Abstract
Purpose: :
The pathogenesis of diabetic retinopathy (DR), while not well understood, has been prominently associated with processes of chronic inflammation. Microglia, the resident immune cells of the retina, are activated in close proximity to DR lesions, including DME. Therapies that inhibit microglial activation can effectively decrease retinal inflammation and neuronal death in animal models of DR. The objective of this study is to investigate the safety and efficacy of minocycline, an inhibitor of microglial activation, for the treatment of DME.
Methods: :
The study was a prospective, open-label, Phase I/II pilot study, enrolling five participants with DME involving the center of the fovea. Oral minocycline (100mg twice daily) was administered for at least 6 months, and up to 24 months. The primary outcome measure was the change in best-corrected visual acuity (BCVA) at 6 months from baseline. Other measures included central macular thickness (CMT) as measured by OCT, area of late leakage on fluorescein angiography (FA), and safety outcomes. Results up to Month 6 of the study were analyzed.
Results: :
Study drug was well tolerated and associated with few adverse events. At Month 6, 5/5 study eyes and 4/5 fellow eyes demonstrated increases in BCVA from baseline; 1/5 study eye improved by >15 letters. Mean measures of vision and DME thickness were also noted to improve progressively as a function of time in the first 6 months. Mean improvement in BCVA was +5.8±2.4 (mean + standard error) letters for study eyes (p=0.074, paired t-test, n = 5), and+5.1±1.4% for all eyes (p=0.005, n = 10). Mean OCT central macular thickness (CMT) decreased by -8.1±6.5% for study eyes (p=0.28, n = 5), and -7.3±5.2% for all eyes (p=0.20, n = 10). Late leakage on FA decreased in 5/5 of study eyes and in 9/10 of all eyes.
Conclusions: :
Minocycline was not associated with significant safety concerns in patients with DME. In this small study, patients treated with minocycline monotherapy demonstrated improved visual function and decreased central macular edema and vascular leakage. Microglial inhibition, possibly in combination with other treatment modalities, may be a promising therapeutic strategy targeted at the inflammatory etiology of DR for the treatment of DME.
Clinical Trial: :
http://www.clinicaltrials.gov NCT01120899
Keywords: diabetic retinopathy • edema • microglia