Oregon Health & Science University

Increasing the Efficacy of Gold Nanorod Uptake in Stem Cell-Derived Therapeutic Cells: Implications for Stem Cell Labeling and Optical Coherence Tomography Imaging

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The advancement of safe nanomaterials for use as optical coherence tomography (OCT) imaging and stem cell-labeling agents to longitudinally visually track therapeutic derived retinal stem cells to study their migration, survival rate, and efficacy is challenged by instability, intracellular aggregation, low uptake, and cytotoxicity. Here, we describe a series of hybrid lipid-coated gold nanorods (AuNRs) that could solve these issues. These nanomaterials were made via a layer-by-layer assembly approach, and their stability in biological media, mechanism, efficiency of uptake, and toxicity were compared with a commercially available set of AuNRs with a 5 nm mesoporous silica (mSiO 2 )-polymer coating. These nanomaterials can serve as stem cell labeling and OCT imaging agents because they absorb in the near-infrared (NIR) region away from biological tissues. Although both subtypes of AuNRs were taken up by retinal pigment epithelial, neural progenitor, and baby hamster kidney cells, sl...

Association of Optical Coherence Tomography–Measured Fibrovascular Ridge Thickness and Clinical Disease Stage in Retinopathy of Prematurity

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Importance Accurate diagnosis of retinopathy of prematurity (ROP) is essential to provide timely treatment and reduce the risk of blindness. However, the components of an ROP examination are subjective and qualitative. Objective To evaluate whether optical coherence tomography (OCT)–derived retinal thickness measurements at the vascular-avascular junction are associated with clinical diagnosis of ROP stage. Design, Setting, and Participants This cross-sectional longitudinal study compared OCT-based ridge thickness calculated from OCT B-scans by a masked examiner to the clinical diagnosis of 2 masked examiners using both traditional stage classifications and a more granular continuous scale at the neonatal intensive care unit (NICU) of Oregon Health & Science University (OHSU) Hospital. Infants who met ROP screening criteria in the OHSU NICU between June 2021 and April 2022 and had guardian consent were included. One OCT volume and en face image per patient per eye showing ...

Volume-based, layer-independent, disease-agnostic detection of abnormal retinal reflectivity, nonperfusion, and neovascularization using structural and angiographic OCT

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Optical coherence tomography (OCT) is widely used in ophthalmic practice because it can visualize retinal structure and vasculature in vivo and 3-dimensionally (3D). Even though OCT procedures yield data volumes, clinicians typically interpret the 3D images using two-dimensional (2D) data subsets, such as cross-sectional scans or en face projections. Since a single OCT volume can contain hundreds of cross-sections (each of which must be processed with retinal layer segmentation to produce en face images), a thorough manual analysis of the complete OCT volume can be prohibitively time-consuming. Furthermore, 2D reductions of the full OCT volume may obscure relationships between disease progression and the (volumetric) location of pathology within the retina and can be prone to mis-segmentation artifacts. In this work, we propose a novel framework that can detect several retinal pathologies in three dimensions using structural and angiographic OCT. Our framework operates by detecting ...

Comparing Retinal Structure in Patients with Achromatopsia and Blue Cone Monochromacy Using OCT

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Purpose: To compare foveal hypoplasia and the appearance of the ellipsoid zone (EZ) at the fovea in patients with genetically confirmed achromatopsia (ACHM) and blue cone monochromacy (BCM). Design: Retrospective, multi-center observational study. Subjects: Molecularly confirmed patients with ACHM (n = 89) and BCM (n = 33). Methods: We analyzed high-resolution spectral domain optical coherence tomography (SD-OCT) images of the macula from aforementioned patients with BCM. Three observers independently graded SD-OCT images for foveal hypoplasia (i.e. retention of one or more inner retinal layers at the fovea) and four observers judged the integrity of the EZ at the fovea, based on an established grading scheme. These measures were compared with previously published data from the ACHM patients. Main outcome measures: Presence of foveal hypoplasia and EZ grade. Results: Foveal hypoplasia was significantly more prevalent in ACHM than in BCM (p<0.001). In addition, we observed a signi...

