Advances in Diabetic Retinopathy

Advances in Diabetic Retinopathy

Feener Edward P
US Endocrinology - Volume 4 - Issue II
Published: April 2009
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Diabetic retinopathy (DR) is a sight-threatening and chronic ocular disorder that eventually develops to some degree in nearly all people with diabetes. DR is characterized by the progressive development of well-defined morphological abnormalities in the retinal microvasculature that can remain relatively stable or progress to diabetic macular edema (DME) and/or proliferative DR (PDR), which are leading causes of both moderate and severe vision loss in working-age adults.1,2 A recent report from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) showed that the 25-year cumulative progression to DR and PDR was 83 and 42%, respectively, for people with type 1 diabetes.3 The rate of progression of DR can vary markedly among individuals, and this has been attributed to a number of factors including genetics, the management of risk factors, and residual insulin production.4–6 The prevalence of DME has been estimated from large epidemiological population-based surveys to be approximately 20–26% in patients with type 1 diabetes.7,8 The occurrence of PDR and DME in type 2 diabetes is comparable to that observed for type 1 diabetes of similar diabetes duration,2 and DR risk is increased in earlier-onset type 2 diabetes.9 While the prevalence of diabetes is increasing and DR is its most frequent vascular complication, medical treatments to prevent and reverse DR remain unmet clinical needs.

Pathogenesis of Diabetic Retinopathy Diabetes-associated Retinal Dysfunctions Before the Onset of Clinical Diabetic Retinopathy
Abnormalities in both vascular and neuronal retinal functions in diabetes can be detected before the clinical diagnosis of DR, based on the appearance of its morphological characteristics (see Figure 1). One of the earliest retinal changes in diabetes is a decrease in retinal blood flow,10 which has been attributed to the prolongation of blood transit time through retinal arterioles and capillaries. Although this hemodynamic change provides early evidence of retinal vascular dysfunction, the longterm significance of diabetes-induced changes in blood flow is not yet available. Diabetes has been shown to increase retinal vascular permeability (RVP) and the adherence of leukocyte to the retinal endothelium, suggesting the local activation of inflammatory processes (reviewed in reference 11). Diabetes without DR has also been associated with prolonged retinal implicit time delays detected using a multifocal electroretinogram,12 suggesting early and regional abnormalities in neuroretinal responses or conduction. Although these abnormalities in retinal function associated with diabetes may provide biomarkers for DR, it is not known whether the mechanisms that induce these early functional changes are the same as the mechanisms that drive the morphological changes associated with advanced stages of DR.

Non-proliferative Diabetic Retinopathy
The first clinical signs of DR include the appearance of microaneurysms and small retinal hemorrhages. Histological studies have revealed decreased numbers of retinal pericytes and the appearance of acellular capillaries. These changes indicate a breakdown of small-vessel and capillary endothelium integrity. Pericytes play a critical role in the maintenance of endothelial tight junctions and microvascular blood flow. Pericyte loss, along with the appearance of acellular capillaries, indicates microvascular damage that could eventually lead to areas of nonperfusion. The occurrence of retinal hemorrhages indicates disruption of endothelium and basal lamina, enabling blood components to diffuse into the neuroretina. The degree and severity of microaneurysms and intraretinal hemorrhages compared with well-established clinical photograph standards is a common marker used to define the level of non-proliferative (NP) DR, graded as mild, moderate, and severe. Additional retinal abnormalities including hard exudates and vitreoretinal abnormalities can also emerge during the progression of NPDR. Although these early retinal abnormalities are not typically associated with vision loss, it is believed that these pathological changes contribute to the sequel of advanced DR.

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