COMMENTARY

Doxycycline: Double Duty in Eye Disease?

Brianne N. Hobbs, OD

Disclosures

July 17, 2014

Effect of Doxycycline vs Placebo on Retinal Function and Diabetic Retinopathy Progression in Patients with Severe Nonproliferative or Non-High-Risk Proliferative Diabetic Retinopathy: A Randomized Clinical Trial

Scott IU, Jackson GR, Quillen DA, et al
JAMA Ophthalmol. 2014;132:535-543

Doxycycline in Eye Disease

Doxycycline already plays an important role in the management of meibomian gland dysfunction, but it is possible that this agent might be effective in the treatment of another common eye condition: diabetic retinopathy.

Currently, the therapeutic strategies for diabetic retinopathy center around strict control of blood glucose, blood pressure, and cholesterol levels, but another option for preventing the ocular effects of diabetes would certainly be welcomed. Evidence suggests that the pathogenesis of diabetes includes an inflammatory process, a component that could potentially be minimized by the anti-inflammatory properties of doxycycline.[1,2,3]

Study Summary

A proof-of-concept trial is an investigational trial that seeks to explore a possible relationship between an intervention and an outcome in a small group of subjects. One such trial was conducted to describe the relationship between low-dose doxycycline and retinal function in patients with diabetes. The results of this randomized, placebo-controlled, clinical trial were recently published.

Thirty patients with severe nonproliferative diabetic retinopathy or early, non-high-risk proliferative diabetic retinopathy were randomly assigned to receive 50 mg of doxycycline daily or placebo for 24 months. Baseline characteristics of the treatment and control groups were similar overall, although patients in the control group had diabetes for 7 years longer on average than the doxycycline group, which may have contributed to superior outcomes in the treatment group.

Study Findings

The primary endpoints were retinal function and stage of diabetic retinopathy at 24 months, but a myriad of anatomical and functional parameters were also quantified.

The trial attempted to increase the likelihood of detecting subtle changes in retinal function by selecting an endpoint that is theorized to be sensitive to early retinal changes: frequency doubling perimetry (FDP). In a previous study, FDP mean foveal sensitivity was superior to other modalities for detecting subtle inner retinal changes.[4]

The FDP foveal sensitivity was lower in the placebo group by an average of 1.9 decibels (-1.9 dB) and increased by 1.8 dB (+1.8 dB) in the doxycycline group. This difference became significant after 6 months (P = .04). Although this difference remained statistically significant at the conclusion of the study (P = .02), it is of questionable clinical significance because of the fluctuation inherent in a subjective test such as a visual field and the relatively small size of the treatment effect.

Although a multitude of other factors were assessed, including the Swedish interactive thresholding algorithm (SITA) 24-2 test, contrast sensitivity, dark adaptation, visual acuity, quality of life, and anatomical measurements, no significant differences in any of these factors were found between the 2 groups. Four patients (27%) in the doxycycline group dropped out of the study, although no adverse effects of doxycycline were reported.

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