Abstract
Purpose :
Diabetic Retinopathy (DR), a retinal microvascular disease, is the major cause of preventable vision loss globally and is expected to affect ~191 million individuals by 2030. A major challenge in treating DR is its ‘Clinical Silence’; wherein, the disease progression is not accompanied with easily observable symptoms. Currently, diabetic patients are annually examined using fundoscopy for onset or progression of vision threatening DR. However, fundoscopy, the gold standard for DR screening is time-consuming, expensive, uncomfortable, requires expertise and instrumentation. To overcome these limitations and to prevent DR-associated vision loss, we focused on identifying DR-associated biomarkers in urine, which would help in developing an alternative, rapid, and point-of-care (POC) screening procedure to predict the onset and progression of DR.
Methods :
A total of 96 diabetic patients were recruited in a clinical study approved by the University of Missouri (MU) IRB committee. Four biomarkers that are related to onset of DR, 8-hydroxydeoxyguanosine (8-OHdG), Angiopoeitin-2, Membrane attack complex (C5b-9), Placental growth factor (PLGF), were chosen for evaluation. Urine samples were collected and the levels of four biomarkers were determined for various stages of DR as identified from the Fundus examination.
Results :
The urinary biomarker levels were compared between mild and moderate stages of DR as this transition represents the clinically significant inflection point of disease. The average levels of three biomarkers (8-OHdG, Angiopoietin, and C5b-9) were found to be increased during mild to moderate transition, while for the PLGF the levels decreased. Classification into Low-risk and High-risk DR groups based on severity of the disease shows significantly higher levels of C5b-9 in high-risk groups compared to low-risk.
Conclusions :
The change in the levels of the biomarker from mild to moderate stage of DR suggests their role as potential biomarkers for identifying progression of DR. Further analysis based on different demographic factors can provide crucial cues on onset of DR. However, it is important to validate the combination of biomarkers with larger sample set and subsequently integrate them into a single panel for a sensitive and reliable screening of DR. The design of POC lateral flow devices for the biomarkers is in progress.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.