PURPOSE: To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in theSirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. METHODS: SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6). RESULTS:24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42µm in group 1 and +81.5µm in group 2 at M6. CONCLUSIONS: Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months.
RCT Entities:
PURPOSE: To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. METHODS: SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6). RESULTS: 24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42µm in group 1 and +81.5µm in group 2 at M6. CONCLUSIONS: Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months.
Authors: D A Jabs; J T Rosenbaum; C S Foster; G N Holland; G J Jaffe; J S Louie; R B Nussenblatt; E R Stiehm; H Tessler; R N Van Gelder; S M Whitcup; D Yocum Journal: Am J Ophthalmol Date: 2000-10 Impact factor: 5.258