DIABETIC RETINOPATHY

Ines Serrano MD
Evan Waxman MD PhD
LEARNING OBJECTIVES
• Recognize the importance of diabetic retinopathy as a public
health problem
• Discuss diabetic retinopathy as a leading cause of blindness in
developed countries
• Identify the risk factors for diabetic retinopathy
• Describe and distinguish between the stages of diabetic
retinopathy
• Understand the role of risk factor control and annual dilated eye
exams in the prevention of vision loss
DIABETES MELLITUS
Diabetes Mellitus is a group of diseases characterized by high blood glucose
levels. Diabetes results from defects in the body's ability to produce and/or use
insulin.
• Type 1 diabetes is usually diagnosed in children and young adults, and was
previously known as juvenile diabetes. In type 1 diabetes, the body does not
produce insulin. 5% of people with diabetes have this form of the disease.
• In Type 2 diabetes, either the body does not produce enough insulin or the
cells ignore the insulin. This is the most common form of diabetes.

http://www.diabetes.org/diabetes-basics/?loc=GlobalNavDB
DIABETIC RETINOPATHY (DR)
DEFINITION
• Progressive dysfunction of the retinal blood vessels
caused by chronic hyperglycemia.
• DR can be a complication of diabetes type 1 or
diabetes type 2.
• Initially, DR is asymptomatic, if not treated though it
can cause low vision and blindness.

http://www.mdconsult.com/das/book/pdf/282715756-3/978-0-323-04332-8/4-u1.0-B978-0-323-04332-8..00092-5..DOCPDF.pdf?isbn=978-0-323-04332-8&eid=4-u1.0-B978-0-323-04332-8..00092-5..DOCPDF
WHAT IS THE RETINA?
• The retina is a multilayered, light sensitive neural tissue
lining the inner eye ball. Light is focused onto the retina
and then transmitted to the brain through the optic
nerve.
• The macula is a highly sensitive area in the center of
the retina, responsible for central vision. The macula is
needed for reading, recognizing faces and executing
other activities that require fine, sharp vision.
RETINA
Healthy Retina Diabetic Retinopathy
DIABETIC RETINOPATHY
EPIDEMIOLOGY

• The total number of people with diabetes is

projected to rise from 285 million in 2010 to
439 million in 2030.
• Diabetic retinopathy is responsible for 1.8
million of the 37 million cases of blindness
throughout the world .
• Diabetic retinopathy (DR) is the leading
cause of blindness in people of working age
in industrialized countries.

http://www.who.int/bulletin/volumes/82/11/en/844.pdf
http://www.ncbi.nlm.nih.gov/pubmed/19896746
Causes of global blindness in millions of people
(WHO 2002)
20
18
16
14
12
10
8
6
4
2
0

A. Foster S.Resnikoff. The impact of vision 2020 on global

blindness. Eye 2005; 19:1133-1135
DIABETIC RETINOPATHY
EPIDEMIOLOGY

• The best predictor of diabetic retinopathy is the duration of

the disease
• After 20 years of diabetes, nearly 99% of patients with type 1
diabetes and 60% with type 2 have some degree on diabetic
retinopathy
• 33% of patients with diabetes have signs of diabetic
retinopathy
• People with diabetes are 25 times more likely to become blind
than the general population.
Ophthalmology Myron Yanoff MD and Jay S. Duker
Basic and Clinical Science Course, Section 12: Retina and Vitreous AAO
http://www.aao.org/eyecare/news/upload/Eye-Health-Fact-Sheet.pdf -
PREVALENCE OF DIABETIC RETINOPATHY AFTER
20 YEARS OF DIAGNOSIS
http://www.who.int/bulletin/volumes/82/11/en/844.pdf
DIABETIC RETINOPATHY SYMPTOMS
Diabetic retinopathy is asymptomatic in early stages of the disease
As the disease progresses symptoms may include
• Blurred vision
• Floaters
• Fluctuating vision
• Distorted vision
• Dark areas in the vision
• Poor night vision
• Impaired color vision
• Partial or total loss of vision
Risk factors

• Duration of diabetes
• Poor Blood Sugar control
• HTN
• Hyperlipidemia
• Barriers to care

http://jama.ama-assn.org/content/304/6/649.short?rss=1
The Effect of Intensive Diabetes Treatment
On the Progression of Diabetic Retinopathy
In Insulin-Dependent Diabetes Mellitus

The Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial Research Group

Intensive control reduced the risk of developing retinopathy by 76%

and slowed progression of retinopathy by 54%; intensive control
also reduced the risk of clinical neuropathy by 60% and albuminuria
by 54%.

