In a new study published in the January 2009 issue of the journal Ophthalmology, Japanese researchers found high levels of inflammatory factors, including vascular endothelial growth factor (VEGF), the primary proangiogenic growth factor, in the vitreous of people with diabetic macular edema (DME). These findings may lead to the development of new treatments in people with the disease.

DME is a serious complication of diabetic retinopathy that typically develops over many years in people with diabetes. It impacts the retina, the area at the back of the eye that focuses images for transmission to the brain. Advanced complications of retinopathy include the growth of abnormal blood vessels on the retina and optic nerve, and DME, in which there is swelling of the macula at the center of the retina as fluid leaks from hyperpermeable blood vessels. Precisely how DME develops is unclear, but the condition is similar to chronic inflammation that can occur in other areas of the body. When inflammation occurs, the body's immune system releases chemical messengers into the blood or affected tissues in an attempt to rid the body of a perceived infection, irritant, or injury. Some of the chemicals cause leakage of fluid into the tissues, resulting in swelling.

Hideharu Funatsu, M.D. and colleagues at the Tokyo Women's Medical University, Japan, measured levels of four inflammatory factors and one anti-inflammatory factor in the vitreous gel, which fills the eye between the lens and the retina, of 53 patients with DME, 15 patients with nondiabetic ocular disease, and 8 diabetic patients without retinopathy. They selected for measurement VEGF, intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and the anti-inflammatory pigment epithelium-derived factor (PEDF) because earlier research had linked these factors to the development or exacerbation of DME.

Levels of all four inflammatory factors were significantly higher, and PEDF significantly lower, in the vitreous of in patients with DME compared with the two other patient groups. VEGF and ICAM-1 had a stronger influence on the severity of DME than the other factors. VEGF is a strong vascular permeability factor that is overproduced in response to reduced oxygen levels (hypoxia) in the retinas of people with retinopathy. It is also the primary stimulant of tumor blood vessel growth. Dr. Funatsu's research suggests VEGF is the key to the inflammatory response in DME. Building on earlier, similar findings, the study also indicates that PEDF may block the expression and actions of the key inflammatory factors.

Although this study suggests that intravitreal injection of steroids such as triamcinolone acetonide may be useful in treating DME, further clinical trials are required to confirm this finding.

"Triamcinolone acetonide down-regulates VEGF and ICAM-1, inhibits inflammatory cells, stabilizes cell membranes, and increases PEDF levels. It appears to control more of the cytokine messengers that contribute to abnormal blood vessel permeability," said Dr. Funatsu. He adds that further focus on VEGF and ICAM-1 may further illuminate the mechanisms of blood vessel breakdown in DME and lead to new treatments.

With a new study from the Centers for Disease Control and Prevention predicting that diabetic retinopathy will triple from 5.5 million in 2005 to 16 million in 2050, improved treatments are urgently needed for this leading cause of blindness in working-age people. The CDC study is the latest indicator of a worldwide diabetes epidemic that is motivating ophthalmic research around the globe. For more information, visit www.aao.org.

By Roderick Smith, M.S.

References: Funatsu H, Noma H, Mimura T, Eguchi S, Hori S. Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 2009;116:73-79.