title: Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.
abstract: OBJECTIVE
  To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA).
  
  
  METHODS
  The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area.
  
  
  RESULTS
  The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months.
  
  
  CONCLUSIONS
  Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).
authors.affiliation: Unit on Neuron–Glia Interactions in Retinal Disease, Building 6, Room 215, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. wongw@nei.nih.gov
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
authors.forename: Samuel
authors.initials: S
authors.lastname: Dresner
authors.forename: Farzin
authors.initials: F
authors.lastname: Forooghian
authors.forename: Tanya
authors.initials: T
authors.lastname: Glaser
authors.forename: Lauren
authors.initials: L
authors.lastname: Doss
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Denise
authors.initials: D
authors.lastname: Cunningham
authors.forename: Katherine
authors.initials: K
authors.lastname: Shimel
authors.forename: Molly
authors.initials: M
authors.lastname: Harrington
authors.forename: Keri
authors.initials: K
authors.lastname: Hammel
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cukras
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D057092:Geographic Atrophy / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D056965:Injections, Intraocular; D008297:Male; D009887:Ophthalmoscopy; D010781:Photography; D011446:Prospective Studies; D012160:Retina / Q000503:physiopathology; D015593:Retinal Drusen / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage*; D014792:Visual Acuity / Q000187:drug effects; D058609:Visual Field Tests
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
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