Impact of Doxycyline vs. Placebo on Retinal Function and DR Progression in Patients with Severe Nonproliferative or Non-High-Risk Proliferative DR
Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR). In a proof-of-concept clinical trial, researchers investigated whether low-dose oral doxycycline monohydrate can: slow the deterioration of, or improve, retinal function; or induce regression or slow the progression of DR in patients with severe nonproliferative DR (NPDR) or non-high-risk proliferative (PDR); and sought to determine the potential usefulness of visual function end points sought to expedite the feasibility of conducting proof-of-concept clinical trials in patients with DR. They conducted a randomized, double-masked, 24-month proof-of-concept clinical trial.
They included 30 patients (from hospital-based retina practices) with one or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study (ETDRS)-defined high-risk PDR. The researchers randomized patients to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months. Main outcome measures were 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 (ETDRS DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters). From baseline to month 24, the researchers noted that mean FDP foveal sensitivity decreased in the placebo group (–1.9 dB) and increased in the doxycycline group (+1.8 dB) (p=0.02). They detected a higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group at six months (p=0.04), and this significant difference persisted at 12 and 24 months. They did not detect a difference between the groups with respect to the other visual function outcomes and all anatomic outcomes assessed.
To the researchers' 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.