The conquest of diabetes
Aretaeus (130-200) was the first
physician to give diabetes its
proper name. In his treatise 'On 
the causes and symptoms of 
chronic diseases Book II'. He
used the Greek word diabetes 
(meaning siphon) to describe the disease. He stated that ' Diabetes
is a remarkable affection not very
frequent among men being a 
melting down of the flesh and 
blood into urine.' Mellitus was 
added later by others to denote 
the sweet taste of urine. Mellitus 
means honey in Greek.
Claude Bernard (1813-1878). The
father of 'experimental physiology' 
showed that the liver stores 
glycogen which can be converted 
into glucose.
Oscar Minkowski (1858-1931) 
discovered in the laboratory of 
the Medical Clinic of Strassburg 
in 1889 removal of pancreas 
from dog caused it to develop 
severe diabetes with excessive
thirst and polyuria.
Frederick Banting (1891-1941)
revolutionized the treatment 
of diabetes after successfully 
isolating insulin from his 
dog Marjory in 1921.



Section 2 Clinical Features of Diabetic Retinopathy
(for an enlarged view of the retina please click the picture)
Diabetic retinopathy is classified as:
  • background retinopathy
  • proliferative retinopathy
Each has a different prognosis for vision.
Background diabetic retinopathy (BDR) is further classified as:
  • minimal
  • moderate
  • severe
  • very severe
Precise grading for each level of BDR is based on the Airlie House
Grading system (see below) 13. Severe and very severe BDR are 
commonly referred to as preproliferative diabetic retinopathy (PDR).
BDR which affects the macula is described as:
  • diabetic maculopathy
Diabetic maculopathy (DM) is further classified as:
  • focal oedema (also known as exudative maculopathy

  • diffuse oedema

  • ischaemia or 

  • mixed
Proliferative diabetic retinopathy (PDR) is described according to 
location as:
  • new vessels on the disc (NVD) or within 1 disc diameter 

  • of the disc (DD)
  • new vessels elsewhere in the retina (NVE) (more than 

  • 1 DD from the disc)
and according to severity as early PDR, established PDR, florid PDR 
and gliotic PDR. 'Involutionary' PDR is used to describe new vessels 
which have regressed in response to treatment or (rarely) 
BDR, also described as non-proliferative diabetic retinopathy (NPDR), 
is so-called because the lesions lie within the retina (i.e. they form 
a 'background' to lesions on the retinal surface such as new vessels 
or within the vitreous such as forward new vessels and vitreous 
haemorrhage). Initially, background retinopathy consists of micro-
aneurysms only (Fig 1), progressing to microaneurysms and small 
haemorrhages ('dots and blots') (Fig 2) which can be graded as mild, 
moderate and severe (Fig 3). Splinter haemorrhages 
are also seen in combined hypertensive/diabetic retinopathy (Fig 4). 
Some grading centres consider a minimum of 4 microaneurysms are
required to diagnose background retinopathy and that they should 
be bilateral.
Figure 1 Background diabetic 
retinopathy (BDR) showing 
microaneurysms only (arrow). 
Figure 2 BDR showing 
microaneurysms and small 
dot/blot haemorrhages (arrow).
Figure 3 Moderate sized blot 
haemorrhages (arrows). Note also 
the venous dilatation and beading 
Figure 4. Splinter haemorrhages and 
intraretinal microvascular abnormalities 
(IRMAs) (arrows) associated with 
combined hypertensive and diabetic 
Exudates, more common in NIDDM, are waxy yellow deposits with discrete 
edges, extending to the equatorial fundus often in clusters or forming 
circinate patterns whose centre may be a leaking microaneurysms (Fig 5). 
'Cotton wool spots' (CWS), previously called soft exudates, are fluffy 
white lesions representing infarcts of the nerve fibre layer hence are only 
found in the posterior retina where the nerve fibre layer is of appreciable 
thickness (Fig 6). They may appear suddenly during periods of changing 
glucose regulation and in association with hypertension.
Figure 5 hard exudates forming a ring 
or circinate pattern around a leaking microaneurysm (arrow). 
Figure 6 Soft exudates (cotton wool 
spots, CWS) in the posterior fundus in 
moderate DR (see arrow).
Venous dilatation may occur as an early sign (see Fig 3) but become 
more pronounced as more of the capillary bed is closed. A general 
dilatation of the veins is observable even when the retinopathy is very 
mild and is to be distinguished from venous beading which is a sign of 
preproliferative retinopathy (Fig 7). Beading is indicative of extensive 
ischaemia of the retina and manifests as saccular bulges in the wall of 
the vein (Fig 7). Fluorescein angiography will invariably show closure 
of the capillary bed on either side of the vessel (Fig 8).
Figure 7 Venous beading (arrow) 
indicating widespread retinal ischaemia.
Figure 8 Extensive venous beading 
associated with areas of capillary 
closure (arrows)
Other signs of preproliferative retinopathy retinopathy are dilated 
capillaries which can mimic new vessels but are better described as 
intraretinal microvascular abnormalities (IRMA) (see Fig 4). They 
frequently occur adjacent to CWS's, and may be associated with 
other signs such as 'omega' venous loops (Fig 9), venous reduplication 
and white lines which represent occluded arterioles (Fig 10). According 
to the Early Treatment for Diabetic Retinopathy Study (ETDRS) report, 
preproliferative retinopathy is definitely present if the signs conform to 
the 1-2-3 rule: i.e.. the presence of venous beading and/or IRMA and/or 
large blot haemorrhages in 1-3 quadrants of the fundus.
Figure 9 Omega loop (arrow), IRMA 
and CWS in moderate/severe BDR.
Figure 10 'White line' indicating an 
occluded vessels.
Precise classifications for the purposes of clinical trials and other 
studies based on the Airlie House grading system have used the 
following criteria to define each of the grades of BDR:
    • mild BDR: at least one microaneurysm

