sirolimus and Uveitis--Anterior

To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis.. Prospective, nonrandomized, open-label clinical trial.. This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis. The study drug was administered as a single subconjunctival injection of 30 μL (1320 μg) sirolimus in the study eye at the baseline visit. Study visits were performed at baseline, at 2 weeks, at 4 weeks, and monthly until 4 months, and included a complete ophthalmic examination, review of systems, adverse event assessment at each visit, physical examination, and ancillary ophthalmic testing at some visits. The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug.. There were 3 female and 2 male patients; 4 patients had idiopathic anterior uveitis and 1 had psoriatic arthritis-associated anterior uveitis. Three of the 5 patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks; 2 patients showed a 1-step decrease in inflammation within the same time frame. No recurrence was encountered during a 4-month follow-up. There were no serious adverse events.. Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis. Larger studies are needed to assess its usefulness in uveitis.

Topics: Adult; Chronic Disease; Conjunctiva; Female; Humans; Immunosuppressive Agents; Injections, Intraocular; Male; Middle Aged; Pilot Projects; Prospective Studies; Sirolimus; Treatment Outcome; Uveitis, Anterior; Visual Acuity

Anti-inflammatory actions of dexamethasone (DEXA), Cyclosporin A (CSA) and Rapamycin (RAPA) were assessed on uveitis induced by intravitreal E-coli Endotoxin (100ng) in rabbits at 24 hrs. In this model, endotoxin caused a breakdown of the blood-aqueous barrier (BAB) and polymorphonuclear neutrophils (PMN) infiltration into the aqueous humor (AH) and iris-ciliary body (ICB). Intramuscular (I.M.) DEXA (2mg/kg) but not topical DEXA (0.1% 6 x daily) inhibited AH leukocytes and protein level. However, both routes caused an inhibition of AH Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4). In the ICB, I.M. DEXA significantly inhibited PGE2 synthesis and myeloperoxidase (MPO) activity. I.M. CSA (25mg/kg) and I.M. RAPA (10mg/kg) inhibited the AH leukocytes and protein content and MPO activity in the ICB. RAPA also inhibited AH protein and eicosanoid (except AH LTB4) levels in both the AH and ICB. Interestingly, castor oil, a vehicle of CSA, also inhibited AH leukocytes and the release of PGE2 into AH and from ICB. In summary, systemic administration of DEXA and other immunosuppressive drugs CSA and RAPA significantly inhibited endotoxin-induced uveitis in rabbits.

Topics: Animals; Aqueous Humor; Ciliary Body; Cyclosporine; Dexamethasone; Dinoprostone; Disease Models, Animal; Endotoxins; Immunosuppressive Agents; Iris; Leukocyte Count; Leukotriene B4; Neutrophils; Peroxidase; Polyenes; Rabbits; Sirolimus; Uveitis, Anterior