1. Diabetic Retinopathy
Waseem Al-Zamil, MD.

2. the two main types of diabetes :
Insulin-dependent diabetes (IDD):
- known as type 1 .
- develops most frequently between 10 and 20 years of age .
Non-insulin-dependent diabetes (NIDD):
- also known as type 2.
- develops most frequently between the ages of 50 and 70 years.

3. Prevalence
Diabetic retinopathy is a leading cause of new cases of blindness in people aged 20 to 74 years .
It has a considerable impact on both the patient and the society because it typically affects individuals in their most productive years .

4. Prevalence
Blindness is 25 more common in diabetics than non diabetics.
Prevalence of PDR is much more in type I than type II.
Diabetic retinopathy more sever in type I than type II.

5. Prevalence Macular edema : NPDR : 2 -6 % PDR : 20-63 %
20.1 % in younger onset group.
25.4 % in older onset group taking insulin
13.9 % in older onset group not taking insulin

6. Prevalence
The 25-year cumulative rate of progression of DR in Type I was:
- progression of DR was 83%.
- progression to PDR was 42%.
- macular edema was 26%.
( WESDR Ophthalmology Nov;115(11): (

7. RISK FACTORS The duration of diabetes : is the most important factor.
In patients diagnosed as having diabetes before the age of 30 years, the incidence of DR :
- after 10 years is 50%
- after 30 years is 90%

8. RISK FACTORS
It is extremely rare for DR to develop within 5 years of the onset of diabetes.
about 5% of Type II have NPDR at presentation perhaps due to the lag between onset and diagnosis.

9. RISK FACTORS 2 . Glycemic control :
Good metabolic control of diabetes will not prevent DR, although it may delay its development by a few years.
increased severity of diabetic retinopathy is associated with poorer glucose control.
insulin treatment is associated with a decreased risk of either the development or progression of diabetic retinopathy in patients with type 1 diabetes.

10. RISK FACTORS With strict control of DM:
- risk of developing retinopathy was reduced by 75% .
- 50% reduction in the rate of progression of retinopathy in existing retinopathy
- early worsening of retinopathy is unlikely to threaten vision .
Diabetes Control and Complications Trial Research Group N Engl J Med 1993; 329:

11. RISK FACTORS 3 . Miscellaneous factors :
- pregnancy. (Hormonal changes )
- systemic hypertension.
- renal disease .
- anaemia.( ↓oxygen )
- elevated serum lipid.
- carotid artery occlusive disease.
- Alcohol. ( ? )
- Obesity.

12. Ocular Risk Factors PVD : due to degenerative changes in the vitreous.
significantly more common in diabetic subjects.
complete PVD may prevent the development of PDR because the hyaloid is needed as a scaffold for retinal neovascularization.
attached posterior hyaloid has also been associated with an increased risk for DME

13. Ocular Risk Factors High myopia :
choroidal degeneration and extensive old chorioretinopathy protect against DR.
believed to act in the same manner as pan retinal photocoagulation by reducing the metabolic needs of the retina

14. Ocular Risk Factors Removal of cataract :
DR may progress after cataract surgery.
Patient who have CSME, SNPDR or PDR should undergo photocoagulation if the media is sufficiently clear.
If the cataract preclude retina evaluation and treatment, prompt postoperative retinal evaluation and treatment should considered.

15. PATHOGENESIS
Diabetic retinopathy is a microangiopathy affecting the retinal precapillary arterioles, capillaries and venules .
Retinopathy has features of both:
- microvascular leakage. (mild- mod NPDR)
- microvascular occlusion .(sever NPDR-PDR)

17. PATHOGENESIS Microvascular occlusion :
thickening of the capillary basement membrane.
capillary endothelial cell damage and proliferation.
changes in red blood cells leading to defective oxygen transport, and increased stickiness and aggregation of platelets

18. PATHOGENESIS Microvascular occlusion retinal ischaemia retinal hypoxia
Arteriovenous shunts
( IRMA )
Fibrous glial cell
proliferation
Neovascularization

19. IRMA Tractional RD RD New vessel proliferation
Fibrous glial tissue proliferaion
Tractional RD RD

20. PATHOGENESIS Microvascular leakage :
- due to reduction in the number of pericytes .
- The pericytes are wrapped around the capillaries and are thought to be responsible for the structural integrity of the vessel wall.
- Development of retinal edema requires accumulation of fluid which occurs if :
Absorption :
Leakage :
- Uptake from adjusent capillaries
- Healthy RPE cells
- Microanurerysms.
- Incompetent capillaries

21. Microvascular leakage
PATHOGENESIS
Loss pericytes
Microvascular leakage
haemorrhage
retinal oedema
Localized
Microanurysm” ”
Diffuse

22. CLINICAL FEATURES Microaneurysms :
- located in the inner nuclear layer .
- the first clinically detectable lesions .
- small round dots .( μ)
- mostly located near and temporal to the macula.
- When coated with blood they may be indistinguishable from dot haemorrhages.

