Diabetic Retinopathy Associated With Type 2 Diabetes Mellitus

This study aims to test the impact of new-generation anti-diabetic drugs, such as SGLT2 inhibitors and DPP-4 inhibitors, on the development of diabetic retinopathy (DR). The study hypothesizes that these drugs have protective effects in diabetic retinopathy by delaying its incidence compared to older agents (including metformin) only. Early intervention is critical, as treatment options for advanced stages of DR are limited in terms of their ability to restore impaired vision and their high associated costs. By focusing on delaying the occurrence of diabetic retinopathy, the investigators aim to reduce the burden of DR and improve the quality of life for diabetic patients.

Diabetes mellitus is a disorder of sugar and fat metabolism which results in damage to the small blood vessels in various organs, this includes the retina - the part of the eye that processes light into a nerve impulse. This leads to damage and blindness via various different mechanisms that are not fully understood. In this study the objective is to recruit people with diabetes and various stages of diabetic eye disease and measure a large number of different chemicals within the blood that might be associated with damage and dysfunction within the retina. Additionally, it will examine the different bacteria within the gut that might affect disease in the eye via chemicals circulating in the blood. This will require participants to have blood samples taken and to provide urine samples. The blood will be analysed with specialised instruments to identify specific molecules circulating within the blood. Participants will also need to allow researchers to look at their medical records, previous photographs and specialist scans of the back of the eye to grade their diabetic retinopathy. This will allow us to identify potential ways in which these could be targeted for future benefit for people with diabetes to hopefully prevent deterioration of their vision.

Despite the evidence that diabetic retinopathy (DR) remains the first cause of blindness among the working-age population, it lacks a specific preventive treatment. This is because early mechanisms leading to the development of DR have been, until recently, unknown. Recent studies have suggested that the early stages of DR could be preceded by neuronal abnormalities, in particular retinal ganglion cell death, coupled with widespread retinal inflammation. According to these studies, endothelial dysfunction and the development of microaneurysms, the classic hallmarks of DR, could be the consequence of these early abnormalities. This project will aim to verify whether neurodegeneration could represent at the same time: 1) a risk factor for subsequent development of DR (this will be investigated through a follow-up study in type 2 diabetic patients free of diabetic retinopathy). 2) a biomarker of the complication (if so, patients with long-standing diabetes in the absence of retinopathy should show no signs of neurodegeneration).