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.
Author(s): Scott IU(1), Jackson GR(2), Quillen DA(3), Klein R(4), Liao J(5), Gardner TW(6).
Affiliation(s): Author information:
(1)Penn State Hershey Eye Center, Penn State College of Medicine,
Hershey2Department of Public Health Sciences, Penn State College of Medicine,
Hershey. (2)Penn State Hershey Eye Center, Penn State College of Medicine,
Hershey3MacuLogix, Inc, Hershey, Pennsylvania. (3)Penn State Hershey Eye Center,
Penn State College of Medicine, Hershey. (4)Department of Ophthalmology and
Visual Sciences, University of Wisconsin School of Medicine and Public Health,
Madison. (5)Department of Public Health Sciences, Penn State College of Medicine,
Hershey. (6)Kellogg Eye Center, University of Michigan School of Medicine, Ann
Arbor.
Publication date & source: 2014, JAMA Ophthalmol. , 132(9):1137-42
IMPORTANCE: 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).
DESIGN, SETTING, AND PARTICIPANTS: 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.
MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00917553.
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