Pharmacy & Therapeutics - December 2008 - (Page 721)

MEETING HIGHLIGHTS Fourth Annual Ophthalmic Drug Development and Delivery Summit and Third Annual Onmark National Payor/Provider Forum Walter Alexander Ophthalmic Summit This year’s meeting brought together approximately 80 representatives from the ophthalmic industry, clinical practice, academia, and biotech research. Chair and founder Kay D. Rittenhouse, PhD, underscored a high and growing worldwide incidence of glaucoma, age-related Drugs for Diabetes-Related Eye Diseases • Jeffrey L. Edelman, PhD, Research Investigator, Biological Sciences, Drug Discovery, Allergan Pharmaceuticals Although the FDA has not yet approved any drugs for treating diabetic retinopathy and its complications, agents from a number of classes are in development and antioxidants are being investigated for their possible benefits. Gaining regulatory approval, however, has been a formidable obstacle because of the requirement for new drugs to show superiority to or equivalency with laser treatments and vitrectomy. Still, research is spurred by the significant unmet medical need. Diabetic retinopathy is the leading cause of blindness in working-age individuals in the U.S. and is responsible for 12,000 to 24,000 new cases of blindness each year. Among the 230 million people worldwide with diabetes mellitus, nearly all with type-1 diabetes and 60% with type-2 diabetes will develop retinopathy. Half of those patients will be found to have retinopathy after having diabetes for 10 years, and 90% will be affected after having diabetes for 25 years. Although the lack of approved agents means a wide-open field for drug developers, many potential agents are still in the testing stages. The primary pathophysiological impact in diabetes is on vascular integrity. Characteristic retinal damage includes capillary nonperfusion, ischemia, and dropout of vascular endothelial cells and pericytes (the slender, relatively undifferentiated, connective tissue cells found around small blood vessels). Normal capillaries have a 1:1 ratio between endothelial cells and pericytes. In individuals with diabetes, however, the ratio is 4:1, leading to a breakdown of the blood–retina barrier, ischemia, neovascularization, and retinal detachments. “The blood vessels grow on the inner retinal surface out into the vitreous and can form attachments, which pull the retina off the back of the eye,” Dr. Edelman said. Animal studies have shown that the vitreous has the same concentration of glucose as the blood, suggesting that other Mr. Alexander is a freelance medical writer living in New York City. macular degeneration, dry eye, and other ocular diseases that are causing much of the world’s blindness. Two key presentations from the Pfizer-sponsored event are reviewed in the first part of this article. tissues in the eye may also be affected. Diabetic retinopathy can be nonproliferative or proliferative. The nonproliferative type is associated with microaneurysms, hemorrhages, diabetic macular edema (DME), and hard exudates. The proliferative type is characterized by new blood vessel formation and fibrous tractional bands that are formed from the optic disc. Conventional treatment targets glycemic control. Some evidence suggests a risk of worsening retinopathy with antihyperglycemic agents (along with the threat of hypoglycemic episodes and diabetic ketoacidosis), but glycemic control is the one approach with proven benefit. A reduction in retinal microaneurysms has also been observed with aspirin in combination with dipyridamole (Aggrenox, Boehringer Ingelheim) or ticlopidine (Ticlid, Roche). Clinical research has confirmed the efficacy of laser treatments and surgical vitrectomy. Vitrectomy is indicated for vitreous hemorrhage and proliferative diabetic retinopathy. For some patients, vitrectomy can improve vision; it has also been effective for some individuals with DME that has been refractory to laser treatments. Steady advances in surgical techniques are widening the number of indications. For patients with severe nonproliferative or proliferative retinopathy, pan-retinal photocoagulation has become the standard of care. Treating the associated DME with 1,500 laser burns preserves vision for many, but the method is not without hazards. Among potential risks of adverse events are constriction of the visual field, night blindness, changes in color vision, misplaced laser burns that exacerbate DME, acute glaucoma, and traction retina detachment. Dr. Edelman said, however, “Despite all these risks, it is still the benchmark.” The list of pharmacological agents that have been tested in diabetic retinopathy is extensive. Aldose reductase inhibitors showed no significant effects on endpoints or progression. The protein kinase C inhibitor ruboxistaurin (Eli Lilly) reduced the risk of vision loss, but the benefit was modest. Insulin-like growth factor (IGF)–inhibiting microspheres Vol. 33 No. 12 • December 2008 • P&T® 721

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Pharmacy & Therapeutics - December 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Interpreting Estimates of Treatment Effects Chemotherapy Foundation Symposium XXVI: Innovative Cancer Therapy for Tomorrow Third Annual Onmark National Payor/Provider Forum Fourth Annual Ophthalmic Drug Development and Delivery Summit Classification and Pharmacological Management Of Obesity CE Test and Forms Season’s Greetings: Thanks to Our Readers and Reviewers

Pharmacy & Therapeutics - December 2008

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