Retinal Vein Occlusion

BackgroundDiabetic retinopathy and retinal vein occlusion are vision threatening retinal vascular diseases. Current first-line therapy targets the vascular component, but many patients are treatment-resistant due to unchecked inflammation. Non-invasive inflammatory imaging biomarkers are a significant unmet clinical need for patients. Imaging of macrophage-like cells on the surface of the retina using clinical optical coherence tomography (OCT) is an emerging field. These cells are increased in patients with retinal vascular disease, and could be a potential inflammatory biomarker. However, since OCT is limited by an axial resolution of 5-10 microns, the exact location and identity of these retinal cells is currently unknown.MethodsWe performed OCT followed by confocal immunofluorescence in wild-type mice to identify macrophages within 5-10 microns of the vitreoretinal interface. Next, we used Cx3cr1CreER/+; Rosa26zsGreen/+ mice to fate map retinal surface macrophages. Using confocal immunofluorescence of retinal sections and flatmounts, we quantified IBA1+Tmem119+CD169neg microglia, IBA1+Tmem119negCD169neg perivascular macrophages, and IBA1+Tmem119negCD169+ vitreal hyalocytes. Finally, we modeled neuroinflammation with CCL2 treatment and characterized retinal surface macrophages using flow cytometry, OCT, and confocal immunofluorescence.ResultsWe were able to detect IBA1+ macrophages within 5-10 microns of the vitreoretinal interface in wild-type mice using OCT followed by confirmatory confocal immunofluorescence. Retinal surface macrophages were 83.5% GFP+ at Week 1 and 82.4% GFP+ at Week 4 using fate mapping mice. At steady state, these macrophages included 82% IBA1+Tmem119+CD169neg microglia, 9% IBA1+Tmem119negCD169+ vitreal hyalocytes, and 9% IBA1+Tmem119negCD169neg perivascular macrophages. After CCL2-driven neuroinflammation, many Ly6C+ cells were detectable on the retinal surface using OCT followed by confocal immunofluorescence.ConclusionsMacrophages within close proximity to the vitreoretinal interface are self-renewing cells, and predominantly microglia with minor populations of perivascular macrophages and vitreal hyalocytes at steady state. In the context of neuroinflammation, monocytes and monocyte-derived macrophages are a significant component of retinal surface macrophages. Human OCT-based imaging of retinal surface macrophages is a potential biomarker for inflammation during retinal vascular disease.

PurposeAge-related macular degeneration (AMD) and retinal vein occlusion (RVO) are irreversible chorioretinal diseases, which might induce severe damage in visual function. The metabolic factor and inflammatory factors might play important roles in the pathogenesis of AMD and RVO. The levels of irisin and 14 cytokines were analyzed in aqueous humor of AMD and RVO eyes to evaluate the roles of irisin and inflammatory factors.MethodsWe collected aqueous humor samples from patients with AMD (n = 27), RVO (n = 30), and cataract (as control, n = 23) eyes. Samples were assayed using ELISA kit for irisin and a multiplex immunoassay kit for 14 cytokines. The macular thickness (MT) was measured with OCT in all included eyes.ResultsMT in the RVO group is significantly higher than that in the AMD or control group. Irisin levels in the aqueous samples of AMD and RVO eyes were both significantly lower than that in the control. Furthermore, a positive correlation was found between irisin and MT in the RVO. Compared with the controls, AMD eyes had significantly higher levels of BDNF, VEGF-A, VEGF-R1, VEGF-R2, IL-10, TNF-α, VCAM-1, IP-10, and MCP-1. Similarly, RVO eyes had significantly higher levels of BDNF, VEGF-A, VEGF-R1, VEGF-R2, IL-6, IL-8, IL-10, TNF-α, ICAM-1, VCAM-1, IP-10, and MCP-1. However, there was no significant difference between the levels of PDGF-BB or TNF-β in these three groups. A negative correlation was found between VEGF-A and MT in AMD, as well as in control. Furthermore, a positive correlation was found between IL-6 and MT in the 80 included eyes, as well as in RVO. A positive correlation was found between ICAM-1 and MT in the 80 included eyes, as well as in RVO.ConclusionsThe metabolic factor, irisin levels in the aqueous humor are decreased in AMD and RVO eyes and show a positive correlation between irisin and MT in RVO eyes, prompting researchers to explore the relationship between irisin and macular edema. We also identified the higher expression of vascular growth factors (VEGF-A, VEGF-R1, and PDGF-BB), inflammatory cytokines (IL-6, IL-8, IL-10, and TNF-α), and chemokines (ICAM-1, VCAM-1, IP-10, and MCP-1) in AMD and RVO eyes.

PurposeTo investigate the clinical features of a macrophage-like cell (MLC) obtained by en face optical coherence tomography (OCT) in retinal vein occlusion (RVO).MethodsThe study involved 36 patients with treatment-naïve unilateral acute RVO, including 21 branch RVO (BRVO) and 15 central RVO. Vessel density and macular thickness were quantified using OCT angiography. A 3-μm en face OCT slab on the inner limiting membrane in the optic nerve head (ONH) region or macular region was used to visualize the MLCs. The MLCs were binarized and quantified using a semiautomated method. The unaffected fellow eyes served as the control group.ResultsThe morphology of MLCs appeared larger and plumper in RVO eyes. The mean MLC density in the ONH and macular regions was 2.46 times and 2.86 times higher than their fellow eyes, respectively (p p = 0.01). The ONH and macular MLC densities in the non-perfused region were significantly lower than those in the perfused region in all RVO eyes (p p = 0.012). Both ONH and macular MLC densities were positively correlated with macular thickness (r = 0.505, p = 0.002; r = 0.385, p = 0.02, respectively).ConclusionThe increased density and changes of morphology characterized by OCT may indicate generalized activation and aggregation of MLCs in RVO. More MLCs are recruited in the perfused region rather than the non-perfused region. RVO eyes with a higher density of MLCs tend to suffer from the thicker macula.

Background/objectivesThis study reported real-world visual acuity (VA), treatment patterns, and ocular safety outcomes from patients with macular oedema secondary to branch, central, or hemi-retinal vein occlusion (BRVO, CRVO, HRVO) treated with anti-vascular endothelial growth factor (VEGF).MethodsData were collected from Medisoft electronic medical records across 16 NHS ophthalmology sites in England over 60 months.Results3511/3465 eyes/patients with BRVO and 3568/3514 eyes/patients with CRVO or HRVO were included; ConclusionsVA improvements were observed soon after anti-VEGF treatment, but were lower with longer follow-up through 60 months, alongside lower annual injection numbers, suggesting that current single-target intravitreal anti-VEGFs may not be sufficiently durable for long-term RVO management in routine practice.