A Dry AMD Treatment?; Some Long-Term Diabetics Escape PDR

Main Category: Eye Health / Blindness
Also Included In: Seniors / Aging;??Diabetes;??Clinical Trials / Drug Trials
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At the American Academy of Ophthalmology (AAO) - Middle East-Africa Council of Ophthalmology (MEACO) Joint Meeting yesterday, Oct. 17, researchers reported progress on two top eye disease challenges: treating advanced "dry" age-related macular degeneration, and preventing blindness in people with diabetes. The Joint Meeting is in session October 16 through 19 at McCormick Place, Chicago. The AAO-MEACO meeting is the world's largest, most comprehensive ophthalmic education conference.

Proven Arthritis Drug Shows Promise versus Dry AMD

While ophthalmologists can turn to several medications for patients with vision-threatening "wet" age-related macular degeneration (AMD), there are no effective treatments for advanced "dry" AMD, the more common form. Today a research group led by Jason S. Slakter, MD, New York University School of Medicine, reports on a phase-two clinical trial of fenretinide, a synthetic derivative of vitamin A. Risk of developing wet AMD decreased almost two-fold in dry AMD patients who took the medication. Geographic atrophy (GA) lesion growth was also reduced in the fenretinide group. This reduced growth correlated with lowered blood levels of the biomarker retinol binding protein (RBP) - an indication that fenretinide was working. Patients whose RBP decreased 60 percent or more also had the most significant reductions in lesion growth. GA lesions degrade the area of the eye called the retinal pigment epithelium (RPE), which can result in significant vision loss.

Advanced AMD, in either wet or dry form, can destroy the detailed, central vision we need to recognize faces, read, drive, and enjoy daily life. It is a major cause of vision loss in the United States. In the advanced wet form abnormal new blood vessels develop under the retina, then bleed or leak fluid and form scars. Advanced dry AMD sometimes abruptly converts to the wet form.

Fenretinide works on three key AMD disease mechanisms: it has strong anti-inflammatory properties, inhibits abnormal blood vessel growth (angiogenesis) and reduces vitamin-A derived toxins such as A2E and lipofuscin. These toxins accumulate in the RPE and interfere with its ability to nourish light-receptor cells in the retina.

"Evidence from our study and others points to fenretinide's potential to treat and prevent diseases of the retina," Dr. Slakter said.

This randomized controlled trial included 246 patients at 30 sites around the United States. Tests showed that patients' visual acuity and other markers of eye health were not adversely affected by fenretinide. Side effects, including delayed ability to adapt to dark conditions, were minor and reversible when the medication was stopped. Years of use of fenretinide to treat cancers, rheumatoid arthritis, and other diseases have shown it to be safe and well tolerated. ReVision Therapeutics, the company supporting the continued clinical development of fenretinide, is planning a Phase 3 clinical trial to begin in 2011.

Financial disclosures: This research was supported by a grant to the Digital Angiography Reading Center; Dr. Slakter served as a consultant to Sirion Therapeutics.

Clues to Retinopathy from Survivors of 50+ Years of Diabetes

Doctors assume that the longer a person has diabetes, the more likely he or she is to develop serious eye disease and, if untreated, become blind. But a new study of patients who have had type 1 diabetes for at least 50 years tells a different story. Many of these patients appear to be protected against proliferative diabetic retinopathy (PDR), and the majority of them escape vision loss despite extremely long-duration diabetes, according to Jennifer Sun, MD, Beetham Eye Institute at Joslin Diabetes Center, a Harvard School of Medicine affiliate.

With one exception, development of PDR occurred within the first two decades in these Joslin patients (in 96 of 97 patients). If PDR did not develop during that period, then retinopathy progressed slowly and in some cases stopped altogether. PDR development was associated with higher blood pressure, but not with glycemic (blood sugar) control. This confirmed an earlier, larger study's surprising finding that neither glycemic control nor duration of diabetes correlated with the severity or presence of diabetic retinopathy (DR) in patients who successfully survived 50 or more years with type 1diabetes. Decreased blood levels of the protein tyrosine phosphatase SHP-1 was also associated with protection from development of any DR, and Dr. Sun recommends further study of SHP-1 to learn whether it might be a target for treatment.

