Orbital Apex Syndrome

Orbital apex syndrome is a constellation of neuro ophthalmic signs caused by a lesion at the orbital apex, where the optic nerve (cranial nerve II), oculomotor (III), trochlear (IV), the ophthalmic division of the trigeminal (V1), abducens (VI), and sympathetic fibres converge. The distinguishing feature is optic neuropathy in addition to ophthalmoplegia.

• Related syndromes: superior orbital fissure syndrome (the same cranial nerves III, IV, V1, VI without optic nerve involvement) and cavernous sinus syndrome (also V2 sensory loss and often bilateral).
• Causes:
  • Infection: invasive fungal sinusitis (mucormycosis, Aspergillus), bacterial sinusitis with orbital extension, herpes zoster, tuberculosis, and syphilis.
  • Inflammation: idiopathic orbital inflammation, Tolosa-Hunt syndrome, IgG4-related disease, sarcoidosis, granulomatosis with polyangiitis, giant cell arteritis, and thyroid eye disease with compressive neuropathy.
  • Neoplasm: meningioma, nasopharyngeal carcinoma, lymphoma, adenoid cystic carcinoma, schwannoma, metastases, and pituitary tumour extension.
  • Vascular: carotid cavernous fistula, aneurysm, and cavernous thrombosis.
  • Trauma with fracture and haematoma.
• Risk factors for fungal disease: diabetes with ketoacidosis, haematological malignancy, transplantation, neutropenia, steroids, and iron overload.

• Visual loss, relative afferent pupillary defect, dyschromatopsia, and optic disc swelling or pallor (or a normal disc in retrobulbar disease).
• Ophthalmoplegia (partial or complete), ptosis, diplopia, and dilated or fixed pupil (III and sympathetic).
• Loss of sensation over the forehead and cornea (V1), with reduced corneal reflex.
• Proptosis and chemosis when the lesion is anterior or when there is orbital spread; absent in some infiltrative or posterior apical lesions.
• Pain behind the eye and headache, particularly in inflammatory, infective, and Tolosa-Hunt disease.
• Features of the cause: black eschar of the nasal mucosa (mucormycosis), jaw claudication (arteritis), zoster rash, and cranial polyneuropathy.

• Neuro ophthalmic assessment with acuity, colour vision, visual fields, pupils, motility, sensation, and fundus; measure proptosis.
• MRI of orbits, cavernous sinus, and brain with gadolinium and fat suppression (best for apex and soft tissue), with MR angiography or CT angiography for vascular causes; CT with bone windows for fracture and bone destruction.
• Laboratory: full blood count, glucose and HbA1c, ketones, inflammatory markers (ESR, CRP), ANCA, ANA, angiotensin converting enzyme, IgG4, serum syphilis and tuberculosis tests, HIV, thyroid function, and blood cultures.
• Nasal endoscopy with biopsy and culture for fungal disease (frozen section for hyphae); orbital biopsy for refractory or atypical disease; lumbar puncture for meningeal disease.
• Chest imaging for sarcoidosis and tuberculosis.

• Urgent, cause directed treatment because the optic nerve is at risk.
• Invasive fungal infection (a surgical and medical emergency): liposomal amphotericin B 5 mg/kg/day intravenously (up to 10 mg/kg/day for cerebral disease), with correction of hyperglycaemia, ketoacidosis, and neutropenia, withdrawal of immunosuppression, and repeated surgical debridement (endoscopic sinus surgery, sometimes orbital exenteration); step down to isavuconazole 372 mg (as isavuconazonium) every 8 hours for 6 doses then 372 mg daily, or posaconazole 300 mg every 12 hours for 2 doses then 300 mg daily. Aspergillus: voriconazole 6 mg/kg every 12 hours for 2 doses then 4 mg/kg every 12 hours.
• Bacterial sinusitis with orbital spread: intravenous ceftriaxone 2 g every 12 hours, vancomycin 15 mg/kg every 8 to 12 hours, and metronidazole 500 mg every 8 hours, with drainage.
• Herpes zoster: intravenous aciclovir 10 mg/kg every 8 hours for 7 to 10 days then oral valaciclovir 1 g three times daily, with corticosteroids for inflammation.
• Inflammatory and idiopathic disease: methylprednisolone 1 g intravenously daily for 3 days (or prednisolone 60 to 80 mg daily orally for severe optic neuropathy), tapering over 6 to 12 weeks; steroid sparing agents (methotrexate 15 to 25 mg weekly, azathioprine 2 mg/kg daily, mycophenolate 1 g twice daily, or rituximab 1 g twice 2 weeks apart) for relapsing disease, IgG4-related disease, and granulomatosis with polyangiitis (rituximab 375 mg/m2 weekly for 4 weeks with prednisolone). Tolosa-Hunt syndrome typically responds to prednisolone 1 mg/kg within 72 hours, and non-response mandates re-evaluation for malignancy or infection.
• Giant cell arteritis: immediate methylprednisolone 1 g intravenously daily for 3 days and prednisolone 1 mg/kg daily with tocilizumab.
• Neoplasm: biopsy, radiotherapy, chemotherapy, or surgical decompression according to histology (lymphoma by rituximab based chemotherapy; nasopharyngeal carcinoma by chemoradiotherapy).
• Vascular: endovascular treatment of carotid cavernous fistula; anticoagulation for cavernous thrombosis with antibiotics.
• Decompression of the orbital apex and optic canal for traumatic and compressive optic neuropathy.
• Monitoring: serial visual function (acuity, colour, fields), pupils, and imaging; the visual prognosis depends on speed of treatment.
• Complications: permanent blindness, ophthalmoplegia, neuropathic pain, exposure keratopathy, cerebral extension, and death in fungal disease.