Arch Ophthalmol. 1995; 113:36-51

RISK FACTORS DIABETIC RETINOPATHY

Duration of diabetes is a major risk

factor associated with the development
of diabetic retinopathy

The severity of hyperglycemia is the

key alterable risk factor associated with
the development of diabetic retinopathy

http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=d0c853d3-219f-487b-a524-326ab3cecd9a
HOW DIABETES CAUSES VISION LOSS
How diabetes cause vision loss

Macular Clinical
significant
edema
macular edema

Preclinical Background Vision

Diabetes changes DR loss

Vitreous hemorrhage
Preproliferative Proliferative and/or Retinal
DR DR detachment and/or
neovascular glaucoma
 PATHOPHYSIOLOGY
Diabetic Retinopathy is a microvasculopathy that
causes:
• Retinal capillary occlusion
• Retinal capillary leakage
MICROVASCULAR OCCLUSION
Microvascular occlusion is caused by:
• Thickening of capillary basement membranes
• Abnormal proliferation of capillary endothelium
• Increased platelet adhesion
• Increased blood viscosity
• Defective fibrinolysis

Retina in systemic disease : a color manual of ophthalmoscopy / Homayoun

Tabandeh, Morton F. Goldberg 2009
 Microvascular
Occlusion

Ischemia

Infarction

Increased VEFG

Cotton – wool spot

Neovascularization

Vitreous Neovascular
Fibrovascular bands
hemorrhage glaucoma

Tractional retinal
detachment Retina in systemic disease : a color manual of
ophthalmoscopy / Homayoun Tabandeh, Morton F.
Goldberg 2009
MICROVASCULAR LEAKAGE
Microvascular leakage is caused by:
• Impairment of endothelial tight junctions
• Loss of pericytes
• Weakening of capillary walls
• Elevated levels of vascular endothelial growth factor (VEGF)

Retina in systemic disease : a color manual of ophthalmoscopy / Homayoun Tabandeh,

Morton F. Goldberg 2009
 Microvascular Leakage

Retinal
Edema Hard exudates
hemorrhage

Retina in systemic disease : a color manual of

ophthalmoscopy / Homayoun Tabandeh, Morton F.
Goldberg 2009.
RECOMMENDED
DiabeticEYE EXAMINATION
Eye Disease
SCHEDULE Key Points
Diabetes Type Recommended Time of Recommended Follow-
First Examination up*

Type 1 3-5 years after Yearly

diagnosis

Type 2 At time of diagnosis Yearly

Prior to pregnancy • Treatments

Prior exist but workNobest
to conception retinopathy to mild
(type 1 or type 2) and early in the first moderate NPDR every
before vision
trimesteris lost 3-12 months
Severe NPDR or worse
every 1-3 months.

*Abnormal findings may dictate more frequent follow-up examinations

h ttp://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=d0c853d3-219f-487b-a524-326ab3cecd9a
 International Clinical Diabetic Retinopathy Disease Severity
Scale
Findings Observable upon Dilated
Proposed Disease Severity Level Ophthalmoscopy
Findings Obsd
No apparent retinopathy No abnormalities

Mild nonproliferative diabetic retinopathy Microaneurysms only

More than just microaneurysms but less than severe NPDR

Moderate nonproliferative diabetic retinopathy

Any of the following:

Severe nonproliferative diabetic retinopathy More than 20 intraretinal hemorrhages in each of four
quadrants
Definite venous beading in two or more quadrants
Prominent IRMA in one or more quadrants
and no signs of proliferative retinopathy.

