Association between Inflammatory Factors in the Aqueous Humor and Hyperreflective Foci in Patients with Intractable Macular Edema Treated with Antivascular Endothelial Growth Factor

Li, Min; Li, Jing; Chen, Kaichuan; Jia, Wang; Sheng, Mao; Li, Bing

doi:10.1155/2021/5552824

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…Moreover, the literature suggests that dot HRF may be key clinical indicators for a range of conditions (Brand, 2012). Their number has been used as indicators of the effectiveness of treatment before and after anti-vascular endothelial growth factor injection into the eyes of patients with macular oedema (Li et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Hyper‐reflective dots in optical coherence tomography imaging and inflammation markers in diabetic retinopathy

et al. 2023

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The aim of this study is to correlate small dot hyper‐reflective foci (HRF) observed in spectral domain optical coherence tomography (SD‐OCT) scans of an animal model of hyperglycaemia with focal electroretinography (fERG) response and immunolabelling of retinal markers. The eyes of an animal model of hyperglycaemia showing signs of diabetic retinopathy (DR) were imaged using SD‐OCT. Areas showing dot HRF were further evaluated using fERG. Retinal areas enclosing the HRF were dissected and serially sectioned, stained and labelled for glial fibrillary acidic protein (GFAP) and a microglial marker (Iba‐1). Small dot HRF were frequently seen in OCT scans in all retinal quadrants in the inner nuclear layer or outer nuclear layer in the DR rat model. Retinal function in the HRF and adjacent areas was reduced compared with normal control rats. Microglial activation was detected by Iba‐1 labelling and retinal stress identified by GFAP expression in Müller cells observed in discrete areas around small dot HRF. Small dot HRF seen in OCT images of the retina are associated with a local microglial response. This study provides the first evidence of dot HRF correlating with microglial activation, which may allow clinicians to better evaluate the microglia‐mediated inflammatory component of progressive diseases showing HRF.

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Section: Discussionmentioning

confidence: 99%

Hyper‐reflective dots in optical coherence tomography imaging and inflammation markers in diabetic retinopathy

et al. 2023

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“…Moreover, the immunologic trafficking into and out from the retina parallels CNS dynamics, suggesting the presence of a retinal glymphatic system, prone to react to systemic or local pathologic processes. 41 This reactivity might explain the modification of retinal layer thickness during CNS inflammation or therapies acting on the BRB 24 , 42 and the effect of disease-modifying therapies in reducing INL thickness. 38 The recognition of the INL as an inflammatory site supports the view of its thickening as inflammatory lesion.…”

Section: Discussionmentioning

confidence: 99%

“… 23 Finally, a moderate association with HRF and inflammatory markers (i.e., interleukin [IL]-8 and vascular cell adhesion molecule 1) in the aqueous humor has been described. 24 Recently, HRF have been reported within the inner retinal layers (IRLs) of patients with Fabry disease. 25 In this study, HRF correlated with lyso-Gb3, a serum biomarker of disease severity.…”

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confidence: 99%

Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis

Pengo

Miante

Franciotta

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesMicroglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS).MethodsAt baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study.ResultsCompared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (β: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002).DiscussionWe found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation.Classification of EvidenceThis study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA.

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“…Moreover, in relapsing–remitting multiple sclerosis (RRMS) HRF are increased compared to healthy controls ( 3 ) and associated with MRI parameters of cortical inflammation ( 6 ). Finally, the reported association between HRF and inflammatory markers (i.e., IL-8, V-CAM-1) in aqueous humor in patients with intractable macular edema also speaks in favor of the microglia-origin hypothesis ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, beside advanced neuroimaging methodologies that have been tested for the in vivo evaluation of activated microglia in the brain, OCT with a single linear scan through the macula proved to identify and correlate the HRF with different parameters of local inflammation and damage ( 3 , 5 , 7 – 10 ). Moreover, a strong correlation of HRF with cortical lesion load and clinical and radiological disease activity have been observed in MS ( 3 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid

et al. 2022

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BackgroundIncreasing evidence suggests that retinal hyper-reflecting foci (HRF) might be clusters of activated and proliferating microglia. Since microglia are widespread activated in multiple sclerosis (MS) brain, its evaluation in retina may help to understand and monitor MS-related pathology.AimThis study aims at investigating the association of HRF with cerebrospinal fluid (CSF) cytokines and MRI parameters in relapsing–remitting MS (RRMS).MethodsNineteen RRMS at clinical onset and 15 non-inflammatory neurological disorders (NIND) underwent brain 3T MRI and CSF examination. Optical coherence tomography (OCT) analysis, including HRF count, was performed on RRMS patients. Sixty-nine cytokines/chemokines were analyzed in the CSF by multiplex technology.ResultsIn RRMS, HRF count in the ganglion cell layer (GCL) was associated with IL-1Ra, IL-9, IL-15, IFN-γ, and G-CSF. Moreover, in RRMS patients CSF concentrations of IL-1Ra and G-CSF associated with global cortical thickness. The HRF count in the inner nuclear layer (INL) correlated with IL-22, IL-34, IL-35, CXCL-2, CXCL-10, and CXCL-13, and multivariate analysis confirmed a strong association (r2: 0.47) with both CXCL-2 (β: -0.965, p = 0.0052) and CXCL-13 (β: 0.241, p = 0.018). This latter cytokine increased in RRMS with high HRF count compared with NIND and RRMS with low HRF count. Finally, the CXCL-13/CXCL-2 ratio strongly associated with HRF count (r: 0.8, p < 0.005) and cortical lesion volume (r: 0.5, p < 0.05).ConclusionsThe association of HRF with intrathecally produced monocyte/microglia-derived cytokines confirms their microglial origin and indicates they are worth further evaluating as markers of activated microglia.

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Association between Inflammatory Factors in the Aqueous Humor and Hyperreflective Foci in Patients with Intractable Macular Edema Treated with Antivascular Endothelial Growth Factor

Cited by 6 publications

References 26 publications

Hyper‐reflective dots in optical coherence tomography imaging and inflammation markers in diabetic retinopathy

Hyper‐reflective dots in optical coherence tomography imaging and inflammation markers in diabetic retinopathy

Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis

Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid

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