Definition of Diabetic Retinopathy

Diabetic Retinopathy can be defined as progressive dysfunction of the retinal vasculature secondary to chronic hyperglycaemia. Since the retina is easy to view or image and careful monitoring can ensure that sight threatening lesions can be detected in time for effective therapy, it is important that the stages of diabetic retinopathy are defined and classified in a clear and unambiguous manner. This entry explains the Diabetic Retinopathy Disease Severity Scale, and describes the characteristic features associated with each stage of progression of retinopathy.

Grading of Diabetic Retinopathy

Although most grading scales for DR are broadly similar, achieving consensus on a diabetic severity scale has been problematic. One of the earliest and best recognised grading scales is the clinical classification system is based on the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) publications [1][2]. In 2003, the Global Diabetic Retinopathy Group published the “Proposed International Clinical Diabetic Retinopathy and Diabetic Macular Edema Scales” in order to promote understanding, communication and co-ordination of care amongst those caring for patients with diabetic retinopathy [3]. The Diabetic Disease Severity Scale is described below.

Diabetic Retinopathy Disease Severity Scale

  • No apparent retinopathy
  • Mild non-proliferative diabetic retinopathy
  • Moderate non proliferative diabetic retinopathy
  • Severe non-proliferative diabetic retinopathy
  • Proliferative diabetic retinopathy
  • Macular oedema apparently absent
  • Macular oedema apparently present*

*If macular oedema is present it can be sub-classified as mild, moderate, or severe.

Clinical Signs of Diabetic Retinopathy


Microaneurysms are the first clinically detectable sign of diabetic retinopathy. Clinically microaneurysms are seen as small red dots found in the middle layers of the retina. Microaneurysms are formed from out-pouchings of the capillary walls, and when the wall becomes sufficiently weakened, the wall may rupture giving rise to an intraretinal haemorrhage. Distinguishing microaneurysms from dot haemorrhages is difficult by clinical examination, however fluorescein angiography is helpful: microaneurysms leak fluorescein but haemorrhages will block fluorescence [4].


Haemorrhages can be described as dot, blot, or flame shaped. During clinical examination it is important to take note of the shape of a haemorrhage. The shape, colour and size of a haemorrhage can give important information as to the underlying pathology. Flame shaped haemorrhages are superficial: their shape results from their location in the nerve fibre layer. Flame shaped haemorrhages are usually not indicative of diabetic retinopathy, but are characteristic of hypertension and other vascular disorders.

Dot and blot haemorrhages are found deeper in the retina, either in the nuclear layer or the outer plexiform layer. They are common in DR, and in general the larger the haemorrhage, the more profound the ischaemia. Haemorrhages that are greenish in colour usually lie beneath the retinal pigment epithelium. These haemorrhages are not usually seen in diabetic retinopathy but are indicative of disorders that cause choroidal neovascularisation, such age-related macular degeneration.


Exudates are yellow deposits with well-defined edges which are caused by deposition of lipids within the retina. The distribution of exudates can be variable, in some cases exudates are widely distributed throughout the macula, whereas in others, exudates are arranged in a ring-like distribution around a group of microaneurysms or an area of capillary non-perfusion. This appearance is known as circinate retinopathy. Circinate retinopathy tends to respond better to treatment by laser photocoagulation than the more diffuse types of maculopathy.

Macular Oedema

Macular oedema is caused by leakage of intercellular fluid either from microaneurysms or from leaking, incompetent capillaries. Macular oedema causes retinal thickening which is not easily detectable by direct ophthalmoscopy, and best detected clinically by stereo biomicroscopy. As macular oedema progresses, pockets of fluid in the outer plexiform layer can be seen. This appearance is described as cystoid macular oedema. Traditionally this has been best seen on fluorescein angiography as a petaloid pattern however more recently optical coherence tomography (OCT) can show this in detail and is non-invasive. OCT monitoring is excellent for demonstrating progression or resolution of macular oedema [4][5][6].

Cotton Wool Spots

As diabetic retinopathy progresses, signs of intraretinal hypoxia become evident. Features of increasing ischaemia include multiple, often large, retinal haemorrhages, cotton wool spots, venous changes such as venous dilatation, and venous beading and loops. As the disease progresses, intraretinal microvascular abnormalities (IRMAs) appear. Cotton wool spots (also often referred to as soft exudates) result from ischemia of the nerve fibre layer obstructing the flow of axoplasm. Cotton wool spots are caused by swelling of the nerve fibres, leading to a characteristic fluffy appearance. Clinically, cotton wool spots are distinguishable by being much larger, whiter, and having less well defined edges than lipid exudates.

Venous Changes

Although venous changes are a very important indication of progression of diabetic retinopathy, they are often under-appreciated. Venous calibre changes and abnormalities are indicative of increasing hypoxia, and are often found on the edge of areas of non-perfusion. The normal ratio of arteriolar to venous calibre is 2:3, whereas in advancing diabetic retinopathy this ratio is often altered to 1:2 or less. As the veins become more dilated, beading or ‘cattle-trucking’ can be seen in areas of profound ischemia. In severe cases the veins can form loops. The ETDRS reported that IRMAs, multiple retinal haemorrhages, and widespread capillary non-perfusion were all significant risk factors for progression to proliferative retinopathy. Unexpectedly, cotton wool spots were not associated with progression [7].

