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F. Bandello et al. |
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Fig. 2.5 (a) Color photo of the posterior pole shows exterior flame-shaped hemorrhages (black arrow), deep dot-blot hemorrhages (green arrow), and initial exudates in the superior macular area (white arrow). FA allows to assess a larger amount of microaneurysms which appear early hyperfluorescent (b) and lately leaking (c)
2.1.2Classification of NPDR
Non-proliferative diabetic retinopathy is classified into different stages according to the severity of its progression.
In 1981, the Diabetic Retinopathy Study (DRS) Research Group proposed a widely applied classification of DR [12], based upon the already present Airlie House classification [13]. The severity of the retinopathy is classified using the seven standard 30° photographic fields of the retina. This scale is based on three stages of gravity of the disease including the absence of DR, the NPDR and the PDR forms, using 11 additional levels of severity. In particular, in the NPDR stage, six different levels of severity are listed: very mild NPDR, mild NPDR, moderate NPDR (two distinct stages), severe NPDR, and very severe
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Fig. 2.6 (a) Color image of early NPDR: dilated pupil allows to detect an exudation from vascular ectasia in the nasal mid-periphery (arrow). (b) Early lesions may occur outside the macular area, which is confirmed by normal OCT scan
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Fig. 2.7 (a) NPDR with small cotton wool (arrow) or soft exudate, which in red-free image appears as a whitening small dot with poorly defined rims. FA shows early hypofluorescence (arrow) (b) corresponding to the acute impairment of perfusion at the level of the lesion: a diffuse breakdown of the blood-retinal barrier is present in the late phase (c)
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Fig. 2.8 Abnormal vessels (arrows) in the superior sector in a young diabetic woman without other retinal lesions. Color (a) and red-free (b) photographs, FA images (c, d) showing anomalous vascular network without fluorescein leakage
NPDR (Table 2.1). The Early Treatment Diabetic Retinopathy Study Research
(ETDRS) Group showed that severe NPDR has a great chance of progression to the high-risk PDR, estimated about 15 and 56 % within 1 and 5 years, respectively, while the very severe NPDR has an increased risk of progression to PDR of about 45 and 71 % within 1 and 5 years, respectively [14].
The proposed classification, defined as the gold standard, even if well exhaustive, resulted to be difficult to remember and complex in the everyday clinical practice. Thus, additional simplified classifications were created in different countries to help physicians in the management of the severity of DR [15–17]. Nevertheless, the data that emerged from several studies using these multiple heterogeneous classifications were difficult to compare; therefore, a further standardized scale of gravity of the disease resulted to be necessary.
Therefore, in 2003, the American Academy of Ophthalmology (AAO) proposed a new standardized [18], evidence-based classification, using data emerged by the Diabetic Retinopathy Study Research Group scheme and the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) [19, 20]. According to this new scale, the DR was classified into five stages, based on the observable findings on dilated fundus ophthalmoscopy: no apparent DR, mild NPDR, moderate NPDR, severe NPDR, and PDR. Thus, clinically the NPDR consisted in only three
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Table 2.1 Classification of the severity of NPDR, modified from the DRS scheme |
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Level of severity |
Visible findings on dilated fundus ophthalmoscopy |
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Very mild NPDR |
Only microaneurysms |
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Mild NPDR |
Hard exudates, cotton wool spots, and/or mild intraretinal hemorrhages |
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Moderate NPDR |
Divided in two levels of gravity |
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(level 43) |
A. Retinal hemorrhages moderate in 4 quadrants or severe in 1 quadrant |
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B. Mild IRMA in 1–3 quadrants |
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Moderate NPDR |
Divided in four levels of gravity |
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(level 47) |
A. Both levels of gravity of moderate NPDR (level 47) |
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B. Mild IRMA in 4 quadrants |
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C. Severe retinal hemorrhages in 2–3 quadrants |
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D. Venous beading in 1 quadrant |
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Severe NPDR |
Divided in four levels of gravity |
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A. ≥2 levels of gravity of moderate NPDR (level 47) |
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B. Severe retinal hemorrhages in 4 quadrants |
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C. Moderate to severe IRMA in ≥1 quadrant |
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D. Venous beading in ≥2 quadrants |
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Very severe NPDR |
Two level characteristics of severe NPDR |
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This is the part of the well-known standardized scheme, related to the NPDR. The DRS classification is based on seven standard 30° photographs, describing the severity of the disease, organized in several detailed levels
Table 2.2 Classification of the severity of the NPDR, modified from the AAO scheme
Level of severity |
Visible findings on dilated fundus ophthalmoscopy |
Mild NPDR |
Only microaneurysms |
Moderate NPDR |
More than mild NPDR and less than severe NPDR |
Severe NPDR |
No signs of PDR and any of the following (4:2:1 rule) |
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≥20 intraretinal hemorrhages in 4 quadrants |
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Venous beading in ≥2 quadrants |
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IRMA in ≥1 quadrant |
This could be a practical and evidence-based classification of grading the severity of the NPDR that could be used in the everyday clinical practice. It is an internationally accepted approach, widely employed in research settings and publications
sublevels of gravity (mild, moderate, and severe), which could represent to retinal specialists the indicators to the progression of the disease (Table 2.2).
•The mild NPDR was defined by the presence of only microaneurysms.
•The moderate stage was intended as an intermediate stage between the mild and the severe forms.
•Finally, the severe form of NPDR was defined, in the absence of any signs of PDR, by any of the following findings: the presence of more than 20 intraretinal hemorrhages in the four quadrants, venous beading in two or more quadrants, and prominent IRMA in at least 1 quadrant (“4:2:1 rule”).
The AAO classification is a helpful tool in the standardization of the gravity
degree of the DR and could facilitate ophthalmologists in the clinical decision, predicting when the NPDR could progress to the more threatening stage of PDR.