23. CLINICAL FEATURES Haemorrhages :
The clinical appearance depending on location
- 'dot' and 'blot' :
* originating from the venous end of the capillaries. *located in the compact middle layers of the retina .
- Flame-shaped :
* originate from the more superficial precapillary arterioles, follow the course of the retinal nerve fibre layer. (liner disribution)

24. CLINICAL FEATURES Hard exudates :
- located between the inner plexiform and inner nuclear layers of the retina.
- They are often distributed in a (circinate pattern) .
- The centres of rings of hard exudates usually contain microaneurysms .
- Made up of accumulated lipoproteins .

26. CLINICAL FEATURES Retinal oedema :
located between the outer plexiform and inner nuclear layers.
Later it may involve the inner plexiform and nerve fibre layers, until eventually the entire thickness of the retina may become oedematous.
with further accumulation of fluid, the fovea assumes a cystoid appearance .

27. Macular edema types: (FFA + Clinical)
Focal ME :which has identifiable leakage source.
Diffuse ME: which has multiple unidentifiable source of leakage.
Cystoid ME: in which fluid accumulate in OPL and INL to form cystoid spaces.

28. Optical coherence tomographic patterns of diabetic macular edema
(1) spongelike retinal swelling.
(2) cystoid macular edema (CME).
(3) serous retinal detachment (SRD).
Figure Diabetic macular edema. Color fundus photograph (left) of a 63-year-old man with diabetic macular edema and nonproliferative diabetic retinopathy. Retinal edema is appreciated along with numerous exudates adjacent to the foveal center. Horizontal optical coherence tomography scan (right) through the fovea shows diffuse intraretinal cystic thickening with loss of the normal foveal depression. Intraretinal hyperreflective foci with posterior optical shadowing correspond to areas of retinal exudates seen clinically. A focal area of shallow subretinal fluid is noted centrally.
Kim BY, Smith SD, Kaiser PK: Optical coherence tomographic patterns of diabetic macular edema. Am J Ophthalmol 142(3): , 2006

29. CLINICAL FEATURES Vascular changes :
venous changes :in the form of 'beading', 'looping' and 'sausage-like' segmentation.
It represent endothelial cell proliferation.
arterioles may also be narrowed and even obliterated, resembling a BRAO .
- The most powerful predictors for development of PDR.

30. CLINICAL FEATURES Cotton-wool spots : (Soft exudates )
- Nerve fiber layer infarction.
- caused by capillary occlusion in the retinal nerve fibre layer.
The interruption of axoplasmic flow caused by the ischaemia, and subsequent build-up of transported material within the nerve axons, is responsible for the white and opaque appearance of these lesions.
Disappear within weeks to months.

31. CLINICAL FEATURES Intraretinal microvascular abnormalities (lRMA) :
Dilated, tortous retinal capillaries that act as a shunt between arterioles and venules.
frequently seen adjacent to areas of capillary closure.
IRMA may resemble focal areas of flat NVE . But in IRMA :
intraretinal location.
absence of profuse leakage on fluorescein angiography.
failure to cross over major retinal blood vessels.

32. CLINICAL FEATURES New Vessels:
Unlike IRMA, they arise on the retinal surface and may extend or be pulled into the vitreous cavity.
NVD : NV appears on or within one DD of disc margin . {most important prognostic factor for the risk of sever visual loss in DR, DRStudy}
NVE : any other location .

33. CLINICAL FEATURES Fibrous Glial proliferation :
Accompained growth of new vessels.
It is proliferation between the posterior vitreous gel and the ILM.
Derived from retinal glial cells and fibrocytes.

34. Classification of severity of diabetic retinopathy
Nonproliferative DRP :
Microaneurysms, retinal hemorrhage and hard exudate
Mild NPDR
Mild NPDR plus cotton wool spots .
Moderate NPDR
Moderate NPDR plus one of :
Intraretinal Hges in four quadrants .
marked venous beading in two or more quadrants
IRMA one or more quadrants.
Severe NPDR
Two or more of the above features described in severe NPDR
Very severe NPDR
4 : 2 : 1
Rule

35. Classification of severity of diabetic retinopathy
Proliferative DRP :
New vessels and/or fibrous proliferations; or preretinal and/or vitreous hemorrhage
Early PDR
NVD ≥ 1/3 of DD.
less extensive NVD, if vitreous or preretinal hemorrhage is present .
NVE ≥ half disc area, if vitreous or preretinal hemorrhage is present
PDR with HRC
Extensive vitreous hemorrhage precluding grading.
retinal detachment involving the macula.
phthisis bulbi .
Advanced PDR

36. Diagnostic Testing Fluorescein Angiography :
Not needed to identify CSME or PDR.
But :
As a guide during CSME treatment.
Identify macular capillary nonperfusion.
Identify subtle areas of NV causing recurrent vitreous hemorrhage despite full PRP.

