Diagnosis & Management of Diabetic Eye Disease Part 7

1. Diagnosis & Management of Diabetic Eye DiseasePart 7 A. Paul Chous, M.A., O.D., F.A.A.O. Tacoma, WA Specializing in Diabetes Eye Care & Education

2. Newest Therapies for DR • VEGF Inhibitors: MacugenTM, LucentisTM, AvastinTM in trials • Macugen & Lucentis both improved VA and reduced OCT thickness in DME • Macugen & Avastin caused regression of PDR; Avastin reduced iris neovascularization • Avastin caused rapid resolution of VH (n=2) • DRCR.net now links multiple researchers & centers

3. VEGF in Diabetic Retinopathy • Retinal VEGF levels elevated in experimental diabetes • VEGF165 injected in primates induces vascular leakage within 30 minutes • Increased VEGF levels found in vitreous of eyes with proliferative DR & DME • DR patients have higher VEGF levels in the aqueous Quam et al. IOVS. 2001; Tolentino et al. Ophthalmology. 1996; Funatsu et al. AJO. 2002; Adamis et al. AJO. 1994; Aiello et al. NEJM. 1994. Courtesy of Jeffry Gerson, O.D., F.A.A.O.

4. Newest Therapies for DR • PKC Inhibitors: • Ruboxistaurin (ArxxantTM, Lilly/Alcon) showed modest benefit for DME • FDA approval in question • Inflammatory Modulators: • Steroids reduce VEGF production (IV/sub-tenon’s) • Sustained release steroids: RetisertTM, AlimeraTM, PosurdexTM • Infliximab: a monoclonal antibody against TNF-a that inhibits breakdown of the blood-retinal barrier (in trials)

5. Newest Therapies for DR • Micro-pulsed laser: lower duration & energy causes less retinal damage, possibly less severe scotomata and improved scotopic visual function • Nutraceuticals • Benfotiamine: fat-soluble form of thiamine that blocks all 4 biochemical pathways of hyperglycemic insult in vivo & totally prevented DR in rats • Pycnogenol: patented pine bark extract reduces capillary leakage and reduced retinal thickening in one RCCT of DME

6. Newest Therapies for DR Low energy laser: Reduces visual field Defects, improves Night vision, lower Risk of pain during procedure SDM Laser Sub-threshold Diode Micropulse Laser

7. By dramatically increasing levels of intracellular thiamine, benfotiamine reduces F-6-P and G-3-P via the pentose phosphate shunt Glucose Metabolism Glucose Polyol Pathway Glucose-6-phosphate Fructose-6-phosphate Hexosamine Flux Glyceraldehyde-3-phosphate G-3-P Protein Kinase C Advanced Glycation Endproducts GAPDH 1,3 Diphosphoglycerate (harmless metabolite)

8. Benfotiamine Update • A recent trial of 600 mg benfotiamine daily for 3 weeks in patients with longstanding T1DM • Normalized elevated activity in: • Polyol Pathway • Hexosamine Pathway • AGE Pathway • PKC not assessed (too much blood required) Brownlee M. Diabetologia Sept 2008

9. Effective Communication Use positive language Avoid scare tactics Build a Relationship through Knowledge & Compassion • Clear explanation of the patient’s ocular conditions & treatment options • Information about the link between diabetes & eye disease (& vice versa) • Realistic appraisal of the individual risk of vision loss • risk of blindness < risk of CV disease • risk of blindness ranges from 0.5%-19%

10. Key Points • Diabetes and diabetic eye disease are epidemic • Ocular complications are myriad and associated with large blood vessel disease • State-of-the-art care is evolving rapidly

11. “The only thing to do with good advice is to pass it on to others… It is of absolutely no use to oneself.” - Oscar Wilde

12. Thank You!! • Paul Chous, O.D. • dr.chous@diabeticeyes.com