JDRF Research

Drug Shown to Protect Against Diabetic Retinopathy

For the first time, an oral drug has been shown in human studies to protect against progression of diabetic retinopathy, the most common and serious eye-related complication of diabetes, and the leading cause of adult blindness in the U.S.

The drug, ruboxistaurin, was found to be effective in a three-year, Phase III clinical trial funded by Eli Lilly and Company and conducted at 70 sites across the U.S.  Patients treated with the compound fared significantly better than those who received a placebo, suffering sustained visual loss at about half the rate of the placebo group. The study was led by Lloyd Aiello, M.D., Ph.D., of Joslin Diabetes Center, and published in the journal Ophthalmology.

Despite the positive results of the Lilly study, it is unclear when the drug might be approved for use by people with diabetes, as the FDA has asked that additional testing be conducted.

Ruboxistaurin inhibits an enzyme in the body called protein kinase C beta or PKC beta, which contributes to blood vessel damage leading to diabetic retinopathy. JDRF funded early research on PKC’s effect by George King, M.D. professor of medicine at Harvard Medical School. Dr King’s work and collaboration with Lilly led to ruboxistaurin’s development.

Retinopathy often has no overt symptoms in the earliest stages (“background retinopathy”) but progresses over time to a proliferative phase in which blood vessels of the eye leak and rupture easily, eventually causing blindness.  A related condition, diabetic macular edema, results when swelling in the center of the retina, known as the “macula,” disrupts forward vision. Currently, the only effective treatments are laser surgery and vitrecomy, both of which inflict minor damage on part of the eye.

Ruboxistaurin was originally tested with the expectation that it would delay progression from background to proliferative retinopathy. The new study shows that the compound does not actually inhibit this progression, but it does reduce worsening of macular edema and visual acuity.

In an editorial published in Ophthalmology, Thomas Gardner, M.D., and David Antonetti, Ph.D., of the JDRF Center for Diabetic Retinopathy at Penn State College of Medicine, emphasize that the positive results — even for unexpected reasons — demonstrate the importance of testing basic laboratory discoveries with rigorous hypothesis-driven clinical trials: “Does the failure to support the original hypothesis make the findings any less important for patients? Not at all. In fact, this is the best possible outcome for patients because the drug improved the parameter with which they are most concerned — vision.”

Drs. Gardner and Antonetti also note that the effects of ruboxistaurin represent “the beginning of a new era in diabetes complications treatments,” with more emphasis on drugs and medical therapy and less emphasis on surgical procedures.