"There is no doubt that lack of glycemic control is a major factor in the development of eye complications for patients with shorter-duration diabetes. But our data from this unique group of individuals who have survived extremely long-duration diabetes may help identify other factors that protect against retinopathy complications," said Dr. Sun. "These findings also suggest that protective mechanisms are activated very early in diabetes."

Source:
Mary Wade
American Academy of Ophthalmology

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Lifestyle intervention for overweight patients with diabetes provides long-term benefits

ScienceDaily (Sep. 27, 2010) ? An intensive lifestyle intervention appears to help individuals with type 2 diabetes lose weight and keep it off, along with improving fitness, control of blood glucose levels and risk factors for cardiovascular disease, according to a report in the September 27 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Improving blood glucose control and cardiovascular risk factors in patients with type 2 diabetes is critical in preventing long-term complications of the disease, according to background information in the article. Emphasis has been placed on screening and pharmacologic management of these parameters. "Lifestyle-based weight loss interventions are also recommended to improve glycemic control and risk factors, but the evidence supporting the efficacy of lifestyle approaches is limited to short-term studies of typically less than one year," the authors write.

The Look AHEAD (Action for Health in Diabetes) Research Group conducted a multicenter randomized clinical trial comparing the effects of an intensive lifestyle intervention to diabetes support and education among 5,145 overweight or obese individuals (average age 58.7) with type 2 diabetes. Of these, 2,570 were assigned to the lifestyle intervention, a combination of diet modification and physical activity designed to induce a 7 percent weight loss in the first year and maintain it in subsequent years. Participants were seen and contacted by phone at least monthly for all four years. The 2,575 individuals assigned to the diabetes support and education group were invited to three group sessions each year focusing on diet, physical activity and social support.

On average, across the four-year period, individuals in the lifestyle intervention group lost a significantly larger percentage of their weight than did those in the diabetes support group (6.2 percent vs. 0.9 percent). They also experienced greater improvements in fitness, hemoglobin A1c level (a measure of blood glucose), blood pressure and levels of high-density lipoprotein (HDL, or "good" cholesterol). Individuals in the diabetes support group, on the other hand, experienced greater reductions in low-density lipoprotein (LDL, or "bad") cholesterol, owing to greater use of cholesterol-lowering medications in this group.

At the end of four years, the lifestyle intervention group maintained greater improvements in weight, fitness, hemoglobin A1c levels, systolic (top number) blood pressure and HDL levels. "Although the differences between the two groups were greatest initially and decreased over time for several measures, the differences between the groups averaged across the four years were substantial and indicate that the intensive lifestyle intervention group spent a considerable time at lower cardiovascular disease risk," the authors write.

"The critical question is whether the differences between groups in risk factors will translate into differences in the development of cardiovascular disease," they continue. "These results will not be available for several additional years. However, effects of the magnitude that we observed for fitness, HDL-C and hemoglobin A1c levels and blood pressure have been associated with decreased cardiovascular events and mortality in previous medication trials and observational studies. Moreover, there may be long-term beneficial effects from the four-year period in which intensive lifestyle intervention participants have been exposed to lower cardiovascular disease risk factors, as seen in other clinical trials."

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by JAMA and Archives Journals.

Journal Reference:

The Look AHEAD Research Group. Long-term Effects of a Lifestyle Intervention on Weight and Cardiovascular Risk Factors in Individuals With Type 2 Diabetes Mellitus: Four-Year Results of the Look AHEAD Trial. Archives of Internal Medicine, 2010; 170 (17): 1566-1575 DOI: 10.1001/archinternmed.2010.334

Note: If no author is given, the source is cited instead.

View the original article here