Ocular Myasthenia Gravis: A Current Overview

Abstract

Ocular myasthenia gravis (OMG) is a neuromuscular disease characterized by autoantibody production against post-synaptic proteins in the neuromuscular junction. The pathophysiological auto-immune mechanisms of myasthenia are diverse, and this is governed primarily by the type of autoantibody production. The diagnosis of OMG relies mainly on clinical assessment, the use of serological antibody assays for acetylcholine receptors (AchR), muscle-specific tyrosine kinase (MusK), and low-density lipoprotein 4 (LPR4). Other autoantibodies against post-synaptic proteins, such as cortactin and agrin, have been detected; however, their diagnostic value and pathogenic effect are not yet clearly defined. Clinical tests such as the ice test and electrophysiologic tests, particularly single-fiber electromyography, have a valuable role in diagnosis. The treatment of OMG is primarily through cholinesterase inhibitors (pyridostigmine), and steroids are frequently required in cases of ophthalmoplegia. Other immunosuppressive therapies include antimetabolites (azathioprine, mycophenolate mofetil, methotrexate) and biological agents such as B-cell depleting agents (Rituximab) and complement inhibitors (eculizumab). Evidence is scarce on the effect of immunosuppressive therapy on altering the natural course of OMG. Clinicians must be vigilant of a myasthenic syndrome in patients using immune-check inhibitors. Reliable and consistent biomarkers are required to assess disease severity and response to therapy to optimize the management of OMG. The purpose of this review is to summarize the current trends and the latest developments in diagnosing and treating OMG.

Keywords: anti-MuSK antibodies; anti-acetyl-choline receptor antibody; generalized myasthenia; ocular myasthenia.

Figure 1

The pathophysiology of myasthenia gravis. Peripheral naive B-cells encounter an antigen and then, with the aid of T-cells in the thymus, produce memory antibody-producing B-cells, which later differentiate into either short-lived or long-lived plasma cells. These cells can secrete both AchR antibodies and Anti-MuSK antibodies. Both autoantibodies migrate to the neuromuscular junction and can interfere with the neuromuscular transmission, binding with AchR or by binding MuSK and impairing the neuromuscular transmission by blocking the interaction between LRP4 and MuSK, which is essential for the clustering of the AchR. Most of the AchR antibodies are of the IgG1 subclass, which can induce the complement cascade, while anti-MuSK antibodies are of the IgG4 subclass and are less effective in activating the complement pathway.

Figure 2

A 73-year-old lady was referred with a history of diplopia. Examination shows right ptosis and left upper lid retraction (Hering’s law). She had a bilateral adduction deficit (pseudo-bilateral internuclear ophthalmoplegia). MRI of the brain was normal, the ice test was positive, and she had positive AchR-antibodies.

Figure 3

The ice test is unequivocally positive in this patient, presenting with progressive ptosis worsening with fatigue (above). Significant improvement is noticed after placing ice packs for 2 minutes over the eyelids (below).