In a study of five diabetic patients with persistent macular edema, breathing supplemental oxygen for three months reduced fluid buildup and swelling in the macula and, in some cases, improved visual acuity. Researchers think the therapy could be used in conjunction with laser treatments that also improve oxygenation in the retina to provide long-term stability in these patients.
"The results were really dramatic," says Peter A. Campochiaro, M.D., senior author of the study and a professor of ophthalmology and neuroscience at Hopkins' Wilmer Eye Institute.
For the study, published in a recent issue of the journal Investigative Ophthalmology & Visual Science, the researchers studied nine eyes of three men and two women, ages 52 to 69, who had type 2 diabetes for an average of nine years. All patients had received at least one laser eye treatment. Despite an average of 2.7 treatments per eye, all eyes except one had persistent edema.
Patients were given 4 liters per minute of oxygen delivered by small tubes inserted into their noses, and instructed to use the oxygen continuously every day for three months, removing the tube only when taking showers. They were provided with a stationary oxygen concentrator for home and portable oxygen tanks to use outside the home.
After three months, excess thickness of the macula was reduced by an average of 43 percent in all nine eyes. Excess thickness of the fovea, the part of the eye responsible for the sharpest vision, was reduced by 42 percent, and macular volume dropped by 54 percent. In addition, three eyes improved in visual acuity, with the ability to see two lines higher on a standard eye chart.
"The likelihood that these measurements would change by such magnitudes by chance is very small," Campochiaro says.
Once the oxygen therapy was discontinued, vision slowly worsened in some eyes. But in four eyes in which retinal thickness had returned to the normal range while on oxygen, the improvement was maintained even after oxygen was stopped. Since these patients all had previous laser therapy, it is possible that the reduced thickening of the macula achieved by oxygen allowed the laser to exercise a stabilizing effect.
Diabetic macular edema affects up to 10 percent of all patients with diabetes. It is caused when high blood sugar, through a cascade of events, causes damage in normal retinal blood vessels and a decrease in the supply of oxygen and nutrients. Campochiaro and Quan Dong Nguyen, M.D., the principal investigator on the study, hypothesize that the retina, when faced with a decrease in oxygen, releases vascular endothelial growth factor (VEGF) and other substances that cause retinal blood vessels to become leaky and ultimately stimulate the growth of new blood vessels. The leakage of fluid into the macula causes it to become thickened and results in vision loss.
Supplemental oxygen reduces production of VEGF and similar proteins, which in turn reduces the amount of leaking in retinal vessels and lessens the severity of macular edema. The treatment could reduce the thickness of the retina before laser treatment, making the laser more effective and more likely to maintain stability without supplemental oxygen. Alternately, supplemental oxygen could be combined with newer treatments that directly target VEGF. For example, Campochiaro and colleagues also studied an oral drug that blocks receptors for VEGF, called PKC412, which was found to significantly reduce macular edema and improve visual acuity in diabetics. This first demonstration of directly targeting VEGF was reported by the researchers in another study published in the March issue of the journal.
"This confirms that VEGF is a good target for treatment of diabetic macular edema," Campochiaro says.
Several drugs that antagonize VEGF in different ways are now being tested in patients with diabetic macular edema.
The study was supported by the National Eye Institute. Coauthors were Quan Dong Nguyen, Syed Mahmood Shah, Elizabeth Van Anden and Jennifer U. Sung of Hopkins, and Susan Vitale of the National Eye Institute.
Nguyen, Q.D. et al, "Supplemental Oxygen Improves Diabetic Macular Edema: A Pilot Study," Investigative Ophthalmology & Visual Science, February 2004, Vol. 45, No. 2, pages 617-624.
Campochiaro, P.A., and the C99-PKC412-03 Study Group, "Reduction of Diabetic Macular Edema by Oral Administration of the Kinase Inhibitor PKC412," Investigative Ophthalmology & Visual Science, March 2004, Vol. 45, No. 3, pages 922-931.
Johns Hopkins' Wilmer Eye Institute
Investigative Ophthalmology & Visual Science
National Eye Institute