    • moderate BDR: severe retinal haemorrhages in at least one 

    • quadrant, or CWS, venous beading or IRMA definitely present
    • severe BDR: severe retinal haemorrhages in four quadrants; 

    • or venous beading in 2 quadrants; or extensive IRMA in one 
    • very severe BDR: any two of the features of severe BDR. 
However, such classifications are difficult to use in clinical practice on a 
routine basis since certain features such as venous beading are common 
to both moderate and severe retinopathy. It is preferable, therefore to 
consider BDR as either midl or 'low risk' (i.e. not requiring regular close 
observation by an ophthalmologist) and severe or 'high risk' (i.e. requiring 
regular close observation as prelude to panretinal photocoagulation, PRP).
For the purposes of defining those patients at risk of developing new 
vessels, the features of 'low risk' (mild) BDR are:
    • mildly dilated veins
    • microaneurysms
    • small haemorrhages
    • hard exudates
    • occasional CWS's
and the features of 'high risk', preproliferative (severe) BDR are
    • IRMA
    • venous beading and 'omega' loops
    • clusters of large 'blot' or 'blotch' haemorrhages
    • multiple CWS's
Proliferative retinopathy (PDR) usually appears late in the disease. 
However, PDR may occur with little warning in young adolescent 
or post adolescent individuals and have a particularly aggressive 
course. These individuals require extensive counselling (see below). 
It is important to emphasize that new vessels by themselves rarely 
produce symptoms; their sequelae are the cause of visual loss. 
New Vessels mostly arise from the venous side of the circulation 
and are recognizable by their abnormal location and their unusual 
pattern (Fig 11). Unlike normal vessels which have a branching 
pattern that divides dichotomously, new vessels form loops or rete 
(arcades). While norm vessels appear to be supplying or draining an 
area of retina, it may be difficult to identify such a role for new 
vessels. For example, a rete of vessels may arise from the main trunk 
of a vein and criss-cross the vessel randomly or a venule may arise 
from the disc and after forming a tortuous loop wind back towards 
the disc (Fig 12, 13). Early new vessels usually lie flat on the surface 
of the retina, but when the vitreous is detached, they are drawn 
forward as a result of vitreous traction.
Figure 11 New vessels elsewhere (NVE) 
(arrow); note that new vessels have an 
abnormal branching pattern, are very fine 
and tend to form closed loops and fronds.
Figure 12 NVE showing three sites of new 
vessel growth from one vessel. 
Figure 13 New vessels of the disc (NVD) 
showing backward looping of the new 
vessel growth towards the disc (arrow)
New vessels arise from the disc (NVD) (Fig 13, 14, 15) or the retina 
(NVE) (Fig 11, 12). Most new vessels arise from veins in a central, 
circular areas about 3½ disc diameter from the disc margin in any of 
4 quadrants. Where there is sectoral ischaemia, new vessels 
characteristically arise at the junction of the perfused and non-
perfused area as demonstrated on fluorescein angiograms (Fig 16a, b). 
In eyes with widespread ischaemia, NVD are common. Disc NVD may 
be flat or forward depending on the position of the posterior vitreous 
Figure 14 Early NVD showing a small 
frond of vessels arising below the disc 
Figure 15 Advanced active NVD.
Figure 16 Corresponding fundus photograph a) and fluorescein angiogram b) showing 
site of new vessels (arrow) on edge of area of ischaemia.
Untreated NV (D or E) lead to vitreous haemorrhage (VH) and blindness. 
VH may be subhyaloid before the vitreous is fully detached and present 
as small 'crescents' with a level superior border if the PVD is present 
(Fig 17, 18).
In the late stage of the natural history of proliferative disease, fibrous 
tissue (gliosis) gathers around the new vessels and contraction of this 
tissue causes repeated bleeding and eventually, tractional retinal 
detachment. Occasionally, fine epiretinal gliosis occurs with minimal 