One or both of the following:

Proliferative diabetic retinopathy Neovascularization
Vitreous/preretinal hemorrhage

Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales
Ophthalmology Volume 110, Number 9, September 2003
No retinopathy
 MILD NONPROLIFERATIVE
DIABETIC RETINOPATHY
Characteristics
• Microaneurysms only
MILD NONPROLIFERATIVE DIABETIC
RETINOPATHY

Microaneurysms
MODERATE NONPROLIFERATIVE DIABETIC
RETINOPATHY (NPDR)

Characteristics
• More than just microaneurysms but less than severe NPDR but
less than severe NPD
MODERATE NONPROLIFERATIVE DIABETIC
RETINOPATHY (NPDR)

Microaneurysm

Hard exudates

Flamed shaped
hemorrhage
MODERATE NONPROLIFERATIVE
DIABETIC RETINOPATHY (NPDR)

Hard exudates

microaneurysm
SEVERE NONPROLIFERATIVE
DIABETIC RETINOPATHY (NPDR)
Any of the following:
• More than 20 intraretinal hemorrhages in each of four
quadrants
• Definite venous beading in two or more quadrants
• Prominent Intraretinal Microvascular Abnormalities
(IRMA) in one or more quadrants
• And no signs of proliferative retinopathy
Severe Nonproliferative Diabetic Retinopathy
(NPDR)

Venous beading
Proliferative Diabetic Retinopathy (PDR)

Characteristics
• Neovascularization
• Vitreous/preretinal
hemorrhage
PROLIFERATIVE
DIABETIC
RETINOPATHY Cotton-wool
spot

Neovascularization

Neovascularization
Hard exudate
Blot hemorrhage
HIGH-RISK PROLIFERATIVE DIABETIC
RETINOPATHY

At risk for serious vision loss

Any combination of three of the following four findings
• Presence of vitreous or preretinal hemorrhage.
• Presence of new vessels (neovascularization, NV)
• Location of NV on or near the optic disc.
• Moderate to severe extent of new vessels.

Basic and Clinical Science Course, Section 12: Retina and Vitreous AAO
DIABETIC MACULAR EDEMA
• Diabetic macular edema is the leading cause of legal
blindness in diabetics.
• Diabetic macular edema can be present at any stage of
the disease, but is more common in patients with
proliferative diabetic retinopathy.
Meta analysis and review on the effect on bevacizumab id diabetic macular edema
Graefes Arch Clin Exp Ophthalmol(2011) 249:15-27
Why is Diabetic macular edema so important?
• The macula is responsible for central vision.
• Diabetic macular edema may be asymptomatic at
first. As the edema moves in to the fovea (the center
of the macula) the patient will notice blurry central
vision. The ability to read and recognize faces will be
compromised.

Macula
Fovea
Normal Macular Edema
CLINICALLY SIGNIFICANT MACULAR EDEMA
(CSME)
• Thickening of the retina at or within 500 µm of the
center of the macula.
• Hard exudates at or within 500 µm of the center of the
macula, if associated with thickening of the adjacent
retina.
• Area of retinal thickening 1 disc area or larger, within 1
disc diameter of the center of the macula.

ETDRS
INTERNATIONAL CLINICAL DIABETIC MACULAR EDEMA
DISEASE SEVERITY SCALE

Proposed disease severity level Findings observable upon dilated

ophthalmoscopy
DME apparently absent No apparent retinal thickening or hard exudates in
posterior pole

DME apparently present Some apparent retinal thickening or hard exudates in

posterior pole

DME present Mild DME (some retinal thickening or hard exudates in

posterior pole but distant from the center of the
macula)

Moderate DME (retinal thickening or hard

exudates approaching the center of the macula but not
involving the center)

Severe DME (retinal thickening or hard exudates

Proposed International Clinical Diabetic involving the center of the macula)
Retinopathy and Diabetic Macular Edema
Disease Severity Scales
Ophthalmology Volume 110, Number 9, September 2003
Imaging of macular edema with optical
coherence tomography
PREVENTION
90 percent of diabetic eye disease can
be prevented simply by proper regular
examinations, treatment and by
controlling blood sugar.

http://www.aao.org/newsroom/release/20091030.cfm
Primary prevention
Strict glycemic control
Blood pressure control

Secondary prevention
Annual eye exams

Tertiary prevention
Retinal Laser photocoagulation
Vitrectomy
DIABETIC RETINOPATHY TREATMENT

The best measure for prevention of

loss of vision from diabetic
retinopathy is strict glycemic control
LASER PHOTOCOAGULATION
Laser Photocoagulation is recommended for eyes with:
• Clinical significant macular edema CSME
• High risk Proliferative diabetic retinopathy
DIABETIC RETINOPATHY TREATMENT
ONCE DR THREATENS VISION TREATMENTS CAN INCLUDE:

Laser therapy to seal leaking blood vessels

(focal laser)

