Diabetic Retinopathy Dr. Pradeep Bastola, MBBS, MD, MPH Professor, Department of Ophthalmology, Chitwan Medical College, Nepal

1. Dr. Pradeep Bastola, MD
Chitwan Medical College,
Department of Ophthalmology,
22 April 2022
DIABETIC RETINOPATHY

2. 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

3. 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

4. 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

5. 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.

6. RETINA

7. Healthy Retina Diabetic Retinopathy

8. 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

9. 0
2
4
6
8
10
12
14
16
18
20
Causes of global blindness in millions of people
(WHO 2002)
A. Foster, S.Resnikoff. The impact of vision 2020 on global blindness. Eye 2005; 19:1133-1135

10. 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 -

11. Prevalence of diabetic retinopathy after 20 years of diagnosis

12. http://www.who.int/bulletin/volumes/82/11/en/844.pdf

13. 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

14. 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

15. 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

16. 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

17. HOW DIABETES CAUSES VISION LOSS
Preclinical
changes
Macular
edema
Proliferative
DR
Diabetes
Background
DR
Clinical
significant
macular edema
Vitreous hemorrhage
and/or Retinal
detachment and/or
neovascular glaucoma
Preproliferative
DR
Vision
loss

18. Pathophysiology
Diabetic Retinopathy is a microvasculopathy that causes:
• Retinal capillary occlusion
• Retinal capillary leakage

19. 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

20. Cotton – wool spot
Neovascularization
Ischemia
Neovascular
glaucoma
Microvascular
Occlusion
Fibrovascular bands
Vitreous
hemorrhage
Increased VEFG
Tractional retinal
detachment
Retina in systemic disease : a color manual of
ophthalmoscopy / Homayoun Tabandeh, Morton F.
Goldberg 2009
Infarction

21. Pathogenesis of diabetic retinopathy

22. Consequences of retinal ischaemia

23. Consequences of chronic leakage

24. Location of lesions in background
diabetic retinopathy

25. Signs of background diabetic retinopathy
Microaneurysms usually
temporal to fovea
Intraretinal dot and
blot haemorrhages
Hard exudates frequently
arranged in clumps or rings
Retinal oedema seen as
thickening on biomicroscopy

26. Classification
Modified Airlie House classification and Early Treatment and Diabetic Retinopathy Study (ETDRS)
Non proliferative DR
• Mild non proliferative diabetic retinopathy (NPDR) : Presence of at least one retinal micro aneurysm, but
hemorrhages and micro aneurysm less than those in ETDRS standard photograph No. 2A.
• Moderate NPDR: Hemorrhages or micro aneurysms or both greater than and equal to those pictured in ETDRS
standard photograph No. 2A. Soft exudates, venous beading, intra retinal micro vascular anomaly (IRMA) are
definitely present in mild degree.
• Severe NPDR (4:2:1 rule): Hemorrhages or micro aneurysms in all four quadrants of the retina
Venous beading in at least two quadrants
IRMA in at least one quadrant
• Very severe NPDR: Any two or more of the findings listed in severe NPDR reflects very severe NPDR

27. Proliferative diabetic retinopathy (PDR)
• Diabetic retinopathy marked by neo vascularization of the optic disc (NVD) or neo vascularization
elsewhere (NVE) in the retina or pre retinal or vitreous hemorrhage by fibrous tissue proliferation is
designated as PDR. PDR again was classified as following in the study subjects.
• Early PDR: NVD <1/3 or NVE <1/2 dis area
• High risk PDR: NVD =>1/3 or NVE =>1/2 disc area or NVD greater than ETDRS standard photograph
10A approximately, with pre retinal hemorrhage or vitreous hemorrhage
• Advanced PDR (Advanced diabetic eye disease): Fibrous tissue proliferation in the form of tractional
retinal detachment, epiretinal membrane, new vessels in the anterior chamber angle or iris, neo
vascular glaucoma (NVG), phthisis bulbi and or absolute blind eye

