By Michael Rubin, MD

Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

SYNOPSIS: More than two-thirds of patients with ocular myasthenia will have a positive antibody test, and a high level may predict progression to generalized disease.

SOURCE: Peeler CE, et al. Clinical utility of acetylcholine receptor antibody testing in ocular myasthenia gravis. JAMA Neurol 2015;72:1170-1174.

Among patients with generalized myasthenia gravis (GMG), 80-90% have antibodies against the acetylcholine receptor (AchR Ab), 5-8% have antibodies against muscle-specific kinase (MuSK), and the remainder are “seronegative.” Among patients with ocular myasthenia gravis, AchR Ab seropositivity is approximately 50%, with a few case reports of MuSK Ab positivity, and even fewer with positive LRP4 (low-density lipoprotein receptor-related protein 4) antibodies. Are these results accurate, and do they correlate with progression to generalized myasthenia?

Following institutional review board approval, a retrospective observational cohort study was performed on 223 ocular myasthenia gravis patients seen by the Neuro-Ophthalmology Service, Massachusetts Eye and Ear Infirmary, and the Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, between July 1986 and May 2013. Data extracted included gender, age at symptom onset, ocular symptoms of ptosis and/or diplopia, duration of follow-up, and, if relevant, time to progression to GMG. AchR binding antibody testing was performed on all, with values > 0.02 nmol/L considered positive. Statistical analysis included two-sample t tests, multiple logistic regression, Kaplan-Meier estimates, and log-rank tests.

Of 223 ocular myasthenia patients, 62.3% (n = 139) and 37.7% (n = 84) were male and female, respectively, with a mean age at diagnosis of 59.2 years. Ptosis or diplopia alone were seen in 11.2% and 34.1%, respectively, with 54.7% having both ptosis and diplopia. AchR binding antibody was positive in 70.9% (n = 158), more frequent in men than women, with a mean level of 6.13 nmol/L. Progression to GMG occurred in 20.2% during a mean follow-up of 5 years. Older age at diagnosis (61.1 years vs 54.7 years in seronegative patients) and progression to GMG were significantly associated with seropositivity, and progression to GMG correlated with significantly higher antibody levels, 12.7 nmol/L compared to 4.2 nmol/L, in those who did not generalize. This is the first report to note an association between elevated AchR antibody levels and progression from ocular to generalized myasthenia.

COMMENTARY

What is safe, effective, and tolerable therapy for ocular myasthenia gravis? EPITOME (Effectiveness of Prednisone for the Treatment of Ocular Myasthenia) recently addressed this question in a superbly designed, double-blind, randomized, parallel-group, controlled trial among six academic centers across Canada and the United States.

Unfortunately, after 34 months, a mere 11 patients were randomized, with only nine completing the 16 weeks of therapy. Among 145 patients asked to participate, 107 failed prescreening and 23 declined. Of the remaining 15 OMG patients of new or recent onset who failed pyridostigmine and had not previously received immunosuppressive or immunomodulating therapy, 11 were randomized to receive either placebo or prednisone 10 mg daily, increased to a maximum of 40 mg/day over 16 weeks. Prednisone resulted in improvement over a median of 14 weeks, at an average dose of 15 mg/day, with infrequent and mild adverse effects.1

It is disappointing that so little return was achieved for such a herculean effort. Indeed, there are more authors on this paper than participants in the study. Thus, one wonders why a letter to the editor would not have sufficed to disseminate this small study.

REFERENCE

  1. Benetar M, et al. Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): A randomized controlled trial. Muscle Nerve 2015; July 14. doi: 10.1002/mus.24769 [Epub ahead of print].