To report a case of MOG antibody-associated optic perineuritis following bisphosphonate exposure, highlighting a potential role for bisphosphonate-induced immune activation as a non-infectious trigger of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). 

Bisphosphonates, widely used for osteoporosis, can induce immune activation through T-cell stimulation and cytokine release and have been associated with rare cases of bisphosphonate-associated orbital inflammation (BAOI). MOGAD is a steroid-responsive demyelinating disorder that typically presents with optic neuritis but may also cause optic perineuritis and, less commonly, orbital inflammation. The relationship between BAOI and MOGAD remains poorly understood.

A case report.

A 59-year-old woman with history of hyperthyroidism presented with subacute onset of left eye pain approximately five days after intravenous zoledronic acid infusion. Examination revealed left eye proptosis with preserved visual acuity and no disc edema but severe left eye pain with extraocular movements. MRI orbits demonstrated prominent left optic nerve sheath enhancement with associated periorbital soft tissue edema, conjunctival edema, and retrobulbar fat stranding. A presumptive diagnosis of BAOI was made and the patient was treated with high-dose intravenous methylprednisolone for three days with rapid resolution of symptoms. Serum MOG IgG testing obtained during the initial evaluation returned positive at 1:100 titer (live cell-based assay). Follow-up MRI at four weeks demonstrated near-complete resolution of optic nerve sheath enhancement and orbital inflammation. The patient was continued on a prolonged prednisone taper over approximately four months with no subsequent disease relapse.

To our knowledge, this is the first reported case of MOG antibody-associated optic perineuritis following bisphosphonate exposure. This case highlights temporal, radiologic, and clinical overlap between BAOI and MOGAD and suggests that, in some cases, bisphosphonates may serve as a non-infectious trigger of MOG autoimmunity. These findings support consideration of MOG antibody testing in select patients with presumed BAOI, particularly when optic perineuritis is present.