Laser therapy to reduce retinal oxygen

demand (scatter laser)

Surgical removal of blood from the eye

(vitrectomy)
 DIABETIC RETINOPATHY TREATMENT
NEWER DEVELOPMENTS:

The use of anti-vascular endothelial growth

factor antibodies has been shown to be
useful in the treatment of DR

Anti-VEGF antibody treatment appears to

be useful for both macular edema and
proliferative retinopathy

Studies to determine the exact role of anti-

VEGF treatment in relation to laser
treatment in specific situations are
underway.

http://drcrnet.jaeb.org
 CONCLUSIONS

Diabetic Retinopathy is
preventable through strict
glycemic control and annual
dilated eye exams by an
ophthalmologist.
"Alone we can do so little, together we can do so
much.”

Helen Keller
The Guerrilla Eye Service of the UPMC Eye Center is dedicated
to eliminating barriers to eye care for patients in the Western
Pennsylvania area.
Authors
Ines Serrano, is am ophthalmologist trained in Peru
at the Universidad Nacional Mayor de San Marcos.
She is currently pursuing her multidisciplinary
Masters in Public Health at the Graduate School of
Public Health at the University of Pittsburgh. She
has a long standing interest in minority health and
health care disparities.

Evan (Jake) Waxman, is currently Assistant

Professor and vice Chair for Education at the
University of Pittsburgh Department of
Ophthalmology. He is the recipient of multiple
medical student and resident teaching awards. His
current areas of focus include the use of interactive
fiction in the creation of virtual patients for training
health care providers and research into delivery of
eye care in underserved populations.
REFERENCES
• Retina in systemic disease : a color manual of ophthalmoscopy /
Homayoun Tabandeh, Morton F. Goldberg 2009
• Goyal S, Laavalley M, Subramanian ML, Meta analysis and review on
the effect on bevacizumab in diabetic macular edema, Graefes Arch
Clin Exp Ophthalmol(2011) 249:15-27
• C. P. Wilkinson, MD,1 Frederick L. Ferris, III, MD,2 Ronald E. Klein, MD,
MPH,3 Paul P. Lee, MD, JD,4 Carl David Agardh, MD,5 Matthew Davis,
MD,3 Diana Dills, MD,6 Anselm Kampik, MD,7 R. Pararajasegaram, MD,8
Juan T. Verdaguer, MD,9 representing the Global Diabetic
Retinopathy Project Group, Proposed International Clinical Diabetic,
Retinopathy and Diabetic Macular Edema Disease Severity Scales
Ophthalmology Volume 110, Number 9, September 2003 Proposed
international clinical diabetic retinopathy and diabetic macular edema
disease severity scales
REFERENCES
• Preferred Practice Patterns, Diabetic retinopathy, America Academy of
Ophthalmology 2008.
http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=d0c853
d3-219f-487b-a524-326ab3cecd9a
• Brett J. Rosenblatt and William E. Benson Diabetic Retinopathy Yanoff & Duker:
Ophthalmology, 3rd ed. http://www.mdconsult.com/das/book/pdf/282715756-
3/978-0-323-04332-8/4-u1.0-B978-0-323- 04332- 8..00092-
5..DOCPDF.pdf?isbn=978-0-323-04332-8&eid=4-u1.0-B978-0-323-04332-8..00092-
5..DOCPDF
• Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP,
Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health
Organ. 2004 Nov;82(11):844-51. Epub 2004 Dec 14.
• Basic and Clinical Science Course, Section 12: Retina and Vitreous AAO, 2011-2012.
• The Effect of Intensive Diabetes Treatment On the Progression of Diabetic
Retinopathy In Insulin-Dependent Diabetes Mellitus, The Diabetes Control and
Complications Trial Research Group, Arch Ophthalmol. 1995; 113:36-51
REFERENCES
• http://www.ncbi.nlm.nih.gov/pubmed/19896746
• http://www.aao.org/eyecare/news/upload/Eye-Health-Fact-Sheet.pdf
• http://www.who.int/bulletin/volumes/82/11/en/844.pdf
• http://jama.ama-assn.org/content/304/6/649.short?rss=1
• http://www.aao.org/newsroom/release/20091030.cfm
• http://www.diabetes.org/diabetes-basics/?loc=GlobalNavDB
• http://www.ophed.com/group/2205