Beyond Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies: Alternative Causes of Optic Neuritis

Abstract

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.

MOG antibody-associated optic neuritis

“…In addition to AQP4-ON and MS-ON, a range of other conditions can also present with ON and must be considered in the differential diagnosis of MOGAD [111]. These are outlined below and summarised in Table 2.…”

“…Other systemic autoimmune conditions. Many other systemic autoimmune conditions have also been reported to feature ON, including Sjogren's syndrome, Behcet's disease, ANCA vasculitis, and systemic lupus erythematosus, the latter often occurring in association with AQP4 IgG antibodies [111,121].…”