Subconjunctival Sirolimus for the Treatment of Chronic Active Anterior Uveitis: Results of a Pilot Trial

• Published in: American journal of ophthalmology Vol. 153; no. 6; pp. 1038 - 1042
• Main Authors: Nida Sen, H, Larson, Theresa A, Meleth, Annal D, Smith, Wendy M, Nussenblatt, Robert B
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2012; Elsevier; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Chronic Disease; Conjunctiva - drug effects; Diabetic retinopathy; Drug dosages; Drug therapy; Female; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Injections, Intraocular; Male; Medical imaging; Medical sciences; Middle Aged; Miscellaneous; Ophthalmology; Pilot Projects; Prospective Studies; Sirolimus - administration & dosage; Sirolimus - adverse effects; Studies; Treatment Outcome; Uvea diseases; Uveitis, Anterior - drug therapy; Uveitis, Anterior - physiopathology; Visual Acuity - physiology; Antineoplastic agent; Pilot; Sirolimus; Anterior uveitis; Lactone; Uvea disease; Macrolide; Macrocycle; Eye disease; Antibiotic; Chronic; Treatment; Protein synthesis inhibitor; Immunosuppressive agent; Ophthalmology
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2011.12.018

Purpose To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis. Design Prospective, nonrandomized, open-label clinical trial. Methods 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. Results 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. Conclusions 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.