Biomarker”, a merged word of “biological marker”, refers to a broad subcategory of medical signs that objectively indicate the state of health, and well-being of an individual. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases. Spectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints. OCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.
12 February 2015 in Clinical & Experimental Ophthalmology
To correlate the serum levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) with the severity of retinopathy and disruption of the external limiting membrane (ELM) and inner segment-outer segment (IS-OS) junction in type 2 diabetes mellitus (DM). Study subjects included patients with type 2 DM [diabetes mellitus with no retinopathy (No DR; n=19); non-proliferative diabetic retinopathy (NPDR; n=19); proliferative diabetic retinopathy (PDR; n=20)] and healthy controls (n=19) between the ages of 40 and 65 years. Disruption of the ELM and the IS-OS junction was graded by spectral domain optical coherence tomography as follows: grade 0—no disruption of ELM and IS-OS junction; grade 1—ELM disrupted, inner segment-outer segment (IS-OS) junction intact; grade 2—both ELM and IS-OS junction disrupted. The serum levels of VEGF and ICAM-1were analyzed using the standard protocol. A significant difference was found between the serum levels of VEGF and ICAM-1 and the various study groups (p<0.001). A positive correlation was found between the grade of disruption and the levels of VEGF (r=0.45, p<0.0001) and ICAM-1 (r=0.40, p=0.0003). A significant positive correlation was found between logMAR visual acuity and grade of disruption (r=0.85, p<0.0001). An increase in serum VEGF and ICAM-1 levels is associated with an increase in the severity of diabetic retinopathy and the grade of ELM and IS-OS junction disruption.
1 October 2019 in International Journal of Retina and Vitreous
Background: Elevated serum vascular endothelial growth factor (VEGF) levels are associated with diabetic retinopathy (DR). Serum VEGF levels correlate with vitreous levels. Neuroretinal changes occur even before the appearance of vascular signs in DR. Role of VEGF as a biomarker for DR has not been assessed. Serum VEGF as a biomarker for severity of DR, was evaluated for the first time.Methods: Consecutive cases of type 2 diabetes mellitus [without DR, (no DR, n = 38); non-proliferative DR, (NPDR, n = 38); proliferative DR, (PDR, n = 40)] and healthy controls (n = 40) were included. Serum VEGF was measured using enzyme linked immunosorbent assay. Accuracy of VEGF as a biomarker for severity of retinopathy was measured using the area under the receiver operator characteristic (ROC) curve.Results: Serum VEGF levels in controls, No DR, NPDR and PDR groups showed significant incremental trend from 138.96 ± 63.37 pg/ml (controls) to 457.18 ± 165.69 pg/ml (PDR) (F = 48.47;p < 0.001). Serum VEGF levels were observed to be significantly elevated even before DR had set in clinically. ROC for serum VEGF levels was significant in discriminating between the cases and the controls and had good accuracy in discerning between subjects with and without retinopathy. The area under curve (AUC ± SE) for discrimination was significant: (a) cases and controls (n = 156): AUC = 0.858 ± 0.029,p < 0.001; (b) DR (NPDR + PDR) and No DR (n = 116): AUC = 0.791 ± 0.044,p < 0.001; and (c) NPDR and PDR (n = 78): AUC = 0.761 ± 0.056,p < 0.001, with over 90% projected sensitivity and specificity at various cut off values.Conclusion: Serum VEGF level is a simple, effective laboratory investigative test in predicting the onset of DR in eyes showing no evidence of DR and serves as a reliable biomolecular biomarker for severity of DR.