1. Department of Ophthalmology AIIMS, Rishikesh
DIABETIC RETINOPATHY
Dr.Ajai Agrawal
Additional Professor
Department of Ophthalmology
AIIMS, Rishikesh

2. Acknowledgement
Photographs in this presentation are courtesy of Dr.J J Kanski
( Kanski JJ et al: Retinal vascular disease. In: Kanski JJ et al,
eds: Synopsis of Clinical Ophthalmology. 3rd ed. Philadelphia,
PA: Saunders; 2013: )

3. Diabetes and eye disease – Learning Objectives
At the end of the class, students shall be able to
Recognize the importance of diabetic retinopathy as a public health problem
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 examinations in the prevention of vision loss

4. 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. In type 1 diabetes, the body does not produce insulin. About 10% 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.

5. Diabetic Retinopathy (DR) Definition
Progressive dysfunction of the retinal blood vessels caused by chronic hyperglycemia.
DR can be a complication of type 1 or type 2 diabetes
Initially, DR is asymptomatic
If not treated, it can cause low vision and blindness.

6. 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.

7. Risk factors for 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

8. Duration of diabetes
The best predictor of diabetic retinopathy is duration of the disease
After 20 years of diabetes, more than 90% 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 -

9. Other Risk factors
Poor Blood Sugar control
Hypertension
Hyperlipidemia
Pregnancy
Nephropathy
Others: Smoking, Obesity, Anemia

10. Pathogenesis of Diabetic Micro angiopathy
Diabetic Retinopathy is a microvasculopathy that causes:
Retinal capillary occlusion
Retinal capillary leakage
Microvascular occlusion is caused by:
Thickening of capillary basement membranes
Abnormal proliferation of capillary endothelium
Increased platelet adhesion
Increased blood viscosity
Defective fibrinolysis
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)

11. Microvascular Occlusion Tractional retinal detachment
Ischemia
Infarction
Increased VEGF
Cotton – wool spots
Neovascularization
Vitreous hemorrhage
Fibrovascular bands
Neovascular glaucoma
Tractional retinal detachment

12. Microvascular Leakage
Edema
Hard exudates
Retinal hemorrhages

13. Normal Diabetic retinopathy
Pathogenesis
Normal Diabetic retinopathy

14. Healthy Retina
Diabetic Retinopathy

15. Diabetic retinopathy symptoms
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

16. Natural History of Diabetic Retinopathy
Mild nonproliferative diabetic retinopathy (NPDR)
Moderate NPDR
Severe NPDR
Very Severe NPDR
Proliferative diabetic retinopathy (PDR)
There are several stages of retinopathy. The earliest clinical stage of diabetic retinopathy is identified as mild nonproliferative diabetic retinopathy (NPDR). Progression of disease from NPDR to proliferative diabetic retinopathy (PDR) is related to the level or severity of NPDR, and therefore the severity of NPDR should determine follow-up and management of diabetic retinopathy.
The next four slides will review the clinical findings and management of each stage of retinopathy.

17. International Clinical Diabetic Retinopathy Disease Severity Scale
Proposed Disease Severity Level
Findings Observable upon Dilated Ophthalmoscopy
No apparent retinopathy
No abnormalities
Mild nonproliferative diabetic retinopathy
Microaneurysms only
Moderate nonproliferative diabetic retinopathy
More than just microaneurysms but less than severe NPDR
Severe nonproliferative diabetic retinopathy
Any of the following:
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.
Proliferative diabetic retinopathy
One or both of the following:
Neovascularization
Vitreous/preretinal hemorrhage
Findings Obsd
Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales
Ophthalmology Volume 110, Number 9, September 2003
Ophthalmology Volume 110, Number 9, September 2003

18. No retinopathy

19. Histology of retina 1 RPE 2 Layers of Rods & Cones
3 External Limiting Membrane
4 Outer Nuclear layer
5 Outer Plexiform layer
6 Inner Nuclear layer
7 Inner Plexiform Layer
8 Ganglion Cell layer
9 Nerve Fibre layer
10 Internal limiting membrane

20. Microaneurysms Focal dilatations of retinal capillaries
Appear as red dots.
Seen at the posterior pole, especially temporal to the fovea.
The first ophthalmoscopically detectable change in diabetic retinopathy.

21. Retinal Haemorrhages Dot haemorrhages
In the inner nuclear layer or outer plexiform layer
Bright red dots (same size as large microaneurysms).
Dark Blot/ round haemorrhages
Larger lesions
Located within the mid retina
Extent – marker for neovascularization
Flame Shaped haemorrhages
Superficial and in the nerve fiber layer

22. Non-proliferative diabetic retinopathy (NPDR)

23. Non-proliferative diabetic retinopathy (NPDR)

24. Hard exudates ( Intra-retinal lipid exudates )
Yellowish waxy looking patches with distinct margins
Outer plexiform layer
Surrounding capillaries and microaneurysms, in a circinate pattern.

