Glycolipids implicated as mediators of clinically visible retinal pigment epithelial migration in age-related macular degeneration.

The retinal pigment epithelium (RPE) is the metabolic gatekeeper to the photoreceptors, thus playing many essential roles in healthy vision. Under certain conditions, RPE cells may transdifferentiate and migrate from the RPE layer. Ectopic RPE cells are potential signal sources for hyperreflective foci, prominent clinically visible biomarkers in age-related macular degeneration, which causes central vision loss globally.

Histological Assessment of Foveal Mechanical Instability and Potential Implications for Macular Diseases.

Purpose: To assess areas of mechanical instability in the fovea based on a review of artifactual separations of histological sections.

Methods: A collection of annotated high-resolution retinal histological sections of aged donors was assessed for tissue disruptions in the fovea. Sections belong to Project MACULA (https://projectmacula.

Textural Flow Analysis of United States Commercially Available Baby Foods: Packaging and Delivery Method Comparisons by the International Dysphagia Diet Standardization Initiative Framework.

This study evaluated the flow and textural characteristics of commercial baby food in order to increase clinical knowledge to support patients with pediatric dysphagia. Samples from three organic and non-organic brands included four labeled stages and a variety of ingredients. A standardized method for evaluating the characteristics of room-temperature baby foods was utilized in order to compare, across two geographic regions, the brands and the labeled stages.

Fundus Autofluorescence Variation in Geographic Atrophy of Age-Related Macular Degeneration: A Clinicopathologic Correlation.

Purpose: The purpose of this study was to develop ground-truth histology about contributors to variable fundus autofluorescence (FAF) signal and thus inform patient selection for treating geographic atrophy (GA) in age-related macular degeneration (AMD).

Methods: One woman with bilateral multifocal GA, foveal sparing, and thick choroids underwent 535 to 580 nm excitation FAF in 6 clinic visits (11 to 6 years before death). The left eye was preserved 5 hours after death.

Lysolipids are prominent in subretinal drusenoid deposits, a high-risk phenotype in age-related macular degeneration.

Introduction: Age related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular deposits, including drusen and subretinal drusenoid deposits (SDD; also called reticular pseudodrusen), disrupt cone and rod photoreceptor functions and strongly confer risk for advanced disease. Due to the differential cholesterol composition of drusen and SDD, lipid transfer and cycling between photoreceptors and support cells are candidate dysregulated pathways leading to deposit formation.

Imaging Histology Correlations of Intraretinal Fluid in Neovascular Age-Related Macular Degeneration.

Purpose: Fluid presence and dynamism is central to the diagnosis and management of neovascular age-related macular degeneration. On optical coherence tomography (OCT), some hyporeflective spaces arise through vascular permeability (exudation) and others arise through degeneration (transudation). Herein we determined whether the histological appearance of fluid manifested this heterogeneity.

INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study.

Background: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration.

Methods: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology.

Untargeted Lipidomic Profiling of Aged Human Retina With and Without Age-Related Macular Degeneration (AMD).

The molecular characterization of extracellular deposits is crucial to understanding the clinical progression of AMD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis is a powerful analytical discovery tool capable of identifying lipids in an untargeted manner. NanoLC-MS/MS is an analytical tool capable of identifying lipids with high sensitivity and minimum sample usage.

High-Resolution Imaging Mass Spectrometry of Human Donor Eye: Photoreceptors Cells and Basal Laminar Deposit of Age-Related Macular Degeneration.

Pathologies of the retina are clinically visualized in vivo with OCT and ex vivo with immunohistochemistry. Although both techniques provide valuable information on prognosis and disease state, a comprehensive method for fully elucidating molecular constituents present in locations of interest is desirable. The purpose of this work was to use multimodal imaging technologies to localize the vast number of molecular species observed with matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) in aged and diseased retinal tissues.

HISTOLOGY, DIMENSIONS, AND FLUORESCEIN STAINING CHARACTERISTICS OF NODULAR AND CUTICULAR DRUSEN IN AGE-RELATED MACULAR DEGENERATION.

Purpose: To enable in vivo analysis of drusen composition and lifecycle, the macular nodular and cuticular drusen were assessed using histology.

Methods: Median and interquartile range of base widths of single (nonconfluent) nodular drusen in three sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography; and two eyes of one patient with bilateral "starry sky" cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy.

Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration.

A progression sequence for age-related macular degeneration (AMD) learned from optical coherence tomography (OCT)-based multimodal (MMI) clinical imaging could add prognostic value to laboratory findings. In this work, ex vivo OCT and MMI were applied to human donor eyes prior to retinal tissue sectioning. The eyes were recovered from non-diabetic white donors aged ≥80 years old, with a death-to-preservation time (DtoP) of ≤6 h.

Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration: A Case Study.

Purpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient.

Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation).

Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).

Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration.

Purpose: Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables in vivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging.

Design: Prospective cross-sectional study.

Prolonged Lifetimes of Histologic Autofluorescence in Ectopic Retinal Pigment Epithelium in Age-Related Macular Degeneration.

