The patient arrived with a constellation of symptoms that would puzzle many clinicians: intermittent jaw pain, headache, tenderness over the left temple, blurred vision in the left eye, and intermittent binocular diplopia, the medical term for double vision arising from misalignment of the two eyes. Her history included seropositive rheumatoid arthritis, meaning her blood carried the characteristic autoantibodies such as rheumatoid factor, along with atrial arrhythmia, breast cancer, and osteoporosis. Notably, she was a one-pack-per-day cigarette smoker, a habit the authors highlight as a known risk factor for rheumatoid vasculitis and one that adversely influences the expression of the p53 proto-oncogene in the disease.

Examination revealed measurable deficits. Her visual acuity was 20/40 in the right eye and 20/30 in the left, and Humphrey visual field testing showed a mean deviation of minus 0.50 decibels on the right and minus 3.03 decibels on the left, with an inferior arcuate defect corresponding to the worse left eye. A relative afferent pupillary defect, in which the affected pupil paradoxically dilates when light swings to it, pointed to dysfunction of the left optic nerve pathway. Ocular motility testing showed a minus 2 limitation of both adduction and abduction in the left eye, meaning the eye could not fully turn inward or outward, while the right eye moved normally. Optical coherence tomography measured retinal nerve fiber layer thicknesses of 91 and 96 microns, values within a range that would later prove useful for tracking stability.

The decisive diagnostic tool was magnetic resonance imaging of the brain and orbits with contrast. The scans showed asymmetric enhancement of the left orbital apex, the narrow posterior gateway where the eye’s nerves and vessels pass into the skull, with extension through the left superior orbital fissure into the cavernous sinus, a venous channel flanking the pituitary that carries multiple cranial nerves, and into Meckel’s cave, a dural pocket housing the trigeminal ganglion. This anatomic triad, orbital apex, superior orbital fissure, and cavernous sinus, explains the patient’s combination of eye movement restriction, vision loss, and facial pain, because each structure houses distinct nerve populations vulnerable to inflammatory compression.

Before attributing the syndrome to rheumatoid arthritis, the team systematically excluded competing diagnoses, a critical step because orbital inflammatory syndrome is a diagnosis of exclusion. A temporal artery biopsy returned negative for giant cell arteritis, the dangerous vascular inflammation that mimics this presentation in older patients. Serologic testing for angiotensin-converting enzyme and lysozyme ruled against sarcoidosis, while negative myelin oligodendrocyte glycoprotein and neuromyelitis optica antibodies excluded demyelinating disease. Tuberculosis and Lyme disease testing was negative, serum immunoglobulin G4 was normal, and lumbar puncture showed unremarkable cerebrospinal fluid. Granulomatosis with polyangiitis was considered unlikely given the absence of sinonasal disease, bone destruction, or ANCA positivity, and the multiyear stability of the findings argued against lymphoma.

Treatment began with intravenous high-dose methylprednisolone followed by high-dose oral prednisone with a slow taper, the standard first-line approach for orbital inflammatory disease. Three months later, repeat imaging showed near resolution of the left orbital apex enhancement, though persistent enhancement remained at the right Meckel’s cave, and the patient was started on maintenance infliximab infusions, a tumor necrosis factor inhibitor already part of her rheumatoid regimen. But the story did not end there. Thirteen months after the initial presentation, she developed chemosis, pain, ophthalmoplegia, ptosis, and lid edema in the right eye, the previously unaffected side. Repeat MRI revealed new enhancement of the right orbital apex, cavernous sinus, foramen ovale, and superior orbital fissure, confirming that the inflammatory process had migrated across the midline.

The relapsing course became the defining feature of the case. The patient again improved with intravenous methylprednisolone and high-dose prednisone, but she experienced recurrent diplopia with each attempt to taper the steroid, notably at around 10 milligrams of prednisone. Elevated serum rheumatoid factor of 88 and a C-reactive protein of 1.05 accompanied the flares. Ultimately, stability was achieved with leflunomide and hydroxychloroquine, with stable orbital and cranial imaging and preserved visual function in both eyes at last follow-up. The authors emphasize that this steroid-dependent, relapsing trajectory distinguishes their patient from most previously reported cases, in which glucocorticoids produced partial or complete short-term improvement and sustained remission.

The treatment landscape for orbital inflammatory disease is evolving, and the report situates the case within that evidence base. In a tertiary cohort of orbital inflammatory disease, corticosteroids achieved full remission in roughly half of patients, while rituximab, a B-cell-depleting antibody, achieved full remission in more than 80 percent, giving it the strongest evidence in refractory orbital inflammation. Only one prospective interventional trial exists in this field, a phase 1/2 randomized trial of rituximab, and the authors call for validated orbital disease grading systems and corticosteroid-sparing endpoints to enable the multicenter trials needed to study individually rare presentations like this one. Prior case reports, including migratory orbital inflammation treated with rituximab and adalimumab, and orbital pseudotumor managed with prednisolone alone, illustrate the heterogeneity of responses.

The authors are candid about the limitations of their report. No biopsy was performed because the lesion’s location made tissue sampling unfeasible, leaving the diagnosis presumptive rather than histologically confirmed, the most definitive means of excluding entities such as IgG4-related disease. Serial MRI scans were acquired using non-identical protocols across time points, limiting direct quantitative comparison of inflammation over time, and the authors argue that standardized orbital MRI protocols would strengthen future longitudinal assessment. These caveats matter because treatment decisions in orbital inflammation hinge on distinguishing steroid-responsive inflammation from lymphoma, which can masquerade as the same radiographic pattern.

For clinicians, the message is that rheumatoid arthritis belongs on the differential for painful ophthalmoplegia and orbital apex syndromes, alongside the far more common ocular manifestations such as scleritis and episcleritis. Patients at highest risk of rheumatoid vasculitis and severe extra-articular disease include those with high-titer rheumatoid factor or anti-CCP antibodies, long-standing erosive disease with nodules, prior exposure to disease-modifying antirheumatic drugs, and male sex. Because extra-articular rheumatoid arthritis tracks with more active systemic disease, tighter inflammatory control and earlier immunomodulatory therapy may reduce the incidence of these devastating complications over time. The case also underscores the importance of counseling rheumatoid patients that their disease can progress in unexpected directions, and that symptoms such as double vision, eye pain, or vision loss warrant urgent neuro-ophthalmic evaluation rather than attribution to routine joint disease.

Subject of Research: A rare case of rheumatoid arthritis-associated orbital and intracranial inflammatory disorder affecting the orbital apex, cavernous sinus, and Meckel's cave

Article Title: Case Report: Orbital and intracranial inflammatory syndrome in rheumatoid arthritis

Article References: Case Report: Orbital and intracranial inflammatory syndrome in rheumatoid arthritis. (n.d.). https://doi.org/10.3389/fopht.2026.1929961

Image Credits: AI Generated

DOI: 10.3389/fopht.2026.1929961

Keywords: rheumatoid arthritis, orbital inflammatory disease, cavernous sinus, Meckel's cave, neuro-ophthalmology, autoimmune disease, rituximab, corticosteroids, diplopia, vasculitis, MRI, case report