Study Tracks Factors That Increase Risk of Ocular MG Generalization

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by Marta Figueiredo PhD |

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In people with ocular myasthenia gravis (OMG), disease onset during adulthood, the presence of nerve abnormalities, anti-acetylcholine receptor (AChR) autoantibodies, and a thymus tumor, all increase the risk of disease generalization to the rest of the body, a multicenter study in China has found.

Notably, in contrast to previous research, this study did not include patients who were on immunosuppressive therapy or who underwent surgery to remove the thymus (thymectomy) — two therapeutic approaches that may reduce the risk of disease generalization in this patient population.

As such, these findings may better reflect the risk factors of OMG progression to generalized MG (gMG), thereby helping in the creation of a risk prediction model to allow early identification and treatment of high-risk patients, the researchers noted.

The study, “Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study,” was published in the journal Neurology and Therapy.

MG is an autoimmune disease caused by the abnormal production of self-reactive antibodies against proteins, such as AChR, that facilitate the function of the neuromuscular junction (NMJ), leading to muscle weakness and fatigue. The NMJ is the point of contact between nerve cells and the muscles they control, and where nerve-muscle communication takes place.

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In half of MG patients, the disease first affects the muscles controlling eye and eyelid movements, leading to double vision and droopy eyelids. Notably, up to 80% of these patients subsequently progress to gMG, which may lead to life-threatening complications, usually within two years of a diagnosis.

As such, identifying risk factors of disease generalization “may help stratify [categorize] patients into low- and high-risk groups and select those patients who are optimal choices for starting risk-modifying treatment,” the researchers wrote.

While previous studies have identified several risk factors associated with disease generalization, they included OMG patients on immunosuppressive therapy or those undergoing thymectomy — two therapeutic strategies that have been reported previously to lower the risk of disease generalization.

“A study exploring risk factors in non-immunosuppressed and non-thymectomized patients is required to adequately control for these [potentially influencing] factors,” the researchers wrote.

To address this, a team of researchers in China retrospectively analyzed demographic and clinical data from 572 OMG patients (53% male) followed at seven Chinese tertiary hospitals, who had not received prior immunosuppressive treatment or undergone thymectomy.

Patients’ mean age at disease onset was 45.5 years, with 89.2% having an adult-onset and 10.8% a juvenile-onset. In addition, 3% had other autoimmune diseases. They were followed for a median of 14.5 months and 144 (25.2%) of them progressed to gMG.

Results showed that a significantly greater proportion of patients who progressed to gMG had adult-onset OMG, double vision as a first symptom, abnormal repetitive nerve stimulation (RNS) findings, anti-AChR autoantibodies, and a thymus tumor (also known as thymoma), compared with those whose disease did not progress. RNS is a standard diagnostic test that assesses nerve-muscle communication and supports a MG diagnosis when a nerve’s capacity to send signals worsens with fatigue.

Notably, all but double vision as a first symptom, were confirmed as independent, significant risk factors of OMG generalization when the risk analysis was adjusted for potential influencing factors.

In particular, patients with a disease onset during early adulthood (18–49 years) and late adulthood (50 or older) were five to seven times more likely to progress to gMG relative to those who had a juvenile onset. Those with late-onset disease had the highest risk.

Nerve abnormalities were associated with a threefold higher risk of disease generalization, while patients with autoantibodies against AChR or a thymoma were 1.6 to 2.5 times more likely to see their ocular disease become generalized.

These findings were consistent with those from previous studies, further supporting adult-onset OMG, abnormal RNS findings, anti-AChR autoantibodies, and thymoma as strong risk factors of OMG generalization, the team noted.

“The development of a risk prediction model is warranted to aid early screening of patients at high risk of generalization and enable early initiation of risk-modifying therapy,” the researchers wrote.

Among the study’s limitations, the team noted its retrospective nature and incomplete clinical data for 71 of the included patients. “Future prospective studies with complete datasets are required to address these limitations,” they wrote.

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Myasthenia Gravis News conducted a survey from Feb. 11-March 28 to gain greater insight into the characteristics of the MG community and disease management. Results of the survey have now been published. Click on the image to view the infographic, and click here to read the story.