Clinical Characteristics Associated With Secondary Generalization in Patients With Ocular Myasthenia Gravis: A Systematic Review and Meta-analysis

Abstract

Background and objectives: Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary generalized myasthenia gravis (SGMG) reported in the literature has been varied. The aim of this systematic review was to determine the clinical characteristics of patients with OMG and the proportion of SGMG conversion.

Methods: We conducted an electronic database search for randomized controlled trials, prospective nonrandomized studies, observational studies, and retrospective studies in EMBASE, CENTRAL, MEDLINE, and Web of Science. We included studies with patients with OMG who initially presented with ocular symptoms and signs only and were seen in clinical practice, reporting on the characteristics and outcomes of SGMG. We excluded studies with pediatric and congenital myasthenia gravis populations. Eligible studies included articles written in any language and containing data on patients with OMG. The main outcome measured was the proportion of patients with OMG who converted to SGMG and risk factors associated with secondary generalization of OMG. Two independent reviewers screened titles and abstracts and extracted data from full texts, reporting findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology was evaluated using the Joanna Briggs Institute critical appraisal forms. PROSPERO registration number: CRD2021285257.

Results: Thirty-one studies were included in the quantitative and qualitative analysis. The proportion of generalization ranged from 11% to 84%. The pooled proportion was 39% (95% CI 32%-47%, I ² = 95.86%, p < 0.001 unweighted, low certainty). The pooled risk ratio of female sex for conversion to SGMG was 1.06 (95% CI 0.96-1.17, I ² = 0% p = 0.614, 21 studies included, very low certainty), and the pooled risk ratio of acetylcholine receptor (AChR) positivity was 1.30 (95% CI 1.05-1.56, I ² = 0% p = 0.455, 16 studies included, very low certainty).

Discussion: Risk factors such as female sex and anti-AChR positivity have been identified to have possible associations with SGMG, but there are not enough quality observational studies. There is a need for a prospective global database of patients with OMG, including all countries with different populations.