28. Clinically significant macular edema (CSME)
• Thickening of retina at or within 500 microns from the centre of the macula or
• Hard exudates with thickening of the adjacent retina located at or within 500
microns from the centre of the macula or
• A zone of retinal thickening, >1 disc area located at or within 1 disc area from
the centre of the macula

29. International Council of Ophthalmology (ICO) guidelines and American Academy of Ophthalmology
(AAO) guidelines for outline of Management
Category of the patients Interventions
Severe/Very severe NPDR Early pan retinal photocoagulation (PRP)
High risk PDR/Advanced PDR Urgent PRP
CSME involving Centre of macula Anti VEGFs
CSME not involving centre of the macula Focal/Grid LASER treatment
Dense non clearing vitreous hemorrhage Pars plana vitrectomy (PPV)
Tractional retinal detachment (TRD) involving or threatening macular involvement PPV
Combined tractional and rhegmatogenous retinal detachment (RRD) PPV
Significant recurrent vitreous hemorrhage despite maximal PRP PPV

30. Focal diabetic maculopathy
• Circumscribed retinal thickening
• Associated complete or incomplete
circinate hard exudates
• Focal leakage on FA
• Focal photocoagulation
• Good prognosis

31. Diffuse diabetic maculopathy
• Diffuse retinal thickening • Generalized leakage on FA
• Guarded prognosis
• Grid photocoagulation
• Frequent cystoid macular oedema
• Variable impairment of visual acuity

32. Ischaemic diabetic maculopathy
• Macula appears relatively normal • Capillary non-perfusion on FA
• Poor visual acuity • Treatment not appropriate

33. Clinically significant macular oedema
Hard exudates
within 500 m
of centre of
fovea with adjacent
oedema which may
be outside 500 m
limit
Retinal oedema one disc area or larger any
part of which is within one disc diameter
(1500 m) of centre of fovea
Retinal oedema
within 500 m
of centre of fovea

34. 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

35. Edema
Retinal
hemorrhage
Hard exudates
Microvascular Leakage
Retina in systemic disease : a color manual of ophthalmoscopy / Homayoun Tabandeh, Morton F. Goldberg
2009.

36. 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 Yearly
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.
*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

37. 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
Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales
Ophthalmology Volume 110, Number 9, September 2003

38. No retinopathy

39. MILD NONPROLIFERATIVE DIABETIC RETINOPATHY
Characteristics
• Microaneurysms only

40. MILD NONPROLIFERATIVE DIABETIC RETINOPATHY
Microaneurysms

41. Moderate Nonproliferative Diabetic Retinopathy (NPDR)
Characteristics
• More than just microaneurysms but less than severe NPDR but less than severe
NPD

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

43. Moderate Non-proliferative Diabetic Retinopathy (NPDR)
Hard exudates
microaneurysm

44. 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

45. Severe Nonproliferative Diabetic Retinopathy
(NPDR)
Venous beading

46. Proliferative Diabetic Retinopathy (PDR)
Characteristics
• Neovascularization
• Vitreous/preretinal
hemorrhage

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

48. 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

49. 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.

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

51. 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

52. Normal Macular Edema

53. 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.
Early treatment diabetic retinopathy study (ETDRS)

54. International Clinical Diabetic Macular Edema
Disease Severity Scale
Proposed disease severity level Findings observable upon dilated
Ophthalmoscopy
DME apparently absent
DME apparently present
DME present
No apparent retinal thickening or hard exudates in posterior
pole
Some apparent retinal thickening or hard exudates in posterior
pole
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 involving the
center of the macula)
Proposed International Clinical Diabetic
Retinopathy and Diabetic Macular Edema
Disease Severity Scales
Ophthalmology Volume 110, Number 9, September 2003

55. Imaging of macular edema with optical
coherence tomography

56. PREVENTION
http://www.aao.org/newsroom/release/20091030.cfm
90 percent of diabetic eye disease can be prevented
simply by proper regular examinations, treatment and
by controlling blood sugar.

