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.

Keywords: diabetic macular edema; diabetic retinopathy; eye drops; intravitreal injections; retinal neuroprotection; treatment.

Figure 1

Schematic representation of the main ophthalmologic features of early and advanced stages of DR (ESDR and ASDR) and their main underlying mechanisms and structural features. The approved treatments (blue), and potential treatments (red) that are currently still in the preclinical development or in early clinical development. NVU: Neurovascular unit. IVT: Intravitreal treatment. (*) Fenofibrate has only been approved in few countries.