• Written By: Khalid F. Tabbara, MD

    This open-label pilot study in the June issue of the American Journal of Ophthalmology evaluated the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis. The authors report that this therapy appeared safe and well- tolerated during the study's four-month follow-up and reduced active inflammation in all patients. It shows promise for treating chronic anterior uveitis in patients with active inflammation, particularly those who cannot tolerate subconjunctival corticosteroid injections.

    Sirolimus is an mTOR (mammalian target of rapamycin) and causes suppression of cytokine-driven T-cell proliferation and inhibits the production, signaling and activity of many growth factors that lead to intraocular inflammation. It has been used off-label in one small uncontrolled case series of refractory uveitis patients, and is FDA-approved for the prevention of transplant rejection.

    The current study included five consecutive patients with chronic active anterior uveitis. Four patients had idiopathic anterior uveitis and one had psoriatic arthritis-associated anterior uveitis. Four patients had corticosteroid-induced ocular hypertension in the study eye which limited the use of corticosteroids.

    Each participant received a single 30 µL subconjunctival injection of sirolimus containing 1,320 µg in the study eye at baseline. All five patients showed a marked decrease in anterior chamber cell grade within four weeks.

    Three patients had at least a two-step reduction in inflammation within four weeks, the study's primary outcome measure, and two showed a one-step decrease. Patients with higher grade inflammation showed a more significant improvement than those with mild inflammation.

    All patients were able to decrease or discontinue use of topical corticosteroids. None of the study eyes showed a recurrence in inflammation. The fellow eyes, which did not receive subconjunctival injection, developed mild recurrences at weeks four and 12 in two patients.

    At the last visit, visual acuity had improved by one to five lines in four patients and remained the same in one patient.

    Serum sirolimus levels were undetectable at all times, and no serious adverse events were recorded. The most common side effect was ocular irritation and redness.

    Prospective controlled studies on the effects of subconjunctival sirolimus injection in uveitis patients are needed. It would also be interesting to find out whether this therapy can influence or improve cystoid macular edema in patients with uveitis.