25. Hard exudates ( Intra-retinal lipid exudates )

26. “Soft exudates" or "nerve fibre layer infarctions"
Cotton Wool Spots
Occlusion of retinal pre-capillary arterioles supplying the nerve fibre layer with concomitant swelling of local nerve fibre axons.
“Soft exudates" or "nerve fibre layer infarctions"
White, fluffy lesions in the nerve fibre layer.

27. Cotton Wool Spots

28. Late non proliferative changes
Intra-retinal microvascular abnormalities (IRMA)
Represent intraretinal arteriolar-venular shunts which have not breached the internal limiting membrane of the retina.
Indicate severe non-proliferative diabetic retinopathy that may rapidly progress to proliferative retinopathy.
Venous beading
Focal narrowing and sausage-shaped dilatation of the retinal veins.
Sign of severe non proliferative diabetic retinopathy.

29. Late non proliferative changes

30. MILD NONPROLIFERATIVE DIABETIC RETINOPATHY
Clinical Findings
Microaneurysms
Management/Treatment
Annual follow-up
Mild NPDR is characterized by increased vascular permeability, microaneurysms, and intraretinal hemorrhages. Macular edema can be present at this stage and is defined as retinal thickening within 3,000 m of the fovea (center of vision). Clinically significant macular edema (CSME) occurs when edema threatens the center of vision or is within 500 m of the fovea.
If CSME is present, color fundus photography can be used to determine the extent of macular edema. Fluorescein angiography can be used to identify lesions, and focal photocoagulation used to reduce the risk of vision loss. Decision to treat CSME in patients with mild NPDR should be discussed between the patient and physician. If photocoagulation is not performed the patient should be carefully monitored and examined approximately every three months for progression.

31. MILD NONPROLIFERATIVE DIABETIC RETINOPATHY
Microaneurysms

32. Moderate Nonproliferative Diabetic Retinopathy (NPDR)
Clinical Findings
Microaneurysms/ medium to large Intraretinal haemorrhages in quadrants
Mild Intraretinal Microvascular Abnormalities (IRMA’s)
Venous beading in not more than 1 quadrant
Cotton wool spots
Management/Treatment
6-12 month follow-up without CSME
Color fundus photography
Patients with moderate NPDR experience gradual retinal ischemia, venous caliber abnormalities, intraretinal microvascular abnormalities (IRMAs), and, possibly, CSME.
Patients at this stage of retinopathy without CSME should have ophthalmic exams every six to twelve months to monitor disease progression. Color fundus photography can be helpful in documenting the extent of retinopathy and in comparing changes in disease progression between follow-up visits.
If macular edema is present, once again color fundus photography is used to document the extent of edema, fluorescein angiography is used to locate leaking blood vessels and photocoagulation to seal the vessels. Follow-up is required after three to four months to determine the effectiveness of the treatment.

33. Moderate Nonproliferative Diabetic Retinopathy (NPDR)
Microaneurysm
Hard exudates
Flamed shaped hemorrhage

34. Severe Nonproliferative Diabetic Retinopathy (NPDR)
Clinical Findings
Any of the following: (4-2-1 Rule)
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 to very severe NPDR is characterized by even more extensive hemorrhage and microaneurysms. The microvasculature of the retina begins to deteriorate resulting in retinal ischemia.
Patients at this stage of retinopathy should be evaluated every three to four months for progression to proliferative diabetic retinopathy (PDR). Color fundus photography should be used to document disease progression. Panretinal or “scatter” laser photocoagulation can be considered to shrink abnormal blood vessels. If CSME is present, the same methods of treatment can be used as for moderate NPDR. CSME should be treated prior to performing scatter photocoagulation. Patients should continue to be evaluated at three to four months after laser treatment to determine the effectiveness of the surgery.

35. Severe Nonproliferative Diabetic Retinopathy (NPDR)
Management/Treatment
3-4 month follow-up
Color fundus photography
Possible panretinal photocoagulation
CSME present: color fundus photography, fluorescein angiography, focal photocoagulation, 3-4 month follow-up

36. Severe Nonproliferative Diabetic Retinopathy (NPDR)
Venous beading

37. Proliferative Diabetic Retinopathy (PDR)
Clinical Findings
Ischemia induced neovascularization
at the optic disk (NVD)
elsewhere in the retina (NVE)
New vessels on the iris (NVI)
Vitreous hemorrhage/Pre-retinal haemorrhage
Retinal traction, tears, and detachment
When proliferation of new blood vessels occurs, the patient is diagnosed as having PDR. New blood vessel formation is caused by retinal ischemia. Neovascularization can occur at the optic disk (NVD) or elsewhere in the retina (NVE). These new vessels are weak and, when they break, can cause vitreous hemorrhage. They can also cause retinal traction, retinal tears, and retinal detachment over time.

