Immunosuppressants May Reduce Risk of Ocular MG Progressing to gMG

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by Steve Bryson PhD |

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Treatment with immunosuppressant medications can delay disease progression in patients with ocular myasthenia gravis, which affects only eye muscles, to a more generalized form in which other muscles are affected, a study has found.

The findings also showed that thymus gland abnormalities, as well as irregular results on facial nerve stimulation tests, were both associated with a higher risk of myasthenia gravis (MG) progression. Tests evaluating these parameters should be performed routinely for patients with eye-associated disease symptoms, researchers say.

These findings were reported in the study “Prognostic factors for conversion to generalization in ocular myasthenia gravis,” published in the journal Medicine.

In up to 85% of people with MG, the first symptom is eye muscle weakness, manifesting as double vision or eyelid droopiness. This is caused by the immune system mistakenly launching an attack against certain proteins involved in nerve-muscle communication. The disease is called generalized MG (gMG) when it affects other muscle groups.

Previous studies have identified various factors associated with the development of gMG, including being older than 50, smoking, and having abnormalities in the thymus gland — an organ that is part of the immune system and is thought to be involved in the production of MG self-reactive antibodies.

Progression, or conversion, to gMG is also more likely in people who carry antibodies that target the acetylcholine receptor (AChR) — the protein on the surface of muscle cells that receives signals from nerves to trigger muscle contraction.

This study was conducted to examine and help clarify the factors influencing the conversion of ocular MG to gMG and identify the best available treatments to reduce this likelihood.

Researchers at the Prince of Songkla University in Thailand examined the medical records of patients diagnosed with ocular MG at the eye clinic or neurology center in the local Songklanagarind Hospital. All eligible participants had developed eye symptoms exclusively in less than two years before a formal diagnosis.

In total, the team reviewed the records of 115 patients with ocular MG who had been followed for a median average of 2.9 years. More than two-thirds were female (72.2%), and nearly half (46.1%) had both double vision (diplopia) and eyelid droopiness (ptosis) with limited eye movement.

After diagnosis, 96 participants (83.5%) underwent chest imaging to evaluate the thymus gland. Abnormalities were detected in 17 patients, and from these, 11 had their thymus gland surgically removed (thymectomy).

Patients were initially treated based on clinical symptoms and were categorized according to their treatment regimen. The time from symptom onset to treatment initiation ranged from one to about six months.

A total of 81 participants received immunosuppressant medications. From these, 65 were prescribed multiple doses of prednisolone, four received azathioprine alone, and 12 were given a combination of the two.

Pyridostigmine (sold as Mestinon, among other brand names) was administered to 34 patients (29.6%). This medicine prevents the breakdown of the chemical messenger acetylcholine, which is released from nerve cells to trigger muscle contraction in AChRs that are still functional.

During follow-up, 35 participants (30.4%) went on to develop gMG, with a time to conversion ranging from 1.4 to 5.5 years (median 2.9 years). Based on these data, the likelihood of progressing from ocular MG to gMG was 23.7% at two years, 32.6% at four years, and 34.9% by six years.

These results were “similar to those of recent studies conducted in other Asian countries,” and were “lower than those reported in certain Western countries,” the team wrote.

However, there was a significant difference in the likelihood of gMG progression between treatment regimens. At two years, significantly fewer patients who received immunosuppressants progressed to gMG (16.9%) compared with those who did not receive the medications (40.8%). Similar findings were seen at four years (25.3% vs. 51.9%).

The median time to gMG progression was longer in immunosuppressant-treated patients (3.1 years) than in those who did not receive these medications (1.7 years).

Statistical analysis also showed that thymus abnormalities found by chest imaging or post-surgical examination were significantly associated with the transition from ocular MG to gMG.

Additionally, patients were more likely to progress to gMG if they had an abnormal response to repetitive nerve stimulation tests performed on the face. These tests use electrodes attached to the skin to measure the ability of the nerves to send electrical signals to muscles.

“Because of the low incidence of seropositive AChR [antibodies] and the lack of testing capability in our hospital, we decided not to assess this potential risk factor,” the researchers wrote.

Age, signs and symptoms, thyroid gland function test results, and the presence of antinuclear antibodies (autoimmune disease markers) were not significant predictors of gMG conversion.

“In conclusion, our patients with [ocular] MG had a low risk of developing GMG [two] years after the onset of symptoms,” the researchers wrote. “Our study suggests that treatment with [immunosuppressants] can reduce the risk of the disease developing into a more severe GMG pattern and can also delay GMG onset.”

“We found that thymus abnormalities and positive repetitive facial nerve stimulation test [results] were associated with higher odds of progression to GMG,” they wrote, adding that such tests should be performed routinely for patients with ocular MG.

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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.