Characteristics of intermediate age-related macular degeneration with hyperreflective foci.
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ABSTRACT:
SUBMITTER: Kikushima W
PROVIDER: S-EPMC9626558 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Characteristics of intermediate age-related macular degeneration with hyperreflective foci.
Kikushima Wataru W Sakurada Yoichi Y Sugiyama Atsushi A Yoneyama Seigo S Matsubara Mio M Fukuda Yoshiko Y Shijo Taiyo T Kotoda Yumi Y Fragiotta Serena S Kashiwagi Kenji K
Scientific reports 20221101 1
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 pr ...[more]
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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:PurposeHyperreflective foci (HRF) are OCT biomarkers for the progression of nonneovascular age-related macular degeneration (AMD) attributed to anteriorly migrated retinal pigment epithelial cells. We examined associations between rod- and cone-mediated vision and HRF plus smaller hyperreflective specks (HRS); we identified a histologic candidate for HRS.DesignCross-sectional study and histologic survey.ParticipantsPatients with healthy maculae (n = 34), early AMD (n = 26), and intermediate AMD (n = 41).MethodsAMD severity was determined by color fundus photography. In OCT scans, HRF and HRS were counted manually. Vision tests probed cones (best-corrected visual acuity [VA], contrast sensitivity), mixed cones and rods (low-luminance VA, low-luminance deficit, mesopic light sensitivity), or rods (scotopic light sensitivity, rod-mediated dark adaptation [RMDA]). An online AMD histopathologic resource was reviewed.Main outcome measuresVision in eyes assessed for HRF and HRS; histologic candidate for HRS.ResultsIn 101 eyes of 101 patients, HRF and HRS were identified in 25 and 95 eyes, respectively, with good reliability. Hyperreflective foci were present but sparse in healthy eyes, infrequent in early AMD eyes, and frequent but highly variable among intermediate AMD eyes (mean±standard deviation [SD] number per eye, 0.1 ± 0.2, 0.2 ± 0.5, and 1.9 ± 3.4 for healthy, early AMD, and intermediate AMD eyes, respectively). Hyperreflective specks outnumbered HRF in all groups (mean±SD, 4.5 ± 3.2, 6.3 ± 5.8, and 19.4 ± 22.4, respectively). Delayed RMDA was associated strongly with more HRF and HRS (P < 0.0001). Hyperreflective foci also were associated with worse low-luminance VA (P = 0.0117). Hyperreflective specks were associated with worse contrast sensitivity (P = 0.0278), low-luminance VA (P = 0.0010), low-luminance deficit (P = 0.0031), and mesopic (P = 0.0018) and scotopic (P < 0.0001) sensitivity. By histologic analysis, cone lipofuscin was found in outer retinal layers of 25% of healthy aged eyes.ConclusionsHyperreflective foci and HRS are markers of cellular activity associated with visual dysfunction, especially delayed RMDA, an AMD risk indicator assessing efficiency of retinoid resupply. Hyperreflective specks may represent lipofuscin translocating inwardly within cones. HRF and HRS may serve as structural end points in clinical trials targeting AMD stages earlier than atrophy expansion. These results should be confirmed in a larger sample.
| S-EPMC8709925 | biostudies-literature
Project description:PurposeDescribe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading.DesignProspective cross-sectional study.ParticipantsWe included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD.MethodsBoth eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility.Main outcome measuresWe assessed SD-OCT characteristics at baseline.ResultsIn 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy.ConclusionsMacular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.
| S-EPMC3536919 | biostudies-literature
Project description:PurposeThe purpose of this study was to analyze spatially resolved structural changes at retinal locations in presence (+) or absence (-) of hyper-reflective foci (HRF) in eyes with subretinal pigment epithelium (RPE) drusen in intermediate age-related macular degeneration (iAMD).MethodsPatients with IAMD (n = 40; mean age = 69.7 ± 9.2 [SD] years) and healthy controls (n = 27; 64.2 ± 9.0) underwent spectral-domain optical-coherence-tomography imaging and fundus-controlled perimetry testing. After reviewing retinal layer segmentation, presence of HRF was annotated and retinal layer thicknesses (RLTs) extracted using ImageJ. Localized RLTs were compared between +HRF and -HRF positions. Univariate mixed linear models were used to investigate associations among RLT, HRF presence, and HRF size.ResultsIn iAMD eyes, a mean of 11.1 ± 12.5 HRF were detected with a peak abundance at 0.5 to 1.5 mm eccentricity to the fovea. At +HRF positions, outer nuclear layer (ONL; P = 0.0013, average difference = -12.4 µm) and retinal pigment epithelium drusen complex (RPEDC; P < 0.0001, +45.6 µm) thicknesses differed significantly compared to -HRF positions, even after correcting for accompanying drusen-related RPEDC layer thickening (P = 0.01). Mixed linear models revealed a significant association between increasing HRF area and decreasing ONL (association score = -0.17, P < 0.0001; 95% confidence interval [CI] = -0.22 to -0.11), and inner photoreceptor segments (IS) layer thicknesses (-0.08, P = 0.005; 95% CI = -0.14 to -0.03). Spearman rank correlation analysis yielded a significant correlation between total HRF area and mesopic (P = 0.015), but not scotopic (P = 0.305) retinal sensitivity losses.ConclusionsDescriptive analysis of this study demonstrated a predominant distribution of HRF at a foveal eccentricity of 0.5 to 1.5 mm, whereas further refined topographic analysis revealed a significant ONL layer thinning in presence of HRF even after correction for sub-RPE drusen presence compared to lesions in absence of HRF. Longitudinal studies are further needed to analyze the prognostic impact as well as the role of HRF presence in the context of iAMD.
| S-EPMC9896840 | biostudies-literature
Project description:PurposeTo evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).DesignProspective cohort study within a randomized clinical trial.ParticipantsThe 1185 CATT participants.MethodsMasked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Main outcome measuresPresence of SHRM, as well as location and size, and associations with VA, scar, and GA.ResultsAmong CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05).ConclusionsIn eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.
| S-EPMC4549177 | 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:To identify potential differences between age-related macular degeneration (AMD) patients and controls in fall-relevant gait characteristics.Spatiotemporal gait characteristics using the GAITRite walkway were collected from 29 AMD patients and 20 controls, aged 60 to 90 years, at the Wilmer Eye Institute. Multiple linear regressions, controlling for age, sex, body mass index (BMI), and comorbidities were used to assess associations between gait characteristics and AMD.Study participants were predominantly white (86%) and female (55%). Mean age of the full study population was 73.51 (SD: 8.14) years, and mean BMI was 27.80 (SD: 5.44) kg/m2. Median better-eye acuity (logMAR) was 0.23 (interquartile range [IQR] = 0.18, 0.36) and -0.02 (IQR = -0.08, 0.02), while median binocular log contrast sensitivity was 1.44 (IQR = 1.32, 1.56) and 1.76 (IQR = 1.76, 1.80) for the AMD and control groups, respectively. In multivariable regression models, AMD patients had significantly slower walking speeds (β = -0.118 m/sec [95% confidence interval (CI): -0.229, -0.007], P = 0.038) and stride velocities (β = -0.119 m/sec [95% CI: -0.232, -0.007], P = 0.038), and greater double support time (β = 3.381% of the walk cycle, 95% CI = 1.006, 5.757, P = 0.006) than controls. There were no group differences in base of support, step length, stride length, or gait variability measures.AMD patients exhibited many fall-relevant gait characteristics.The finding of fall-relevant gait characteristics suggests that AMD patients may be at a greater risk of falls during ambulation than those without AMD.
| S-EPMC5539799 | biostudies-other
Project description:Age-related macular degeneration (AMD) is a multifactorial disease, whose complete pathogenesis is still unclear. Local hemodynamics may play a crucial role in its manifestation and progression. To evaluate choroidal and retinal vascular parameters, a total of 134 eyes were analyzed, 100 with intermediate AMD and 34 age matched healthy controls. 131 eyes of 104 patients were eligible for complete image assessment and 3 eyes were excluded for insufficient image quality: Group 1: intermediate AMD (n = 97) and Group 2: healthy controls (n = 34). Spectral domain optic coherence tomography (SD-OCT) with enhanced depth imaging (EDI) and optic coherence tomography angiography (OCT-A) were acquired using Spectralis (Heidelberg Engineering). Choroid and retinal capillary plexus were evaluated and image binarization was used to obtain quantitative data. Mean age was 77.67 years old (YO) and 67.2% were women. Total subfoveal choroidal area and luminal area were significantly reduced in Group 1 compared with Group 2 (0.88 mm2 and 0.40 mm2 vs. 1.24 mm2 and 0.55 mm2, respectively) (p < 0.05). Regarding choriocapillary flow density, AMD eyes recorded reduced values (34.83%) compared with controls (36.25%) (p < 0.05). Chorioretinal vasculature is impaired in intermediate AMD patients and vascular parameters could be attractive new prognostic biomarkers. Future therapeutic approaches may target this vascular dysfunction and delay disease progression.
| S-EPMC9141612 | biostudies-literature
Project description:PurposeThe purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial.MethodsThis post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed.ResultsThere were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61).ConclusionsProphylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD.Translational relevanceThis work investigates the impact of PR on progressive retinal degeneration in a clinical trial.
| S-EPMC10479187 | biostudies-literature