New Insights into Treating Early and Advanced Stage Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is the leading cause of preventable blindness in the working-age population. The disease progresses slowly, and we can roughly differentiate two stages: early-stage (ESDR), in which there are mild retinal lesions and visual acuity is generally preserved, and advanced-stage (ASDR), in which the structural lesions are significant and visual acuity is compromised. At present, there are no specific treatments for ESDR and the current recommended action is to optimize metabolic control and maintain close control of blood pressure. However, in the coming years, it is foreseeable that therapeutic strategies based in neuroprotection will be introduced in the clinical arena. This means that screening aimed at identifying patients in whom neuroprotective treatment might be beneficial will be crucial. Regarding the treatment of ASDR, the current primary course is based on laser photocoagulation and intravitreal injections of anti-angiogenic factors or corticosteroids. Repeated intravitreal injections of anti-VEGF agents as the first-line treatment would be replaced by more cost-effective and personalized treatments based on the results of “liquid biopsies” of aqueous humor. Finally, topical administration (i.e., eye drops) of neuroprotective, anti-inflammatory and anti-angiogenic agents will represent a revolution in the treatment of DR in the coming decade. In this article, all these approaches and others will be critically discussed from a holistic perspective.

Topically Administered NOX4 Inhibitor, GLX7013114, Is Efficacious in Treating the Early Pathological Events of Diabetic Retinopathy

“…GLX7013114 (NOX4 specific inhibitor) protected retinal OS and neuroinflammation damage, but had no effect on neural dysfunction (22). These findings suggested that NOX (1,2,4) are important players in the pathophysiology of retinal disease, whose pathophysiology involves excitotoxicity and OS that lead to alterations in retinal neurons and glia.…”

“…Its clinical hallmarks include the breakdown of the blood-retinal barrier (BRB), vascular microaneurysms, endothelial cell proliferation, and neovascularization (late stage). Mild non proliferative DR (NPDR; early stage) precedes PDR and is characterized by retinal neurodegeneration, glial activation,vasculopathy and leaky vessels (1,2).…”

“…Α close "interdependency" exists among the members of this triad. Studies in experimental animals and patients with diabetes, have suggested that neurodegeneration and neuroinflammation (imbalance of neurotrophic factors and proinflammatory cytokines) are critical components in the pathophysiology of DR, and underlie the mechanisms leading to retinal cell death, suboptimal visual acuity and blindness (1,2,(4)(5)(6)(7). Many of these biochemical defects are present as early events in DR, prior to the development of microangiopathy and neovascularization (6)(7)(8)(9).…”

“…Fenofibrate reduced the progression of Type 2 diabetes in clinical trials and has been recommended for the prevention of DR progression in patients with preexisting disease. However, even though fenofibrate treats neurodegeneration and microangiopathy there are no clinical trials to support its use as treatment of the ESDR (2,6). The only approved medications, anti-VEGF agents and corticosteroids, are indicated to treat diabetic macular edema (DME) a feature of the advanced stages of DR (ASDR).…”

“…The only approved medications, anti-VEGF agents and corticosteroids, are indicated to treat diabetic macular edema (DME) a feature of the advanced stages of DR (ASDR). These treatments are associated with adverse effects and do not reverse visual loss (2).…”