Ординатура / Офтальмология / Английские материалы / Automated Image Detection of Retinal Pathology_Jelinek, Cree_2009

The macula is the central approximately 6 mm diameter area of retina. It is responsible for the fine central vision. The retina beyond the macula is termed the peripheral retina.

2.4Definition and Description

Diabetic retinopathy is defined as a clinical diagnosis, characterized by the presence of one or more of several retinal lesions in a patient with diabetes mellitus (Table 2.3).

Table 2.3: Diabetic Retinopathy Lesions

Microaneurysms (< 60 µm)

Dot-hemorrhages

Hard exudates

Blotchy hemorrhages

Intraretinal microvascular abnormalities (IRMAs)

Venous beading

Cotton wool spots

New vessels on or within one disc diameter of the disc (NVD)

New vessels elsewhere (NVE)

Fibrous proliferation

Preretinal hemorrhage

Vitreous hemorrhage

Traction retinal detachment

Rhegmatogenous retinal detachment

Macular retinal thickening (edema)

Clinically significant macular edema (CSME)

Diabetic retinopathy is a progressive disease. It begins as mild nonproliferative retinopathy characterized by clinical features secondary to capillary changes with increased permeability. It may progress to moderate and severe nonproliferative retinopathy characterized by clinical features secondary to capillary closure as well as increased capillary permeability. Disease progression continues to proliferative retinopathy characterized by growth of new blood vessels, in and on the retina and even on the iris. Diabetic macular edema characterized by intraretinal accumulation of fluid and lipid within the macula can occur at any stage of the disease progression.

The pathology of diabetic retinopathy is a progressive microangiopathy of the retinal capillaries. Early changes are a loss of retinal capillary pericytes, thickening of the basement membrane, and the characteristic appearance of microaneurysms (saccular outpouchings of the capillary wall). There are changes in retinal blood flow. The inner blood-retinal barrier breaks down manifesting as increased retinal

capillary permeability and intraretinal hemorrhage. Retinal capillaries and arterioles close (retinal nonperfusion). Later there is proliferation of blood vessels (termed “new vessels”), first within the retina and then on the retinal surface and onto the posterior surface of the vitreous. Accompanying vessel proliferation is fibrous tissue proliferation on the retinal surface and along the posterior vitreous surface. Contraction of fibrous tissue leads to complications such as vitreous hemorrhage and traction retinal detachment. In advanced disease new vessels proliferate on the iris.

Microaneurysms are almost always the first clinical sign of diabetic retinopathy, and are seen as intraretinal deep red spots 15 to 60 µm in diameter. There is a continuous turnover of microaneurysms; individual microaneurysms may persist for long time periods before eventually disappearing. Rupture of microaneurysms and increased capillary permeability give rise to intraretinal hemorrhage. Small pinpoint intraretinal (dot) hemorrhages are typical of diabetic retinopathy. They may be difficult to distinguish clinically from microaneurysms. Distinguishing between microaneurysms and dot-hemorrhages is of little clinical importance and therefore small intraretinal red lesions can be classified together as “hemorrhages and microaneurysms” (Figure 2.1).

Increased capillary permeability gives rise to intraretinal accumulation of fluid (edema) clinically termed “retinal thickening,” and lipid, seen as yellow-white welldefined intraretinal accumulations termed “hard exudate” (Figure 2.2).

Patches of capillary closure develop and coalesce as areas of nonperfused retina. Capillary closure is not visible clinically without fluorescein angiography. Adjacent to areas of nonperfusion tortuous vessels termed “intraretinal microvascular abnormalities” (IRMA) may arise. It is not clear whether IRMA are new vessel proliferation or abnormal preexisting vessels. Other features associated with capillary closure include large intraretinal hemorrhages (“blotchy hemorrhages”), segmental vein dilatation (“venous beading”) and a halt in axoplasmic flow in the nerve fiber layer seen as fluffy white patches in the innermost retina (“cotton wool spots”) — see Figure 2.2(b)).

Nonperfused retina releases vascular endothelial growth factors (VEGFs). These are a family of peptides produced by a single gene. VEGF isoforms act specifically on vascular endothelial cells leading to new vessel proliferation and increased vessel permeability. VEGF expression, synthesis and release are enhanced by hypoxia from areas of nonperfusion [24]. VEGF diffuses throughout the eye and results in the growth of new vessels on the retinal surface and eventually on the iris. This is termed “proliferative diabetic retinopathy” (PDR) while all retinopathy prior to new vessel formation is “nonproliferative diabetic retinopathy” (NPDR). This is the basis of the classification of diabetic retinopathy discussed later. The presence of severe NPDR (three of the following four in at least two quadrants of the retina: IRMA, cotton wool spots, venous beading, extensive retinal hemorrhages, or microaneurysms) is a predictor of the development of PDR; about 50% will develop PDR within 15 months [25]. However, these features are not universally found with early new vessels. Cotton wool spots are transient; IRMA and retinal hemorrhages may not be seen with more extensive capillary closure.

