Idiopathic Orbital Inflammation Refractory To Rituximab But Sensitive To Methotrexate

Purpose : Idiopathic orbital inflammation (IOI) represents a spectrum of non-infectious orbital processes that are managed with corticosteroids and/or steroid sparing immunosuppressive therapies in refractory or recurrent cases. We present two patients with IOI who were resistant to rituximab infusions but subsequently responded to oral methotrexate (MTX). Methods : Case series Results : Patient #1: A 73-year old man with a 16-year history of biopsy-proven recurrent left IOI involving the inferior rectus (Fig. 1a) presented with diplopia and persistent optic disc edema (ODE) (Fig. 2a) first noted 5 months prior. Previous treatments included prednisone up to 80 mg daily, orbital triamcinolone injections, and two rituximab infusion courses without improvement. He was started on oral MTX 15 mg weekly with a taper of prednisone. His ODE and diplopia improved at 6 weeks;however, treatment was discontinued after six months due to his concerns related to COVID-19. All findings resolved three months after stopping MTX. Patient #2: A 67-year old woman presented with a 3-year history of a right orbital mass involving the lacrimal gland and extraocular muscles (Fig. 1b) causing proptosis and diplopia. Orbital biopsy showed chronic inflammatory changes and was negative for IgG4 or lymphoma. Systemic inflammatory and infectious workup was unremarkable. She had minimal improvement in proptosis and diplopia after two courses of rituximab with intermittent oral prednisone. She later presented with ODE, cystoid macular edema, and an inferotemporal exudative retinal detachment (RD) (Fig. 2b). The ocular manifestations improved with a 10 day course of prednisone 40 mg/day but recurred on prednisone taper. All findings resolved after 2 months of MTX 20 mg weekly. Conclusions : While anti-metabolites are typically used early in the course of recurrent IOI with rituximab reserved for more recalcitrant disease, this study demonstrates that MTX may provide benefit for IOI refractory to rituximab with secondary ocular manifestations. This may be due to more gradual suppression of the immune system with MTX.