg daily.

Stop smoking, and use lubricants, head elevation and sunglasses. In mild disease, give selenium 100 micrograms orally twice daily for 6 months.

Moderate to severe or active disease:

• Methylprednisolone 500 mg IV weekly for 6 weeks then 250 mg weekly for 6 weeks (cumulative dose under 8 g, with liver function monitoring).
• Orbital radiotherapy, teprotumumab or other biologics by specialists.
• Rehabilitative surgery (orbital decompression, strabismus surgery, lid surgery) after the disease is inactive for at least 6 months.

Sight threatening disease (optic neuropathy or corneal breakdown): methylprednisolone 500 mg to 1 g IV daily for 3 days and urgent orbital decompression.

Idiopathic orbital inflammatory syndrome and IgG4 related disease. Prednisolone 40 to 60 mg orally daily (or 1 mg/kg), with slow taper over several weeks to months, after infection and lymphoma are excluded by biopsy; steroid sparing agents (methotrexate, rituximab) by specialists. Sarcoidosis and granulomatosis with polyangiitis: specialist immunosuppression (prednisolone 1 mg/kg daily with rituximab or cyclophosphamide for vasculitis).

Carotid cavernous fistula. Interventional neuroradiology: endovascular embolisation. Low flow dural fistulas may be observed with ocular pressure monitoring.

Tumours. Biopsy and multidisciplinary oncology care: surgical excision (cavernous haemangioma, schwannoma, benign lacrimal gland tumours), radiotherapy (lymphoma, optic nerve sheath meningioma), chemotherapy (rhabdomyosarcoma, lymphoma, metastasis), and observation for stable benign lesions. Capillary haemangioma threatening vision: propranolol 1 to 3 mg/kg daily in 2 to 3 divided doses (specialist; monitor glucose, heart rate and blood pressure) or timolol 0.5 percent gel.

Corneal protection (all patients with exposure). Lubricants (hypromellose 0.3 percent or carbomer gel every 1 to 2 hours; ointment at night), taping the lids at night, and tarsorrhaphy when persistent.

Raised intraocular pressure. Topical timolol 0.5 percent twice daily (avoid in asthma, heart block, bradycardia) or dorzolamide 2 percent three times daily.

Traumatic causes. Orbital fracture repair when indicated, foreign body removal, and tetanus prophylaxis.

Monitoring. Visual acuity, colour vision, fields, pupils and exophthalmometry at each review (weekly in active thyroid eye disease). Repeat imaging for tumours as directed by specialists.

Referral and escalation. Immediate ophthalmology, ENT and neurosurgery for orbital cellulitis, optic neuropathy, haemorrhage, or intracranial extension. Endocrinology for thyroid eye disease. Oncology for tumours. Interventional neuroradiology for fistulas.

Admission criteria. Orbital cellulitis, retrobulbar haemorrhage, optic neuropathy, cavernous sinus disease, mucormycosis, rapidly progressive proptosis, or suspected malignancy needing urgent work up.

Discharge and safety netting. Return for reduced vision, colour fading, double vision, increasing pain or swelling, fever, corneal pain or discharge, severe headache, or new neurological symptoms.