Central posterior hyaloidal fibrosis – A novel optical coherence tomography feature associated with choroidal neovascular membrane

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Purpose: To describe a novel optical coherence tomography (OCT) finding at the vitreomacular interface (VMI), and report its association with advanced choroidal neovascularisation (CNV). Observations: Optical coherence tomography (OCT) scans performed at three retinal imaging centres at Amanat Eye Hospital, Pakistan from May 2016 till May 2021 were reviewed. A specific change at the vitreomacular interface was noted consisting of abnormal hyper reflectivity at the point of attachment of the posterior hyaloid membrane to the foveal center which appears to 'fill in' the foveolar depression.Eight eyes of eight patients were identified. All affected eyes had advanced CNV and persistent vitreofoveolar adhesion. In all eyes, the foveal contour (concavity) was maintained and there was no inner retinal surface wrinkling which differentiates this OCT feature from vitreomacular traction or epiretinal membranes. The authors propose the term Central Posterior Hyaloidal Fibrosis (CPHF) for this ...

Systems and methods for automated widefield optical coherence tomography angiography

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Disclosed are systems and methods for generating wide-field optical coherence tomography angiography (OCTA) images. In embodiments, multiple OCTA scans of a sample are automatically acquired at overlapping locations. The systems and methods include functionality to adaptively control the scanning procedure such that eye blink and eye motion events are detected in real time and accounted for during 3D scan acquisition. Also disclosed are methods for detecting and correcting motion-related artifacts in OCTA datasets which allow for the longer scan times over larger fields of view required for wide-field imaging. These methods may include division of en face angiogram images into a set of motion-free parallel strips, and application of gross and fine registration methods to align overlapping strips into a motion-corrected composite image. A series of overlapping motion-corrected composite images may be combined into a larger montage to enable wide-field OCTA imaging using multiple OCTA...

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography

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Purpose : The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters. Methods : OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis. Results : A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<−6D), low myopia (−6D to −1D), emmetropia (−1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD...

Oregon Health & Science University Receives NIH Grant for Functional and Structural Optical Coherence Tomography for Glaucoma

Oregon Health & Science University Received a 2022 NIH Grant for $590,490 for Functional and Structural Optical Coherence Tomography for Glaucoma. The principal investigator is David Huang. Below is a summary of the proposed work. Glaucoma is a leading cause of blindness in the US. The management of glaucoma is based on early detection, followed by careful evaluation and monitoring to identify those with rapid disease progression and high risk for vision loss. This allows for the rational use of medical, laser, and surgical treatments. Current methods of assessing glaucoma have significant limitations. Visual field (VF) testing has a low sensitivity for detecting early disease, and its reproducibility worsens in advanced stages, reducing its reliability for monitoring disease progression. Optical coherence tomography (OCT) precisely measure the peripapillary nerve fiber layer (NFL) thickness and is the most commonly used technology for objective glaucoma evaluation. However, NFL...

Visual field simulation using optical coherence tomography and optical coherence tomographic angiography

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Disclosed herein are methods for simulating the results of a visual field (VF) test using an optical coherence tomography (OCT) system. The disclosed methods may utilize structural information extracted from OCT image datasets, such as thickness measurements, or may utilize functional information, such as blood perfusion measurements, extracted from OCT angiography (OCTA) image datasets. Other embodiments may be described and claimed. ( Read Full Article )

Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort

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Background: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on S...

