Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study

Abstract

Introduction Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. Methods Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. Results Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0–47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64–17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22–23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97–4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26–5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05–2.49; p = 0.03) were independently associated with increased risk of generalization. Conclusion The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00292-x.

Development and Validation of a Nomogram for Predicting Generalization in Patients With Ocular Myasthenia Gravis

“…It was claimed that the patients who develop GMG very early may be different from other patients with OMG. Several studies also followed the criterion of Oosterhuis ( 10 , 19 , 30 ).…”

“…The diagnosis of OMG was confirmed by at least two neurologists. Research data have been used in previously published articles ( 19 ).…”

“…For time-to-event outcome, following criteria should be required: 1) Small overfitting defined by an expected shrinkage of predictor effects by 10% or less; 2) Small absolute difference of 0.05 in the model’s apparent and adjusted Nagelkerke’s R-squared value; 3) Precise estimation (within +/- 0.05) of the average outcome risk in the population for a key timepoint of interest for prediction. Based on the previous results in our study ( 19 , 30 ), the parameters for calculating sample size are as follows: Cox Snell R-squared: 0.2; prediction time point: 2 years; the average follow-up time: 2.1 years; the proportion of total outcome: 0.23; the number of candidate predictor parameters: 8. The calculated sample size was 319.…”

“…Previous studies have identified various predictive risk factors for generalization, including late onset, abnormal repetitive nerve stimulation (RNS) findings, seropositivity for acetylcholine receptor antibody (AChR-Ab), and the presence of thymoma (14,17,(19)(20)(21)(22)(23)(24)(25)(26). However, there has been a lack of validated instrument to incorporate these risk factors into an individualized prediction of generalization.…”

Association of immunosuppression treatment with generalization among patients with ocular myasthenia gravis: A propensity score analysis

“…It is well known that the positivity rate of AChR-Ab is lower in OMG than in GMG patients, and patients with seronegative AChR-Ab have a lower risk of generalization than patients with seropositive AChR-Ab [24][25][26]. One might speculate that seronegative patients might benefit less from immunosuppressive drugs and may even be exposed to the adverse effects of such treatments.…”