Diabetes-related retinopathy (DR) is the most common micro-vascular (small blood vessels) complication of diabetes (often referred to as diabetes mellitus). Retinopathy is caused by, and defined as damage to the blood vessels in the light sensitive part of the back of the eye called the retina. At first, diabetes-related retinopathy may cause no symptoms or only mild vision problems. Eventually, it can lead to blindness. The condition can develop in anyone who has type 1 or type 2 diabetes. The longer you have diabetes and the more challenging your glucose management is, the more likely you are to develop this eye complication.
Diabetes-related retinopathy is a chronic, progressive and potentially sight-threatening disease of the retinal micro-vasculature (small blood vessels at the back of the eye) that is associated with prolonged hyperglycemia (too much sugar called glucose in the blood) and other conditions linked to diabetes such as hypertension (high blood pressure) and hyperlipidemia (excess lipids/fats). Diabetes-related retinopathy affects the vascular system (blood vessels) of the retina, as well as the inflammatory and the neuronal network of cells which are responsible for the structure of, and signaling within, the retina. Inflammation causes structural and molecular changes associated with diabetes-related retinopathy, while microvascular changes to the retina have been used to classify and determine diabetes-related retinopathy progression.
Diabetes-related Retinopathy occurs in two forms. The early form which is more common is called Non-Proliferative Diabetes-related Retinopathy (NPDR); this means new blood vessels are not growing (proliferating). NPDR involves changes to the very small blood vessels that supply the retina. NPDR is further divided into mild, moderate, and severe stages, as outlined in Table 1 below.
When you have NPDR, the walls of the blood vessels in your retina weaken. Tiny bulges (called microaneurysms) protrude from the vessel walls of the smaller vessels, sometimes leaking fluid and blood into the retina. Larger retinal vessels can begin to dilate and become irregular in diameter. NPDR can progress from mild to severe, as more blood vessels become blocked and leak fluid. Nerve fibres in the retina may also begin to swell (edema). Sometimes the central part of the retina (macula) begins to swell (macular edema), a condition that requires treatment. More information on Diabetes-related Macular Edema (DME) can be found in the DME section below.
The advanced stage of Diabetes-related Retinopathy is called Proliferative Diabetes-related Retinopathy (PDR). In this form of diabetes-related retinopathy, damaged blood vessels close off, causing the growth of new, abnormal and fragile blood vessels on the surface of the retina over time. These vessels can leak fluid into the clear, jelly-like substance that fills the centre of your eye (vitreous); this is called vitreous hemorrhage. If the amount of bleeding is small, you might see only a few dark spots (floaters). In more-severe cases, blood can fill the vitreous cavity and completely block your vision. Vitreous hemorrhage by itself usually doesn’t cause permanent vision loss. The blood often clears from the eye within a few weeks or months. Unless your retina is damaged, your vision may return to its previous clarity. These leaky vessels can also cause the formation of scar tissue which can pull on the retina causing retinal detachment. This may cause spots floating in your vision, flashes of light or severe vision loss. If the new blood vessels interfere with the normal flow of fluid out of the eye, pressure may build up in the eyeball. This can damage the nerve that carries images from your eye to your brain (optic nerve), resulting in glaucoma (for more information please see tool kit section on glaucoma).
The classification of NPDR is based on clinical findings manifested by multiple visible features while PDR is characterised by the hallmark feature of pathologic neovascularisation (abnormal new blood vessel growth). The characterisation of NPDR and PDR is determined by what is visible on fundus image. Features include:
- Microaneurysms: The earliest clinical sign of diabetes-related retinopathy; these occur secondary to capillary wall outpouching due to the loss of cells on the outer wall of the blood vessels (pericyte cells); microaneurysms appear as small, red dots.
- Cotton-wool spots: Nerve fibre layer cell death from blockage of pre-capillary arterioles; they are frequently bordered by microaneurysms and vascular hyperpermeability (a lot of leakage from the blood vessel).
- Venous Beading: Frequently occurs when the walls of major retinal veins loose their normal parallel alignment and begin to appear more like a string of sausages. Their occurrence is the most significant predictor of progression to proliferative diabetes-related retinopathy (PDR).
The International Classification of Disease Severity Scale for Diabetes-related Retinopathy:
|Diabetes-related Retinopathy Stage
||No change in fundus image
||Few microaneurysms (small bulges in blood vessels of the retina that often leak fluid)
||Microaneurysms, intra-retinal hemorrhages (mild venous beading), in the presence or absence of cotton wool spots
||Any of the following (4:2:1 rule)
20 or more retinal hemorrhages in each of 4 quadrants
Venous beading in more than 2 quadrants
Prominent intra-retinal microvascular abnormality in 1 or more quadrants
||Neovascularisation in the pre-retinal space, or vitreous, neovascularisation of the disc, neovascularisation of the retina, iris, angle, or vitreous hemorrhage or tractional retinal detachment.
Both NPDR and PDR may involve the development of Diabetes-related Macular Edema (DME). DME refers to the fluid accumulation and retinal hemorrhages in the macular region as a result of increased vascular permeability (leaky blood vessels). The macula is located in the center of the retina and contains the highest concentration of cones. Cones are a type photoreceptor cell that allow the ability to see colour and details. Because of the central location of the macula, it also means the macula is responsible for central vision.
When the fragile retinal blood vessels burst, the fluid from them accumulates into the surrounding retina, causing a thickening of the retina which is detectable by imaging called OCT (optical coherence topography). This results in distorted or blurry vision. It has been observed that the incidence of DME is higher among type 2 compared to type 1 diabetics, but it is not well understood why this is the case1 2.
DME is defined as retinal thickening within two disc diameters (disc diameters refers to the size of the optic nerve head) of the central retina. The optic disc or optic nerve head is the point of exit for ganglion cell axons (nerve cells that carry the images our eyes see to the brain) leaving the eye. Because there are no rods or cones overlying the optic disc, it corresponds to a small blind spot in each eye. The optic disc is also the entry point for the major blood vessels that supply the retina.
The International Classification of Disease Severity Scale for Diabetes-related Macular Edema:
|Diabetes-related Macular Edema Stage
||No retinal thickening or hard exudates * in posterior pole
|DME present Mild
||Retinal thickening or hard exudates in posterior pole but outside central subfield of the macula (diameter 1000 µm)
|DME present Moderate
||Retinal thickening or hard exudates within the central subfield of the macula but not involving the centre point – also known as “centre-threatening DME”
|DME present Severe
||Retinal thickening or hard exudates involving the centre of the macula within 500 µm —also known as “DME with centre involvement”
*Hard exudates are a sign of current or previous macular edema3. Hard exudates are white/yellow spots observed on the picture of the back your eye called a fundus image. These white/yellow spots are made up of lipid residue from fluid leaked from damaged blood vessels.
The major causes of sight threatening visual impairment are PDR and DME. The threat to sight with PDR is due to growth of new vessels leading to intraocular hemorrhage and possible retinal detachment leading to profound sight loss. The threat to sight with DME is due to localized damage to the macula of the eye with loss of central visual acuity.