Dataset Information

Histologic and Optical Coherence Tomographic Correlates in Drusenoid Pigment Epithelium Detachment in Age-Related Macular Degeneration.

ABSTRACT: Drusenoid 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.Laboratory imaging and histologic comparison, and retrospective, observational cohort study.Four 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.Donor 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.Histologic 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.Intraretinal 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.Multiple 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.

SUBMITTER: Balaratnasingam C

PROVIDER: S-EPMC5992891 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Histologic and Optical Coherence Tomographic Correlates in Drusenoid Pigment Epithelium Detachment in Age-Related Macular Degeneration.

Balaratnasingam Chandrakumar C Messinger Jeffrey D JD Sloan Kenneth R KR Yannuzzi Lawrence A LA Freund K Bailey KB Curcio Christine A CA

Ophthalmology 20170130 5

<h4>Purpose</h4>Drusenoid 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.<h4>Design</h4>Laboratory imaging and histologic comparison, and retrospective, observational cohort study.<h4>Participants</h4>Four donor eye ...[more]

PMID: 28153442

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Project description:PurposeThe aim of this study was to investigate the outcomes of a fixed intravitreal aflibercept regimen in patients with vascular pigment epithelium detachment (vPED) secondary to age-related macular degeneration with refractory subretinal fluid.MethodsA prospective, interventional case series involved 20 eyes of 20 patients with refractory subretinal fluid and vPED treated with at least three injections of intravitreal anti-VEGF prior to study inclusion. After study inclusion, patients were treated with three injections of intravitreal aflibercept 2 mg/0.05 mL monthly followed by injections every 8 weeks. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were evaluated at all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and quarterly. Primary outcomes were effectivity of a fixed treatment as measured in change in BCVA, PED greatest linear diameter (GLD), and PED height from baseline to month 12. In an additional post hoc analysis, vPED patients were differentiated into two groups: (1) vPED lesions that showed persistence of subretinal fluid throughout 1 year of treatment and (2) vPED lesions that showed complete resolution of subretinal fluid at least at one of the monthly performed OCT volume scans. Reflectivity values were determined in the subretinal pigment epithelium (RPE) compartment in OCT scans at baseline, month 6 and 12.ResultsA total of 18 patients completed the study protocol. The mean age was 74.8 ± 10.6 years, and six patients were female. The median BCVA of all patients was 72.0 ± 8.0 EDTRS letters at baseline and 72.5 ± 9.5 EDTRS letters at 12-month follow-up (p = 0.7420). The median PED height in all patients as measured in the OCT images significantly decreased from 372.0 ± 140.0 μm to 149.0 ± 142.0 μm after 12 months of treatment (p = 0.0020). Persistent subretinal fluid was present at every OCT control in six patients (group 1). Twelve patients showed resolution of subretinal fluid at least at one OCT control (group 2). Reflectivity values in the sub-RPE compartment in OCT scans were 41.48 ± 4.48 (group 1) and 42.62 ± 12.34 (group 2) at baseline (p = 0.854) and 65.88 ± 6.74 and 50.87 ± 14.11 at month 12 (p = 0.038).ConclusionsIntravitreal aflibercept in refractory vPED leads to a significant reduction in PED height and disease activity as well as preservation of BCVA over 1 year. Persistent subretinal fluid was present in PED lesions with high values of reflectivity under the RPE, suggesting both a diffusion barrier and an increasing fibrovascular maturization of the choroidal neovascularization.Trial registrationClinicalTrials.gov Identifier: NCT03370380.

Project description:PurposeTo describe and quantify Bruch's membrane (BM) and retinal pigment epithelium (RPE) separation using spectral-domain (SD) optical coherence tomography (OCT) in patients affected by inherited macular degenerations associated with BM thickening.MethodsPatients with molecularly confirmed Sorsby fundus dystrophy (SFD), dominant drusen (DD), and late-onset retinal degeneration (L-ORD) were included in this retrospective study. Each disease was classed as early stage if subjects were asymptomatic, intermediate stage if they had nyctalopia alone, and late stage if they described loss of central vision. The main outcome was measurement of BM-RPE separation on SD-OCT. The BM-RPE separation measurements were compared against those in normal age-matched controls.ResultsSeventeen patients with SFD, 22 with DD, and eight with L-ORD were included. BM-RPE separation on SD-OCT demonstrated a high test-retest and interobserver reproducibility (intraclass correlation coefficients >0.9). BM-RPE separation was not identified in normal subjects. In SFD, there was greater BM-RPE separation in late-stage disease compared with intermediate-stage patients both at subfoveal (P < 0.05) and juxtafoveal (P < 0.01) locations. In DD, there was increased BM-RPE separation in late-stage disease compared with early stage at subfoveal (P < 0.001) and juxtafoveal (P < 0.05) topographies. There was no significant difference in BM-RPE separation between disease stages in L-ORD.ConclusionsBM-RPE separation is a novel, quantifiable phenotype in the three monogenic macular dystrophies studied, and may be an optical correlate of the histopathological thickening in BM that is known to occur. BM-RPE separation, as measured by OCT, varies with stage of disease in SFD and DD, but not in L-ORD.Translational relevanceSFD, DD, and L-ORD are associated with BM thickening. In this group of patients, OCT assessment of macular structure identifies a separation of the usually single, hyperreflective line thought to represent BM and the overlying RPE. This separation is a novel and quantifiable feature of disease staging in SFD and DD.

Dataset Information

Histologic and Optical Coherence Tomographic Correlates in Drusenoid Pigment Epithelium Detachment in Age-Related Macular Degeneration.

Publications

Histologic and Optical Coherence Tomographic Correlates in Drusenoid Pigment Epithelium Detachment in Age-Related Macular Degeneration.

Similar Datasets

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