Study IDs risk factors for ocular MG progression to generalized MG

Ocular myasthenia gravis (OMG) patients with abnormalities in the thymus gland, antibodies against the AChR protein, or a history of smoking are at a higher risk of progression to generalized myasthenia gravis, according to a study in Thailand.

Higher doses of pyridostigmine (sold as Mestinon, among others, with generics available) were also linked to an increased risk of progression.

The results show that “evaluating for thymic abnormalities and conducting AChR antibody tests should be standard practices for all OMG patients,” the researchers wrote.

The study, “Factors Influencing the Conversion of Ocular Myasthenia Gravis to Generalized Myasthenia Gravis: A Retrospective Cohort Study,” was published in the Journal of Ophthalmology.

Myasthenia gravis (MG) is caused by the body’s erroneous production of self-reactive antibodies against certain proteins involved in nerve-muscle communication, most commonly AChRs. Abnormalities in the thymus, a gland involved in immune responses, are thought to contribute to the production of these abnormal antibodies.

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This abnormal immune attack leads to MG symptoms such as muscle weakness and fatigue. In some people, MG affects only the muscles that move the eyes and lift the eyelids, causing drooping eyelids and double vision. This form is called OMG.

As many as 80% of OMG patients may progress to generalized MG, in which multiple parts of the body are affected, within two years of the onset of eye symptoms.

Previous studies have reported several factors that may increase the risk of OMG progressing to generalized MG, but these have been based on small numbers of patients or short follow-up times.

“Definitive predictive factors for the generalization of OMG remain incompletely understood, underscoring the need for validation in larger [studies] and the investigation of additional factors,” the researchers wrote.

The team retrospectively analyzed data from 200 people diagnosed with OMG at a tertiary care center in Bangkok between January 2007 and December 2019. Most patients (60%) were women, and their mean age at disease onset was 49.17.

Of these, 78 people (39%) progressed to generalized MG after a median of 16 months (nearly 1.5 years). The remaining 122 (61%) did not develop generalized symptoms over a median of 63.5 months (little over five years). By two years, 26% had progressed into generalized MG, with rates increasing to 34% at four years, and 39% at six years.

All participants received pyridostigmine, which is often recommended as a first-line treatment for MG. Immunosuppressive treatment was also initiated in patients who showed severe OMG symptoms that did not respond to pyridostigmine and those who progressed to generalized MG. A total of 133 patients received prednisolone, an oral corticosteroid used to suppress the immune system, as a first-line immunosuppressive treatment.

Statistical analyses adjusted for potential influencing factors identified several risk factors of progression to generalized MG. Testing positive for anti-AChR antibodies was significantly linked to a nearly threefold higher risk, while a history of smoking, abnormalities in the thymus, and pyridostigmine dosages exceeding 180 mg/day were each significantly associated with an about twofold higher risk.

Although earlier studies have suggested that immunosuppressive therapy, including corticosteroids, may delay OMG progression to generalized MG, prednisolone use was not significantly linked to a reduced risk of progression.

Further analyses demonstrated that smoking, thymic abnormalities, anti-AChR antibodies, and higher pyridostigmine dosages were also significantly associated with a shorter median conversion time. Initiating pyridostigmine within one month of OMG onset was also linked to a shorter conversion time.

Again, no significant link between prednisolone treatment and a longer median conversion time was detected.

Overall, the findings suggest that certain clinical features — particularly anti-AChR antibody positivity, thymic abnormalities, and smoking — may help identify people with OMG who are more likely to develop generalized symptoms and who may benefit from closer monitoring.