• Written By: Ramana S. Moorthy, MD

    This retrospective study found that short-term, high-dose chlorambucil therapy provides sustained periods of drug-free remission in patients with sympathetic ophthalmia.

    Sympathetic ophthalmia is a rare, bilateral, granulomatous panuveitis caused by traumatic exposure of melanin-associated proteins to the host’s immune system. The resulting reaction causes severe chronic ocular inflammation that can lead to vision loss and blindness in both the traumatized and fellow eye. This condition requires early initiation of steroid-sparing immunomodulatory therapy for many years. Since this rare disease is a lifelong illness with high recurrence rates when therapy is discontinued, long-term remission with therapeutic agents is desirable but not easy to achieve.  

    The evidence for the efficacy of alkylating agents in achieving durable remission (> 5 years off all meds) is increasing in the uveitis literature. This reports adds to this growing body of evidence and points to the excellent outcomes and mitigation of side effects, as well as potential long-term consequences (neoplasia and sterility) when chlorambucil is judiciously used in a short-term high-dose regimen. Caution must be exercised in the use of chlorambucil. It should be prescribed only by those knowledgeable about its dosing and treating its side effects.

    The authors reviewed the charts of 16 patients with sympathetic ophthalmia treated at three clinics who had severe sight-threatening disease that was not controlled with aggressive systemic corticosteroid therapy, other immunomodulatory agents or both. The median age at presentation was 42 years. Eleven had sympathetic ophthalmia after penetrating trauma and five after intraocular surgery

    The 16 patients were treated for a median of 14 weeks (12 to 19 weeks) with 2 mg/day of chlorambucil for week one, increasing 2 mg/day each week titrated to a nadir of white blood cell count of 2.4 X 10^9 cells/L and/or platelet count of 100,000-125,000 X 10^9 cells/L. As the chlorambucil dose increased, attempts were made to taper the corticosteroids and other immunomodulatory agents. The median cumulative dose given was 1,449 mg. Only one patient received more than 2,000 mg.

    After a median follow up of eight years, all patients had control of inflammation and were able to be tapered off of corticosteroids and all immunosuppressive therapy. Twelve patients (75 percent) had BCVA improvement of at least one line. Most sympathizing eyes (81.3 percent) retained 20/40 or better vision.

    Four patients had relapses of anterior segment inflammation treated with topicals alone; one developed a second recurrence that required periocular corticosteroids and a short course of systemic corticosteroids, and went on to be disease free for another 43 months. There were no identifiable demographic or clinical risk factors identified among patients that relapsed. 

    Seven patients (44 percent) had side effects including nausea and vomiting (four patients), asthenia and weakness (four patients), muscle cramps (two patients), elevated liver transaminases (one patient) and opportunistic nonserious oral fungal infection (one patient). Conjunctival Kaposi's sarcoma developed in one patient. No patient demonstrated systemic malignancy.

    The authors conclude that, given its ability to induce long-term drug-free remission, a feature not yet reported with other treatment methods, high-dose chlorambucil therapy should be considered early in the course of treatment for patients with severe disease, potentially obviating the need for life-long immunomodulatory therapy. Although long-term serious health consequences are always a concern, they have been uncommon in this group of patients. Longer-term follow-up should continue to further validate these findings.