Thymic Abnormalities, Positive AChR Antibodies Associated With Generalized MG

A new study published in the Journal of Ophthalmology found that patients with ocular myasthenia gravis (OMG) should be routinely assessed for thymic abnormalities and positive acetylcholine receptor antibody (AChR Ab), as they were both associated with the development of generalized MG (GMG). Additional risk factors for the development of GMG included smoking.¹

AChR Ab are mediators of OMG, which targets neuromuscular function in those affected, primarily causing ptosis or binocular diplopia. Progression to GMG is common in patients with OMG,² which can lead to other parts of the body also experiencing muscular weakness, including limbs and respiratory muscles. The conversion of OMG to GMG has previously been studied, but is not completely understood. This study aimed to identify the factors associated with the conversion of OMG to GMG in order to help prevent that progression.¹

Patients diagnosed with OMG at the Siriaj Hospital between January 2007 and December 2019 were considered for this study. Patients were eligible if they had fluctuating and fatigable weakness of ocular muscles, had a positive test result for diagnosis, and had an official diagnosis from a neuro-ophthalmologist or neurologist. Patients with congenital or juvenile OMG, incomplete records regarding the onset of OMG or GMG, had presented with symptoms of GMG, had prior eyelid or strabismus surgery, had incomplete medical data, or had thyroid-associated ophthalmopathy were excluded from the study.

Electronic medical records were used to extract demographic data. All patients were monitored through the conversion to GMG or until their last follow-up visit. Patients who developed any muscle weakness in their limbs, axial, or facial muscles were considered to have converted to GMG.

There were 200 patients who were included in the study who had a diagnosis of OMG between January 2007 and December 2019. A total of 39% of these patients developed GMG by the end of the study, whereas 61% continued to have OMG. The conversion group had a median (IQR) follow-up time of 16 (7.88-33.75) months, whereas the nonconversion group had a median follow-up time of 63.5 (31-107.5) months. More than 60% of all participants were women, and the mean (SD) age of onset of OMG was 49.17 (15) years.

History of smoking (adjusted HR [aHR], 1.78; 95% CI, 1.04-3.03), thymic abnormalities (aHR, 2.30; 95% CI, 1.41-3.74), positive AChR Ab (aHR, 2.88; 95% CI, 1.79-4.63), and pyridostigmine dosages that were greater than 180 mg/day (aHR, 2.33; 95% CI, 1.41-3.87) were all associated with progression from OMG to GMG. Significant associations were not found between conversion and sex, history of smoking, thymic abnormalities, or pyridostigmine dosage when looking at patients who were AChR Ab-positive.

The likelihood of progression from OMG to GMG was 26% at 2 years, 34% at 4 years, and 39% at 6 years, with the probability of conversion not decreasing after receiving immunosuppressive agents.

The study had a few limitations. The study was retrospective and could have had missing or incomplete data. The follow-up period was relatively short. The number of patients tested was limited due to the availability of the test for anti-MuSK antibodies was limited. The small number of patients who presented with thyroid and autoimmune diseases prevented assessment of any associations between them and conversion. There could have been selection bias due to all patients being from a tertiary referral center, which could have had patients with different risk profiles and may limit generalizability.

“Thymic abnormalities and a positive AChR Ab test result were found to be significant risk factors strongly associated with progression to GMG. Hence, evaluating for thymic abnormalities and conducting AChR Ab tests should be standard practices for all OMG patients,” the authors concluded.

References

1. Chuenkongkaew W, Chirapapaisan N, Chatchutimakorn P, et al. Factors influencing the conversion of ocular myasthenia gravis to generalized myasthenia gravis: a retrospective cohort study. J Ophthalmol. 2026;2026:6652248. doi:10.1155/joph/6652248
2. Myasthenia gravis. Cleveland Clinic. Updated November 10, 2023. Accessed February 16, 2026. https://my.clevelandclinic.org/health/diseases/17252-myasthenia-gravis-mg