1. Diagnosis & Management of Diabetic Eye Disease Part 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: Macugen TM, Lucentis TM, Avastin TM in trials VEGF Inhibitors: Macugen TM, Lucentis TM, Avastin TM in trials Macugen & Lucentis both improved VA and reduced OCT thickness in DME Macugen & Lucentis both improved VA and reduced OCT thickness in DME Macugen & Avastin caused regression of PDR; Avastin reduced iris neovascularization Macugen & Avastin caused regression of PDR; Avastin reduced iris neovascularization Avastin caused rapid resolution of VH (n=2) Avastin caused rapid resolution of VH (n=2) DRCR.net now links multiple researchers & centers DRCR.net now links multiple researchers & centers

3. VEGF in Diabetic Retinopathy Retinal VEGF levels elevated in experimental diabetes Retinal VEGF levels elevated in experimental diabetes VEGF 165 injected in primates induces vascular leakage within 30 minutes VEGF 165 injected in primates induces vascular leakage within 30 minutes Increased VEGF levels found in vitreous of eyes with proliferative DR & DME Increased VEGF levels found in vitreous of eyes with proliferative DR & DME DR patients have higher VEGF levels in the aqueous 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: PKC Inhibitors: Ruboxistaurin (Arxxant TM, Lilly/Alcon) showed modest benefit for DME Ruboxistaurin (Arxxant TM, Lilly/Alcon) showed modest benefit for DME FDA approval in question FDA approval in question Inflammatory Modulators: Inflammatory Modulators: Steroids reduce VEGF production ( IV/sub- tenon’s) Steroids reduce VEGF production ( IV/sub- tenon’s) Sustained release steroids: Retisert TM, Alimera TM, Posurdex TM Sustained release steroids: Retisert TM, Alimera TM, Posurdex TM Infliximab: a monoclonal antibody against TNF-a that inhibits breakdown of the blood- retinal barrier (in trials) 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 Micro-pulsed laser: lower duration & energy causes less retinal damage, possibly less severe scotomata and improved scotopic visual function Nutraceuticals Nutraceuticals Benfotiamine: fat-soluble form of thiamine that blocks all 4 biochemical pathways of hyperglycemic insult in vivo & totally prevented DR in rats 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 Pycnogenol: patented pine bark extract reduces capillary leakage and reduced retinal thickening in one RCCT of DME

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

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

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

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

10. Key Points Diabetes and diabetic eye disease are epidemic Diabetes and diabetic eye disease are epidemic Ocular complications are myriad and associated with large blood vessel disease Ocular complications are myriad and associated with large blood vessel disease State-of-the-art care is evolving rapidly 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!! A. Paul Chous, O.D. dr.chous@diabeticeyes.com