New Treatments for Diabetic Retinopathy
Several new medicines are now becoming available for the treatment of diabetic retinopathy. They belong to a class of agents called VEGF inhibitors (vascular endothelial growth factor inhibitors). VEGF is a biochemical produced by blood vessels when they are exposed to high levels of glucose, and plays a critical role in the development of the abnormal new blood vessels characteristic of proliferative diabetic retinopathy (PDR), the most serious form of this eye disease. The trade names of these agents are Macugen™, Lucentis™ and Avastin™. Avastin is FDA approved for treating certain forms of colorectal cancer (forms that rely on new blood vessels generated by increased levels of VEGF), but is not approved for use in the eye; nonetheless, many retinal specialists are starting to use Avastin to treat PDR (and 'wet,' neovascular age-related macular degeneration) because it appears to be very effective and is quite inexpensive. Only time and research will tell if these new agents should replace laser therapy as the "gold standard" for treatment of PDR.
Updated ADA Guidelines
The American Diabetes Association recently released its updated guidelines and recommendations for detection and treatment of diabetic eye disease.
Analysis: This position statement reflects the best scientific evidence regarding the prevention, detection and treatment of diabetic retinopathy. Most notably, the recommendation for annual dilated eye examinations by an optometrist or ophthalmologist experienced with diabetes remains unchanged, despite the controversial position of a paper appearing in the Journal of the American Medical Association that questioned the cost benefits of annual dilated exams for Type 2 patients. The distinguished panel of ADA experts recognize the fact that retinopathy is not the only eye disease for which Type 2 patients are at risk, and justifiably (in my view) maintains ADA's position regarding the importance of yearly eye examinations in detecting the early stages of not only retinopathy, but cataract, glaucoma and age-related macular degeneration as well.
Synthetic Vitamin B1 May Prevent Diabetic Retinopathy
In a study that may represent a major breakthrough in the prevention and treatment of diabetic retinopathy and other microvascular complications of diabetes, a multinational team of researchers has announced that a lipid soluble form of Vitamin B1 (thiamine) prevented the development of diabetic retinopathy in rats over a 36 week period. The synthetic thiamine derivative, called benfotiamine, has been used safely for more than a decade in Europe, where it is prescribed to treat painful neuropathies. Benfotiamine apparently boosts levels of a cellular enzyme called transketolase by 300-400%, a factor that prevents high blood sugar levels from forming chemical compounds known to damage the cells lining the inner walls of blood vessels (including chemicals known as "advanced glycation end products" or AGEs, and "protein kinase C" or PKC, both of which are discussed in my book). Naturally occurring Vitamin B1 (thiamine) boosts transketolase levels by a mere 20%.
For over 30 years, scientists have known of four biochemical pathways responsible for the blood vessel damage that causes many diabetes complications - damage that makes diabetes a leading cause of eye disease, kidney disease, nerve disease and heart disease. This study, appearing in the March 2003 issue of Nature Medicine, shows that benfotiamine completely blocked three of these four chemical pathways, and prevented the development of retinopathy in diabetic rats, whereas control animals all developed some degree of retinopathy. As the biochemical pathways in human blood vessels are very similar to those of rats, it is believed that benfotiamine may be very beneficial for treating human diabetics. Clinical trials are expected to begin within the next year.
Analysis: This research holds great promise for preventing or at least minimizing the deleterious effects of hyperglycemia on blood vessels throughout the body. Drugs designed to block just one of these four harmful biochemical pathways currently are being developed (e.g. PKC inhibitors), and benfotiamine appears to block at least three of these pathways simultaneously. Moreover, this compound has long been used in Germany without reported side effects.
However, benfotiamine has not been tested rigorously in humans, and no one knows what constitutes either a safe dose or an effective dose for humans. Although it is derived from a naturally occurring substance (thiamine), benfotiamine is a synthetic derivative with a different chemical structure, and that can make all the difference (both good and bad). It is also important to know that thiamine is water soluble, meaning that excessive amounts are eliminated rather easily in the urine. Benfotiamine is lipid (fat) soluble, a fact that undoubtedly increases its retention within the body and its effectiveness, but also potentially increases its toxicity (just as Vitamin A, a lipid soluble substance, is healthful in moderation but harmful in excess). Nonetheless, I suspect benfotiamine may become a major tool in our arsenal against diabetes complications, including eye disease.