Researchers make major breakthrough in treatment for age-related blindness

Scientists at Trinity College, Dublin say they have made a major breakthrough in treatment for age-related macular degeneration (AMD) – the leading cause of blindness in people over 50.

Through their research, they have discovered that interleukin-18 (IL-18), a component of the immune system, can protect patients from vision loss, and it can be administered in a non-invasive way.  Since current treatments for AMD involve periodically injecting medication directly into the eyeball, this could have significant implications for AMD therapy.

“[IL-18] has already entered into clinical trials [for cancer research], and it has a very good safety profile when administered intravenously. It was never injected into the eye,” study author Matthew Campbell, research assistant professor in genetics at Trinity, told

“So all the signs show this could be another tool in the arsenal against wet AMD.”

AMD has two major forms: “dry,” the more common form, and “wet,” which accounts for 90 percent of the severe vision loss caused by macular degeneration.  When a patient suffers from wet AMD, the blood vessels grow into the retina, the layer of tissue lining the inner surface of the eye, and begin to leak blood or fluid – causing immediate retinal blindness. Retinal blindness can be especially challenging for patients, as the retina provides sharp, central vision for reading, driving and perceiving small details.

In order to combat wet AMD, patients must undergo eye injections of antibodies that inhibit a molecule called VEGF – which is responsible for stimulating the overgrowth of blood vessels into the retina.  These injections are effective, but they can be extremely uncomfortable, and patients must receive them on a monthly basis.

Campbell and his team say IL-18 can work just as effectively as these anti-VEGF injections, as it produces cells that prevent wet AMD.

“[IL-18] can serve a similar function to these anti-VEGF molecules,” he said.  “While the current therapies for wet AMD are like sponges and mop up the VEGF, this stops its development completely.”

To test their findings, Campbell and Sarah Doyle, an assistant professor in immunology at Trinity and first author of the study, analyzed IL-18’s effects in mice. They mimicked the damage that wet AMD patients experience by using a very fine laser to damage the backs of the mice’s eyes. They then administered a form of IL-18 that GlaxoSmithKline had been developing as a potential cancer therapy.

This drug screening showed that IL-18 was able to prevent the leakiness of the blood vessels into the retina, as well as stop their overgrowth. Since IL-18 is pro-inflammatory, the researchers were concerned about patient tolerance, but preliminary human trials have shown that low doses have no adverse side effects, other than a very low-grade fever.

Given the early success of their study, Campbell is hopeful that IL-18 may be used as an adjunct therapy to anti-VEGF therapies, until further research can confirm it as a viable replacement. Since the cells produced by IL-18 tend to linger in the body for six to eight weeks, this treatment could potentially lessen – if not eliminate – the number of injections wet AMD patients must receive each year.

“In the short term, [anti-VEGF injections] are very effective and can improve people’s vision.  But the main problem with anti-VEGF treatment is when do we stop? The simple answer is we don’t, and some people can become resistant, which is very unfortunate. So we need to explore ways to extend length of time between injections… We need things like IL-18.”

The research was published online in Science Translational Medicine.