Hyperreflective Foci and Subretinal Fluid Are Potential Imaging Biomarkers to Evaluate Anti-VEGF Effect in Diabetic Macular Edema

Abstract

Purpose: The aim was to investigate the effect and underlying mechanism of anti-vascular endothelial growth factor (anti-VEGF) in diabetic macular edema (DME) by optical coherence tomography angiography (OCTA).Methods: Twenty-five eyes in 18 treatment-naïve patients with DME were included. All eyes were imaged by OCTA at baseline and 1 week after monthly intravitreal aflibercept injection (IAI). Visual acuity was measured as best corrected visual acuity (BCVA). Additional parameters were evaluated by OCTA, including central macular thickness (CMT), the number of hyperreflective foci (HRF), foveal avascular zone (FAZ), vessel density (VD) in the deep capillary plexus (DCP), the en-face area of cystoid edema in DCP segmentation, and subretinal fluid (SRF) height.Results: The mean time between baseline and final follow-up by OCTA was 79.24 ± 38.15 (range, 28–163) days. Compared with baseline, BCVA was increased significantly after the 3rd IAI, while CMT was decreased significantly from the 1st IAI. SRF height and the area of cystoid edema in DCP segmentation were decreased significantly after the 2nd IAI compared with baseline. The number of HRF was decreased significantly after the 1st IAI (8.87 ± 9.38) compared with baseline (11.22 ± 10.63). However, FAZ’s area and perimeter as well as VD in DCP showed no significant changes post-treatment.Conclusion: Anti-VEGF is effective in treating DME, improving visual acuity and decreasing macular edema. The decreased HRF indicates anti-inflammatory effects of aflibercept to deactivate retinal microglia/macrophages. The decreased cystoid edema and SRF height indicated improved drainage function of Müller glial cells and retinal pigment epithelium after IAI.

Retinal changes after fluocinolone acetonide implant (ILUVIEN®) for DME: SD-OCT imaging assessment using ESASO classification

“…30,31 They may be active inflammatory cells and a reflection of damaged retinal tissue. 32 The number of hyperreflective spots has previously been reported to decline significantly after dexamethasone implantation, 29 which is consistent with our findings of a (non-significant) decline in the percentage of eyes with > 30 hyperreflective foci.…”

“…30,31 They may be active inflammatory cells and a reflection of damaged retinal tissue. 32 The number of hyperreflective spots has previously been reported to decline significantly after Hyperreflective foci were included only if they were < 30 μm in diameter, had reflectivity similar to that of the nerve fiber layer, and had no backshadowing (as such characteristics are thought to signify activated microglial cells rather than hard exudates and microaneurysms). 17 d DRIL was defined as the loss of clear demarcation between the ganglion cell -inner plexiform layer complex, the inner nuclear layer, and the outer plexiform layer in the central fovea.…”

Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications

“…In our previous clinical observation in diabetic patients with DME, there was a strong positive correlation between INL thickness, where somas of Müller cells are located, and the CSFT, indicating that the Müller intracellular edema might contribute to DME development [ 32 ]. The Müller glia intracellular edema was also observed and reported in patients with DR when examined with OCTA, as indicated by the hypo-reflective cystoid edema spaces in the deep capillary network in both b-scan and en face of OCTA [ 2 , 29 , 33 ].…”

Progress of Imaging in Diabetic Retinopathy—From the Past to the Present

“…The presence of hard exudates indicates chronic leakage from MAs or retinal vessels. In OCT, hard exudates are detected as hyper-reflection in various sizes, and look like tiny hyper-reflective foci, which is also possibly a precursor of hard exudates [ 54 ]. Following early changes of microcapillary structure, i.e., loss of pericytes, breaks of tight junction of capillary endothelium, or formations of Mas, loss of vascular unit of capillary networks connected arterioles or venules progress [ 55 , 56 ], also with disruption of neural networks [ 57 ], retinal area with loss of blood flow with obstructing vessels is termed as retinal nonperfused areas (NPAs), and it leads to tissue ischemia [ 55 , 56 , 57 ].…”

“…Association of macular non-perfusion assessed by FA and central subfield thickness measured with OCT was examined [ 71 ]. OCT has elucidated numerous changes and understanding of this pathology in DME, such disorganization of retinal inner layers (DRIL) [ 72 , 73 ], hyper-reflective foci [ 54 ], or that disruption of Elipsoid zone or ELM indicates macular dysfunction [ 74 , 75 , 76 ]. The application of each imaging modality to any stages of DR in clinical settings is reviewed and summarized in Table 2 .…”