This document summarizes diabetic retinopathy, including its types, pathogenesis, risk factors, diagnosis, management, and biomarkers. Diabetic retinopathy occurs when diabetes damages the tiny blood vessels inside the retina. It is classified into non-proliferative and proliferative stages. Risk factors include duration of diabetes, poor control, hypertension, and nephropathy. Diagnosis involves eye exams and tests like fluorescein angiography. Management includes laser surgery, injections, and vitrectomy. Novel biomarkers being studied to predict diabetic retinopathy include fibrinogen, apolipoproteins, retinal arteriolar tortuosity, and inflammatory markers like interleukin-6 and C-reactive protein.

1. Presented By
Ms. Sonali B. Diwate
M.Pharm Pharmacology
Sem. II
Guided By
Prof. Chanshetti R.
P. E. Society’s
Modern College Of Pharmacy
Moshi, Pune-44
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2. Introduction to Diabetic Retinopathy
Types of Diabetic Retinopathy
Pathogenesis
Risk factors
Diagnosis
Management of DR
Introduction to Biomarkers
Biomarkers of DR
Conclusion
References
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3. Retinopathy (damage to the retina) caused by
complications of diabetes.
Which can eventually lead to blindness.
It is an ocular manifestation of diabetes, a
systemic disease.
Affects up to 80 percent of all patients who
had diabetes for 10 years or more.
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4. 4

5. Definition:
Is a complication of diabetes and a leading
cause of blindness. It occurs when diabetes
damages the tiny blood vessels inside the
retina, the light-sensitive tissue at the back of
the eye. (See diagram below.) A healthy retina
is necessary for good vision.
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6. 6

7. Clinical classification:
1. Non-proliferative diabetic retinopathy
2. Proliferative diabetic retinopathy.
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8. 8

