Stage-specific risk stratification of diabetic retinopathy progression based on integration of OCT parameters and systemic biomarkers of inflammation and endothelial dysfunction
DOI:
https://doi.org/10.31288/Ukr.j.ophthalmol.202633646Keywords:
diabetic retinopathy, type 2 diabetes mellitus, optical coherence tomography, biomarkers, inflammatory mediators, vascular endothelium, treatment failure, branch retinal vein occlusion, retinaAbstract
Purpose. To assess the prognostic value of clinical and instrumental parameters and serum biomarkers of inflammation and endothelial dysfunction for the development of stage-specific risk stratification of rapid progression of diabetic retinopathy (DR) and prediction of treatment failure in patients with type 2 diabetes.
Material and methods. A prospective study (2 years of follow-up) included 358 patients with type 2 diabetes and DR: 189 with nonproliferative (NPDR), 96 with preproliferative (PPDR) and 73 with proliferative (PDR). Biomarker analysis was performed in a subgroup (n=136). General clinical indicators, OCT parameters – central retinal thickness (CRT) and macular volume (MV) and serum biomarker levels – von Willebrand factor (vWF), L-selectin (LS), E-selectin (ES), endothelin-1 (ET-1), high-sensitivity C-reactive protein, endothelial-monocyte activating polypeptide II (EMAP II), endothelial NO synthase (eNOS), tumor necrosis factor α (TNF-α), interleukin-1β and -6 (IL-1β, IL-6), NO metabolites were determined. Patients received stage-specific treatment (conservative, laser, anti-VEGF, vitrectomy or their combination). Ineffectiveness of therapy (rapid progression of DR) was assessed using multivariate logistic regression and ROC-analysis.
Results. Among the clinical and instrumental parameters, the highest independent prognostic value was possessed by OCT indices, glycosylated hemoglobin (HbA1c), the presence of maculopathy and diabetic macular edema. The maximum discriminatory ability of CRT and MV was observed in PPDR (AUC 0.834 and 0.824, respectively). Among the biomarkers, the most informative were LS, EMAP II, ES, IL-1β and eNOS. The best stage-specific accuracy was found in: LS in NPDR (AUC 0.979), IL-1β in PPDR (AUC 0.990), as well as EMAP II (AUC 0.988) and eNOS (AUC 0.952) in PDR. The use of optimized thresholds allowed to identify high-risk groups, where the proportion of rapid progression exceeded 80–85% regardless of the chosen treatment method.
Conclusion. Treatment failure in DR in patients with T2DM is markedly stage-specific. Integration of OCT parameters with serum biomarkers of inflammation and endothelial dysfunction provides clinically meaningful risk stratification and can be used for early identification of patients with a high probability of rapid disease progression on standard initial therapy.
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