Abstract
Background and objectiveTo evaluate the safety and efficacy of intravitreal sirolimus for persistent, exudative age-related macular degeneration (AMD).MethodsThis institutional review board approved, registered (NCT02357342), prospective, subject-masked, single center, randomized controlled trial in subjects with persistent, exudative Age-related macular degeneration compared intravitreal sirolimus monotherapy (every 2 months) versus monthly anti-vascular endothelial growth factor (VEGF) over six months.Results20 subjects were randomized to each arm of the trial. Upon completion of the trial 20 patients were analyzed in the control (anti-vascular endothelial growth factor) group and 17 patients were analyzed in the treatment (sirolimus) group. On average, subjects had 33 previous anti-VEGF injections prior to entry. The primary end-point, mean central subfield thickness (CST), increased by 20 µm in the anti-vascular endothelial growth factor group and decreased by 40 µm in the sirolimus group (p = 0.03). Visual acuity outcomes were similar between groups. Serious ocular adverse events in the sirolimus group included one subject each with anterior uveitis, central retinal artery occlusion and subretinal hemorrhage.ConclusionMonotherapy with intravitreal sirolimus for subjects with persistent, exudative age-related macular degeneration appears to have a limited positive anatomic benefit. The presence of adverse events in the experimental group merits further evaluation, potentially as an adjuvant therapy.Trial registration This trial was registered with the clinicaltrials.gov, NCT02357342, and was approved by the institutional review board at Advarra. Funding was provided by an investigator-initiated grant from Santen. Santen played no role in the design or implementation of this study.
Highlights
Background and objectiveTo evaluate the safety and efficacy of intravitreal sirolimus for persistent, exudative agerelated macular degeneration (AMD)
For the subjects who did not complete a total of 3 sirolimus injections, one patient died prior to the second scheduled injection, one patient missed an appointment at the second scheduled injection and one patient was rescued over to anti-vascular endothelial growth factor (VEGF) therapy due to the development of anterior uveitis with an elevated intraocular pressure of 36 mmHg at month 2
Sirolimus targets the mammalian target of rapamycin, which is involved in a complex set of cellular functions, including serving as a central regulator of cell metabolism, growth, proliferation, permeability, and survival [17,18,19,20]
Summary
To evaluate the safety and efficacy of intravitreal sirolimus for persistent, exudative agerelated macular degeneration (AMD). The generic name for rapamycin, is a macrolide compound produced by the bacterium Streptomyces hygroscopicus. It has been FDA approved for the Minturn et al Int J Retin Vitr (2021) 7:11 prevention of kidney transplant rejection and coronary stent coating. In mouse retinal laser photocoagulation models, oral treatment with sirolimus significantly reduced the extent of neovascularization, in a VEGF-independent manner [9]. Our desire is to build upon previous research and examine a larger cohort in a randomized monotherapy comparison of anti-VEGF treatments and intravitreal sirolimus for persistent, wet AMD
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