Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

Quan Dong Nguyen, University of Nebraska Medical Center
Mohamed A. Ibrahim, Johns Hopkins University
Anthony Watters, Johns Hopkins University
Millena Bittencourt, Johns Hopkins University
Jithin Yohannan, Johns Hopkins University
Yasir J. Sepah, University of Nebraska Medical Center
James P. Dunn, Johns Hopkins University
Joel Naor, Santen Pharmaceuticals
Naveed Shams, Santen Pharmaceuticals
Ovais Shaikh, Johns Hopkins University
Henry A. Leder, Johns Hopkins University
Diana V. Do, University of Nebraska Medical Center


BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.

RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug.

CONCLUSION: Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.