Treatment of Ocular Myasthenia With Corticosteroids: Yes

O CULAR findings often represent the first, and sometimes the sole manifestation of acquired MG. Ocular MG, with weakness restricted to the ocular muscles, is generally considered a mild subtype of MG. Nonetheless, the diagnosis and management of purely ocular MG may be particularly challenging and frustrating. Diplopia and ptosis, resulting from dysfunction of neuromuscular junctions (NMJs) of extraocular skeletal muscles and levator palpebral muscles in ocular MG, often impair vision sufficiently to interfere with work and quality of life. Whereas ocular symptoms are often the presenting symptoms of MG, they also tend to be the symptoms most refractory to treatment. Response to anticholinesterases is often incomplete, and pharmacological suppression of the NMJ immune attack or thymectomy is often required for resolution of symptoms. The judicious use of corticosteroids represents a key component of management of individual patients with ocular MG. A second consideration is that half the patients with MG, with weakness restricted to ocular muscles clinically, reveal decrement on repetitive nerve stimulation in extremity muscles. Furthermore, most patients with purely clinical ocular MG at the onset of disease develop generalized weakness, especially within the first year. This represents a subgroup of patients with ocular MG at risk for rapid deterioration. Myasthenic crisis is better prevented than treated. In this context, immune treatment is warranted in individual patients with ocular MG and electrophysiological evidence of generalized MG. A third consideration arises from recent observations suggesting that withholding immune treatment in mild ocular MG may predispose to severe disease. Myasthenia gravis commences with ocular symptoms in 75% of patients, a susceptibility that may be related to antigenic structure and/or a reduced safety factor at the ocular muscles. Generalized MG may result from increased antibody production and expansion of antigenic molecular targets. Patients treated with immune intervention early in the course of ocular MG are less likely to develop generalized disease. The duration of the initial period of NMJ immune attack may be an important determinant for subsequent severity of disease. Correlation of increased duration and severity of subsequent disease with the duration of the initial immune attack occurs in other autoimmune conditions, including relapsing experimental autoimmune encephalomyelitis. It is possible that an unchecked immune response in ocular MG leads to structural changes in selfantigens at the NMJ and destruction of the NMJ architecture. In turn, exposure of novel antigens may potentiate the autoimmune attack, leading to disease persistence and increased disease severity. Symptomatic treatment with anticholinesterases may improve clinical symptoms but mask ongoing autoimmune damage. Abrogation of the immune attack would limit end organ damage and resultant long-term immune stimulation,constitutinganadditional reason to support the use of immune treatments in selected patients early in the course of the disease. Patients with MG treated with corticosteroids require close supervision.Optimally, corticosteroidsare used to help induce and maintain a clinical remission. Remission induction generally requires high oral doses for a period of 2 to 3 months. Potential complications include MG worsening during the first 2 weeks of therapy, asepticbonenecrosis,hyperglycemia,hypertension,osteoporosis, immune compromise, psychological disturbance, growth retardation inchildren, cataracts, glaucoma, proximalmyopathy,anddysmorphic soft tissue changes. Complications are to be identified and treated early; they are best prevented. Ancillary treatmentssuchaselandronatetoprevent osteoporosis are useful. Most steroid complications correlate with cumulativedose.Animportantmeans to prevent complications in patients receiving steroids is to limit the totalsteroiddose.Thismaybeachieved, and relapses kept to a minimum, by dose reduction in a slow, monitored fashionoverseveralmonths.Alternateday therapy reduces hypothalamicpituitary suppression. Additional strategies that may limit the need for long-term high steroid doses include thymectomy early in the course of the disease, as well as azathioprine during the period of steroid dose reduction. The differential diagnosis of ocular MG includes oculopharyngeal dystrophy, mitochondrial disorders, congenital MG and other NMJ disorders, oculomotor neuropathies, and brainstem lesions. In autoimmune ocular MG, the usual laboratory findings that support a diagnosis of MG may be absent. SeFrom the Department of Neurology, University of California, Davis. CONTROVERSIES IN NEUROLOGY