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Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration.

ABSTRACT: To use spectral domain optical coherence tomography (SD-OCT) to investigate risk factors predictive for the development of atrophy of drusenoid lesions (DLs) (drusen and drusenoid pigment epithelium detachment) in eyes with non-neovascular age-related macular degeneration (NNVAMD).Cohort study.Forty-one eyes from 29 patients with NNVAMD.Patients with NNVAMD who underwent registered SD-OCT imaging over a minimum period of 6 months were reviewed. Drusenoid lesions that were accompanied by new atrophy onset at 6 months or last follow-up (FUL) were further analyzed. Detailed lesion change was described throughout the study period. Odds ratios (ORs) and risk for new local atrophy onset were calculated.Drusenoid lesion features and longitudinal changes in features, including maximum lesion height, lesion diameter, lesion internal reflectivity, and presence and extent of overlying intraretinal hyperreflective foci (HRF). Subfoveal choroidal thickness (SFCT) and choroidal thickness (CT) were measured below each lesion.A total of 543 individual DLs were identified at baseline, and 28 lesions developed during follow-up. The mean follow-up time was 21.3±8.6 months (range, 6-44 months). Some 3.2% of DLs (18/571) progressed to atrophy within 18.3 ± 9.5 months (range, 5-28 months) of the initial visit. Drusenoid lesions with heterogeneous internal reflectivity were significantly associated with new atrophy onset at 6 months (OR, 5.614; 95% confidence interval [CI], 1.277-24.673) and new atrophy onset at FUL (OR, 7.005; 95% CI, 2.300-21.337). Lesions with the presence of HRF were significant predictors of new atrophy onset at 6 months (OR, 30.161; 95% CI, 4.766-190.860) and FUL (OR, 11.211; 95% CI, 2.513-50.019). Lesions with a baseline maximum height >80 ?m or CT ? 135 ?m showed a positive association with the new atrophy onset at FUL (OR, 7.886; 95% CI, 2.105-29.538 and OR, 3.796; 95% CI, 1.154-12.481, respectively).The presence of HRF overlying DLs, a heterogeneous internal reflectivity of these lesions, was found consistently to be predictive of local atrophy onset in the ensuing months. These findings provide further insight into the natural history of anatomic change occurring in patients with NNVAMD.

SUBMITTER: Ouyang Y

PROVIDER: S-EPMC5340146 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration.

Ouyang Yanling Y Heussen Florian M FM Hariri Amirhossein A Keane Pearse A PA Sadda SriniVas R SR

Ophthalmology 20130704 12

<h4>Purpose</h4>To use spectral domain optical coherence tomography (SD-OCT) to investigate risk factors predictive for the development of atrophy of drusenoid lesions (DLs) (drusen and drusenoid pigment epithelium detachment) in eyes with non-neovascular age-related macular degeneration (NNVAMD).<h4>Design</h4>Cohort study.<h4>Participants</h4>Forty-one eyes from 29 patients with NNVAMD.<h4>Methods</h4>Patients with NNVAMD who underwent registered SD-OCT imaging over a minimum period of 6 month ...[more]

PMID: 23830761

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Project description:ObjectiveTo define quantitative indicators for the presence of intermediate age-related macular degeneration (AMD) via spectral-domain optical coherence tomography (SD-OCT) imaging of older adults.DesignEvaluation of diagnostic test and technology.Participants and controlsOne eye from 115 elderly subjects without AMD and 269 subjects with intermediate AMD from the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study.MethodsWe semiautomatically delineated the retinal pigment epithelium (RPE) and RPE drusen complex (RPEDC, the axial distance from the apex of the drusen and RPE layer to Bruch's membrane) and total retina (TR, the axial distance between the inner limiting and Bruch's membranes) boundaries. We registered and averaged the thickness maps from control subjects to generate a map of "normal" non-AMD thickness. We considered RPEDC thicknesses larger or smaller than 3 standard deviations from the mean as abnormal, indicating drusen or geographic atrophy (GA), respectively. We measured TR volumes, RPEDC volumes, and abnormal RPEDC thickening and thinning volumes for each subject. By using different combinations of these 4 disease indicators, we designed 5 automated classifiers for the presence of AMD on the basis of the generalized linear model regression framework. We trained and evaluated the performance of these classifiers using the leave-one-out method.Main outcome measuresThe range and topographic distribution of the RPEDC and TR thicknesses in a 5-mm diameter cylinder centered at the fovea.ResultsThe most efficient method for separating AMD and control eyes required all 4 disease indicators. The area under the curve (AUC) of the receiver operating characteristic (ROC) for this classifier was >0.99. Overall neurosensory retinal thickening in eyes with AMD versus control eyes in our study contrasts with previous smaller studies.ConclusionsWe identified and validated efficient biometrics to distinguish AMD from normal eyes by analyzing the topographic distribution of normal and abnormal RPEDC thicknesses across a large atlas of eyes. We created an online atlas to share the 38 400 SD-OCT images in this study, their corresponding segmentations, and quantitative measurements.

Project description:PurposeDrusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes.DesignLaboratory imaging and histologic comparison, and retrospective, observational cohort study.ParticipantsFour donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment [PED]) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter.MethodsDonor eyes underwent multimodal ex vivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography.Main outcome measuresHistologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD.ResultsIntraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits.ConclusionsMultiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials.

Project description:PurposeDetect changes in the neurosensory retina using spectral-domain optical coherence tomography (SD OCT) imaging over drusen in age-related macular degeneration (AMD). Quantitative imaging biomarkers may aid in defining risk of disease progression.DesignCross-sectional, case-control study evaluating SD OCT testing in AMD.Participants and controlsSeventeen eyes of 12 subjects with nonneovascular AMD and drusen and 17 eyes of 10 age-matched control subjects.MethodsSpectral-domain OCT imaging across the fovea in the study eye with multiple 10- to 12-mm scans of 1000 A scans each.Main outcome measuresIn summed SD OCT scans, the height of individual retinal layers either over drusen or at corresponding locations in the control eye and qualitative changes in retinal layers over drusen. Secondary measures included photoreceptor layer (PRL) area, inner retinal area, and retinal pigment epithelium (RPE)/drusen area.ResultsThe PRL was thinned over 97% of drusen, average PRL thickness was reduced by 27.5% over drusen compared with over a similar location in controls, and the finding of a difference was valid and significant (P=0.004). Photoreceptor outer segments were absent over at least 1 druse in 47% of eyes. Despite thinning of the PRL, inner retinal thickness remained unchanged. We observed 2 types of hyperreflective abnormalities in the neurosensory retina over drusen. Distinct hyperreflective speckled patterns occurred over drusen in 41% of AMD eyes and never in control eyes. A prominent hyperreflective haze was present in the photoreceptor nuclear layer over drusen in 67% of AMD eyes and more subtly in the photoreceptor nuclear layer in 18% of control eyes (no drusen).ConclusionsWith SD OCT as used in this study, we can easily detect and measure changes in PRL over drusen. Decreased PRL thickness over drusen suggests a degenerative process, with cell loss leading to decreased visual function. The hyperreflective foci overlying drusen are likely to represent progression of disease RPE cell migration into the retina and possible photoreceptor degeneration or glial scar formation. A longitudinal study using SD OCT to examine and measure the neurosensory retina over drusen will resolve the timeline of degenerative changes relative to druse formation.

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.

Dataset Information

Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration.

Publications

Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration.

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