Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

Abstract

Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working-age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti-vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity.

The progress in understanding and treatment of diabetic retinopathy

“…proposed as the pathogenic basis of this complication. A detailed analysis of these pathogenic pathways and their role in diabetic retinopathy is beyond the scope of this review since they have been discussed in detail previously (for example see (Antonetti et al, 2012;Curtis et al, 2009;Heng et al, 2013;Stitt et al, 2013). Nevertheless, it is important to note that diabetes-related biochemical processes such as increased aldose reductase activity, oxidative stress, nitrosylation, activation of the hexosamine pathway flux, accumulation of advanced glycation end-products (AGEs) and over-activation of protein kinase C (PKC) should not necessarily be regarded as independent phenomena ( Figure 15).…”

High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1

“…The events occurring in non-proliferative proliferative diabetic retinopathy cause regression of the retinal vasculature, causing focal areas to become avascular and hypoxic (7). Consequently, hypoxia increases the synthesis of vascular endothelial cell growth factor and other hypoxia-dependent growth factors/ cytokines that elicit a pathologic, vasoproliferative response resulting in the formation of pathologic pre-retinal vascular structures (8). Their appearance defines the late vasoproliferative stage of DR (proliferative diabetic retinopathy); they are leaky and fragile, and can lead to vision loss by promoting vitreous hemorrhage and tractional retinal detachment (9).…”

“…Scatter (pan-retinal) photocoagulation of the avascular peripheral retina has been the mainstay treatment for decades, however, this procedure destroys post-mitotic retinal neurons, greatly reduces peripheral vision, and does not impact the underlying disease process (8). In recent years, anti-vascular endothelial cell growth factor therapies have been used offlabel for the treatment of proliferative diabetic retinopathy; but they are administered by intravitreal injection, which carries the risk of endophthalmitis (10).…”

Serum C-Reactive Protein and Diabetic Retinopathy

“…Early detection of PDR and follow up of patients by serum biomarkers beside the clinical picture may play a role in prevention and control of PDR [3] [4].…”