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, Mohamed A. Ibrahim, Anthony Watters, Millena Bittencourt, Jithin Yohannan, Yasir J. Sepah, James P. Dunn, Joel Naor, Naveed Shams, Ovais Shaikh, Henry Alexander Leder, Diana V. Do

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalJournal of Ophthalmic Inflammation and Infection
Volume3
Issue number1
DOIs
StatePublished - Dec 1 2013

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Intravitreal Injections
Uveitis
Sirolimus
Visual Acuity
Adrenal Cortex Hormones
Injections
Reducing Agents
Pharmaceutical Preparations

Keywords

  • Intravitreal
  • Sirolimus
  • Subconjunctival
  • Uveitis
  • mTOR

ASJC Scopus subject areas

  • Ophthalmology
  • Infectious Diseases

Cite this

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. / Nguyen, Quan Dong; Ibrahim, Mohamed A.; Watters, Anthony; Bittencourt, Millena; Yohannan, Jithin; Sepah, Yasir J.; Dunn, James P.; Naor, Joel; Shams, Naveed; Shaikh, Ovais; Leder, Henry Alexander; Do, Diana V.

In: Journal of Ophthalmic Inflammation and Infection, Vol. 3, No. 1, 01.12.2013, p. 1-15.

Research output: Contribution to journalArticle

Nguyen, Quan Dong ; Ibrahim, Mohamed A. ; Watters, Anthony ; Bittencourt, Millena ; Yohannan, Jithin ; Sepah, Yasir J. ; Dunn, James P. ; Naor, Joel ; Shams, Naveed ; Shaikh, Ovais ; Leder, Henry Alexander ; Do, Diana V. / 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. In: Journal of Ophthalmic Inflammation and Infection. 2013 ; Vol. 3, No. 1. pp. 1-15.
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abstract = "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.",
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T1 - Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis

T2 - Primary 6-month results of the SAVE Study

AU - Nguyen, Quan Dong

AU - Ibrahim, Mohamed A.

AU - Watters, Anthony

AU - Bittencourt, Millena

AU - Yohannan, Jithin

AU - Sepah, Yasir J.

AU - Dunn, James P.

AU - Naor, Joel

AU - Shams, Naveed

AU - Shaikh, Ovais

AU - Leder, Henry Alexander

AU - Do, Diana V.

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N2 - 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.

AB - 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.

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