FIGURE 2.1

Moderate nonproliferative diabetic retinopathy with moderate diabetic macular edema. (See color insert following page 174.)

New vessels are usually first evident within 45 degrees of the optic disc, 15% on or within one disc diameter of the optic disc, termed “new vessels disc” (NVD); 40% only outside of this area termed “new vessels elsewhere” (NVE); and 45% had vessels in both areas [26].

Early NVD are loops or networks of fine vessels on the optic disc. As they grow the vessel complex extends outside the optic disc margin and the vessel caliber increases. NVE begin as small loops or networks usually near a retinal vein. As they grow they form networks that distinctively pass across the underlying retinal veins and arterioles. The new vessels grow into the scaffold of the posterior vitreous surface. New vessels are fragile and highly permeable. Vitreous traction on these fragile new vessels may lead to preretinal and vitreous hemorrhage (Figure 2.3).

With time fibroglial tissue develops adjacent to the new vessels and within the new vessel complexes. The combination of fibrous and vascular tissue is termed fibrovascular tissue. As the fibrovascular tissue grows, the proportion of the fibrous component increases. Eventually new vessels may regress. Fibrovascular tissue is

FIGURE 2.2

Nonproliferative diabetic retinopathy (NPDR). (a) Moderate NPDR and severe diabetic macular edema; hard exudates involve the center of the macula. (b) Moderate NPDR; microaneurysms/dot hemorrhages, hard exudate (ring) and cotton wool spots. (c) Severe NPDR; > 20 intraretinal hemorrhages in four quadrants (three shown here) and IRMA (possibly NVE). Biomicroscopy showed the latter lesion to be intraretinal, hence it is IRMA. (d) Venous beading. (See color insert.)

FIGURE 2.3

Proliferative diabetic retinopathy (PDR). (a) PDR with moderate diabetic macular edema. There are new vessels disc, new vessels elsewhere, IRMA, blotchy hemorrhages, microaneurysms/dot-hemorrhages, and hard exudates. Hard exudate approach the center of the macula. Pan retinal photocoagulation scars are seen in the top left and top and bottom far right. (b) New vessels elsewhere. (c) PDR with preretinal hemorrhage. Hemorrhage is contained within the space between the retina and the posterior vitreous face. The hemorrhage obscures the retinal new vessels.

(d) Fibrous proliferation with traction macular detachment. PDR has regressed. Regressed fibro-vascular tissue along the inferior temporal vascular arcade has contracted causing traction macular detachment. Traction lines can be seen extending into the central macula. (See color insert.)

adherent to both the retina and the posterior vitreous surface. In many eyes the fibrovascular tissue contracts, and via these adhesions exerts traction on the retina. Traction may cause retinal edema, striation, and heterotropia (dragging), and retinal detachments; either without retinal tear (traction retinal detachment) or with retinal tear (rhegmatogenous retinal detachment).

Diabetic macular edema (DME) is defined as intraretinal accumulation of fluid within two disc diameters of the center of the macula. DME may develop at any stage of diabetic retinopathy. Macular abnormalities found in diabetic retinopathy include DME, capillary nonperfusion, intraretinal hemorrhage, preretinal hemorrhage, macular surface traction from fibrovascular proliferation, preretinal membrane (avascular fibrous tissue proliferation) and partial or full thickness macular hole.

2.5Classification of Diabetic Retinopathy

The Early Treatment Diabetic Retinopathy Study (ETDRS) classification system [25] is the gold standard used in clinical trials. It is complex and not easy to use in clinical practice.

Proposed to replace the ETDRS classification for use in clinical practice are the International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scales [27]. These are scientifically based and practical classification systems derived from the ETDRS and the Wisconsin Epidemiological Study of Diabetic Retinopathy study (WESDR) [28; 29]. The major modifications to previous classification systems are based on scientific evidence. IRMA and venous beading are included as they are the most predictive for progression to PDR. A separate stage for severe NPDR is made on the basis of the evidence that early treatment is beneficial for patients with type 2 diabetes with severe NPDR. A severity scale for DME is a new and important addition. Included are the factors that determine if macular edema is sight threatening; the location and area of retinal thickening and hard exudates.

2.6Differential Diagnosis of Diabetic Retinopathy

A number of retinal vascular diseases share many of the clinical signs seen in diabetic retinopathy; these include central retinal vein occlusion, branch retinal vein occlusion, hypertensive retinopathy, ocular ischemic syndrome (hypoperfusion retinopathy), the retinopathies of blood dyscrasias such as anemia and leukemia, parafoveal telangiectasis and other retinal telangiectases, sickle cell retinopathy, and radiation retinopathy.

One of the more common of these diseases such as branch retinal vein occlusion or central retinal vein occlusion may well be seen concurrently with diabetic retinopathy and may be difficult to differentiate. If suspected from the clinical features, ocular