Purpose: The purpose of this study was to investigate histologic autofluorescence lifetimes and spectra of retinal pigment epithelium (RPE) on the transition from normal aging to RPE activation and migration in age-related macular degeneration (AMD).

Methods: Autofluorescence lifetimes and spectra of 9 donor eyes were analyzed in cryosections by means of 2-photon excited fluorescence at 960 nm. Spectra were detected at 483 to 665 nm.

Correlation of Optical Coherence Tomography Angiography of Type 3 Macular Neovascularization With Corresponding Histology.

Importance: By validating optical coherence tomography angiography (OCTA) in the analysis of type 3 macular neovascularization secondary to age-related macular degeneration, the overall value of clinical OCTA for disease observation, diagnosis, and staging is increased.

Objective: To assess the association of in vivo OCTA of type 3 macular neovascularization secondary to age-related macular degeneration with corresponding ex vivo histology.

Design, Setting, And Participants: This study included clinical imaging, laboratory microscopy, and eye-tracked clinicopathologic correlation of a single case from a community-based practice evaluated at a university-based research laboratory from 2014 to 2019.

Histology and Clinical Lifecycle of Acquired Vitelliform Lesion, a Pathway to Advanced Age-Related Macular Degeneration.

Purpose: To evaluate hypotheses about the role of acquired vitelliform lesion (AVL) in age-related macular degeneration pathophysiology.

Design: Laboratory histology study; retrospective, observational case series.

Methods: Two donor eyes in a research archive with AVL and age-related macular degeneration were analyzed with light and electron microscopy for AVL content at locations matched to ex vivo B-scans.

Histology and clinical imaging lifecycle of black pigment in fibrosis secondary to neovascular age-related macular degeneration.

Purpose: Melanotic cells with large spherical melanosomes, thought to originate from retinal pigment epithelium (RPE), are found in eyes with neovascular age-related macular degeneration (nvAMD). To generate hypotheses about RPE participation in fibrosis, we correlate histology to clinical imaging in an eye with prominent black pigment in fibrotic scar secondary to nvAMD.

Methods: Macular findings in a white woman with untreated inactive subretinal fibrosis due to nvAMD in her right eye were documented over 9 years with color fundus photography (CFP), fundus autofluorescence (FAF) imaging, and optical coherence tomography (OCT).

Tissue fixation effects on human retinal lipid analysis by MALDI imaging and LC-MS/MS technologies.

Imaging mass spectrometry (IMS) allows the location and abundance of lipids to be mapped across tissue sections of human retina. For reproducible and accurate information, sample preparation methods need to be optimized. Paraformaldehyde fixation of a delicate multilayer structure like human retina facilitates the preservation of tissue morphology by forming methylene bridge crosslinks between formaldehyde and amine/thiols in biomolecules; however, retina sections analyzed by IMS are typically fresh-frozen.

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium.

Purpose: By 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.

Methods: In clinical OCT (61 eyes, 44 patients with AMD, 79.

Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling.

Age-related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single-cell RNA sequencing to analyze the transcriptomes of ~ 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen adult human donors with and without AMD. Analysis of our single-cell data identified 267 cell-type-specific genes.

Correlation of in vivo/ex vivo imaging of the posterior eye segment.

Background: For an understanding of the pathology of retinal diseases, direct comparisons of high-resolution in vivo retinal imaging and ex vivo histological preparations are desirable.

Material And Methods: Multimodal in vivo and ex vivo imaging of a human donor eye with secondary alterations showing atrophic retina due to central retinal arterial occlusion. The subsequent correlation with the histological examination was carried out on identical tissue localizations.

Fundus Autofluorescence in Neovascular Age-Related Macular Degeneration: A Clinicopathologic Correlation Relevant to Macular Atrophy.

Purpose: Macular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with antiangiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histologic analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD.

Design: Case study and clinicopathologic correlation.

Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration.

Purpose: Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).

Stages of Drusen-Associated Atrophy in Age-Related Macular Degeneration Visible via Histologically Validated Fundus Autofluorescence.

Purpose: To determine histologic correlates for stages of drusen-associated atrophy observed with fundus autofluorescence (FAF) and color fundus photography (CFP), of eyes with advanced age-related macular degeneration (AMD).

Design: Case study and clinicopathologic correlation.

Participant: A white woman with AMD findings of inactive subretinal fibrosis (right eye) and untreated nonexudative type 1 macular neovascularization (left eye) was followed for 9 years before death at 90 years of age.

Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration.

Purpose: Basal laminar deposit (BLamD) is a consistent finding in age-related macular degeneration (AMD). We quantified BLamD thickness, appearance, and topography in eyes of aged donors with and without AMD and evaluated its relationship to other components of the retinal pigment epithelium-basal lamina/Bruch's membrane (RPE-BL-BrM) complex.

Methods: Donor eyes (n = 132) were classified as normal (n = 54), early to intermediate AMD (n = 24), geographic atrophy (GA; n = 13), and neovascular AMD (NV; n = 41).