38. Proliferative Diabetic Retinopathy (PDR)
Management/Treatment
2-4 month follow-up
Color fundus photography
Panretinal photocoagulation (3-4 month follow-up)
Vitrectomy
PDR should be managed with panretinal laser photocoagulation, color fundus photography, and follow-up every 3-4 months to monitor treatment success. If panretinal photocoagulation is not performed, patients should be evaluated every two to three months because of the high risk of developing CSME, retinal detachment, or vitreous hemorrhage that can lead to vision loss. Vitrectomy should be considered when there is substantial amount of hemorrhaging in the vitreous fluid, and when neovascularization causes retinal traction or retinal detachment. CSME is treated in the same manner as described for severe NPDR.

39. PROLIFERATIVE DIABETIC RETINOPATHY
Cotton-wool
spot
Neovascularization
Neovascularization
Hard exudate
Blot hemorrhage

40. PROLIFERATIVE DIABETIC RETINOPATHY

41. High-Risk Proliferative diabetic retinopathy
At risk for serious vision loss
Any combination of three of the following four findings
NVD <1/4 disc area with vitreous or preretinal hemorrhage.
NVE > 1/2 disc area with vitreous or preretinal hemorrhage.
NVD 1/4 to 1/3 disc area with or without vitreous or preretinal hemorrhage.

42. 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.

43. Meta analysis and review on the effect on bevacizumab in diabetic macular edema
Graefes Arch Clin Exp Ophthalmol(2011) 249:15-27

44. 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

45. Normal
Macular Edema

46. Clinically significant Diabetic macular edema (CSDME)
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.

47. Imaging of macular edema with optical coherence tomography

48. Ischaemic Maculopathy
Maculopathy in type 1 diabetics is often due to drop out of the perifoveal capillaries with non perfusion.
Enlargement of the foveal avascular zone (FAZ) is frequently seen on fluorescein angiography.
Ischaemic maculopathy is not uncommon in type 2 diabetics
Maculopathy in this group may show both changes due to ischaemia and retinal thickening.

49. Advanced diabetic eye Disease
Persistent vitreous haemorrhage
Diabetic tractional retinal detachment
Neovascular Glaucoma

50. Clinical Stages of Retinopathy
Vitreous hemorrhage

51. Late Complications
TRACTIONAL RETINAL DETACHMENT

52. Clinical Stages of Retinopathy
New vessel growth

53. Diabetic Eye Disease Key Points
RECOMMENDED EYE EXAMINATION SCHEDULE
Diabetes Type
Recommended Time of First Examination
Recommended Follow-up*
Type 1
3-5 years after diagnosis
Yearly
Type 2
At time of diagnosis
Prior to pregnancy (type 1 or type 2)
Prior to conception and early in the first trimester
No retinopathy to mild moderate NPDR every 3-12 months
Severe NPDR or worse every 1-3 months.
Diabetic Eye Disease Key Points
Treatments exist but work best before vision is lost
*Abnormal findings may dictate more frequent follow-up examinations
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54. Screening for diabetic eye problems should ideally include the following
The history of any visual symptoms or changes in vision
Measurement of visual acuity
Iris examination by slit lamp biomicroscopy prior to pupil mydriasis.
Pupil mydriasis. ( tropicamide 0.5 %
Patients should be accompanied by a relative and instructed not to drive home.
Examination of the crystalline lens
Fundus examination

55. PREVENTION
90 percent of diabetic eye disease can be prevented simply by proper regular examinations, treatment and by controlling blood sugar.

56. Primary prevention Secondary prevention Tertiary prevention
Strict glycemic control
Blood pressure control
Secondary prevention
Annual eye examination
Tertiary prevention
Retinal Laser photocoagulation
Intravitreal Injections of Anti-VEGF
Vitrectomy

57. DIABETIC RETINOPATHY TREATMENT
The best measure for prevention of loss of vision from diabetic retinopathy is strict glycemic control

58. Laser Photocoagulation
Laser Photocoagulation is recommended for eyes with:
Clinical significant macular edema CSME
High risk Proliferative diabetic retinopathy

59. Treatment

60. Panretinal laser photocoagulation

61. Anti VEGF Injections
Aflibercept
Ranibuzumab
Bevacizumab

62. Remove vitreous hemorrhage Repair retinal detachment
VITRECTOMY
Remove vitreous hemorrhage
Repair retinal detachment
Allow treatment with PRP

63. Treatment

64. CONCLUSIONS
Diabetic Retinopathy is preventable through strict glycemic control and annual dilated eye examination by an ophthalmologist.