title: Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in mild to moderate nonproliferative diabetic retinopathy: a randomized proof-of-concept clinical trial.
abstract: OBJECTIVE
  Microglia have been associated with inflammatory changes underlying diabetic retinopathy.
  
  
  OBJECTIVE
  To investigate whether low-dose oral doxycycline monohydrate, a drug capable of inhibiting microglial activation, can improve or slow the deterioration of retinal function and whether it can induce regression or slow progression of diabetic retinopathy in patients with mild to moderate nonproliferative diabetic retinopathy (NPDR).
  
  
  METHODS
  Randomized, double-masked, 24-month proof-of-concept clinical trial. We randomized 33 patients (from the Penn State Hershey Eye Center) with at least 1 eye with mild to moderate NPDR (Early Treatment Diabetic Retinopathy Study level 20-43) to doxycycline monohydrate, 50 mg/d, or daily placebo for 24 months.
  
  
  METHODS
  Mean change at 24 months compared with baseline in the foveal sensitivity of matrix frequency-doubling perimetry in each treatment group. We also compared the 2 groups with respect to change from baseline to 24 months in functional variables (Humphrey photopic visual field testing using the Swedish interactive thresholding algorithm 24-2 strategy, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomical variables (diabetic retinopathy severity level, area of retinal thickening, central subfield thickness on optical coherence tomography, and macular volume on optical coherence tomography).
  
  
  RESULTS
  From baseline to month 24, no significant difference was detected between groups with respect to all visual function and anatomical outcomes assessed.
  
  
  CONCLUSIONS
  Although a link between low-dose oral anti-inflammatory agents and subclinical improvement in inner retinal function has been suggested in patients with severe NPDR or non-high-risk proliferative diabetic retinopathy, the same association was not found in the present study of patients with mild to moderate NPDR. The different findings in the 2 patient populations may relate to a differential effect of doxycycline on different stages of diabetic retinal dysfunction, or the sample size of the present study may be too small to detect a treatment effect of doxycycline in patients with mild to moderate NPDR.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00917553.
authors: Penn State Hershey Eye Center, Penn State College of Medicine, Hershey2Department of Public Health Sciences, Penn State College of Medicine, Hershey.
authors: Ingrid U
authors: IU
authors: Scott
authors: Penn State Hershey Eye Center, Penn State College of Medicine, Hershey3MacuLogix, Inc, Hershey, Pennsylvania.
authors: Gregory R
authors: GR
authors: Jackson
authors: Penn State Hershey Eye Center, Penn State College of Medicine, Hershey.
authors: David A
authors: DA
authors: Quillen
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors: Ronald
authors: R
authors: Klein
authors: Department of Public Health Sciences, Penn State College of Medicine, Hershey.
authors: Jason
authors: J
authors: Liao
authors: Kellogg Eye Center, University of Michigan School of Medicine, Ann Arbor.
authors: Thomas W
authors: TW
authors: Gardner
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015350:Contrast Sensitivity / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D018450:Disease Progression; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000187:drug effects*; D008875:Middle Aged; D055351:Retinal Neurons / Q000502:physiology*; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline