Drug Shows Results in Combating Diabetic Retinopathy

By: Diana Barnes-Brown for Diabetes1

One of the most dreaded complications of type 1 diabetes is diabetic retinopathy, which causes vision problems and blindness. But at the beginning of 2007, human clinical trials of an oral drug therapy have shown the drug to be effective in preventing the progress of diabetic retinopathy. This represents a significant breakthrough in retinopathy treatment, for which surgical methods using lasers and traditional cutting techniques were the norm.

Learn More Signs and symptoms of diabetic retinopathy: Blurred or distorted vision Difficulty reading or doing “close work” Floating spots in the visual field, flashes in the visual field Partial or total loss of vision or a shadow or veil across the visual field, especially if sudden Eye pain

The drug is called ruboxistaurin, and its effectiveness was proven in a three-year, Phase II clinical trial funded by Eli Lilly and Company, the drug’s maker, and led by Lloyd Aiello, MD, PhD of the Joslin Diabetes Center. The study was conducted at 70 sites throughout the United States. Patients who took ruboxistaurin had significantly better outcomes than those who took the placebo at the end of the three-year trial period, with loss of vision slowed to about half the rate as compared to the placebo group.

Ruboxistaurin works by blocking the activity of an enzyme known as kinase C beta, or PKC beta. PKC beta is instrumental in causing the blood vessel damage that results in diabetic retinopathy. Past research on PKC conducted by Harvard researchers in collaboration with Eli Lilly led to the development of ruboxistaurin.

Diabetic retinopathy strikes when the blood vessels that supply the retina (the light-sensitive part of the eye) become damaged and begin acting abnormally. It progresses gradually, with no symptoms in early stages, then with worsening symptoms as the blood vessels in the retina become more damaged, and finally with blindness. The first stage of retinopathy is known as background retinopathy, and symptomatic stages are known as non-proliferative and proliferative retinopathy. When blood vessels break in non-proliferative retinopathy, swelling from the buildup of fluid in the retina can cause a related condition called macular edema, which results in problems with forward vision.

Ruboxistaurin was originally thought to slow progress from background to proliferative retinopathy, a capability not supported by the Lilly study. But the drug was found to be effective in reducing the rate at which macular edema grows worse, and the resulting loss of visual acuity. 

The FDA has requested additional testing and research before it will approve the drug for widespread use in humans, so it is not yet clear when the drug will be available to the general population. The study results are published in the journal Ophthalmology.

In a press release from Lilly, Steven Paul, MD, Executive Vice President of Science and Technology, stated “While we are disappointed in the outcome of the trials for SDPN, we are extremely pleased to be one step closer to providing a possible solution for patients with diabetic retinopathy." He added, “If ruboxistaurin is approved by the FDA, it would be the first oral medication for the treatment of this serious complication of diabetes."

Lilly is continuing research on the drug, with hopes of bringing the new drug to market once it can be tested for safety and its applications are more fully understood.