Lc 02-2012-natural history

Uploaded on


  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads


Total Views
On Slideshare
From Embeds
Number of Embeds



Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

    No notes for slide
  • Terminal retinal vessels (arrows) point to dark central macula. Difficult to see capillary detail in normal angiogram. The normal central fovea (circle) is avascular, and known as the foveal avascular zone (FAZ).
  • Capillaries more easily seen because: 1) Capillary closure (nonperfusion) causes dark spaces; 2) Compensatory capillary dilation makes residual capillaries more visible. FAZ is larger and more irregular than normal due to perifoveal capillary closure. Note hyperfluorescent dots (microaneurysms) adjacent to areas of nonperfusion.
  • Normal retinal capillaries. Whole-mount autopsy specimen digested with proteolytic enzyme (trypsin). Retinal vessels more resistant to digestion than is neural retina. Residual vessels stained to show nuclei: round dark pericyte nuclei; elongated paler endothelial cell nuclei. Normal ratio of pericytes to endothelial cells 1:1.
  • Diabetic retinal capillaries. Trypsin digest preparation. Acellular capillaries presumably nonperfused in life cause local hypoxia. Dilated hypercellular capillaries presumably develop in response to local hypoxic conditions; larger caliber dilated vessels more readily visible in fluorescein angiography; may also be seen in color fundus photographs as prominent red capillary pattern.
  • Treat due to poor compliance?
  • Fluorescein represented in green. Retinal vessels have tight junctions that prevent fluorescein molecules (bound to albumin) from leaking out of capillaries. Choroidal capillaries (below) normally leak fluorescein through fenestrations in endothelium. RPE tight apical junctions prevent fluorescein from passing from choroid to retina.
  • Fluorescein leakage from retinal capillaries as in previous slide. Retina thickened by accumulated fluid (edematous). Note convex curvature of the inner retinal surface due to edema.
  • Effect of blood glucose control on progression of retinopathyAccording to clinical data from the Diabetes Control and Complications Trial (DCCT), with every 10% reduction in A1C (ie, from 8% to 7.2%), there was a 45% decrease in the progression of retinopathy in the conventionally-treated group and a 43% decrease in the group that was treated more intensively.1 This emphasizes the importance of maintaining A1C levels in accordance with the recommendations of the American Diabetes Association (ADA) and the American Academy of Clinical Endocrinologists (AACE).
  • Looking at retinopathy as an endpoint over the course of 8 years after the end of the DCCT, those who were originally in the intensive group continued to have much less progression of retinopathy compared with those who were in the original conventional control.[10,11] That just suggests that perhaps there is some kind of a metabolic memory of the benefit from good glycemic control that persists for a long time, even when the glycemic control subsequently may not stay as good as it was in the past. Thus, this study has shown us the benefits of glycemic control early on with persistently long-term benefits. We will continue to follow them for the next many years to see when the conventional group will start getting the benefits from this intensive therapy.At the end of the DCCT, the A1C difference between the 2 groups was about 2%: 9% vs. 7%. However, 1 year after the study ended, the difference between the two groups actually became far less, as happens in any clinical trial. People who were in the intensive group got tired of taking four shots of insulin and measuring their blood glucose six times a day. And their A1C started to go up. And those in the conventional treatment group actually saw the light, and they immediately started improving their glycemic control and their A1C improved. So within the first year, the curves became closer together. Subsequently, in the several years that we followed these people, the A1C levels between the two groups have remained more or less the same; no difference between the two groups--about 7.8%/7.9%.
  • In one of the new analyses, ACCORD Eye, the pairing of fenofibrate with simvastatin for intensive dyslipidemia therapy (compared with simvastatin alone) as well as glycemia therapy to achieve A1c levels of <6.0% (vs a target of 7.0% to 7.9%) significantly slowed the progression of diabetic retinopathy over four years The corresponding intensive strategy for hypertension, in which treatment aimed for a blood pressure target of <120 mm Hg (compared with <140 mm Hg), had no apparent effect on retinopathy progression.


