Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker.
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ABSTRACT:
SUBMITTER: Augustin S
PROVIDER: S-EPMC9906876 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker.
Augustin Sebastien S Lam Marion M Lavalette Sophie S Verschueren Anna A Blond Frédéric F Forster Valérie V Przegralek Lauriane L He Zhiguo Z Lewandowski Daniel D Bemelmans Alexis-Pierre AP Picaud Serge S Sahel José-Alain JA Mathis Thibaud T Paques Michel M Thuret Gilles G Guillonneau Xavier X Delarasse Cécile C Sennlaub Florian F
Journal of neuroinflammation 20230208 1
Retinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmo ...[more]
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Project description:AimsTo assess hyperreflective foci (HF) number in angioid streaks (AS) by means of spectral-domain optical coherence tomography (SD-OCT).MethodsObservational and cross-sectional study. Sixty-two eyes with AS and 62 controls underwent best-corrected visual acuity (BCVA), fundoscopy, and SD-OCT. HF were assessed on the horizontal scan of a six-line radial OCT, in the fovea (1500-μm diameter) and parafovea (500 μm external to the fovea), and sub-classified as retinal or choroidal, small or large. Eyes were distributed in one of four groups, as carrying foveal AS without choroidal neovascularization (CNV) (14 eyes), extra-foveal AS without CNV (14), active CNV (20), and inactive CNV (14). Primary outcome was HF assessment in AS. Secondary outcomes included their correlations with BCVA.ResultsAS-affected eyes had higher HF numbers. Our sub-analysis revealed that patients with active CNV had a larger number of retinal and choroidal HF than all the other groups, whereas retinal and choroidal foci were significantly increased in inactive CNV only with respect to controls. Interestingly, patients with foveal AS showed HF number increase in the choroid and fovea. BCVA deterioration positively correlated with the total HF number found in the fovea and the choroid.ConclusionHF are significantly increased in patients with AS. Despite being especially evident in active CNV, the increasing number in eyes without CNV might suggest new pathogenetic aspects of the disease.
| S-EPMC7002726 | biostudies-literature
Project description:PurposeDrusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression.DesignProspective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study.ParticipantsPatients (n=299) with 1 enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT imaging at 1-year and 2-year visits.MethodsThe number and location of HF were scored in SD-OCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution (AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with logistic regression analysis.Main outcome measuresThe mean change in number of HF, transverse and axial distribution of HF in the macula, and AxD per eye.ResultsIn 299 study eyes, the 2-year increase in the number of HF (P<0.001) and the AxD (P<0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with the presence of baseline HF (P<0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43-9.80), greater number of baseline HF (P<0.001; OR, 1.61 per HF; 95% CI, 1.32-2.00), and greater baseline AxD (P<0.001; OR, 1.58 per AxD point; 95% CI, 1.29-1.95).ConclusionsProliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SD-OCT HF proliferation and migration may serve as biomarkers for AMD progression.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.
| S-EPMC3640702 | biostudies-literature
Project description:PurposeBy optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia.MethodsIn clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells).ResultsPlume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries.ConclusionsHRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial-mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.
| S-EPMC8399556 | biostudies-literature
Project description:ImportanceThe morphologic changes and their pathognomonic distribution in progressing age-related macular degeneration (AMD) are not well understood.ObjectivesTo characterize the pathognomonic distribution and time course of morphologic patterns in AMD and to quantify changes distinctive for progression to macular neovascularization (MNV) and macular atrophy (MA).Design, setting, and participantsThis cohort study included optical coherence tomography (OCT) volumes from study participants with early or intermediate AMD in the fellow eye in the HARBOR (A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration) trial. Patients underwent imaging monthly for 2 years (July 1, 2009, to August 31, 2012) following a standardized protocol. Data analysis was performed from June 1, 2018, to January 21, 2020.Main outcomes and measuresTo obtain topographic correspondence between patients and over time, all scans were mapped into a joint reference frame. The time of progression to MNV and MA was established, and drusen volumes and hyperreflective foci (HRF) volumes were automatically segmented in 3 dimensions using validated artificial intelligence algorithms. Topographically resolved population means of these markers were constructed by averaging quantified drusen and HRF maps in the patient subgroups.ResultsOf 1097 patients enrolled in HARBOR, 518 (mean [SD] age, 78.1 [8.2] years; 309 [59.7%] female) had early or intermediate AMD in the fellow eye at baseline. During the 24-month follow-up period, 135 (26%) eyes developed MNV, 50 eyes (10%) developed MA, and 333 (64%) eyes did not progress to advanced AMD. Drusen and HRF had distinct topographic patterns. Mean drusen thickness at the fovea was 29.6 μm (95% CI, 20.2-39.0 μm) for eyes progressing to MNV, 17.2 μm (95% CI, 9.8-24.6 μm) for eyes progressing to MA, and 17.1 μm (95% CI, 12.5-21.7 μm) for eyes without disease progression. At 0.5-mm eccentricity, mean drusen thickness was 25.8 μm (95% CI, 19.1-32.5 μm) for eyes progressing to MNV, 21.7 μm (95% CI, 14.6-28.8 μm) for eyes progressing to MA, and 14.4 μm (95% CI, 11.2-17.6 μm) for eyes without disease progression. The mean HRF thickness at the foveal center was 0.072 μm (95% CI, 0-0.152 μm) for eyes progressing to MNV, 0.059 μm (95% CI, 0-0.126 μm) for eyes progressing to MA, and 0.044 μm (95% CI, 0.007-0.081) for eyes without disease progression. At 0.5-mm eccentricity, the largest mean HRF thickness was seen in eyes progressing to MA (0.227 μm; 95% CI, 0.104-0.349 μm) followed by eyes progressing to MNV (0.161 μm; 95% CI, 0.101-0.221 μm) and eyes without disease progression (0.085 μm; 95% CI, 0.058-0.112 μm).Conclusions and relevanceIn this study, drusen and HRF represented imaging biomarkers of disease progression in AMD, demonstrating distinct topographic patterns over time that differed between eyes progressing to MNV, eyes progressing to MA, or eyes without disease progression. Automated localization and precise quantification of these factors may help to develop reliable methods of predicting future disease progression.
