What type of study is this?

September 10, 2025Open Access

Topographic associations of hyperreflective materials in diabetic retinopathy: a multimodal correlation with microvascular pathology, structural remodeling and systemic metabolic dysregulation

LZLan ZhouJinan University HSHongyan SunSouth China Agricultural University CLCunzi Li

Key Points

Hyperreflective materials serve as biomarkers for diabetic retinopathy, revealing spatial patterns and correlations.
Quantitative analysis identified 75.4% colocalization of inner retinal hyperreflective spots with intraretinal microvascular abnormalities.
Retrospective cross-sectional study used multimodal optical coherence tomography to classify six HRMs subtypes across 205 eyes.
Dyslipidemia was found to be a significant predictor of hyperreflective materials density, emphasizing its impact on diabetic retinopathy.

Abstract

Background Hyperreflective materials (HRMs), enigmatic biomarkers observed in diabetic retinopathy (DR), exhibit poorly characterized pathophysiological origins and clinical implications. Methods This retrospective cross-sectional study investigates the spatial distribution patterns of HRMs subtypes and their integrative relationships with retinal microvascular architecture, structural remodeling, and systemic metabolic parameters in 205 DR eyes. HRMs were systematically classified via multimodal optical coherence tomography angiography (OCTA) analysis, incorporating topographic localization (inner vs. outer retinal), reflectivity profiles, morphometric dimensions, posterior shadowing artifacts, and decorrelation signal. Quantitative correlations were established between HRMs subtypes and OCTA-derived vascular parameters (intraretinal microvascular abnormalities IRMA, non-perfusion NP areas, microaneurysms), diabetic macular edema (DME) status, and systemic metabolic indices (glycemic control, lipid profiles, renal function, inflammatory markers). Results Six distinct HRMs phenotypes were identified: inner retinal hyperreflective spots (IRHFs), outer retinal hyperreflective spots (ORHFs), intraretinal hard exudates (IRHE), outer retinal hard exudates (ORHE), decorrelation-positive HRMs, and cotton-wool spots. Spatial mapping revealed predominant HRMs colocalization with IRMA territories (75.4% IRHFs, 89.5% ORHFs, 90.8% IRHE, 94% ORHE), while 19% of IRHFs and 8.7% of ORHFs overlapped NP zones. Decorrelation-positive HRMs demonstrated dual associations with IRMA (77.6%) and microaneurysms (21.0%). DME eyes exhibited significantly elevated HRMs density within IRMA and NP regions ( P 0.001). Multivariate analysis identified dyslipidemia as a strong predictor of HRMs burden. Conclusions These findings establish HRMs as spatially resolved biomarkers of diabetic retinal pathophysiology, reflecting compartment specific interactions between microvascular incompetence (IRMA-associated barrier failure), ischemic remodeling (NP zones), and systemic metabolic dysregulation. The colocalization of HRMs subtypes with IRMA walls and leakage-prone microaneurysms supports their putative role as optical signatures of lipoprotein extravasation and inflammatory lipidotoxicity in DR progression.

Ask AI

Helpful

Bookmark

View Full Paper