  • 1. The Natural History of Diabetic Retinopathy and How Primary Care Makes A DifferenceWe will discuss- How exactly does blood sugar control affect retinopathy?- What are other factors that we measure in Primary Care that affectretinopathy?- How long does it take to develop vision impairment from diabetes?Please shareyour questions, comments, and experiences with us. February 27, 2012 12:30 – 1:00 PM Pacific Time Call In Number: 800.747.5150 Access Code: 9438735
  • 2. The Burden of Diabetic Retinopathy:  Prevalence of retinopathy in adults > 40 years in the U.S. is 3.4% (4.1 million persons)  Prevalence of VISION-THREATENING retinopathy is 0.75% (899,000 persons)*  The main cause of blindness among adults 25 to 70 years (12,000 to 24,000 persons per year)  Los Angeles Latino Eye Study: 18% with diabetes of more than 15 years duration had proliferative diabetic retinopathy  21% of patients with type 2 diabetes have retinopathy at the time of first diagnosis***•Kempen JH, OColmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United States. ArchOphthalmol 2004;122:552-63.**Varma R, Torres M, Pena F, et al. Prevalence of diabetic retinopathy in adult Latinos: the Los Angeles Latino eye study.Ophthalmology 2004;111:1298-306.***Klein R, Klein BE, Moss SE, Davis MD, DeMets DL: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. II. Prevalenceand risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 102:520-526, 1984
  • 3. Diabetic Retinopathy in YourClinics:Data derived from EyePACS cases: 33% + or – 14.8% have diabetic retinopathy 9.1% + or – 0.7% have sight-threatening retinopathy ?? % have vision impairment from diabetes
  • 4. Anatomy of the eye:
  • 5. 5Normal Retina Retinal Arcades Macula Optic Nerve
  • 6. Fluorescein angiogram Normal maculaNormal capillaries barely visible
  • 7. Fluorescein angiogramDiabetic maculaDilated capillaries interspersed withNonperfused dark spaces and hyperfluorescentdots (microaneurysms)
  • 8. Normal RetinalCapillariesTrypsin DigestRegular capillary caliberRound dark pericytes;elongated endothelialnuclei
  • 9. Diabetic RetinalCapillariesTrypsin DigestAcellular (nonperfused)capillariesHypercellular (dilated)capillaries
  • 10. 10Severe NonproliferativeRetinopathy (NPDR) Latin American male, DM II X 12 years, Last eye exam 5 years ago
  • 11. 11Neovascularization (NewBlood Vessels)49 year old Caucasian male, DM IIX 13 years, IDDM X 10years, subjective DM control:“Good”; last eye exam: more than5 years
  • 12. Normal Blood-Retinal Barrier Retinal vascular endothelial cells have tight junctions Tight junctions present a physiological barrier to the passage of larger molecules such as albumin Barrier maintains normal retinal thickness
  • 13. Normal Blood Retinal Barrier (BRB)Fluorescein AngiographyInner BRB-retinal capillary endothelium(Outer BRB-retinal pigment epithelium )
  • 14. Increased Retinal VesselPermeability in DiabeticRetinopathy  Breakdown of normal BRB  Abnormal (albumin-bound) fluorescein leakage from retinal capillaries  Microaneurysms major leakage source Results in retinal edema (swelling)
  • 15. Macular EdemaBreakdown of BRBRetinal thickening
  • 16. Increased Retinal VesselPermeability andMacular Edema:
  • 17. 66 yr old, DM X 14 yrs, HbA1C=5.5 19
  • 18. 60 yr. old, DM X 9yrs, HbA1C=9.1 21
  • 19. 60 yr. old, DM X 9yrs, HbA1C=9.1 22
  • 20. 60 yr. old, DM X 9yrs, HbA1C=9.11 yr. later,HbA1C=5.5: 23
  • 21. 26 yr. old Type I African-AmericanHbA1C=9.6 4/27/2005 24
  • 22. 26 yr. old Type I African-AmericanHbA1C=6.1 1/24/2007 25
  • 23. 26 yr. old Type I African-AmericanHbA1C=6.1 1/24/2007 26
  • 24. 24 yr. old Latin American female - Gail Ellias, OD and Karina Lomeli, MPH Type 1 DM since 2005 HbA1c = 9.5 Meds: prenatal vitamins, humalog/NPH insulin Photographed on 9/21/2011 at 12:21 PM Consultation on 9/21/2011 at 5:01 PM:  Large areas of neovascularization of the optic disk right eye Neovascularization elsewhere left eye  High risk proliferative diabetic retinopathy right eye Refer to Retina Specialist 24-48 hours  Patient is at risk for severe vision loss without treatment
  • 25. Case 2: 24 year old Latin Americanfemale
  • 26. Case 2: 24 year old Latin Americanfemale New Blood Vessels
  • 27. Case 2: 24 year old Latin AmericanfemaleImage from EyePACS visit on 7/16/2009:HbA1c 9.3 – Pregnant“Per pt, around July 4th, started seeing "webs" on theright eye.”Referred for treatment within one week.
  • 28. Case 2: 24 year old Latin AmericanfemaleImage from EyePACS visit on 1/31/2006:HbA1c 12.6 – Pregnant!DM Type 1 since 7 monthsAdvised to have close follow up due to pregnancy.Pregnancy accelerates retinopathy – Type 1 DM usuallyhas no retinopathy for first 5 years. Prominent “IRMA”
  • 29. 43 yr. old Hispanic Male
  • 30. 43 yr. old Hispanic Male 6 monthslater – blind in both eyes
  • 31. 37 yr. old Caucasian female,type I diabetic since age 5
  • 32. 2 days later..
  • 33. You Can Make A Difference…