Ocular Myasthenia in Seniors: A Case for Treatment
Abstract & Commentary
By Marc Dinkin, MD, Assistant Professor of Ophthalmology, Division of Neuro- Ophthalmology, Weill Cornell Medical College. Dr. Dinkin reports no financial relationships relevant to this field of study.
Synopsis: Immunomodulatory therapy reduces the rate of conversion to generalized myasthenia gravis in seniors with pure ocular myasthenia.
Source: Allen JA, Scala S, Jones HR. Ocular myasthenia in a senior population: Diagnosis, therapy and prognosis. Muscle Nerve 2009 Nov 13. [Epub ahead of print].
Myasthenia gravis (mg) is an autoimmune disorder that targets the acetylcholine receptor at the neuromuscular junction, causing fatigable weakness. Clinical presentation ranges from isolated fluctuating ptosis and strabismus (ocular myasthenia gravis [OMG]) to systemic fatigable weakness (generalized myasthenia gravis [GMG]), which may affect ambulation, swallowing and respiration. Early epidemiological studies led to the impression that myasthenia was rare after the age of 70, but more recent studies, including a prospective analysis,1 showed that the incidence rates were actually higher in patients older than 65 and that 46.2% of patients were older than 70 years of age.
The risk of conversion of OMG to GMG is highest in the first two years after diagnosis.2 For patients with pure OMG, the use of immunomodulatory therapy has been controversial, since the potential side effects could outweigh the benefits of ptosis and diplopia reduction. However, one retrospective analysis of 94 patients with OMG found that treatment with prednisone reduced the conversion to GMG at two years from 36% to 7%.≥ Additionally, the presence of a positive acetylcholine receptor antibody titer increased the chances of conversion from 14% to 48%. There is some evidence that seniors with OMG have a high rate of progression to GMG within 5 years4 and a greater risk of respiratory crisis and death if older than 50.2
Allen et al have retrospectively reviewed their institution's experience with OMG in patients older than 70 years of age and found relatively bright outlook for this population. In their study, 43% of seniors with myasthenia presented with ocular symptoms only. Of these patients, only 31% went on to develop GMG over a mean follow-up period of 47 months, a smaller conversion rate than the 50% rate observed in some non-senior studies. In contrast to observations in non-senior studies,sup> the authors were not able to show that antibody status affected conversion rate to GMG.
A majority of senior patients who presented with OMG were treated with immunomodulation, mostly prednisone or azathioprine, but a good many were not treated until after they generalized. There was only an 8% rate of side effects requiring discontinuation and 49% of patients were in complete remission at the last available follow-up. Most significantly, the authors found a powerful effect of initial treatment on conversion rate to GMG in seniors with OMG (7% if treated and 46% if untreated). Furthermore, 79% of the treated patients achieved remission of the ocular symptoms, in contrast to only 5% of the untreated patients. Once untreated OMG patients generalized, the remission rate with treatment decreased to 54%. The authors also noted that in women with a second auto-immune disorder, usually thyroid disease, the rate of conversion to GMG was much higher.
Commentary
Despite evidence that immunotherapy can reduce the risk of conversion to GMG in ocular myasthenics, its use has remained controversial since ocular symptoms themselves are not life-threatening. In the elderly population, practitioners may be even more judicious with the use of steroids. As this study shows, however, patients older than 70 years of age with pure OMG are likely to benefit from immunotherapy just as younger patients do. Moreover, this effect on conversion rate appears to last 4-5 years in this population. Since patients who generalized required higher doses of steroids than OMG patients who were treated initially, and enjoyed less effect on remission, a strong case for early treatment is made. Treatment's profound effect on the remission of ocular symptoms, which may be quite disabling in the elderly, buttressed that argument furthermore.
The ability of corticosteroids, not only to reduce inflammation in myasthenia gravis, but also to increase the expression of acetylcholine receptors in cultured human muscle cells was discussed. This in vitro observation may contribute to the reduction in conversion rate by early steroid treatment, but the duration of the effect in vivo remains unclear. Would patients treated with steroids for a limited time return to the non-treated rate of conversion, or would a long-lasting effect on receptor density decrease the rate?
The study is limited by its retrospective design, so that biases on who went into remission based on knowledge of treatment may have been introduced. A prospective, double-blind, placebo-controlled trial would provide stronger data but would be difficult to conduct given the positive retrospective evidence for treatment. The authors finding that acetylcholine-receptor antibody status did not affect conversion rate differs from some prior reports, but may simply reflect a sample size too small to detect such a difference. Despite these limitations, this paper provides an important description of OMG in seniors and makes a convincing argument that outcomes in this population are better than previously thought, especially in those who are treated early with immunomodulatory therapy.
References
1. Aragonès JM, Bolíbar I, Bonfill X, et al. Myasthenia gravis: A higher than expected incidence in the elderly. Neurology 2003;60:1024-1026.
2. Bever CT Jr., Aquino AV, Penn AS, et al. Prognosis of ocular myasthenia. Ann Neurol 1983;14:516-519.
3. Kupersmith MJ, Latkany R, Homel P. Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol 2003;60:243-248.
4. Antonini G, Morino S, Gragnani F, et al. Myasthenia gravis in the elderly: A hospital based study. Acta Neurol Scand 1996;3:260-262.
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