title: Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.
abstract: OBJECTIVE
  Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME.
  
  
  METHODS
  A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA).
  
  
  RESULTS
  Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors.
  
  
  CONCLUSIONS
  In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).
authors.affiliation: Division of Epidemiology and Clinical Applications, National Institutes of Health, Bethesda, Maryland 20892, USA. cukrasc@nei.nih.gov
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cukras
authors.forename: Philip
authors.initials: P
authors.lastname: Petrou
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Meyerle
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005451:Fluorescein Angiography; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D006442:Glycated Hemoglobin; D008911:Minocycline; C517652:hemoglobin A1c protein, human