9. 1. Non-proliferative diabetic retinopathy:
The lesions in the retina at this stage are
within the retina and include:
micro-aneurysms,
small ‘dot and blot’ hemorrhages,
‘splinter’ hemorrhages,
Intraretinal Microvascula Abnormalities
(IRMA) and ‘cotton wool’ spots.
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10. Proliferative Diabetic Retinopathy:
The unchecked progression of proliferative
diabetic retinopathy can lead ultimately to
tractional retinal detachment, which may or
may not involve the macula.
Vitreous haemorrhage may require B-scan
ultrasonography to determine if a tractional or
rhegmatogenous (retinal break or hole) retinal
detachment is present.
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11. Four stages:
1. Mild Nonproliferative Retinopathy.
At this earliest stage, microaneurysms occur.
They are small areas of balloon-like swelling
in the retina's tiny blood vessels.
2. Moderate Nonproliferative Retinopathy.
As the disease progresses, some blood vessels
that nourish the retina are blocked.
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12. 3. Severe Nonproliferative Retinopathy.
Many more blood vessels are blocked,
depriving several areas of the retina with their
blood supply.
4. Proliferative Retinopathy. At this
advanced stage, the signals sent by the retina
for nourishment trigger the growth of new
blood vessels. This condition is called
proliferative retinopathy.
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13. Diabetic retinopathy is the result of
microvascular retinal changes.
Hyperglycemia-induced intramural pericyte
death and thickening of the basement
membrane lead to incompetence of the
vascular walls.
These damages change the formation of the
blood-retinal barrier and also make the retinal
blood vessels become more permeable.
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15. Duration of Diabetes
Poor control of Diabetes
Pregnancy
Hypertension
Nephropathy
Obesity & Hyperlipidemia
Smoking
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16. Diabetic retinopathy is detected during an eye
examination that includes:
1. Visual acuity test
2. Pupil dilation
3. Ophthalmoscopy
4. Fundus Fluorescein angiography(FFA)
5. Digital Retinal Screening Programs
6. Slit Lamp Biomicroscopy Retinal Screening
Programs
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17. 1.Laser surgery,
2.Injection of corticosteroids or Anti-VEGF
into the eye
3.Vitrectomy
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18. A biomarker is a substance or activity that can
be measured and serves as a marker of a
specific biological activity.
A biomarker may be a substance measured in
the blood or urine, for example, or may be a
measurement of a parameter such as blood
pressure or brain activity.
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19. It improve the understanding of a disease
process.
It predicts disease severity/complications.
Improves treatment targeting.
Monitor treatment efficacy.
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20. Novel Biomarkers
1. Plasma alpha 2 antiplasmine complex(PAP)
2. fibrinogen
3. Serum Apolipoprotein AI and B
4. Retinal arteriolar tortuosity
5. Urinary Albumin-to-Creatinine (UAC) ratio
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21. Inflammatory biomarkers:
1. C- Reactive Protein (CRP)
2. IL6- Interleukin 6
3. PgE1- Prostaglandin E1
4. PgE2- Prostaglandin E2
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22. Serum lipids:
1. Triglycerides
2. Low density lipoprotein
3. Total cholesterol
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23. Other Biomarkers:
1. Vascular Endothelial Growth Factor
(VEGF)
2. Homocysteine
3. Cytokinine
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24. Fibrinogen (factor I) is a soluble, plasma
glycoprotein, that is converted by thrombin
into fibrin during blood clot formation.
Fibrinogen is synthesized in the liver by the
hepatocytes.
The concentration of fibrin in the blood
plasma is 200-400 mg/dL .
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25. An increased blood viscosity due to high
fibrinogen level as well as an elevated
intravessel pressure play a role in the
development of diabetic retinopathy
the patients with the severest retinopathy had
the highest fibrinogen concentrations
fibrinogen metabolism is increased in diabetes
and bears a relationship to diabetic retinopathy
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26. The apolipoproteins associated with serum
lipoprotein particles give structural stability as
well as regulatory control in lipid metabolism.
The association between lipids and diabetic
retinopathy (DR) remains unclear.
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27. Only a few studies have reported the
association between proliferative diabetic
retinopathy (PDR) and the serum
concentrations of apolipoprotein A1 (apoA1),
apolipoprotein B (apoB) and apolipoprotein E
(apoE).
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28. Low apolipoprotein A1/apolipoprotein B ratio
in serum was associated with PDR in type 2
diabetic patients of long duration.
ApoA1 overexpression is an early event in the
retina of diabetic patients and can be involved
in the physiopathology of diabetic retinopathy.
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29. The blood vessels become tortuous, i.e. they
become dilated and take on a serpentine path. The
dilation is caused by radial stretching of the blood
vessel and the serpentine path occurs
because of longitudinal stretching.
In persons with diabetes, increased arteriolar
tortuosity was associated with mild and moderate
stages of DR. This suggests that retinal vascular
tortuosity might be an early indicator of
microvascular damage in diabetes
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30. C-reactive protein (CRP) is a protein found
in the blood, the levels of which rise in
response to inflammation (i.e. C-reactive
protein is an acute-phase protein).
higher levels of CRP were more likely to have
PDR
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31. Acts as both a pro-inflammatory cytokine and
an anti-inflammatory myokine. In humans, it
is encoded by the IL6 gene.
IL-6 is secreted by T cells and macrophages to
stimulate immune response, e.g. during
infection and after trauma, especially burns or
other tissue damage leading to inflammation.
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32. Increased levels of interleukin-6 (IL-6) are
detected in vitreous fluid of patients with PDR
and diabetic macular edema.
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33. Diabetic retinopathy is a complication of diabetes
and a leading cause of blindness. It occurs when
diabetes damages the tiny blood vessels inside the
retina, the light-sensitive tissue at the back of the
eye.
The prevalence of diabetic retinopathy is
increasing worldwide. interleukin 6 (IL-6), and
C-reactive protein (CRP) are two inflammatory
markers which have been shown to predict the
development of diabetic retinopathy.
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34. Recent studies have suggested that,Plasma
alpha 2 antiplasmine complex, fibrinogen,
Serum Apolipoprotein AI and B,Retinal
arteriolar tortuosity,Urinary Albumin-to-
Creatinine (UAC) ratio are the novel
biomarkers for DR and that might be a better
predictor of diabetic retinopathy.
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35. 1)Harsh Mohan, Textbook of Pathology, 5th edition
2005, published by JAYPEE brother’s medical
publishers (P) LTD, 133.
2)Thanh T., Ekaterina A., Inflammatory,
Hemostatic, and “Other Novel Biomarkers for
Diabetic Retinopathy” Diabetes care, volume 32,
number 9, September 2009.
3)Izuora KE, Chase HP, Jackson WE, Coll JR,
Osberg IM, Gottlieb PA, Rewers MJ, Garg SK.
Inflammatory markers and diabetic retinopathy in
type 1 diabetes. Diabetes Care 2005;28:714–715
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36. 4)Mohamed Q, Gillies MC, WongTY.
Management of diabetic retinopathy: a
systematicreview.JAMA2007;298:902–916.
5) Brazionis L, Rowley K, Sr, Itsiopoulos C
Harper CA, O’Dea K. Homocysteine and
diabetic retinopathy. Diabetes Care 2008;
31:50–56
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