Abstract
With the increasing prevalence of diabetes in developing and developed countries, the socio-economic burden of diabetic retinopathy (DR), the leading complication of diabetes, is growing. Diabetic retinopathy (DR) is currently one of the leading causes of blindness in working-age adults worldwide. Robust methodologies exist to detect and monitor DR; however, these rely on specialist imaging techniques and qualified practitioners. This makes detecting and monitoring DR expensive and time-consuming, which is particularly problematic in developing countries where many patients will be remote and have little contact with specialist medical centres. Diabetic retinopathy (DR) is largely asymptomatic until late in the pathology. Therefore, early identification and stratification of vision-threatening DR (VTDR) is highly desirable and will ameliorate the global impact of this disease. A simple, reliable and more cost-effective test would greatly assist in decreasing the burden of DR around the world. Here, we evaluate and review data on circulating protein biomarkers, which have been verified in the context of DR. We also discuss the challenges and developments necessary to translate these promising data into clinically useful assays, to detect VTDR, and their potential integration into simple point-of-care testing devices.
Highlights
Diabetes mellitus (DM) is a complex group of diseases characterized by high blood glucose levels due to either an inability to produce insulin or an insensitivity to insulin
The risk of vision-threatening DR (VTDR) was increased 11fold in patients with serum cystatin C levels over 1.25 mg/L (He et al, 2013; Wong et al, 2015) and revealed that serum Cystatin C (CysC) in type 2 diabetes mellitus (T2DM) patients correlated positively with moderate Diabetic retinopathy (DR), suggesting that CysC may play a role in the pathogenesis of DR, the mechanisms are unclear
Elevated serum levels of ApoAI and ApoCIII are associated with T2DM risk (Onat et al, 2009; Brahimaj et al, 2017), and analyses of vitreous fluid demonstrate a positive correlation between ApoA1 levels and proliferative DR (PDR) (Simo et al, 2008)
Summary
Diabetes mellitus (DM) is a complex group of diseases characterized by high blood glucose levels due to either an inability to produce insulin or an insensitivity to insulin. Whilst early detection and tight control of risk factors have decreased DR prevalence in some western countries (Wong et al, 2009; Liew et al, 2014; Liew et al, 2017; Claessen et al, 2018), this is not the case in LMICs where all forms of DR continue to be on the rise (Leasher et al, 2016; Flaxman et al, 2017). Diabetic retinopathy (DR) is currently diagnosed through imaging of the retina, revealing changes consequent to damage of the retinal vasculature. This requires specialist equipment and trained practitioners to both operate cameras and grade the images and is highly effective and efficient to detect referable cases of DR, as documented in countries with comprehensive healthcare systems. Only large-scale clinical validation will reveal if simple and cheap blood tests, accessible to all people with diabetes, can be considered as an effective option in the arsenal of DR screening pathways
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