Ocular Myasthenia Gravis

Autoimmune neuromuscular junction disease limited to the levator palpebrae, extraocular muscles and orbicularis oculi, with fatigable weakness and no limb or bulbar involvement.

• Antibodies against the acetylcholine receptor (positive in about 50 percent of ocular cases, higher in generalised disease), muscle specific kinase (MuSK) and LRP4 reduce receptor numbers at the postsynaptic membrane.
• About 50 to 60 percent of patients presenting with ocular symptoms develop generalised disease, mostly in the first 2 years; double seronegative cases are common.
• Associated: thymoma or thymic hyperplasia, thyroid disease, other autoimmune conditions; drug triggers include fluoroquinolones, aminoglycosides, macrolides, beta blockers, magnesium and botulinum toxin.

• Variable asymmetric ptosis, worse at the end of the day or on sustained upgaze, improving with rest.
• Fluctuating diplopia, horizontal or vertical, with a pattern that does not follow a single cranial nerve.
• Any pattern of ophthalmoplegia can occur, including pseudo internuclear ophthalmoplegia, gaze palsies and pupillary sparing (pupils are always normal).
• Signs: Cogan lid twitch (overshoot of the upper lid after looking down then up to primary position), curtain sign (lifting one lid makes the other droop more), orbicularis oculi weakness (cannot bury eyelashes), peek sign, quiver movements.
• Symptoms often worsen with heat, fatigue and stress.

• Bedside:
  • Ice pack test: place ice in a glove on the closed ptotic lid for 2 minutes; improvement of 2 mm or more in lid height is positive (sensitivity about 80 percent for ptosis, lower with diplopia).
  • Rest test (2 to 5 minutes of eye closure) and sustained upgaze for 60 seconds.
• Serology: acetylcholine receptor binding antibody; if negative, MuSK and LRP4 antibodies.
• Electrophysiology: repetitive nerve stimulation (low yield in ocular disease), single fibre electromyography of the frontalis or orbicularis oculi (sensitivity above 90 percent in ocular disease).
• Imaging: CT or MRI chest for thymoma in all patients; MRI brain and orbits to exclude compression and thyroid eye disease if atypical.
• Thyroid function, antinuclear antibody, vitamin B12, and glucose before steroids; bone density and infection screening (hepatitis B, tuberculosis).
• Differential: thyroid eye disease, chronic progressive external ophthalmoplegia, third nerve palsy, Lambert-Eaton syndrome, Horner syndrome, orbital myositis, brainstem lesions.

• Avoid fluoroquinolones, aminoglycosides, macrolides, beta blockers, magnesium and botulinum toxin; educate about generalisation symptoms (dysphagia, dysarthria, dyspnoea, limb weakness) that need urgent care.
• Pyridostigmine 30 to 60 mg three to four times daily (maximum 120 mg four times daily); improves ptosis in about half of patients and diplopia less often. Side effects: cholinergic abdominal cramps, diarrhoea, bronchial secretions; glycopyrrolate 1 mg can control them.
• Prednisolone for persistent symptoms: start 10 to 20 mg daily (or on alternate days) increasing by 5 mg every 3 to 5 days to 0.5 to 0.75 mg/kg daily (maximum 60 to 80 mg), continued until remission then tapered slowly over 6 to 12 months to the lowest effective dose. Provide calcium, vitamin D, bone protection, gastric protection and glucose monitoring. Steroids reduce the risk of generalisation.
• Steroid sparing therapy: azathioprine 2 to 3 mg/kg daily (check thiopurine methyltransferase activity), mycophenolate mofetil 1 g twice daily, methotrexate 10 to 20 mg weekly with folic acid, or tacrolimus 3 mg daily. Rituximab 375 mg/m2 weekly for 4 weeks (or 1 g twice 2 weeks apart) for MuSK-positive or refractory disease.
• Thymectomy when thymoma is present, and considered for AChR-positive patients under 50 with generalised disease.
• Symptomatic ocular measures: Fresnel or ground in prisms for small stable deviations; ptosis crutches; eyelid tape; strabismus surgery after at least 6 months of stable measurements with corticosteroid therapy complete; ptosis surgery when disease is stable, with care for exposure.
• Crisis plan: generalised myasthenic crisis needs intravenous immunoglobulin 2 g/kg over 2 to 5 days or plasma exchange (5 exchanges over 10 days), with respiratory support.