REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
94
VOLUME 7 NUMBER 3 • SEPTEMBER 2010
of clinical research have provided excellent data on the natural
course of the disease and on treatment strategies that are highly
effective in preventing the occurrence of severe vision loss. These
studies include the following major clinical trials: DCCT, UKPDS,
the Diabetic Retinopathy Study (DRS), the Early Treatment Diabetic
Retinopathy Study (ETDRS) and the Diabetic Retinopathy Vitrectomy
Study (DRVS).
The earliest clinically apparent stage of retinopathy is called
non-proliferative diabetic retinopathy (NPDR) and is characterised
by retinal vascular abnormalities, including micro-aneurysms, intra-
retinal haemorrhages and cotton-wool spots (Table 1). Increased
retinal vascular permeability that occurs at this or later stages of
retinopathy may result in diabetic maculopathy, characterised by
retinal thickening (oedema) and/or lipid deposits (hard exudates) in
the macular region (central 5–6-mm diameter area of the posterior
pole) (Table 2). Clinically significant macular oedema (CSME) is a
term commonly used to describe retinal thickening and/or adjacent
hard exudates that involve either the centre of the macula or
threaten to spread into it (Figures 1 and 2).
As diabetic retinopathy progresses, there is a gradual closure of
retinal vessels, resulting in impaired perfusion and retinal ischaemia.
Signs of increasing ischaemia include venous abnormalities (e.g.
beading, loops), intra-retinal microvascular abnormalities (IRMA),
and more severe and extensive retinal haemorrhages and exudation.
When these signs progress beyond certain defined thresholds,
severe NPDR is diagnosed (Table 1).
The more advanced stage, proliferative diabetic retinopathy
(PDR), is characterised by the onset of neovascularisation of the
inner surface of the retina, induced by vascular endothelial growth
factor (VEGF), a substance released by the ischaemic retina. New
vessels at the optic disc (NVD) and new vessels elsewhere in the
retina (NVE) are prone to bleed, resulting in vitreous haemorrhage.
These new vessels may undergo fibrosis and contraction and may
result in epi-retinal membrane formation, vitreo-retinal traction
bands, retinal tears, and tractional or rhegmatogenous retinal
detachments.
When new vessels are accompanied by vitreous haemorrhage,
or when new vessels at the optic disc occupy about one-quarter
to one-third or more of the disc area, even in the absence of
vitreous haemorrhage, PDR is deemed to be ‘high-risk’ (Figure 3).
Neovascular glaucoma can result from new vessels growing on the
iris (NVI) and anterior chamber angle structures.
Prevention and early detection
A healthy lifestyle with exercise and weight control may decrease
the risk of developing diabetes, but cannot completely prevent it.
By contrast, the blinding complications of diabetes mellitus can
be prevented or moderated in the majority of patients if their
blood glucose control is tight (monitoring serum glycosylated
haemoglobin levels), other risk factors such as hypertension
and hyperlipidaemia are managed and they are referred to the
ophthalmologist timeously (Table 3).
Table 1.
Classification of diabetic retinopathy by severity based on clinical
findings.
Disease severity level
Findings on dilated ophthalmoscopy
No apparent retinopathy No abnormalities
Mild NPDR
Micro-aneurysms only
Moderate NPDR
More than just micro-aneurysms, but less than
severe NPDR
Severe NPDR
Any of the following (4-2-1 rule) and no signs of
proliferative retinopathy:
• severe intra-retinal haemorrhages and micro-
aneurysms in each of four quadrants
• definite venous beading in two or more
quadrants
• moderate IRMA in one or more quadrants
PDR
One or both of the following:
neovascularisation
vitreous or pre-retinal haemorrhage
IRMA
=
intraretinal microvascular abnormalities; NPDR
=
non-proliferative
diabetic retinopathy; PDR
=
proliferative diabetic retinopathy.
Note: Any patient with two or more of the characteristics of severe NPDR is
considered to have very severe NPDR.
Table 2.
Classification of diabetic maculopathy.
Disease severity level
Findings on dilated ophthalmoscopy
Diabetic macular oedema
apparently absent
No apparent retinal thickening or hard
exudates at posterior pole
Diabetic macular oedema
apparently present
Some apparent retinal thickening or
hard exudates at posterior pole
If diabetic macular oedema is present, it can be categorised as follows:*
• mild
Retinal thickening or hard exudates in
posterior pole but distant from centre
of macula
• moderate
Retinal thickening or hard exudates
in posterior pole approaching but not
involving the centre of the macula
• severe
Retinal thickening or hard exudates in
the posterior pole involving the centre
of the macula
*Hard exudates are a sign of current or previous macular oedema.
Diagnosing retinal thickening requires a three-dimensional assessment,
best performed using slit-lamp biomicroscopy and/or stereoscopic fundus
photography.
Table 3.
Recommended intervals for eye examinations for patients with
diabetes.
Diabetes type
Recommended time
of first examination Recommended follow-up*
Type 1
3–5 years after
diagnosis
Yearly if no retinopathy or mild
NPDR
Type 2
At time of diagnosis
Yearly if no retinopathy or mild
NPDR
Prior to
pregnancy type
1 or type 2**
Prior to conception
and early in the first
trimester
Every 3–12 months for mild
or moderate NPDR. Every 1–3
months for severe NPDR or worse
NPDR
=
non-proliferative diabetic retinopathy.
*Abnormal findings may dictate more frequent follow-up examinations – see
management section.
**Women who develop gestational diabetes do not require an eye
examination during pregnancy, because such individuals are not at increased
risk for diabetic retinopathy during pregnancy.
