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Future therapies for diabetic retinopathy look promising
Many approaches are currently being studied. Protein Kinase C beta selective inhibitor may hold promise.
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DALLAS — Many potential new therapies for diabetic retinopathy are under study. If they fulfill early promise, the future may hold hope for patients with diabetic retinopathy, according to a retinal subspecialist speaking here.
Numerous potential targets for future therapies have been identified, said L. Paul Aiello, MD, PhD, here at the annual meeting of the American Academy of Ophthalmology.
“We’re aware that certain specific factors play critical roles in the development of diabetic retinopathy,” said Dr. Aiello, an assistant professor at Harvard University Medical School.
“This is fortunate because, despite the relative convenience of delivery and the remarkable effectiveness of panretinal photocoagulation for proliferative diabetic retinopathy, and the more limited but significant benefit of focal and grid photocoagulation for diabetic macular edema, therapeutic limitations remain,” he said.
Inhibitors
There are multiple steps along the diabetic pathway, from initial hyperglycemic insult to ultimate retinal complications. Certain enzymes, such as the beta isoform of protein kinase C, are critical.
“So, inhibitors, such as protein kinase C beta, would be expected to suppress at least some of hyperglycemia’s detrimental effects on the retina,” Dr. Aiello explained.
Studies have shown that protein kinase C beta selective inhibitors can suppress vascular endothelial growth factor (VEGF)-induced retinal permeability. “Oral ingestion of protein kinase C beta isoform selective inhibitors can also suppress retinal neovascularization subsequent to laser-induced retinal vein occlusion in pigs and can dose-dependently normalize the diabetes-associated abnormalities in human retinal blood flow after only 30 days of oral use by patients,” he added.
These data and other studies have led to the clinical evaluation of this protein kinase C beta selective inhibitor in randomized, double-masked, placebo-controlled, clinical trials to determine their effect on preventing proliferative diabetic retinopathy and slowing or reversing progression of macular edema.
“Several other clinical trials using other VEGF and/or protein kinase C inhibitors are currently in or entering clinical trial as well,” he said.
Preventive, interventional approaches
Other approaches are under study. “Preventive approaches include compounds such as advanced glycation end product blockers and antioxidants. Interventional approaches include anti-permeability agents, a wide array of antiangiogenic agents and anti-proliferative agents. Some of these agents have shown positive results in small clinical studies, such as high doses of vitamin E, which normalized retinal and renal hemodynamics in patients with short-duration diabetes, despite no effect on glycemic control, suggesting that vitamin E therapy might provide additional risk reductions for diabetic retinopathy above those observed for intensive insulin therapy alone,” Dr. Aiello said.
Also being studied are medical, surgical and technological approaches to visual restoration.
Interactions with other diseases
Another approach to future therapy entails understanding the interactions of diabetic retinopathy with other concomitant systemic diseases. For example, hypertension is known to be an independent risk factor for diabetic retinopathy. Studies have shown that hypertension increases both VEGF and its receptors in the retinas of animals.
“Studies suggest that anti-VEGF therapies may ameliorate the deleterious effects of concomitant hypertension on diabetic and retinal disease,” he added.
Anti-VEGF agents have shown early promising results in clinical trials. Both VEGF receptor inhibitors and VEGF neutralizing monoclonal antibodies have been reported to improve colon cancer response rates, decrease time to disease progression and increase median survival time. Similar results have been seen with metastatic breast cancer and lung cancer. However, with lung cancer, complications from hemorrhage from the tumor were noted.
“The near future should bring us substantially more data regarding the non-destructive suppression of retinal neovascularization and retinal vascular leakage in patients. Results from current, ongoing, large-scale clinical trials will become available shortly,” he said.
According to Dr. Aiello, the more distant future may hold therapeutic approaches that may address the prevention of non-proliferative diabetic retinopathy as well as the deleterious effects of concomitant systemic disease.
For Your Information:
- L. Paul Aiello, MD, PhD, can be reached at 1 Joslin Place, Boston, MA 02215; (617) 732-4426; fax: (617) 732-2637. Dr. Aiello has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.