title: Subconjunctival sirolimus in the treatment of diabetic macular edema.
abstract: BACKGROUND
  Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data.
  
  
  METHODS
  In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 μl (440 μg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes.
  
  
  RESULTS
  Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar.
  
  
  CONCLUSIONS
  Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Nupura
authors.initials: N
authors.lastname: Krishnadev
authors.forename: Farzin
authors.initials: F
authors.lastname: Forooghian
authors.forename: Catherine
authors.initials: C
authors.lastname: Cukras
authors.forename: Wai
authors.initials: W
authors.lastname: Wong
authors.forename: Leorey
authors.initials: L
authors.lastname: Saligan
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.forename: Robert
authors.initials: R
authors.lastname: Nussenblatt
authors.forename: Frederick
authors.initials: F
authors.lastname: Ferris
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyerle
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005451:Fluorescein Angiography; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D056965:Injections, Intraocular; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007166:Immunosuppressive Agents; D020123:Sirolimus; C517652:hemoglobin A1c protein, human