1. The Natural History
of Diabetic Retinopathy and How
Primary Care Makes A Difference
We will discuss
- How exactly does blood sugar control affect retinopathy?
- What are other factors that we measure in Primary Care that affect
retinopathy?
- 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, O'Colmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United States. Arch
Ophthalmol 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. Prevalence
and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 102:520-526, 1984
3. Diabetic Retinopathy in Your
Clinics:
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
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
24. 26 yr. old Type I African-American
HbA1C=9.6 4/27/2005
24
25. 26 yr. old Type I African-American
HbA1C=6.1 1/24/2007
25
26. 26 yr. old Type I African-American
HbA1C=6.1 1/24/2007
26
27. 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
29. Case 2: 24 year old Latin American
female
New Blood
Vessels
30. Case 2: 24 year old Latin American
female
Image from EyePACS visit on 7/16/2009:
HbA1c 9.3 – Pregnant
“Per pt, around July 4th, started seeing "webs" on the
right eye.”
Referred for treatment within one week.
31. Case 2: 24 year old Latin American
female
Image from EyePACS visit on 1/31/2006:
HbA1c 12.6 – Pregnant!
DM Type 1 since 7 months
Advised to have close follow up due to pregnancy.
Pregnancy accelerates retinopathy – Type 1 DM usually
has no retinopathy for first 5 years.
Prominent “IRMA”
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.
