title: Subconjunctival sirolimus in the treatment of autoimmune non-necrotizing anterior scleritis: results of a phase I/II clinical trial.
abstract: OBJECTIVE
  To investigate the safety, tolerability and efficacy of subconjunctival sirolimus injections as a treatment for active, autoimmune, non-necrotizing anterior scleritis.
  
  
  METHODS
  Phase I/II, single-center, open-label, nonrandomized, prospective pilot study.
  
  
  METHODS
  Five participants with active, autoimmune, non-necrotizing anterior scleritis with scleral inflammatory grade of ≥1+ in at least 1 quadrant with a history of flares were enrolled. A baseline injection was given, with the primary outcome measure of at least a 2-step reduction or reduction to grade zero in the study eye by 8 weeks. Secondary outcomes included changes in visual acuity and intraocular pressure, ability to taper concomitant immunosuppressive regimen, and number of participants who experienced a disease flare requiring reinjection. Safety outcomes included the number and severity of systemic and ocular toxicities, and vision loss ≥15 ETDRS letters. The study included 6 visits over 4 months with an extension phase to 1 year for participants who met the primary outcome.
  
  
  RESULTS
  All participants (N = 5, 100%; 95% CI [0.60, 1.00]) met the primary outcome in the study eye by the week 8 visit. There was no significant change in mean visual acuity or intraocular pressure. Three out of 5 patients (60%) experienced flares requiring reinjection. No systemic toxicities were observed. Two participants (40%) experienced a localized sterile inflammatory reaction at the site of the injection, which resolved without complication.
  
  
  CONCLUSIONS
  Subconjunctival sirolimus leads to a short-term reduction in scleral inflammation, though relapses requiring reinjection do occur. There were no serious adverse events, though a local sterile conjunctival inflammatory reaction was observed.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nirali
authors.initials: N
authors.lastname: Bhatt
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Monica
authors.initials: M
authors.lastname: Dalal
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Tucker
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dominic
authors.initials: D
authors.lastname: Obiyor
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Nussenblatt
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: senh@nei.nih.gov.
authors.forename: H Nida
authors.initials: HN
authors.lastname: Sen
mesh_terms: D000328:Adult; D000368:Aged; D000869:Anterior Eye Segment; D001327:Autoimmune Diseases / Q000188:drug therapy*; D003228:Conjunctiva / Q000187:drug effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D056965:Injections, Intraocular; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015423:Scleritis / Q000188:drug therapy*; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus