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Fig. 2.1 (a) Background DR: color fundus photography demonstrates microaneurysms (large arrow) and small hemorrhages (small arrows) located temporally to the macula. (b) After 1 year, microaneurysms may obliterate and small hemorrhages regress. In early phases of the disease, color photos are useful to document change of the lesions over time
2.1Clinical Overview
2.1.1Clinical Findings
Classically, non-proliferative diabetic retinopathy (NPDR), or background retinopathy, is characterized by microvascular and intraretinal changes seen on dilated fundus examination, including microaneurysms, hemorrhages, hard exudates, cotton wool spots, intraretinal microvascular abnormalities (IRMA), and venous beading. Macular edema could occur in both non-proliferative and proliferative diabetic retinopathies.
Microaneurysms are the typical earlier signs of DR. They consist in outward ballooning of the capillary wall and dilatation of the terminal arterioles or small venules in areas of selective loss of intramural pericyte [1]. Their size could range from 25 to 100 μm in diameter and their location is predominately at the posterior pole, more often temporally to the macula [2] (Fig. 2.1). Two types of microaneurysms have been described, according to the extension of the vessel wall dilatation: fusiform (only one side of the vessel wall) and saccular (both sides) microaneurysms. The presence of only microaneurysms is generally asymptomatic and could be detected variably in the early stages of the DR, according the property of the blood glucose control. Microaneurysms are clearly identified on dilated fundus examination; nevertheless, with fluorescein angiography (FA), a wider number could be detected (Fig. 2.2).
In the different levels of severity of NPDR, intraretinal hemorrhages could be noticed, produced by the rupture of the microaneurysms (intraretinal punctate hemorrhages), IRMAs, and leaking capillaries. Two types of intraretinal hemorrhages have been defined: flame-shaped and dot-blot hemorrhages, based on their
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Fig. 2.2 (a) Color photo in a mild NPDR. (b–d) Sequent phases of FA show early dot hyperfluorescence related to microaneurysms with increasing leakage in the late frames
appearance and location in the retina. Flame-shaped hemorrhages are situated in the nerve fiber layer, while dot-blot hemorrhages are located in the inner nuclear layer and in both inner and outer plexiform layers of the retina. The appearance of the flame-shaped hemorrhages is related to the course of the nerve fiber layer, which runs parallel to the retinal surface, whereas the dot-blot hemorrhages are located in the other layers that course perpendicular to the retina (Figs. 2.3, 2.4, and 2.5).
Hard exudates are yellow, cereus intraretinal lipids, usually deposed at the posterior pole, secondary to the fluid accumulation [3]. Clinically they are organized in cluster and often assume the typical distribution of the circinate pattern surrounding one or more microaneurysms [4] (Fig. 2.6). When the location of the circinate is centered on the fovea, a macular star pattern is represented. The detection of hard exudates, usually at the border of an area of retinal thickening, is a marker of clinically significant diabetic macular edema and thus is often associated with a decreased visual acuity.
Cotton wool spots could be seen as gray lesions, with indistinct borders, and consist in nerve fiber infarctions. Their location runs parallel to the nerve fiber layer and adjacent to the blood vessels (Fig. 2.7). The formation of cotton wool spots is
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Fig. 2.3 Color (a) and red-free (b) photographs which show mild NPDR with confluent vascular microectasias along the superior-temporal vascular branch, a small hemorrhage, and initial lipoproteic trasudation detectable as microexudates (arrow). Microaneurysms are hyperfluorescent in the early phase of FA (c) and leaking in the later phases (d, e). (f) OCT vertical scan shows a normal retinal section
due to the interruption of the axoplasmic flow, which results in the accumulation of cytoplasmic debris and swollen nerve ending appearance [5].
The fluctuation of the venous caliber is defined as venous beading and consists in a focal venous dilation [6]. This may occur in areas of capillary occlusion and IRMAs, in the severe NPDR. Other venous caliber abnormalities include diffuse venous dilatation and venous loop formation [7] (Fig. 2.8). These alterations are
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Fig. 2.4 Deep blot small hemorrhages and several microaneurysms in color (a) and FA (early, b, and late, c) photographs of NPDR. (d) Magnification of central area in early angiographic phase allows to detect some early abnormalities of the FAZ (foveal avascular zone) and of the anastomotic perifoveal arcade
caused in response to the hyperglycemic changes and the subsequent impairment of the venous autoregulation [8].
IRMA (intraretinal microvascular abnormalities) is a nonspecific term referring to shunt vessels that could be detected as a capillary widening adjacent to an area of nonperfusion [9, 10]. They are considered as dilated telangiectatic capillaries, growth within the neural retina and often associated with hard exudates, leakage and hemorrhages. The detection of IRMA is a predictive indicator for a severe form of NPDR, because the growth of these shunt vessels is related to the presence of ischemic areas [11].
Summary 2.1
Biomicroscopic findings in NPDR include microaneurysms, hemorrhages, hard exudates, cotton wool spots, intraretinal microvascular abnormalities (IRMAs), and venous beading.