1. Diabetic Retinopathy Waseem Al-Zamil, MD.

2. the two main types of diabetes : the two main types of diabetes : Insulin-dependent diabetes (IDD): Insulin-dependent diabetes (IDD): - known as type 1. - known as type 1. - develops most frequently between 10 and 20 years of age. - develops most frequently between 10 and 20 years of age. Non-insulin-dependent diabetes (NIDD): Non-insulin-dependent diabetes (NIDD): - also known as type 2. - also known as type 2. - develops most frequently between the ages of 50 and 70 years. - 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. 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. 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. Blindness is 25 more common in diabetics than non diabetics. Prevalence of PDR is much more in type I than type II. Prevalence of PDR is much more in type I than type II. Diabetic retinopathy more sever in type I than type II. Diabetic retinopathy more sever in type I than type II.

5. Prevalence Macular edema : Macular edema : NPDR : 2 -6 % NPDR : 2 -6 % PDR : 20-63 % PDR : 20-63 % Macular edema : Macular edema : 20.1 % in younger onset group. 20.1 % in younger onset group. 25.4 % in older onset group taking insulin 25.4 % in older onset group taking insulin 13.9 % in older onset group not 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: The 25-year cumulative rate of progression of DR in Type I was: - progression of DR was 83%. - progression of DR was 83%. - progression to PDR was 42%. - progression to PDR was 42%. - macular edema was 26%. - macular edema was 26%. ( WESDR Ophthalmology. 2008 Nov;115(11):1859-68 ( ( WESDR Ophthalmology. 2008 Nov;115(11):1859-68 (

7. RISK FACTORS 1. The duration of diabetes : is the most important factor. is the most important factor. In patients diagnosed as having diabetes before the age of 30 years, the incidence of DR : In patients diagnosed as having diabetes before the age of 30 years, the incidence of DR : - after 10 years is 50% - after 10 years is 50% - after 30 years is 90% - after 30 years is 90%

8. RISK FACTORS It is extremely rare for DR to develop within 5 years of the onset of diabetes. 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. 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. 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. 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. 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: With strict control of DM: - risk of developing retinopathy was reduced by 75%. - risk of developing retinopathy was reduced by 75%. - 50% reduction in the rate of progression of retinopathy in existing retinopathy - 50% reduction in the rate of progression of retinopathy in existing retinopathy - early worsening of retinopathy is unlikely to threaten vision. - early worsening of retinopathy is unlikely to threaten vision. Diabetes Control and Complications Trial Research Group N Engl J Med 1993; 329:977-986. Diabetes Control and Complications Trial Research Group N Engl J Med 1993; 329:977-986.

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

12. Ocular Risk Factors PVD : PVD : due to degenerative changes in the vitreous. due to degenerative changes in the vitreous. significantly more common in diabetic subjects. 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. 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 attached posterior hyaloid has also been associated with an increased risk for DME

13. Ocular Risk Factors High myopia : High myopia : choroidal degeneration and extensive old chorioretinopathy protect against DR. 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 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 : Removal of cataract : DR may progress after cataract surgery. DR may progress after cataract surgery. Patient who have CSME, SNPDR or PDR should undergo photocoagulation if the media is sufficiently clear. 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. 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. Diabetic retinopathy is a microangiopathy affecting the retinal precapillary arterioles, capillaries and venules. Retinopathy has features of both: Retinopathy has features of both: - microvascular leakage. (mild- mod NPDR) - microvascular leakage. (mild- mod NPDR) - microvascular occlusion.(sever NPDR-PDR) - microvascular occlusion.(sever NPDR-PDR)

17. PATHOGENESIS Microvascular occlusion : Microvascular occlusion : 1. thickening of the capillary basement membrane. 2. capillary endothelial cell damage and proliferation. 3. 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 ) Neovascularization Fibrous glial cell proliferation proliferation

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

20. PATHOGENESIS Microvascular leakage : Microvascular leakage : - due to reduction in the number of pericytes. - 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. - 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 : - Development of retinal edema requires accumulation of fluid which occurs if : Leakage : Absorption : - Microanurerysms. - Incompetent capillaries - Uptake from adjusent capillaries - Healthy RPE cells

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

22. CLINICAL FEATURES Microaneurysms : Microaneurysms : - located in the inner nuclear layer. - located in the inner nuclear layer. - the first clinically detectable lesions. - the first clinically detectable lesions. - small round dots.(20-200 μ) - small round dots.(20-200 μ) - mostly located near and temporal to the macula. - mostly located near and temporal to the macula. - When coated with blood they may be indistinguishable from dot haemorrhages. - When coated with blood they may be indistinguishable from dot haemorrhages.

