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

Abstract

BackgroundThe 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.ResultsAt 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.ConclusionLocal 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.

Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery

“…NIU affects patients of different age groups and it may be chronic and recurrent (1). However, management of NIU is far more challenging than anterior uveitis which leads to irreversible vision loss/impairment.…”

“…Rapamycin, an immunosuppressant, may severely compromise immune function if administered through systemic route (22). To deliver rapamycin locally to the eye, various strategies such as route of administration (periocular, subconjunctival, intravitreal implants/injections), and formulations (nanoparticles, liposomes) based have been implemented (1,20,23). Strategies such as periocular, subconjunctival, and intravitreal implants/ injections of rapamycin are invasive and associated with side effects such as retinal detachment or damage, endophthalimitis, and pseudoendophthalmitis.…”

Uveitic macular edema

“…87 The efficacy of sirolimus has been suggested on vitreous inflammation without significant difference between subconjonctival and intravitreal injections. 88 In case of ME related to inflammatory CNV, the longterm efficacy of intravitreal bevacizumab has been reported by Mansour et al in a study of 81 patients with uveitis. 89 They have observed a significant increase in VA in patients with histoplasmosis, multifocal choroiditis, punctate inner chorioretinopthy and toxoplasmosis, as well as a significant decrease in foveal thickness in the overall patient group.…”

The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig Retinal Progenitor Cell Allotransplants

“…17 Due to all the above information, the necessity and choice of potential local and systemic immunosuppressive and anti-inflammatory therapy for RPC allotransplantation remain an open question with several options available. 18 In the current allograft study, we evaluated the effect on survival and engraftment of a single intravitreal injection of rapamycin (sirolimus) 19 and dexamethasone 20 from several local regimens that have been tested previously: fujimycin (tacrolimus), 21 triamcinolone, 22 cyclosporine, 23 and amethopterin (methotrexate). 24 Cyclosporine A and other calcineurin inhibitors prevent the subsequent activation of T-cells by reducing interleukin (IL)-2 production.…”