Novel Blood-Biomarkers to Detect Retinal Neurodegeneration and Inflammation in Diabetic Retinopathy

To investigate levels of specific plasma-biomarkers related to neurodegeneration and inflammation in patients with different chronic degenerative retinal diseases, using an ultrasensitive technology called 'single molecule array' (SiMoA). Also, to investigate if biomarkers were measurable in the patient's blood, dependent on age and medical comorbidities, and useful for stratifying the diseases. This exploratory, cross-sectional study recruited 151 adults at the Department of Ophthalmology, Rigshospitalet, Denmark (period 2019 to 2020). Clinical data came from the electronic medical-record system. The study population consisted of 131 patients: 32 with diabetic retinopathy (DR; 51 diabetes, DM), 27 with glaucoma, 53 with inherited retinal degeneration (IRD and 20 healthy controls (HC). Medical comorbidities included organ failure, other active eye diseases, and comorbidities. Three biomarkers, neurofilament-light-chain (NFL), glial-fibrillary-acidic-protein (GFAP), and CXC-motif chemokine ligand 13 (CXCL13), were measured with SiMoA technology. The age-adjusted values were reported as fold differences (FD) with 95% confidence intervals (CI). Increased NFL levels were found in DR patients compared to HCs (FD 1.81 95%CI 1.43, 2.28, <i>p</i> < 0.001, adj-<i>p</i> < 0.001). Similarly increased NFL levels were reported in advanced DR (PDR, DME), compared to both DM (FD 2.52 (95%CI: 1.71; 3.72, <i>p</i> < 0.001, adj-<i>p</i> < 0.001, and FD 2.04 (95%CI: 1.33; 3.12, <i>p</i> < 0.001, adj-<i>p</i> < 0.001), respectively) and HCs (FD 2.35 (95%CI: 1.67; 3.30, <i>p</i> < 0.001, adj-<i>p</i> < 0.001), and FD 1.89 (95%CI: 1.28; 2.79, <i>p</i> < 0.001, adj-<i>p</i> < 0.001) respectively). Independent of comorbidities, decreased NFL-levels were seen in IRD compared to DR (FD 0.49 (95% CI 0.39; 0.61, <i>p</i> < 0.001; adj-<i>p</i> < 0.001), ±comorbidities). Decreased GFAP levels were seen in DM patients compared to HCs (FD 0.69; 95%CI 0.55, 0.87, <i>p</i> = 0.002, adj-<i>p</i> = 0.02), but contrary to an increasing trend in advanced DR compared to DM (-comorbidities). These results imply that these biomarker-tests are useful for detecting and monitoring development of retinopathy in the circulations of diabetes patients. Plasma-biomarkers may be useful to stratify between retinal disease types. Prospective studies are underway to explore this hypothesis in depth.