1. Isfahan University Of Medical Sciences
IN THE NAME OF GOD
Gholamali Naderian MD
Isfahan University Of Medical Sciences
Feiz Eye Center

2. DIABETIC RETINOPATHY RISK FACTORS PATHOGENESIS CLINICAL FEATURES
EPIDEMIOLOGY
RISK FACTORS
PATHOGENESIS
CLINICAL FEATURES
CLASSIFICATION
MANAGEMENT

3. Diabetic Retinopathy Epidemiology
Two forms of diabetes are recognised:
- Type 1 or juvenile-onset or insulin dependent
- Type 2 or adult onset or non-insulin dependent
One of the leading causes of blindness in ages
90% of patients with diabetes have type 2 diabetes
Since 90% of patients with diabetes suffer from type 2 diabetes, this group comprises a substantial proportion of patients with visual impairment secondary to diabetic retinopathy, even though type 1 diabetes is associated with more frequent and severe ocular complications.

4. Prevalence of Diabetic Retinopathy
Type 1 diabetes %
Type 2 diabetes (not on insulin) - 39%
Type 2 diabetes (on insulin) %
Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR)
Prevalence quantifies the proportion of individuals in a population who have the disease in question at a specific point in time.
Prevalence = all existing cases at a given time / total population at risk.
According to the WESDR (Wisconsin Epidemiologic Study of Diabetic Retinopathy), 71% of type 1 diabetes, 39% of type 2 not on insulin and 70% of type 2 on insulin have some form of retinopathy.

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

6. PATHOGENESIS

7. Pathogenesis
Microangiopathy which has features of both microvascular leakage and occlusion
Larger vessels may also be involved
Diabetic retinopathy is a microangiopathy affecting retinal capillary arterioles, capillaries and venules. However the larger vessels may also be involved. The microangiopathy has features of both microvascular leakage and occlusion.

8. Pathogenesis Microvascular occlusion
The changes leading to occlusion are:
basement membrane thickening, endothelial cell damage
deformed RBCs causing decreased oxygen transport
changes in platelets leading to increased stickiness and aggregation
The changes that occur in the capillaries in diabetic retinopathy are :
Basement membrane thickening, endothelial cell damage and endothelial cell proliferation in the capillaries.
Deformation of RBCs resulting in decreased oxygen transport.
Changes in platelets leading to increased stickiness and aggregation.
All these above changes lead to microvascular occlusion.
There are many complex theories postulated for basement membrane thickening. One of them is deposition of fibrillar collagen and “swiss cheese” like vacuolisation of the basement membrane.

9. Pathogenesis of diabetic retinopathy

10. Pathogenesis Microvascular leakage
Reduction in the number of pericytes resulting in capillary wall distention producing microaneurysms
Breakdown of blood-retinal barrier results in leakage of plasma constituents into the retina
The cellular elements of retinal capillaries are the endothelial cells and pericytes(mural cells). The pericytes give structural integrity to the vessel wall. The normal pericyte:endothelial cell ratio is 1:1. In diabetics there is a reduction in the number of pericytes. The pericyte loss is linked to the sugar alcohol or polyol pathway. Excess glucose is shifted to its alcohol, sorbitol, by means of an aldose reductase. Sorbitol is poorly metabolised and accumulates in the cell. Owing to its osmotic activity accumulation of sorbitol is toxic to the cells that possess aldose reductase and pericytes have high levels of aldose reductase. This is the theory postulated for the loss pf pericytes.
There is also breakdown of the blood-retinal barrier with leakage of plasma constituents into the retina.

11. Consequences of chronic leakage

12. Pathogenesis Microvascular occlusion
Capillary non-perfusion, retinal ischaemia and retinal hypoxia
Production of vasogenic factors like Vascular Endothelial Growth Factor(VEGF)
VEGF stimulates the growth of shunt and new vessels
Microvascular occlusion results in capillary non-perfusion, retinal ischaemia and retinal hypoxia. The hypoxic retina produces vasogenic factors like Vascular Endothelial Growth Factor (VEGF). This stimulates the production of shunt vessels as well as new vessels or neovascularisation.
Angiogenesis is a complex process involving the growth of new blood vessels from preexisting parental vessels. Diabetic retinopathy is an ischaemic retinopathy characterised by decreased perfusion of the retina, retinal ischaemia and the subsequent development of intraocular angiogenesis. The neovascularisation commonly arises at the border of perfused and nonperfused retina but may also occur at locations distant from the areas of nonperfusion.
The severity of the angiogenesis is correlated with the extent of non perfusion. Neovascularisation is a dangerous sign. It can lead to visual loss as a consequence of fibrosis, haemorrhage or increased vascular permeability.

13. Consequences of retinal ischaemia

14. Location of lesions in background
diabetic retinopathy