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

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

26. CLINICAL FEATURES Retinal oedema : 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) Macular edema types: (FFA + Clinical) 1. Focal ME :which has identifiable leakage source. 2. Diffuse ME: which has multiple unidentifiable source of leakage. 3. 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. (1) spongelike retinal swelling. (2) cystoid macular edema (CME). (2) cystoid macular edema (CME). (3) serous retinal detachment (SRD). (3) serous retinal detachment (SRD). Kim BY, Smith SD, Kaiser PK: Optical coherence tomographic patterns of diabetic macular edema. Am J Ophthalmol 142(3):405-412, 2006

29. CLINICAL FEATURES Vascular changes : 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 ) 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) : 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 : 1. intraretinal location. 2. absence of profuse leakage on fluorescein angiography. 3. failure to cross over major retinal blood vessels.

32. CLINICAL FEATURES New Vessels: 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. - NVE : any other location.

33. CLINICAL FEATURES Fibrous Glial proliferation : 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 : Nonproliferative DRP : Microaneurysms, retinal hemorrhage and hard exudate Mild NPDR Mild NPDR plus cotton wool spots. Moderate NPDR Moderate NPDR plus one of : 1. Intraretinal Hges in four quadrants. 2. marked venous beading in two or more quadrants 3. 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 : Proliferative DRP : New vessels and/or fibrous proliferations; or preretinal and/or vitreous hemorrhage Early PDR 1. NVD ≥ 1/3 of DD. 2. less extensive NVD, if vitreous or preretinal hemorrhage is present. 3. NVE ≥ half disc area, if vitreous or preretinal hemorrhage is present PDR with HRC 1. Extensive vitreous hemorrhage precluding grading. 2. retinal detachment involving the macula. 3. phthisis bulbi. Advanced PDR

36. Diagnostic Testing Fluorescein Angiography : Fluorescein Angiography : - Not needed to identify CSME or PDR. - But : 1. As a guide during CSME treatment. 2. Identify macular capillary nonperfusion. 3. Identify subtle areas of NV causing recurrent vitreous hemorrhage despite full PRP.

37. Diagnostic Testing Color Fundus photography : Color Fundus photography : - For Documentation purpose. Ultrasonography : Ultrasonography : - When opaque media preclude retinal examination. - Useful in ruling out : 1. RD. 2. Traction threatening macular detachment.

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

39. Diagnostic Testing Visual Felid: Visual Felid: - Diabetic individuals often complaining of night vision loss and felid constriction due to: 1. Retinopathy. 2. Retinal non perfusion. 3. Laser surgery. - Higher risk of developing glaucoma.

40. Complications of proliferative diabetic retinopathy 1. Persistent vitreous haemorrhage. 2. Retinal detachment. 3. Opaque membranes. 4. Rubeosis iridis.

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

42. MANAGEMENT OF DIABETIC RETINOPATHY Laser surgery : 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. 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. 1500 µ m) of the centre of the fovea. defined as the presence of any retinal thickening or hard exudates within one disc diameter (i.e. 1500 µ m) of the centre of the fovea. clinically insignificant macular oedema do not require treatment, only should be followed up at 6 monthly intervals. 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: defined as the presence of one or more of the following features: 1. Retinal oedema within 500 µ m of the centre of the fovea. 2. Hard exudates within 500 µ m of the fovea, if associated with adjacent retinal thickening (which may be outside the 500 µ m limit). 3. Retinal oedema that is one disc area (1500 µ m) 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%. 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 : Poor visual outcome after focal laser associated with : 1. Macular ischemia. 2. Hard exudates deposit in the fovea. 3. Marked cystoid macular edema. 4. 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 µ m (two disc diameters) from the centre of the fovea. involves applying laser burns to microaneurysms and microvascular lesions in the centre of rings of hard exudates located between 500 and 3000 µ m (two disc diameters) from the centre of the fovea. - The spot size is : 50-100 µ m. - The spot size is : 50-100 µ m. - The duration of : 0.10 second or less. - The duration of : 0.10 second or less. - The power : sufficient power to obtain a gentle whitening or darkening of the microaneurysm. - The power : sufficient power to obtain a gentle whitening or darkening of the microaneurysm. - Wave length : green – yallow Argon - Wave length : green – yallow Argon