traction on the retina but this is uncommon.
Figure 17. Subhyaloid haemorrhage
associated with new vessels and 
showing a fluid level. 
Figure 18 Large subhyaloid 
haemorrhage in the premacular area. 
Visual loss in diabetic maculopathy is usually the result of macular 
oedema. Macular oedema may be difficult to detect; characteristically 
it appears as 'retinal thickening' on binocular, stereoscopic slit lamp 
examination. When it occurs within one disc diameter of the fovea, it is 
termed clinically significant macular oedema (CSME)14 since under these 
conditions it is visually threatening. Fluorescein angiography also reveals 
vessels with abnormal permeability causing leakage and pooling of dye in 
the late phase. A classification of maculopathy based on ophthalmological 
features is detailed below. However it is important to note than the terms 
'focal' and 'diffuse' are used to convey a sense of the extent of macular 
involvement, and if the ophthalmological findings are interpreted in 
conjunction with the corrected visual acuity a more accurate impression 
of the severity of disease will be obtained. For instance, diabetic 
maculopathy may occur in the relative absence CSME and fluorescein 
leakage on angiography. In this condition, ischaemia is the likely pathology.
2.4.1 Clinical types of diabetic maculopathy Focal maculopathy
The characteristic features of focal maculopathy are well circumscribed, 
leaking areas associated with complete or incomplete rings of hard exudates. 
These are often related to microaneurysms, particularly in the centre of 
exudative rings (Fig 5, 19). The exudative rings have a predilection for the 
perifoveal area where the retina is thickest. The focal areas of leakage are 
thickened by retinal oedema and fluorescein angiography is usually not 
necessary to identify them. Recent studies also suggest that retinal 
pigment epithelial damage may contribute to the macular oedema probably 
by failing to remove the tissue fluid accumulating in the retina from the 
leaking capillaries15.
. Diffuse maculopathy
Diffuse maculopathy consists of generalized leakage from dilated capillaries
in the macular area. Severe oedema is a feature and it is often associated 
with cystic changes. The other features of diabetic retinopathy may not be 
present and in particular there may be no exudates. In severe cases it may 
be impossible to identify the fovea due to the diffuse retinal thickening. The 
fluorescein angiogram is more dramatic than the ophthalmoscopic picture
(FIg 20 a, b).
Figure 19 Focal (exudative) 
maculopathy showing hard 
exudates close to the fovea.
Figure 20 Diffuse maculopathy showing retinal thickening a) and 
extensive leakage on fluorescein angiography b).
. Ischaemia maculopathy
Ischaemia maculopathy is almost a diagnosis of exclusion, based on 
unexplained visual loss in the presence of a relatively normal looking 
macula. Blot haemorrhages in the paramacular region may be indicative 
of ischaemic maculopathy. There may be associated haemorrhages and 
exudates elsewhere. The exact extent of the ischaemia can only be seen 
on fluorescein angiography (Fig 21a, b). It is therefore important that 
patients with maculopathy in which ischaemia is suspected are investigated 
with this technique. There does not appear to be a direct correlation 
between visual acuity Dan the degree of ischaemia.
Figure 21 Ischaemia maculopathy showing relatively non-specific changes at the macular a) with areas of non-perfusion on fluorescein angiography. Mixed maculopathy
Many cases do not fit exactly into the groups described above. Frequently, 
there is combined pathology particularly of diffuse oedema and ischaemia. 
Nevertheless, classifying the maculopathy according to its predominant features 
is useful form a therapeutic prognostic point of view. 
Epidemiology Clinical features Risk factors Screening
Lasers and lenses. NVD,, NVE.. Maculopathy
Vitrectomy. Cataract Special problems Counselling
References.. AAO guidelines Atlas of Retinopathy Contact lenses
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