Diagnosis & Diagnosis & Management of Management of

Diabetic Eye DiseaseDiabetic Eye DiseasePart 7Part 7

A. Paul Chous, M.A., O.D., F.A.A.O.A. Paul Chous, M.A., O.D., F.A.A.O.

Tacoma, WATacoma, WASpecializing in Diabetes Eye Care & EducationSpecializing in Diabetes Eye Care & Education

Newest Therapies for DRNewest Therapies for DR

VEGF Inhibitors: MacugenVEGF Inhibitors: MacugenTMTM, Lucentis, LucentisTMTM, , AvastinAvastinTMTM in trials in trials Macugen & Lucentis both improved VA and Macugen & Lucentis both improved VA and

reduced OCT thickness in DMEreduced OCT thickness in DME Macugen & Avastin caused regression of Macugen & Avastin caused regression of

PDR; Avastin reduced iris PDR; Avastin reduced iris neovascularizationneovascularization

Avastin caused rapid resolution of VH (n=2)Avastin caused rapid resolution of VH (n=2) DRCR.net now links multiple researchers & DRCR.net now links multiple researchers &

centerscenters

VEGF in Diabetic Retinopathy VEGF in Diabetic Retinopathy

Retinal VEGF levels elevated Retinal VEGF levels elevated in experimental diabetesin experimental diabetes

VEGFVEGF165165 injected in primates injected in primates

induces vascular leakage induces vascular leakage within 30 minuteswithin 30 minutes

Increased VEGF levels found Increased VEGF levels found in vitreous of eyes with in vitreous of eyes with proliferative DR & DMEproliferative DR & DME

DR patients have higher DR patients have higher VEGF levels in the aqueousVEGF 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.

Newest Therapies for DRNewest Therapies for DR PKC Inhibitors:PKC Inhibitors:

Ruboxistaurin (ArxxantRuboxistaurin (ArxxantTMTM, Lilly/Alcon) showed , Lilly/Alcon) showed modest benefit for DMEmodest benefit for DME

FDA approval in questionFDA approval in question Inflammatory Modulators:Inflammatory Modulators:

Steroids reduce VEGF production (Steroids reduce VEGF production (IV/sub-IV/sub-tenon’s)tenon’s)

Sustained release steroids: RetisertSustained release steroids: RetisertTMTM, , AlimeraAlimeraTMTM, Posurdex, PosurdexTMTM

Infliximab: a monoclonal antibody against TNF-Infliximab: a monoclonal antibody against TNF-a that inhibits breakdown of the blood-retinal a that inhibits breakdown of the blood-retinal barrier (in trials)barrier (in trials)

Newest Therapies for DRNewest Therapies for DR Micro-pulsed laser: lower duration & Micro-pulsed laser: lower duration &

energy causes less retinal damage, energy causes less retinal damage, possibly less severe scotomata and possibly less severe scotomata and improved scotopic visual functionimproved scotopic visual function

NutraceuticalsNutraceuticals BenfotiamineBenfotiamine: : fat-soluble form of thiamine fat-soluble form of thiamine

that blocks all 4 biochemical pathways of that blocks all 4 biochemical pathways of hyperglycemic insult in vivo & totally hyperglycemic insult in vivo & totally prevented DR in ratsprevented DR in rats

PycnogenolPycnogenol: : patented pine bark extract patented pine bark extract reduces capillary leakage and reduced reduces capillary leakage and reduced retinal thickening in one RCCT of DMEretinal thickening in one RCCT of DME

Newest Therapies for DRNewest Therapies for DR

Sub-threshold Diode Micropulse Laser

Low energy laser:Reduces visual fieldDefects, improves Night vision, lower Risk of pain during procedure

SDMLaser

Glucose MetabolismGlucose 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 levelsof intracellular thiamine, benfotiamine

reduces F-6-P and G-3-P viathe pentose phosphate shunt

G-3-P

Benfotiamine UpdateBenfotiamine Update

A recent trial of 600 mg A recent trial of 600 mg benfotiamine daily for 3 weeks in benfotiamine daily for 3 weeks in patients with longstanding T1DMpatients with longstanding T1DM Normalized elevated activity in:Normalized elevated activity in:

Polyol PathwayPolyol Pathway Hexosamine PathwayHexosamine Pathway AGE PathwayAGE Pathway PKC not assessed (too much blood PKC not assessed (too much blood

requiredrequired))Brownlee M. Diabetologia Sept 2008

Effective CommunicationEffective Communication

Clear explanation of the patient’s Clear explanation of the patient’s ocular conditions & treatment ocular conditions & treatment optionsoptions

Information about the link between Information about the link between diabetes & eye disease (& vice diabetes & eye disease (& vice versa)versa)

Realistic appraisal of the individual Realistic appraisal of the individual risk of vision lossrisk of vision loss risk of blindness < risk of CV diseaserisk of blindness < risk of CV disease risk of blindness ranges from 0.5%-risk of blindness ranges from 0.5%-

19%19%

Use positive language

Avoid scare tactics

Build a Relationship throughKnowledge & Compassion

Key PointsKey Points

Diabetes and diabetic eye Diabetes and diabetic eye disease are epidemicdisease are epidemic

Ocular complications are myriad Ocular complications are myriad and associated with large blood and associated with large blood vessel diseasevessel disease

State-of-the-art care is evolving State-of-the-art care is evolving rapidlyrapidly

“The only thing to dowith good advice is topass it on to others…

It is of absolutely nouse to oneself.”

- Oscar Wilde

Thank You!!

A. Paul Chous, O.D. dr.chous@diabeticeyes.com