Intraretinal Microvascular Abnormalities

IRMAs represent either new vessel growth within the retina or remodelling of existing vessels to act as shunts through areas of non-perfusion. Clinically, IRMAs are seen as foci of fine new vessels or vascular abnormalities which remain within the retina and are flat. Unlike new vessels, IRMAs do not protrude into the vitreous cavity. IRMAs signify progression of diabetic retinopathy and often are precursors of the proliferative stage of diabetic retinopathy.

Neovascularisation and Proliferative Diabetic Retinopathy

Neovascularization is the hallmark of proliferative diabetic retinopathy. Individuals are generally unaware that neovascularisation is present until the onset of vitreous haemorrhage. New vessels usually arise from retinal veins. They are fine calibre vessels which are seen as tufts, either on the surface of the retina or extending into the vitreous cavity. Clinically, new vessels are classified as ‘neovascularisation of the disc’ (NVD) when they arise either on the optic nerve or within one disk diameter of the optic nerve head. When the vessels arise further than one disk diameter away from the disk, they are termed ‘neovascularisation elsewhere’ (NVE). New vessels are not as competent (i.e. tightly sealed) as normal retinal vessels: they leak, giving rise to vitreous haemorrhage. NVD generally carries a higher risk of vitreous haemorrhage than NVE. With early diagnosis, neovascularisation responds well to pan-retinal photocoagulation.

Fibrous Tissue

Progression of retinopathy either in the absence of treatment, or when the individual is non-responsive to laser photocoagulation, will result in fibrous tissue formation accompanying the neovascular fronds. Fibrovascular proliferation leads to tractional retinal detachment. This stage is known as advanced diabetic retinopathy.

Grading of Diabetic Retinopathy

Following detailed clinical examination of the fundus, the level of retinopathy is graded according to severity. The International Diabetic Disease Severity Scale described above is shown in more detail below in Table 1 with the associated clinical signs required for each level of severity.

Table 1

Proposed Disease Severity Level Findings Observable on Dilated Ophthalmoscopy
No apparent retinopathy No abnormalities
Mild non-proliferative diabetic retinopathy Microaneurysms only
Moderate non-proliferative diabetic retinopathy More than just microaneurysms but less than severe non-proliferative diabetic retinopathy
Severe non-proliferative diabetic retinopathy Any of the following: more than 20 intraretinal hemorrhages in each of 4 quadrants: definite venous beading in 2 quadrants: Prominent intraretinal microvascular abnormalities in 1 quadrant. And no signs of proliferative retinopathy
Proliferative diabetic retinopathy One or more of the following: neovascularisation, vitreous/preretinal haemorrhage
Diabetic Macular oedema apparently absent No apparent retinal thickening or hard exudates in the posterior pole
Diabetic Macular oedema apparently present Some apparent retinal thickening or hard exudates in the posterior pole

Diabetic Maculopathy

Diabetic maculopathy can be subdivided into exudative, oedematous and ischaemic types, but frequently patients present with a combined maculopathy. Exudative maculopathy, especially if circinate in nature (i.e. exudates distributed in a circular pattern) generally has a more favourable prognosis. Oedematous maculopathy responds variably to laser photocoagulation, whereas ischaemic maculopathy has the worst prognosis. Signs that indicate ischaemic maculopathy include large intraretinal haemorrhages and a featureless macular appearance. Treatment with anti-VEGF therapy available may lead to improved prognosis in oedematous and ischaemic maculopathy.


  1. ^ Klein R, Klein BE, Moss SE. The Wisconsin epidemiologic study of diabetic retinopathy: an update. Aust N Z J Ophthalmol. 1990;18(1):19-22. Epub 1990/02/01.

  2. ^ Group ETDRSR. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. . Ophthalmology. 1991;98(5 Suppl):766-85. Epub 1991/05/01.

  3. ^ Wilkinson CP, Ferris FL, 3rd, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677-82. Epub 2003/09/18.

  4. ^ Norton EW, Gutman F. Diabetic retinopathy studied by fluorescein angiography. Ophthalmologica Journal international d'ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde. 1965;150(1):5-17. Epub 1965/01/01.

  5. ^ Taylor HR, Munoz B, Rosenthal FS, West S. An abbreviated assessment of ocular exposure to ultraviolet radiation. Aust N Z J Ophthalmol. 1992;20(3):219-23. Epub 1992/08/01.

  6. ^ Lang GE. Optical coherence tomography findings in diabetic retinopathy. Dev Ophthalmol. 2007;39:31-47. Epub 2007/01/25.

  7. ^ Group ETDRSR. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98(5 Suppl):823-33. Epub 1991/05/01.


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