Title: Pre-Treatment Considerations for Ocular Myasthenia Gravis

Managing ocular myasthenia gravis effectively requires a comprehensive and well-planned approach before initiating treatment. Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission, and when it manifests in the ocular muscles, it can lead to symptoms such as ptosis and diplopia. Understanding the treatment options and necessary precautions is essential for optimizing patient outcomes.

Pharmacological Treatment Options

Anticholinesterase Medications

Anticholinesterase drugs are the cornerstone in managing myasthenia gravis. These medications work by inhibiting acetylcholinesterase, thereby increasing the availability of acetylcholine at the neuromuscular junction. This enhances nerve-muscle communication and alleviates symptoms. Commonly prescribed drugs include neostigmine, pyridostigmine, and ambenonium chloride.

Neostigmine is typically administered in doses of 15–45 mg, taken three to four times daily. While effective, it has a shorter duration of action and may cause muscarinic side effects like abdominal cramps and diarrhea. These can be mitigated by co-administering atropine. Pyridostigmine, often prescribed at 60 mg three times daily, offers a longer duration of action and fewer side effects, making it suitable for long-term management. Ambenonium, with a longer half-life but a narrower safety margin, should be initiated at low doses (5–10 mg three times daily) to avoid toxicity.

For ocular symptoms, especially ptosis, 0.5% to 1% pyridostigmine eye drops are considered the first-line local treatment. Adjunctive agents such as ephedrine, guanidine, and spironolactone can enhance anticholinesterase effects by increasing free acetylcholine at nerve terminals. Calcium supplements also play a supportive role in maintaining intracellular calcium levels, which is crucial for neuromuscular function. However, certain drugs—including CNS depressants, antiarrhythmics, and aminoglycoside antibiotics—should be avoided as they interfere with acetylcholine activity and may exacerbate symptoms.

Corticosteroids

Corticosteroids like prednisone are widely used for both generalized and ocular forms of MG. They function by modulating immune activity, including suppressing thymic germinal centers, reducing autoantibody production, and enhancing acetylcholine release. Clinical studies have shown that prednisone therapy can significantly improve ocular symptoms, with ptosis improving within 6–18 days and ophthalmoplegia resolving in 18–26 days.

Two main dosing strategies are employed: the incremental method, starting at 10–20 mg/day and gradually increasing to 70–100 mg before switching to alternate-day dosing, and the decremental method, beginning with high-dose prednisone (100–200 mg) or dexamethasone (10–15 mg), followed by a gradual taper after symptom improvement. Long-term use requires careful monitoring for side effects such as weight gain, immunosuppression, and gastrointestinal bleeding. Patients should also follow a high-protein diet, restrict sodium, and take potassium supplements and antacids as needed.

Other Immunosuppressive Agents

Additional immunosuppressive therapies include cyclophosphamide, azathioprine, and 6-mercaptopurine. These are often used in combination with corticosteroids to reduce steroid dependence and minimize side effects. Regular monitoring of blood counts and clotting parameters is essential when using these medications.

Combination Therapy

Combining pyridostigmine, prednisone, and cyclophosphamide at half the standard doses, followed by a gradual taper over six months, offers several advantages. It reduces overall drug burden, lowers the risk of complications such as infection and muscle weakness crises, and provides better long-term disease control with a lower recurrence rate.

Thyroid-Modulating Drugs

Since hyperthyroidism can exacerbate MG symptoms, managing concurrent thyroid dysfunction is crucial. Antithyroid medications like methimazole or propylthiouracil are often prescribed to stabilize thyroid function, which may lead to improved MG outcomes.

Non-Pharmacological Treatment Approaches

Plasmapheresis

Plasmapheresis removes pathogenic antibodies from circulation and can provide rapid, albeit temporary, relief. However, due to the transient nature of its effects and the need for repeated sessions, it is typically reserved for acute exacerbations or preoperative preparation.

Radiation Therapy

Low-dose whole-body irradiation can suppress lymphocyte activity and may be considered for patients not suitable for thymectomy. A typical regimen involves 2 Gy doses administered every other day, with a total cumulative dose of 3–5 Gy.

Surgical Interventions

Thymectomy

Thymectomy is particularly beneficial for patients under 40 years old with a disease duration of less than five years and inadequate response to medical therapy. It is also the treatment of choice for thymoma. While it can significantly improve symptoms, postoperative exacerbations and myasthenic crises are possible, requiring close monitoring and emergency preparedness.

Corrective Surgery for Ocular Symptoms

For patients with persistent ptosis or strabismus unresponsive to medication, surgical correction may be considered. Criteria for surgery include stable symptoms for at least six months, lack of response to anticholinesterase agents, and presence of amblyopia risk or significant diplopia. Procedures include frontalis suspension for ptosis and muscle repositioning for strabismus.

Management of Amblyopia

In children under five, prompt treatment of amblyopia is critical, especially when ptosis or strabismus is present. Early intervention alongside MG therapy can prevent permanent visual impairment.

Prognosis and Long-Term Outlook

The prognosis of ocular MG varies. While some patients experience spontaneous remission, others may progress to generalized MG. Historical data indicates that 50% of MG cases initially present with ocular symptoms, and within one month, 40% remain ocular-only while another 40% develop generalized weakness. Without proper treatment, mortality rates were historically high (30–60%), but the introduction of anticholinesterase inhibitors and thymectomy has significantly improved survival.