37. Diagnostic Testing Color Fundus photography : Ultrasonography :
For Documentation purpose .
Ultrasonography :
When opaque media preclude retinal examination.
Useful in ruling out :
RD.
Traction threatening macular detachment.

38. Diagnostic Testing Color vision assessment:
DM associated with acquired blue-Yellow defect caused by diabetes itself and macular edema. (patients unable accurately match in self –monitored color-dependant urine or blood-glucose tests)

39. Diagnostic Testing Visual Felid:
Diabetic individuals often complaining of night vision loss and felid constriction due to:
Retinopathy.
Retinal non perfusion.
Laser surgery.
- Higher risk of developing glaucoma.

40. Complications of proliferative diabetic retinopathy
Persistent vitreous haemorrhage .
Retinal detachment .
Opaque membranes .
Rubeosis iridis .

41. MANAGEMENT OF DIABETIC RETINOPATHY
Medical Therapy :
Glycemic control :
DCCT , Tight control decrease risk of progression of retinopathy , nephropathy and neuropathy.
Blood pressure control.
Blood lipids control.

42. MANAGEMENT OF DIABETIC RETINOPATHY
Laser surgery :
The treatment of depends on the severity of retinopathy and the presence or absence of CSME, which may be present at any stage .

43. Macular oedema
defined as the presence of any retinal thickening or hard exudates within one disc diameter (i.e µm) of the centre of the fovea.
clinically insignificant macular oedema do not require treatment, only should be followed up at 6 monthly intervals.

44. Clinically significant macular oedema (CSMO)
defined as the presence of one or more of the following features:
Retinal oedema within 500 µm of the centre of the fovea .
Hard exudates within 500 µm of the fovea, if associated with adjacent retinal thickening (which may be outside the 500 µm limit) .
Retinal oedema that is one disc area (1500 µm) or larger, any part of which is within one disc diameter of the centre of the fovea.

46. Focal laser photocoagulation
All eyes with CSMO should be considered for treatment with laser photocoagulation irrespective of the level of visual acuity because treatment reduces the risk of visual loss by 50%.

47. Focal laser photocoagulation
Poor visual outcome after focal laser associated with :
Macular ischemia .
Hard exudates deposit in the fovea.
Marked cystoid macular edema.
Diffuse fluorescin leakage .

48. Direct treatment
involves applying laser burns to microaneurysms and microvascular lesions in the centre of rings of hard exudates located between 500 and 3000 µm (two disc diameters) from the centre of the fovea.
- The spot size is : µm .
- The duration of : 0.10 second or less.
- The power : sufficient power to obtain a gentle whitening or darkening of the microaneurysm.
- Wave length : green – yallow Argon

49. 1500 mirco
3000 micro
500 micro

50. Direct treatment
Treatment of lesions between 300 and 500 µm from the centre of the fovea should be considered if CSMO persists, in spite of previous treatment and, if visual acuity is less than 6/12.

51. Grid treatment
used for areas of diffuse retinal thickening located more than 500 µm from the centre of the fovea and 500 µm from the temporal margin of the optic disc.
- The spot size is : µm .
- The exposure time : 0.10 second.
- The burns should be of very light intensity and one burn width apart.
- Wave length : green – yallow Argon .

52. Macular oedema treatment
It should be emphasized that the main aim of treatment is to preserve the patient's current visual level.
Only about 15% of eyes show improvement.
It may take up to 4 months for the oedema to resolve, re-treatment should not be considered prematurely .

53. Focal Laser Side Effects
Paracentral scotoma.
Transient increased edema and decresed vision.
Choroidal neovascularization.
Subretinal fibrosis.
Scar expansion.
Foveolar burns.

54. Anti-VGEF & Macular Edema

55. Anti-VGEF & Macular Edema

56. IVTA & Macular edema
Intravitreal triamcinolone acetonide(IVTA) is reported to generate favorable results in the treatment of diffuse DME.
4mg in 0.1 ml.

57. IVTA & Macular edema

58. Algorithm for panretinal scatter coagulation of the retina

59. laser photocoagulation
The following are the clinical features of eyes at high risk PDR:
NVD or neovascularization within one disc diameter of the optic disc more than one-quarter disc in area .
Less extensive NVD associated with vitreous or preretinal haemorrhage.
NVE more than one-half disc in area in association with vitreous or preretinal haemorrhage.