| S-EPMC7206537 | biostudies-literature
Project description:Hyperreflective foci (HRF) are the findings observed in optical coherence tomography (OCT) in several retinal diseases and are believed to be associated with the increased risk of atrophy in eyes with age-related macular degeneration (AMD). In this study, we investigated the clinical and genetic characteristics of intermediate AMD with HRF. We reviewed the medical charts for 155 patients with intermediate AMD, in whom macular neovascularization (MNV) was observed in the contralateral eye. The presence or absence of an HRF was evaluated using a spectral-domain OCT volume scan spanning the macular region. Patients were followed longitudinally for at least 12 months, and the maximum follow-up period was 60 months. Genotyping of ARMS2 A69S and CFH I62V was performed in all participants. Of the 155 patients (mean age: 77.8 ± 7.6 years, male/female: 103/52), HRF was observed in 53 eyes (34.2%) and was significantly associated with type-3 MNV (p = 1.0 × 10-5) in the contralateral eye, pseudodrusen (p = 5.0 × 10-4), thinner subfoveal choroidal thickness (p = 0.013), and risk of ARMS2 A69S (p = 0.023). During follow-up (40.8 ± 17.5), 38 eyes (24.5%) developed advanced AMD. The mean time to the onset of advanced AMD was 29.8 ± 12.9 months in eyes with intermediate AMD. HRF was associated with MNV (p = 1.0 × 10-3), but not with atrophy.
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Project description:PurposeTo investigate variations in the spatial distribution of hyperreflective foci in the choroid of the macula in normal eyes.MethodsWe included eyes with a normal fundus from patients who had undergone optical coherence tomography angiography, covering a 6-mm × 6-mm area centered on the fovea. The macular area was divided into nine sectors according to the modified Early Treatment of Diabetic Retinopathy Study grid. Hyperreflective choroidal foci (HCF) distribution, choriocapillaris vascular density, and choroidal stromal density were determined on en face images of the choroid in each sector.ResultsWe included 35 eyes from 35 participants, with a mean age of 52.7 ± 16.8 years. The mean number and area fraction of HCF at the 5-mm macular area were 35.6 ± 7.8 foci/mm2 and 3.0% ± 0.7%, respectively. The number of HCF in the central circle (50.7 ± 20.9 foci/mm2) was greater than that in the inner (35.1 ± 13.0 foci/mm2) or outer rings (35.6 ± 6.5 foci/mm2) (P < 0.001, P < 0.001, respectively). The area fraction of HCF in the central circle (4.84% ± 3.36%) was greater than that in the inner (2.62% ± 1.17%; P < 0.001) or outer rings (3.12% ± 0.67%; P = 0.004). The HCF distribution did not significantly correlate with the choriocapillaris vascular density or choroidal stromal density in each sector.ConclusionsHCF were more densely distributed in the macular center than in the pericentral or peripheral macular areas.Translational relevanceHCF measurement and spatial distribution could provide additional information for evaluating choroidal stromal characteristics.
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Project description:The purpose of this study is to evaluate choroidal hyperreflective foci (HRF) changes in central serous chorioretinopathy (CSC) on en-face optical coherence tomography (OCT). Retrospective analysis of 42 patients with unilateral CSC (84 eyes, including fellow eyes for controls) and 42 age- and sex-matched controls. With 4.5 × 4.5 mm macular scans, structural en-face OCT choriocapillaris (CC) slabs were used to calculate the density and number of HRF in acute CSC eyes with serous retinal detachment (SRD), resolved CSC eyes without SRD, unaffected fellow eyes, control eyes, and 1-year follow-up eyes. Based on the 2-disc diameter (3000 μm), the en-face OCT scan was divided into foveal and perifoveal lesion and analyzed to consider the impact of SRF in HRF measurement. Regression analyses were performed on the several factors with HRF number and density in the acute and resolved CSC eyes. The perifoveal density and number of CC HRF was significantly lower in the resolved CSC eyes when compared to the acute CSC eyes (P = 0.002, both), fellow eyes (P = 0.042/density, 0.028/number), and controls (P = 0.021/density, P = 0.003/number). There was no significant difference between the acute CSC eyes, fellow eyes, controls, and 1-year follow-up eyes. As subfoveal choroidal thickness decreased and choroidal vascularity (CVI) increased, the perifoveal density and number of HRF was measured higher with a significant correlation in univariate regression analysis of the acute and resolved CSC eyes (all, P < 0.05). The authors hypothesized that stromal edema induced by choroidal congestion and hyperpermeability has the greatest influence on HRF measurement, possibly affected by inflammatory cells and materials extravasation.
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