Background: Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates
prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious
steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and
everolimus) may be contenders for this role.
Methods: A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious
uveitis was performed. Articles were identified by a search of MEDLINE (PubMed/OVID) and EMBASE
(OVID) the terms (uveitis OR non-infectious uveitis) AND (mTOR inhibitor OR sirolimus OR everolimus). Assessment
of study aims, methods, efficacy outcomes and adverse events was performed.
Results: Seven pre-clinical and nine clinical studies were identified. One study in each group was on everolimus,
the rest sirolimus. Preclinical studies have been performed in rabbit, rat, mouse and in-vitro models. Clinical
studies range from comparative open-label trials to case reports, with reported clinical efficacy ranging from 40%
to 100% depending on endpoint assessed. The overall rate of drug-related adverse events (such as ocular irritation,
visual floaters, nausea and vomiting) was 0.640 events per patient-year with sirolimus, and 0.111 events per
patient-year with everolimus.
Conclusion: Published evidence suggests that sirolimus and everolimus may be useful in the management of noninfectious
uveitis. Both appear to be well tolerated, especially when locally administered. Further high-quality
RCTs adopting standardised end-points are required to definitively determine the efficacy of each agent.