title: Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.
abstract: OBJECTIVE
  To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA).
  
  
  METHODS
  The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline.
  
  
  RESULTS
  Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye.
  
  
  CONCLUSIONS
  While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.).
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Petrou
authors.affiliation: Office of the Clinical Director, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Denise
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Office of the Clinical Director, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Shimel
authors.affiliation: The EMMES Corporation, Rockville, Maryland, United States.
authors.forename: Molly
authors.initials: M
authors.lastname: Harrington
authors.affiliation: The EMMES Corporation, Rockville, Maryland, United States.
authors.forename: Keri
authors.initials: K
authors.lastname: Hammel
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cukras
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D057092:Geographic Atrophy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D014792:Visual Acuity
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: age-related macular degeneration; clinical trial; geographic atrophy; sirolimus