60. laser photocoagulation
The aim of treatment is to:
induce involution of new vessels .
prevent vitreous haemorrhage.
Initial treatment involves the placement of about burns in a scatter pattern, extending from the posterior fundus to cover the peripheral retina in one or more sessions.

61. laser photocoagulation
The technique of PRP is as follows:
Topical corneal anaesthesia is adequate in most patients.
- The spot size :depends on which contact lens is being used. ( µm).
- The duration : between 0.10 and 0.05 second
- The power level : produces a gentle burn

62. laser photocoagulation
3. burns spaced about one half burn apart.
4. the power is increased by 50 mW increments until a grey-white burn of gentle intensity is produced .
Follow-up :
- is after an interval of 4-8 weeks.
- In eyes with severe NVD, several treatment sessions with 5000 or more burns may be required the most important cause of persistent neovascularization is inadequate treatment.

64. laser photocoagulation
Signs of involution :
regression of neovascularization leaving only 'ghost' vessels or fibrous tissue.
decrease in venous dilatation.
absorption of retinal haemorrhages .
disc pallor .
Treatment of recurrence :
Further argon laser PRP filling in any gaps between previous laser scars.

65. PARS PLANA VITRECTOMY INDICATIONS
Severe persistent vitreous haemorrhage .
Tractional retinal detachment involving the macula.
Combined tractional and rhegmatogenous retinal detachment .
Progressive fibrovascular proliferation .
Rubeosis iridis associated with vitreous haemorrhage.

66. PARS PLANA VITRECTOMY INDICATIONS
6. Dense, persistent, premacular, subhyaloid haemorrhage .
7. Red Blood Cell-induced glaucoma.
8. Bilateral vitreous haemorrhage .
Dense cataract associated with vitreous haemorrhage .
Persistent diffuse macular edema.

67. Follow up Suggested follow-up Retinal Finding Annually Normal
Every 9 months
Mild NPDR
Every 6 months
Moderate NPDR
Every 4 months
Sever NPDR
Every 2- 4 months
CSME
CNSME
Every 2-3 months
PDR

68. Aspirin & DRP
Is Aspirin effective in preventing progression of diabetic retinopathy ?
Aspirin use did not alter progression of diabetic retinopathy .
Aspirin use did not increase the risk of vitreous hemorrhage .
Aspirin use did not effect visual acuity.
Aspirin use reduce the cardiovascular morbidity and mortality .

69. Sorbinil & DRP Sorbinil is an aldose reductase inhibitor.
Sorbinil does not affect the progression of DRP or Diabetic neuropathy.

70. Emerging Therapies Pharmacologic vitreolysis :
55 IU of vitrase (hyaluronidase ) clear vitreous hemorrhage 1 month after intravitreal application.
Intravitreal microplasmin with induction of PVD and vitreous liquefaction increased intravitreal oxygen tension.

71. Emerging Therapies
- Intravitreal injection of autologous plasmin enzyme before surgery was useful in inducing pharmacological PVD and allowed more complete vitreous removal.

72. Emerging Therapies Fibrates : Lipid –lowering drugs.
FIELD study ,Fenofibrate reduce the progression of DR.
VEGF Trap :
Recombinant fusion protein .
Intravitreal injection was effective with DME.

73. Emerging Therapies Renin- angiotensin system (RAS) blockers:
- Lisinopril reduce both incidence and progression of DR.

74. Practical Points Pregnancy :
DR accelerate during pregnancy and improve postpartum.
Do not hesitate to treat with laser when indicated.
FFA should be avoided in all but the most difficult cases of macular edema.

75. Practical Points
PRP:
Three-mirror lens can be used for both focal laser and PRP.
Do not forget lens magnification , in most lenses use 200μm to produce 500 μm spot in the retina.
Do not count the spots but fill up an appropriate region of retina .

76. Practical Points
Usually PRP performed in 2 sessions spaced 2-4 weeks apart.
If possible start with inferior retina.
If patient discomfortable during PRP:
Reassure the patient it is expected and the treatment going well.
Decrease the duration to about 0.05 s.
Do it in more but shorter sessions.
Retrobulbar anesthetic can be used.

77. Practical Points
Major reason for under treatment is not well dilated pupil.
If NV recur after complete PRP :
Add more PRP in the periphery or between previous laser burns.
Vitrectomy .

78. Practical Points CSME + Capillary non perfusion :
Some recommend doing grid laser for area with capillary non perfusion (decrease possibility of NV )
Lowering serum lipid by Fibrates and ME :
Clofibrate (in several British study)
Reduce amount of hard exudate but macular edema edema persist with only modest improvement in VA .

79. Remember Argon blue : 488 nm. Argon green : 514 nm.
Dye yellow : 577 nm.
Krypton red : 647 nm.