CLINICAL TRIAL SPOTLIGHT

Red Light Offers a Green Light

A clinical trial is testing near infrared light for the treatment of DME.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

While laser is still considered the gold standard for treating diabetic macular edema (DME), even a cursory look through the Clinical Trials Update section of this magazine will tell you that there are several treatments currently under investigation to treat this disease, which is the leading cause of vision loss in the United States among working-age adults.

One option currently in a phase 1 trial is the use of near infrared light (NIR) to treat DME. This pilot study, being undertaken at the Medical College of Wisconsin (MCW), uses a Warp 10 LED device to apply 80 seconds of NIR to the eye. Retinal Physician spoke to Harry T. Whelan, MD, one of the principal investigators on the study, to find out how NIR affects the macula and what implications this sort of treatment may have for the future of the treatment of DME.

"My belief is that diabetes is an energy crisis and that DME is ultimately a result of chronic exposure to abnormal energy metabolism in the retina," Dr. Whelan said. Dr. Whelan, who is professor of neurology, pediatrics, and hyperbaric medicine at MCW, does not dispute the underlying inability of the pancreas to produce insulin or that DME is caused in part by changes in retinal vasculature, but by viewing the retina as primarily a neural tissue, he has been motivated to take an approach that he has used previously in child patients suffering from oral mucositis, a side effect of chemotherapy and radiotherapy. In that case, published in June 2002 edition of the Journal of Clinical Laser Medicine & Surgery, NIR was found to speed healing time in patients to a statistically significant extent.

Though it may seem that severe oral ulcers and DME are far apart, Dr. Whelan explained that the 2 conditions share something in common that makes NIR a treatment worth investigating further. "We believe the mechanism of action in the application or NIR is the alteration of mitochondrial metabolism, thus improving energy utilization in the retinal cell. NIR is absorbed by cytochrome oxidase, which, then being stimulated, reduces oxidative stress and aids in the production of adenosine-5'-triphosphate (ATP)." Greater ATP production results in better cell-to-cell energy transfer and, according to the model, the amelioration of symptoms.

There have also been animal studies conducted, including some funded by the US Department of Defense, which was interested in finding ways of treating laserrelated eye injuries. Most significantly, a study published in March 2003 in the Proceedings of the National Academy of Sciences demonstrated the efficacy of NIR in stimulating photobiomodulation in rats with blindness induced with methanol (wood alcohol).

As for the process of applying NIR to DME-affected eyes, it is a procedure that patients enrolled in the study undertake at home. "The Warp 10 LED device is a handheld device about the size of a computer mouse that emits an LED ray," Dr. Whelan said. Because of concerns about the application of any kind of light to an already damaged retina, Dr. Whelan obtained an FDA nonsignificant risk letter as long as his protocol stipulated that the NIR would be applied through a closed eyelid.

It is far too early to tell whether Dr. Whelan will get statistically significant results in this study to warrant further research, but because his research is focusing on the role of the mitochondria in oxidative stress–related disorders and because the mitochondria has its own specific genome, Dr. Whelan's work does raise the question of whether the underlying model of his research may have implication for a genetic approach to DME.

"Some research suggests that there may be mitochondrial mechanisms involved," Dr. Whelan said. "There are downstream effects after NIR therapy that serve to upregulate and downregulate various gene families." For now, however, Dr. Whelan's emphasis is on NIR's ability to increase cell energy as a way of reducing vision loss due to complications from diabetes. For more information on this trial, please see CLINICAL TRIAL UPDATE. RP