Corneal imaging with blue-light optical coherence microscopy

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Corneal imaging is important for the diagnostic and therapeutic evaluation of many eye diseases. Optical coherence tomography (OCT) is extensively used in ocular imaging due to its non-invasive and high-resolution volumetric imaging characteristics. Optical coherence microscopy (OCM) is a technical variation of OCT that can image the cornea with cellular resolution. Here, we demonstrate a blue-light OCM as a low-cost and easily reproducible system to visualize corneal cellular structures such as epithelial cells, endothelial cells, keratocytes, and collagen bundles within stromal lamellae. Our blue-light OCM system achieved an axial resolution of 12 µm in tissue over a 1.2 mm imaging depth, and a lateral resolution of 1.6 µm over a field of view of 750 µm × 750 µm. ( Read Full Article )

Baseline Microperimetry and OCT in the RUSH2A Study: Structure-Function Association and Correlation with Disease Severity

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Purpose: To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. Design: Natural history study SETTING: 16 clinical sites in Europe and North America STUDY POPULATION: Participants with Usher syndrome type 2 (USH2) (N=80) or autosomal recessive nonsyndromic RP (ARRP) (N=47) associated with biallelic disease-causing sequence variants in USH2A. Observation procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, including best corrected visual acuity (BCVA) and central subfield thickness (CST) within the central 1 mm, were assessed using Spearman correlation coefficients. Main outcome measures: Mean sensitivity on MP; EZ area and CST on OCT RESULTS: All participants (N=127) had OCT...

En Face OCT Detects Preretinal Abnormal Tissues Before and After Internal Limiting Membrane Peeling in Eyes with Macular Hole

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Purpose To assess preretinal abnormal tissue (PAT) using en face optical coherence tomography (OCT) in eyes with idiopathic macular holes (MHs). Design Retrospective, observational study. Participants MH patients who received 6×6-mm spectral-domain OCT scans. Methods PAT was detected by en face OCT images with a custom slab, defined with an anterior boundary of 6 μm anterior to the internal limiting membrane (ILM) and a posterior boundary at 3 μm posterior to the ILM. The PAT was defined as any abnormal tissues observed in en face OCT. Main Outcome Measures Characteristics of preoperative and postoperative PAT. Results Sixty eyes with MH from 60 patients (mean age: 65 years, 32 females) were included. Fifty-one eyes underwent preoperative analysis, and 46 eyes underwent postoperative examination. Prior to surgery, 48 (94%) eyes had a mean (SD) PAT of 6.6 (9.8) mm 2 . The corresponding cross-sectional OCT showed PAT consisting of epiretinal proliferation (EP), epivascular...

In Vivo Imaging of Retinal and Choroidal Morphology and Vascular Plexuses of Vertebrates Using Swept-Source Optical Coherence Tomography

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Purpose: To perform in vivo evaluation of the structural morphology and vascular plexuses of the neurosensory retina and choroid across vertebrate species using swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA) imaging. Methods: A custom-built SS-OCT system with an incorporated flexible imaging arm was used to acquire the three-dimensional (3D) retinal OCT and vascular OCTA data of five different vertebrates: a mouse (C57BL/6J), a rat (Long Evans), a gray short-tailed opossum (Monodelphis domestica), a white sturgeon (Acipenser transmontanus), and a great horned owl (Bubo virginianus). Results: In vivo structural morphology of the retina and choroid, as well as en face OCTA images of retinal and choroidal vasculature of all species were generated. The retinal morphology and vascular plexuses were similar between rat and mouse, whereas distinct choroidal and paired superficial vessels were observed in the opossum retina. The retinal and vascular stru...

Detection of Corneal Ectasia Using OCT Maps of Pachymetry and Posterior Surface Mean Curvature

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Purpose: To quantify the abnormal corneal thinning and posterior surface steepening that is observed in keratoconus with an Ectasia Index. Methods: Optical coherence tomography (OCT) was used to image the corneas of normal individuals and patients with varying stages of keratoconus (manifest, subclinical, and forme fruste). Maps of corneal pachymetry and posterior surface mean curvature were generated, and an Ectasia Index was calculated by multiplying Gaussian fits obtained from the two types of maps. Repeated five-fold cross-validation was used to evaluate the ability of the Ectasia Index to differentiate between normal and keratoconic eyes. The classification performance of the Ectasia Index was compared to minimum pachymetry and maximum posterior mean curvature. Results: Thirty-two eyes from 16 normal individuals, 89 eyes from 63 patients with manifest keratoconus, 16 eyes from 15 patients with subclinical keratoconus, and 26 eyes from 26 patients with forme fruste keratoconus w...

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