49. 1500 mirco 500 micro 3000 micro

50. Direct treatment Treatment of lesions between 300 and 500 µ m 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. Treatment of lesions between 300 and 500 µ m 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 µ m from the centre of the fovea and 500 µ m from the temporal margin of the optic disc. used for areas of diffuse retinal thickening located more than 500 µ m from the centre of the fovea and 500 µ m from the temporal margin of the optic disc. - The spot size is : 50 - 100 µ m. - The spot size is : 50 - 100 µ m. - The exposure time : 0.10 second. - The exposure time : 0.10 second. - The burns should be of very light intensity and one burn width apart. - The burns should be of very light intensity and one burn width apart. - Wave length : green – yallow Argon. - 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. 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. 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. It may take up to 4 months for the oedema to resolve, re-treatment should not be considered prematurely.

53. Focal Laser Side Effects 1. Paracentral scotoma. 2. Transient increased edema and decresed vision. 3. Choroidal neovascularization. 4. Subretinal fibrosis. 5. Scar expansion. 6. Foveolar burns.

54. Anti-VGEF & Macular Edema

56. Algorithm for panretinal scatter coagulation of the retina

57. 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. 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. Less extensive NVD associated with vitreous or preretinal haemorrhage. NVE more than one-half disc in area in association with vitreous or preretinal haemorrhage. NVE more than one-half disc in area in association with vitreous or preretinal haemorrhage.

58. laser photocoagulation The aim of treatment is to: The aim of treatment is to: 1. induce involution of new vessels. 2. prevent vitreous haemorrhage. Initial treatment involves the placement of about 2000-3000 burns in a scatter pattern, extending from the posterior fundus to cover the peripheral retina in one or more sessions. Initial treatment involves the placement of about 2000-3000 burns in a scatter pattern, extending from the posterior fundus to cover the peripheral retina in one or more sessions.

59. laser photocoagulation The technique of PRP is as follows: The technique of PRP is as follows: 1. Topical corneal anaesthesia is adequate in most patients. 2. - The spot size :depends on which contact lens is being used. (500 - 200 µ m). - The duration : between 0.10 and 0.05 second - The duration : between 0.10 and 0.05 second - The power level : produces a gentle burn - The power level : produces a gentle burn

60. 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. - 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. - 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.

62. laser photocoagulation Signs of involution : Signs of involution : 1. regression of neovascularization leaving only 'ghost' vessels or fibrous tissue. 2. decrease in venous dilatation. 3. absorption of retinal haemorrhages. 4. disc pallor. Treatment of recurrence : Treatment of recurrence : Further argon laser PRP filling in any gaps between previous laser scars. Further argon laser PRP filling in any gaps between previous laser scars.

63. PARS PLANA VITRECTOMY INDICATIONS 1. Severe persistent vitreous haemorrhage. 2. Tractional retinal detachment involving the macula. 3. Combined tractional and rhegmatogenous retinal detachment. 4. Progressive fibrovascular proliferation. 5. Rubeosis iridis associated with vitreous haemorrhage.

64. PARS PLANA VITRECTOMY INDICATIONS 6. Dense, persistent, premacular, subhyaloid haemorrhage. 7. Red Blood Cell-induced glaucoma. 8. Bilateral vitreous haemorrhage. 9. Dense cataract associated with vitreous haemorrhage.

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

66. Aspirin & DRP Is Aspirin effective in preventing progression of diabetic retinopathy ? Is Aspirin effective in preventing progression of diabetic retinopathy ? 1. Aspirin use did not alter progression of diabetic retinopathy. 2. Aspirin use did not increase the risk of vitreous hemorrhage. 3. Aspirin use did not effect visual acuity. 4. Aspirin use reduce the cardiovascular morbidity and mortality.

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

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

69. Practical Points PRP: PRP: Three-mirror lens can be used for both focal laser and 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 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. Do not count the spots but fill up an appropriate region of retina.

70. Practical Points Usually PRP performed in 2 sessions spaced 2-4 weeks apart. Usually PRP performed in 2 sessions spaced 2-4 weeks apart. If possible start with inferior retina. If possible start with inferior retina. If patient discomfortable during PRP: 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.

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

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

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