title: Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy: a randomized clinical trial.
abstract: OBJECTIVE
  Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR).
  
  
  OBJECTIVE
  To investigate, in a proof-of-concept clinical trial, whether low-dose oral doxycycline monohydrate can (1) slow the deterioration of, or improve, retinal function or (2) induce regression or slow the progression of DR in patients with severe nonproliferative DR (NPDR) or non-high-risk proliferative (PDR), and to determine the potential usefulness of visual function end points to expedite the feasibility of conducting proof-of-concept clinical trials in patients with DR.
  
  
  METHODS
  We conducted a randomized, double-masked, 24-month proof-of-concept clinical trial. Thirty patients (from hospital-based retina practices) with 1 or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study-defined high-risk PDR.
  
  
  METHODS
  Patients were randomized to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months.
  
  
  METHODS
  Change at 24 months compared with baseline in functional factors (frequency doubling perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2 testing, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomic factors (Early Treatment Diabetic Retinopathy Study DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters).
  
  
  RESULTS
  From baseline to month 24, mean FDP foveal sensitivity decreased in the placebo group (-1.9 dB) and increased in the doxycycline group (+1.8 dB) (P = .02). A higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group was detected at 6 months (P = .04), and this significant difference persisted at 12 and 24 months. A difference between the groups was not detected with respect to the other visual function outcomes and all anatomic outcomes assessed.
  
  
  CONCLUSIONS
  To our knowledge, this is the first observation suggesting a link between a low-dose oral anti-inflammatory agent and subclinical improvement in inner retinal function. Oral doxycycline may be a promising therapeutic strategy targeting the inflammatory component of DR. Furthermore, study results suggest that FDP, which primarily measures inner retinal function, is responsive to intervention and may be a useful clinical trial end point for proof-of-concept studies in patients with DR.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00511875.
authors.forename: Ingrid U
authors.initials: IU
authors.lastname: Scott
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Jackson
authors.forename: David A
authors.initials: DA
authors.lastname: Quillen
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Jason
authors.initials: J
authors.lastname: Liao
authors.forename: Stig
authors.initials: S
authors.lastname: Holfort
authors.forename: Inger Christine
authors.initials: IC
authors.lastname: Munch
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gardner
mesh_terms: D000221:Adaptation, Ocular; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D015350:Contrast Sensitivity; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D058609:Visual Field Tests; D014794:Visual Fields; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline