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The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in Geographic Atrophy
摘要： PURPOSE. Histologic details of progression routes to geographic atrophy (GA) in AMD are becoming available through optical coherence tomography (OCT). We studied the origins and evolution of an OCT signature called plateau in eyes with GA and suggested a histologic correlate. METHODS. Serial eye-tracked OCT scans and multimodal imaging were acquired from eight eyes of seven patients with GA and plateau signatures over a mean follow-up of 7.7 years (range, 3.7–11.6). The histology of unrelated donor eyes with AMD was reviewed. RESULTS. Drusenoid pigment epithelial detachment (PED) on OCT imaging progressed into wide-based mound-like signatures with flattened apices characterized by a hyporeflective yet heterogeneous interior and an overlying hyperreflective exterior, similar to outer retinal corrugations previously ascribed to persistent basal laminar deposit (BLamD) but larger. These new signatures are described as "plateaus." An initial increase of the PED volume and hyporeflectivity of its contents was followed by a decrease in PED volume and thinning of an overlying hyperreflective band attributable to the loss of the overlying RPE leaving persistent BLamD. Both imaging and histology revealed persistent BLamD with defects through which gliotic Müller cell processes pass. CONCLUSIONS. Plateaus can be traced back to drusenoid PEDs on OCT imaging. We hypothesize that during progressive RPE atrophy, Müller cell extension through focal defects in the residual persistent BLamD may contribute to the heterogeneous internal reflectivity of these entities. The role of Müller cell activation and extension in the pathogenesis of AMD should be explored in future studies.
关键词： geographic atrophy,multimodal imaging,optical coherence tomography,histology,drusenoid pigment epithelial detachment
更新于2025-09-23 15:22:29
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[Lecture Notes in Computer Science] Pattern Recognition and Computer Vision Volume 11256 (First Chinese Conference, PRCV 2018, Guangzhou, China, November 23-26, 2018, Proceedings, Part I) || Automated and Robust Geographic Atrophy Segmentation for Time Series SD-OCT Images
摘要： Geographic atrophy (GA), mainly characterized by atrophy of the retinal pigment epithelium (RPE), is an advanced form of age-related macular degeneration (AMD) which will lead to vision loss. Automated and robust GA segmentation in three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) images is still an enormous challenge. This paper presents an automated and robust GA segmentation method based on object tracking strategy for time series SD-OCT volumetric images. Considering the sheer volume of data, it is unrealistic for experts to segment GA lesion region manually. However, in our proposed scenario, experts only need to manually calibrate GA lesion area for the ?rst moment of each patient, and then the GA of the following moments will be automatically detected. In order to fully embody the outstanding features of GA, a new sample construction method is proposed for more e?ectively extracting histogram of oriented gradient (HOG) features to generate random forest models. The experiments on SD-OCT cubes from 10 eyes in 7 patients with GA demonstrate that our results have a high correlation with the manual segmentations. The average of correlation coe?cients and overlap ratio for GA projection area are 0.9881 and 82.62%, respectively.
关键词： HOG features,Spectral-domain optical coherence tomography,Image segmentation,Geographic atrophy
更新于2025-09-23 15:21:01
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Complement inhibition as a therapeutic strategy in retinal disorders
摘要： Introduction: Dry age-related macular degeneration (AMD) and Stargardt Macular Dystrophy (STGD1) result in vision loss, due to progressive atrophy of the macula and lack of effective treatments. Numerous studies have implicated complement-associated inflammation as a contributor to both diseases. Areas covered: The complement factor D inhibitor, lampalizumab, failed to halt geographic atrophy (GA) progression in phase 3 studies. The complement factor 3 (C3) inhibitor, APL-2, has shown potential to reduce GA growth in a phase 2 trial, supporting advancement to phase 3 trials. The intravenous complement factor 5 (C5) inhibitor, eculizumab, failed to halt GA progression in a phase 2 study. Another C5 inhibitor, avacincaptad pegol, is delivered by intravitreal injection, and will be studied for safety and preliminary signs of efficacy for AMD and STGD1 patients in phase 2 trials. LFG316 (C5 inhibitor) and CLG561 (properdin inhibitor) failed to halt GA progression in phase 2 studies. A phase 1 trial is evaluating the effects of combining LFG316 and CL561. Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients. Expert opinion: While complement inhibition has not yet demonstrated ability to halt GA progression in a phase 3 trial, further study is warranted.
关键词： Age-related macular degeneration,Stargardt Macular Dystrophy,geographic atrophy,LFG316,CL561,avacincaptad pegol,eculizumab,complement,APL-2,lampalizumab
更新于2025-09-19 17:15:36
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Autofluorescence Lifetimes in Geographic Atrophy in Patients With Age-Related Macular Degeneration
摘要： PURPOSE. To investigate fluorescence lifetime characteristics in patients with geographic atrophy (GA) in eyes with age-related macular degeneration and to correlate the measurements with clinical data and optical coherence tomography (OCT) findings. METHODS. Patients with GA were imaged with a fluorescence lifetime imaging ophthalmoscope. Retinal autofluorescence lifetimes were measured in a short and a long spectral channel (498–560 nm and 560–720 nm). Mean retinal fluorescence lifetimes were analyzed within GA and the surrounding retina, and data were correlated with best corrected visual acuity and OCT measurements. RESULTS. Fluorescence lifetime maps of 41 eyes of 41 patients (80 ± 7 years) with GA were analyzed. Mean lifetimes within areas of atrophy were prolonged by 624 ± 276 ps (+152%) in the short spectral channel and 418 ± 186 ps (+83%) in the long spectral channel compared to the surrounding tissue. Autofluorescence lifetime abnormalities in GA occurred with particular patterns, similar to those seen in fundus autofluorescence intensity images. Within the fovea short mean autofluorescence lifetimes were observed, presumably representing macular pigment. Short lifetimes were preserved even in the absence of foveal sparing but were decreased in patients with advanced retinal atrophy in OCT. Short lifetimes in the fovea correlated with better best corrected visual acuity in both spectral channels. CONCLUSIONS. This study established that autofluorescence lifetime changes in GA present with explicit patterns. We hypothesize that the short lifetimes seen within the atrophy may be used to estimate damage induced by atrophy and to monitor disease progression in the context of natural history or interventional therapeutic studies.
关键词： GA,geographic atrophy,ophthalmic imaging,fundus autofluorescence,fluorescence lifetimes,AMD,age-related macular degeneration
更新于2025-09-19 17:15:36
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Proteomic Profiles in Advanced Age-Related Macular Degeneration Using an Aptamer-Based Proteomic Technology
摘要： Purpose: To explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA. Methods: We conducted a pilot study of patients with neovascular AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome. Results: In this pilot study, higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor–related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling. Conclusions: We found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described.
关键词： neovascular AMD,aptamer-based technologies,geographic atrophy,proteomics
更新于2025-09-19 17:15:36
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Microperimetry for Geographic Atrophy Secondary to Age-Related Macular Degeneration
摘要： Geographic atrophy (GA) is a progressive, advanced form of age-related macular degeneration leading to visual function impairment and irreversible vision loss. Standard clinical tests to evaluate visual function in patients with GA provide poor anatomic-functional correlation, while fundus imaging does not assess the visual function deficit. Microperimetry is a psychophysical visual function test that spatially maps retinal sensitivity and allows for correlation of anatomic features with visual function. In this review, we present an overview of mesopic microperimetry for GA, including: commercially available microperimetry devices, strategies to capture a mesopic microperimetry test, and strategies to assess and interpret microperimetry data in patients with GA. We demonstrate the importance of microperimetry data for assessing GA progression and for evaluating visual function loss through anatomic-functional correlations. Although valuable, current microperimetry tests require an extensive time commitment from patient and examiner, and the development of faster, more reproducible, and accessible methods is important to enable broader use of microperimetry in both clinical and research settings.
关键词： anatomic-functional correlation,visual function,geographic atrophy,microperimetry,age-related macular degeneration,retinal sensitivity
更新于2025-09-19 17:15:36
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Relationship Between Presumptive Inner Nuclear Layer Thickness and Geographic Atrophy Progression in Age-Related Macular Degeneration
摘要： To analyze inner retinal changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration and identify morphological cues for progression. A total of 100 eyes with GA were assessed in this longitudinal, observational case series. Patients with GA and absent confounding pathology were compared with age-matched controls. The retinal layers on spectral-domain optical coherence tomography, acquired in tracking mode, were segmented manually on central scans through the fixation point. Zones of GA were defined based on choroidal signal enhancement from retinal pigment epithelium loss. An area of unaffected temporal retina was used for comparison. Progression of GA was quantified with fundus autofluorescence. We analyzed 41 eyes of 41 patients (mean age 79.2 ± 6.7 years). In areas of GA, the layer representing the inner nuclear layer (INL) in healthy retina was increased in thickness. Thickness of this presumptive INL was inversely correlated with best-corrected visual acuity (r = ?0.48, P < 0.01). The presumptive INL thickness increase in atrophic areas was less marked in eyes with foveal sparing. Increased INL thickness in areas adjacent to GA was associated with a higher progression rate. Optical coherence tomography findings demonstrate that atrophy of the retinal pigment epithelium-photoreceptor complex in GA is associated with an increase of thickness of the presumptive INL, presumably caused by remodeling of the degenerating retina. Similar alterations in the retina adjacent to areas clinically affected by GA were associated with higher atrophy progression rates.
关键词： geographic atrophy,retinal segmentation,optical coherence tomography,autofluorescence,disease progression
更新于2025-09-10 09:29:36
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Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular Endothelial Growth Factor Treated Age-Related Macular Degeneration
摘要： PURPOSE. To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. METHODS. There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared re?ectance, ?uorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. RESULTS. SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 6 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% con?dence interval [CI] 1.1–8.5, P ? 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular ?elds at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0–8.9, P ? 0.0461 and 95% CI 1.3–32.4, P ? 0.0218, respectively). MA development was not associated with a speci?c SDD phenotype. CONCLUSIONS. MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular ?eld, conferred higher odds of subsequent MA development.
关键词： reticular pseudodrusen,anti-VEGF,neovascular age-related macular degeneration,geographic atrophy,subretinal drusenoid deposits
更新于2025-09-10 09:29:36
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The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in Geographic Atrophy
摘要： We read with interest the article by Tan et al.1 entitled "The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in Geographic Atrophy." We congratulate the authors for the excellent description of the origins and long-term evolution of an optical coherence tomography (OCT) in nascent geographic atrophy and for proposing its histologic correlate. Querques et al.2 first reported this tomographic signature in geographic atrophy with the name of "wedge-shaped subretinal hyporeflectivity." However, the authors renamed this finding for the following reasons.
关键词： wedge-shaped subretinal hyporeflectivity,optical coherence tomography,plateau,geographic atrophy
更新于2025-09-09 09:28:46
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Maximum Reading Speed in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration
摘要： PURPOSE. Geographic atrophy (GA) is an advanced form of age-related macular degeneration. GA often initially spares the center of the fovea, leading to a functional disconnect between reading speed and distance visual acuity. This study was designed to determine the correlation between baseline GA lesion size, change in lesion size, and maximum reading speed (MRS) over 18 months. METHODS. Post hoc analysis included US patients from the phase 2 Mahalo study of intravitreal lampalizumab with Minnesota low-vision reading (MNREAD) assessments at baseline and 6, 12, and 18 months. Binocular MRS was assessed using MNREAD Acuity Charts and GA lesion size by fundus autofluorescence. Correlations were estimated using Spearman’s rank correlation coefficient. RESULTS. Seventy-seven patients were included in the analysis. Baseline MRS correlated with baseline GA lesion size (correlation coefficient, (cid:2)0.47; 95% confidence interval, (cid:2)0.63 to (cid:2)0.28; P < 0.0001). In patients with lesions ?10 mm2 (four disc areas), the proportion reading below a nonfluent level (MRS, <40 words/min) at baseline (26.5%) increased to 64.7% by 18 months, versus patients with lesions <10 mm2 (baseline, 9.3%; 18 months, 7.0%). MRS declined by a median of 40.9% (interquartile range [IQR], (cid:2)70.2 to (cid:2)6.9) in patients with ?2.5 mm2 lesion growth versus 8.2% (IQR, (cid:2)34.6 to 11.0) in patients with <2.5 mm2 lesion growth from baseline to 18 months. CONCLUSIONS. These findings suggest that baseline GA lesion size and magnitude of lesion growth are associated with a decline in MRS over time and support the use of MRS as an evaluation of functional vision in patients with GA.
关键词： quality of life,maximum reading speed,visual function,geographic atrophy
更新于2025-09-04 15:30:14