57. Primary prevention
Strict glycemic control
Blood pressure control
Secondary prevention
Annual eye exams
Tertiary prevention
Retinal Laser photocoagulation
Vitrectomy

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

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

60. 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)

61. 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

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

63. "Alone we can do so little, together we can do so much.”
Helen Keller

64. DIABETIC RETINOPATHY
1. Adverse risk factors
2. Pathogenesis
5. Clinically significant macular oedema
6. Preproliferative diabetic retinopathy
3. Background diabetic retinopathy
4. Diabetic maculopathies
• Focal
• Diffuse
• Ischaemic
7. Proliferative diabetic retinopathy

65. Adverse Risk Factors
1. Long duration of diabetes
• Obesity
• Hyperlipidaemia
2. Poor metabolic control
3. Pregnancy
4. Hypertension
5. Renal disease
6. Other
• Smoking
• Anaemia

66. Treatment of clinically significant
macular oedema
• For microaneurysms in centre of hard
exudate rings located 500-3000 m
from centre of fovea
Focal treatment
• Gentle whitening or darkening of
microaneurysm (100-200 m, 0.10 sec)
• For diffuse retinal thickening located more
than 500 m from centre of fovea and
500 m from temporal margin of disc
Grid treatment
• Gentle burns (100-200 m, 0.10 sec),
one burn width apart

67. Preproliferative diabetic retinopathy
Treatment - not required but watch for proliferative disease
• Cotton-wool spots
• Venous irregularities
• Dark blot haemorrhages
• Intraretinal microvascular
abnormalities (IRMA)
Signs

68. Proliferative diabetic retinopathy
• Flat or elevated
• Severity determined by comparing with area of disc
Neovascularization
Neovascularization of disc = NVD
• Affects 5-10% of diabetics
• IDD at increased risk (60% after 30 years)
Neovascularization elsewhere = NVE

69. Indications for treatment of proliferative
diabetic retinopathy
NVD > 1/3 disc in area Less extensive NVD
+ haemorrhage
NVE > 1/2 disc in area
+ haemorrhage

70. • Spot size (200-500 m) depends
on contact lens magnification
• Gentle intensity burn (0.10-0.05 sec)
• Follow-up 4 to 8 weeks
• Area covered by complete PRP
• Initial treatment is 2000-3000 burns
Laser panretinal photocoagulation

71. Assessment after photocoagulation
• Persistent neovascularization
• Haemorrhage
Poor involution
• Re-treatment required
• Regression of neovascularization
• Residual ‘ghost’ vessels or
fibrous tissue
Good involution
• Disc pallor

72. Indications for vitreoretinal surgery
Retinal detachment involving
macula
Severe persistent vitreous
haemorrhage
Dense, persistent premacular
haemorrhage
Progressive proliferation
despite laser therapy

73. • The role of anti vascular endothelial growth factor (ANTI VEGF) has been
proved and approved for use in Diabetic Retinopathy with ischaemic
retina, proliferative DR, Clinically significant macular edema (CSME)
causing significant visual impairment.
• Lipid lowering agents
• Intravitreal Triamcinolone Injections
• Micropulse diode LASER treatment
• Frequency doubled nd: YAG LASER treatment

74. Poor prognostic factors
• Significant macular ischemia
• Foveal exudates
• Diffuse macular edema
• Cystoid macular edema
• Severe retinopathy at presentation
• Uncontrolled systemic Hypertension (HTN)
• Smoking
• Renal Disease
• Poorly controlled glucose levels in the body

75. Advanced Diabetic Eye Disease (DED)
Serious vision threatening complications in a DR patients who have
had inadequate or unsuccessful previous treatment attempts.

76. Signs:
• Hemorrhage in the eye, pre-retinal, vitreous, intragel or combined
• Tractional Retinal detachment
Treatment:
Pars plana vitrectomy (PPV) and Vitreo-retinal interventions (70% achieve good vision, 10%
worsen and rest are unchanged.

77. 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
• Preferred Practice Patterns, Diabetic retinopathy, America Academy of Ophthalmology 2008. http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=d0c853d3-219f-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
• 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

78. THANK YOU