Purpose: To assess the safety and efficacy of intravenous cyclophosphamide (CP) therapy for patients with severe ocular inflammatory diseases refractory to other immunomodulatory therapies (IMTs).

Methods: We retrospectively reviewed the medical records of 1295 patients who presented to the Byers Eye Institute Uveitis Clinic at Stanford from 2017 to 2022. Seven of these patients (10 eyes) received CP therapy for ocular inflammatory diseases, with at least 1 year of follow-up. Data reviewed included demographics, ocular findings, previous and concomitant therapies, treatment outcomes, and adverse events.

Results: Of the 7 patients, (4 were male and 3 were female). The mean age of the patients was 61.6±14.9 (43.0-89.0) years. Clinical diagnoses included scleromalacia perforans (4 eyes of 3 patients), anterior necrotizing scleritis (1 eye of 1 patient), peripheral ulcerative keratitis (2 eyes of 1 patient), orbital pseudotumor (1 eye of 1 patient), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes of 1 patient). Ocular disease was idiopathic in 3 patients, and associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All patients had history of prior IMT use, including methotrexate (5 patients), mycophenolate mofetil (3 patients), azathioprine (1 patient), tacrolimus (1 patient), adalimumab (2 patients), infliximab (4 patients), and rituximab (1 patient). At CP initiation, all biologics were discontinued. The mean duration of CP therapy was 11.9±8.8 (5-28) months, and the mean follow-up time was 34.4±11.0 (13-45) months. Inflammation improved in all patients. Remission was achieved in 5 patients (71.4%). One patient had resolution of disease but continues CP while waiting for surgical intervention, and another patient had a flare of his scleritis and was restarted on CP therapy, with stabilization of the disease. Four patients (57.1%) experienced transient leukopenia (white blood cell count <4000/mL), 1 patient reported fatigue after the infusions, 1 patient had single episode of fever, 1 patient reported a brief self-limited episode of abdominal pain.

Conclusion: CP therapy is a potentially effective and relatively safe treatment option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors). Leukopenia was the most common side effect of CP, requiring close monitoring with regular blood work throughout therapy.