Diagnosis and Management of Ocular Myasthenia Gravis
Diagnostic Approach
Begin with bedside clinical tests—the ice pack test is highly specific and should be performed immediately in any patient presenting with fatigable ptosis or fluctuating diplopia. 1, 2
Bedside Clinical Tests
Ice pack test: Apply ice directly over closed eyelids for 2 minutes for ptosis or 5 minutes for strabismus/ophthalmoplegia. 1, 2
- Measure baseline ptosis using marginal reflex distance (MRD) and quantify ocular misalignment in prism diopters before ice application. 1
- A positive test shows improvement of ptosis by ≥2 mm or reduction in ocular deviation by ≥50% (or ≥10 prism diopters when baseline exceeds 20 PD). 1
- This test has high specificity for myasthenia gravis because cooling slows acetylcholine breakdown, allowing limited acetylcholine to remain longer in the synaptic cleft. 1
Rest test: Have the patient close their eyes for several minutes; improvement in ptosis or strabismus supports the diagnosis, though this is less standardized than the ice pack test. 1, 2
Edrophonium (Tensilon) test: Demonstrates 86% sensitivity for ocular myasthenia gravis but requires a monitored setting with atropine 0.4–0.5 mg IV readily available for muscarinic side effects (excessive tearing, salivation, bradycardia, bronchospasm). 1, 2, 3
Key Clinical Features to Identify
- Fatigable or fluctuating weakness affecting extraocular muscles, with ptosis and diplopia that worsen with sustained upgaze or at end of day. 1
- Pupils are characteristically spared—pupillary involvement should immediately prompt consideration of third nerve palsy or other etiologies, not myasthenia gravis. 1
- Look for Cogan's lid twitch sign: rapid upward overshoot of the eyelid when returning gaze from downgaze to primary position. 4
- Assess for bulbar symptoms (dysphagia, dysarthria, facial weakness) as dysphagia is present in >50% of cases preceding myasthenic crisis. 1
Serologic Testing
Anti-acetylcholine receptor (AChR) antibodies should be ordered first—positive in 40–77% of ocular myasthenia (compared to 80–85% in generalized disease). 1, 2, 5
Anti-MuSK antibodies must be tested when AChR is negative—positive in approximately one-third of seronegative patients. 1, 2, 5
Anti-LRP4 antibodies should be considered in double-seronegative patients (negative for both AChR and MuSK). 1, 2
Anti-striated muscle antibodies signal increased risk of thymoma and guide imaging decisions. 2, 5
Electrodiagnostic Studies
Single-fiber electromyography (SFEMG) is the gold standard with >90% sensitivity for ocular myasthenia gravis. 1, 2, 5
Repetitive nerve stimulation (RNS) demonstrates characteristic decremental response but is less sensitive (positive in only one-third of ocular cases). 2, 5
Essential Imaging and Ancillary Workup
Chest CT with contrast to screen for thymoma—present in 10–20% of AChR-positive patients and 0.7% of purely ocular cases. 2, 5, 6
Pulmonary function testing (negative inspiratory force and vital capacity) to establish baseline respiratory reserve, as 50–80% of ocular cases progress to generalized disease within 2 years. 1, 2, 5
Cardiac evaluation (troponin, ECG) if respiratory insufficiency or elevated creatine kinase is present to rule out myocarditis. 2, 5
Management Algorithm
Start pyridostigmine 30 mg orally three times daily and titrate to maximum 120 mg four times daily, but recognize that approximately 50% of ocular myasthenia patients show minimal response to pyridostigmine alone and will require escalation to corticosteroids. 1, 2, 5
First-Line Treatment: Pyridostigmine
- Initiate pyridostigmine 30 mg orally three times daily; gradually increase to maximum 120 mg four times daily as tolerated. 1, 2, 5
- Response limitation: Only 50% of ocular patients achieve adequate symptom control with pyridostigmine alone. 1, 2, 5
- Pyridostigmine typically has moderate effect on ptosis but poor effect on diplopia, so additional measures (prism glasses, patching one eye) are often necessary. 7
Critical FDA warning: Overdosage of pyridostigmine can result in cholinergic crisis characterized by increasing muscle weakness and respiratory muscle involvement leading to death. Distinguish cholinergic crisis (requires drug withdrawal and atropine) from myasthenic crisis (requires more intensive anticholinesterase therapy) using edrophonium testing and clinical judgment. 8
Second-Line Treatment: Corticosteroids
- Escalate to prednisone 1–1.5 mg/kg orally daily (or up to 40–60 mg/day) when ocular symptoms persist despite pyridostigmine. 1, 2, 5, 6
- Corticosteroids demonstrate superior efficacy with 66–85% positive response rates compared to pyridostigmine's 50% response rate. 1, 2, 5
- Taper over 5–6 weeks; most patients continue daily or alternate-day doses of 2.5–10 mg to prevent diplopia recurrence. 6
Evidence for early corticosteroid use: A 2003 study showed that prednisone treatment reduced the incidence of generalized myasthenia gravis to 7% at 2 years compared to 36% in untreated patients (odds ratio 0.13,95% CI 0.04–0.45). 6 This is the strongest evidence supporting early corticosteroid therapy in ocular myasthenia to prevent generalization.
Third-Line Treatment: Steroid-Sparing Agents
- Add azathioprine when steroid response is inadequate or to minimize long-term corticosteroid exposure. 1, 2
- Other options include mycophenolate mofetil, methotrexate, or biological agents (rituximab, eculizumab) for refractory cases. 9
Thymectomy Considerations
- Thymectomy is required when thymoma is identified on chest CT. 2, 5
- Thymectomy may confer symptomatic benefit in selected AChR-positive patients without thymoma, based on age and immunologic profile. 2, 5
Non-Pharmacological Management
- Prism glasses or patching one eye for diplopia, as ocular symptoms are highly variable and not readily remedied with prisms alone. 5
- Strabismus surgery should only be considered after disease stabilization, typically requiring 2–3 years of medical treatment, and must be decided in collaboration with an experienced ophthalmologist and neurologist. 5
Critical Medications to Avoid
Immediately review and discontinue medications that exacerbate myasthenia gravis: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics. 1, 2, 5
Monitoring and Prognosis
- 50–80% of patients with initial ocular symptoms will progress to generalized myasthenia gravis within a few years, most commonly within the first 2 years. 1, 2, 5, 6
- Serial pulmonary function tests (NIF, vital capacity) are essential in all patients to detect early respiratory decline. 2, 5
- Inability to count to 15 on a single breath is a reliable clinical marker of imminent respiratory insufficiency requiring urgent evaluation for myasthenic crisis. 1
- Complete remission occurs in 30% of purely ocular cases within 10 years of onset. 7
Referral and Collaborative Care
Urgent neurology referral is mandatory for any suspected myasthenia gravis—primary care clinicians should not initiate disease-specific therapy without specialist input. 2