Aqueous Level of ANGPTL4 Correlates with the OCTA Metrics of Diabetic Macular Edema in NPDR

Abstract

Purpose. To investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coherence tomography angiography (OCTA) metrics. Methods. This study enrolled 21 NPDR eyes with DME (NPDR/DME+), 17 NPDR eyes without DME (NPDR/DME-), and 16 diabetic eyes without retinopathy (DWR). Luminex bead-based multiplex array was used to measure the levels of 25 cytokines. OCTA system with a scan area of 3 × 3 mm was used to measure retinal thickness (RT), retinal volume (RV), superficial vessel density (SVD), deep vessel density (DVD), foveal avascular zone (FAZ) area, perimeter and acircularity index. Results. The levels of ANGPTL4 were significantly different among the three groups ( P < 0.05 ), in which NPDR/DME+ group had the highest level and NPDR/DME- group had a higher level than the DWR group (all, P < 0.0167 ). OCTA examination showed that, compared with DWR and NPDR/DME- group, RT and RV increased and the whole/parafoveal DVD decreased in NPDR/DME+ group (all, P < 0.05 ). Meanwhile, NPDR/DME- group had lower parafoveal DVD than the DWR group ( P < 0.05 ). Correlation analysis showed that the levels of ANGPTL4 were positively correlated with foveal/parafoveal RT and RV and negatively correlated with whole/parafoveal DVD in NPDR patients (all, P < 0.05 ). As the influencing factor of RT, RV, and DVD, every additional 103 pg/ml of ANGPTL4 was associated with an increase in foveal and parafoveal RT of 4.299 μm and 3.598 μm, respectively. Every additional 106 pg/ml of ANGPTL4 was associated with an increase in foveal and parafoveal RV of 3.371 mm3 and 17.705 mm3, respectively. Every additional 104 pg/ml of ANGPTL4 was associated with a decrease in whole and parafoveal DVD of 1.705% and 1.799%, respectively. Conclusions. The level of ANGPTL4 in aqueous humor of NPDR patients with DME was significantly increased and ANGPTL4 might predict RT, RV, and parafoveal DVD of DME in NPDR patients.

Quantitative Parameters Relevant for Diabetic Macular Edema Evaluation by Optical Coherence Tomography Angiography

“…When comparing quantitative parameters between eyes with the same DR severity, in eyes with mild NPDR and DME, there were significantly lower values of this metric in the superficial retinal layer (SRL) and the deep retinal layer (DRL) in the eyes with DME compared to those without DME [ 15 ]. The impact of DME on deep vessel densities (DVD) was also confirmed by another study which showed that patients with NPDR with DME presented with reduced DVD, compared with patients without DR and also compared with patients with NPDR but without DME [ 31 ]. The same study also showed that the level of ANGPTL4, a cytokine correlated with the presence of DME, was an influencing factor for DVD [ 31 ].…”

“…The impact of DME on deep vessel densities (DVD) was also confirmed by another study which showed that patients with NPDR with DME presented with reduced DVD, compared with patients without DR and also compared with patients with NPDR but without DME [ 31 ]. The same study also showed that the level of ANGPTL4, a cytokine correlated with the presence of DME, was an influencing factor for DVD [ 31 ]. Moreover, it was reported that density perfusion metrics were significantly lower in eyes with DME compared to patients with no diabetes and that, in the DME group of patients, PD was significantly lower in the DCP compared to the non-DME group of patients [ 22 ].…”

Downregulation of angiogenic factors in aqueous humor associated with less intraoperative bleeding in PDR patients with NVG receiving conbercept: a randomized controlled trial

“…The levels of 28 cytokines associated with inflammation and angiogenesis were measured with Luminex bead-based multiplex array, including Eotaxin, interferon-γ (IFN-γ), interleukin 1b (IL-1b), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 (p70), IL-17A, IL-18, IL-22, IL-27, interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), monokine induced by interferon-γ (MIG), platelet-derived growth factor AA (PDGF-AA), transforming growth factor α (TGF-α), tumor necrosis factor α (TNF-α), angiopoietin 2 (Ang-2), placental growth factor (PLGF), VEGF-A, epidermal growth factor (EGF), granulocyte colony-stimulating factor (G-CSF), Leptin, hepatocyte growth factor (HGF), and fibroblast growth factor 2 (FGF-2) (cytokine panels, HAGP1MAG-12 K and HCYTA-60 K-20C; Millipore Corporation, Billerica, MA, USA). All assays were performed strictly according to the manufacturer’s guidelines, the detailed procedures of which were described in our previous study [ 22 ]. The xPONENT FlexMAP 3D system on the Luminex platform was used to read the data.…”