University of Vienna

A systematic evaluation of human expert agreement on optical coherence tomography biomarkers using multiple devices

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Objectives To assess the agreement in evaluating optical coherence tomography (OCT) variables in the leading macular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) among OCT-certified graders. Methods SD-OCT volume scans of 356 eyes were graded by seven graders. The grading included presence of intra- and subretinal fluid (IRF, SRF), pigment epithelial detachment (PED), epiretinal membrane (ERM), conditions of the vitreomacular interface (VMI), central retinal thickness (CRT) at the foveal centre-point (CP) and central millimetre (CMM), as well as height and location of IRF/SRF/PED. Kappa statistics (κ) and intraclass correlation coefficient (ICC) were used to report categorical grading and measurement agreement. Results The overall agreement on the presence of IRF/SRF/PED was κ = 0.82/0.85/0.81; κ of VMI condition was 0.77, that of ERM presence 0.37. ICC for CRT mea...

Detection of diabetic neovascularisation using single-capture 65{degrees}-widefield optical coherence tomography angiography

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Aim To assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA). Methods Single-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss’ κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated. Results Fifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between W...

Ultra-widefield OCT Angiography

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Optical Coherence Tomography Angiography (OCTA), a functional extension of OCT, has the potential to replace most invasive fluorescein angiography (FA) exams in ophthalmology. So far, OCTA’s field of view is however still lacking behind fluorescence fundus photography techniques. This is problematic, because many retinal diseases manifest at an early stage by changes of the peripheral retinal capillary network. It is therefore desirable to expand OCTA’s field of view to match that of ultra-widefield fundus cameras. We present a custom developed clinical high-speed swept-source OCT (SS-OCT) system operating at an acquisition rate 8-16 times faster than today’s state-of-the-art commercially available OCTA devices. Its speed allows us to capture ultra-wide fields of view of up to 90 degrees with an unprecedented sampling density and hence extraordinary resolution by merging two single shot scans with 60 degrees in diameter. To further enhance the visual appearance of ...

Detection of diabetic neovascularisation using single-capture 65°-widefield optical coherence tomography angiography

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Aim: To assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA). Methods: Single-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss' κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated. Results: Fifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between WF-O...

OCT Meets micro-CT: A Subject-Specific Correlative Multimodal Imaging Workflow for Early Chick Heart Development Modeling

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Structural and Doppler velocity data collected from optical coherence tomography have already provided crucial insights into cardiac morphogenesis. X-ray microtomography and other ex vivo methods have elucidated structural details of developing hearts. However, by itself, no single imaging modality can provide comprehensive information allowing to fully decipher the inner workings of an entire developing organ. Hence, we introduce a specimen-specific correlative multimodal imaging workflow combining OCT and micro-CT imaging which is applicable for modeling of early chick heart development-a valuable model organism in cardiovascular development research. The image acquisition and processing employ common reagents, lab-based micro-CT imaging, and software that is free for academic use. Our goal is to provide a step-by-step guide on how to implement this workflow and to demonstrate why those two modalities together have the potential to provide new insight into normal cardiac developme...

Birefringent Properties of the Peripapillary Retinal Nerve Fiber Layer in Healthy and Glaucoma Subjects Analyzed by Polarization-Sensitive OCT

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Purpose: To study the circumpapillary retinal nerve fiber layer (RNFL) birefringence (BIR) of early glaucoma and age-matched healthy eyes using polarization-sensitive optical coherence tomography (PS-OCT). Methods: In this prospective cross-sectional study, we compared virtual circular PS-OCT B-scans with a diameter of 3.5 mm centered on the optic disc (OD) acquired with a PS-OCT prototype (860 nm center wavelength). Early glaucoma was defined by the glaucomatous appearance of the OD and a pathologic visual field test with a mean deviation (MD) better than -6 dB. The main outcome parameters were BIR, RNFL-thickness (RNFL-T), and phase retardation (RET). The BIR value at each virtual A-scan position was the quotient of the RET measured at the inner segment/outer segment junction divided by the RNFL-T. Results: The dataset comprised 49 early glaucoma patients (mean ± standard deviation [SD]: 64 ± 10 years) and 49 healthy control subjects (61 ± 9 years). Glaucomato...

Segmentation of Bruch’s Membrane in retinal OCT with AMD using anatomical priors and uncertainty quantification

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Bruch's membrane (BM) segmentation on optical coherence tomography (OCT) is a pivotal step for the diagnosis and follow-up of age-related macular degeneration (AMD), one of the leading causes of blindness in the developed world. Automated BM segmentation methods exist, but they usually do not account for the anatomical coherence of the results, neither provide feedback on the confidence of the prediction. These factors limit the applicability of these systems in real-world scenarios. With this in mind, we propose an end-to-end deep learning method for automated BM segmentation in AMD patients. An Attention U-Net is trained to output a probability density function of the BM position, while taking into account the natural curvature of the surface. Besides the surface position, the method also estimates an A-scan wise uncertainty measure of the segmentation output. Subsequently, the A-scans with high uncertainty are interpolated using thin plate splines (TPS). We tested our method with...

PhD Studentship in Ophthalmic Imaging at the Nicolaus Copernicus University, Torun, Poland

The Bio-Optics & Optical Engineering Lab at the Nicolaus Copernicus University invites applications for the PhD student position in a project entitled Deciphering nano-scale tissue motion in healthy and diseased eyes for next-generation ocular diagnostics financed by the Polish National Science Center (Programme OPUS, 2023-2026). We are seeking a talented young researchers for the position: PhD student.   In this project, we will develop high-speed in vivo optical imaging methods and uncover pulsation-induced nano-scale tissue motion within and in-between eye structures. In this project, the research groups of Dr. Ireneusz Grulkowski at Nicolaus Copernicus University (Poland) and Dr. Bernhard Baumann at Medical University of Vienna (Austria) will team up to tackle the development of next-generation optical imaging technology and investigate nano-deformations in healthy and diseased eyes. These methods will finally enable the quantitative assessment and 4-D mapping of pulsat...

Are Macula or Optic Nerve Head Structures better at Diagnosing Glaucoma? An Answer using AI and Wide-Field Optical Coherence Tomography

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Purpose : (1) To develop a deep learning algorithm to automatically segment connective and neural tissue structures of the optic nerve head (ONH) and macula in 3D wide - field optical coherence tomography (OCT) scans; (2) To exploit such information, to assess whether 3D macula or ONH structures (or the combination of both) provide the best diagnostic power for glaucoma. Methods: A cross - sectional comparative study was performe d which included wide - field swept - source OCT scans from 319 subjects with primary open angle glaucoma (POAG) and 298 non - glaucom a subjects . After acquisition, all scans were compensated to improve deep - tissue visibility. We developed a deep learning algorithm to automatically label all major neural and connective tissue structures by using 270 manually annotated B - scans (from 69 eyes with POAG and 48 eyes without POAG) for training. The performance of our algorithm was assessed using the Dice coefficient (DC) . A classification algorithm (3D - C...

Degeneration of Melanin-Containing Structures Observed Longitudinally in the Eyes of SOD1-/- Mice Using Intensity, Polarization, and Spectroscopic OCT

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Purpose: Melanin plays an important function in maintaining eye health, however there are few metrics that can be used to study retinal melanin content in vivo. Methods: The slope of the spectral coefficient of variation (SSCoV) is a novel biomarker that measures chromophore concentration by analyzing the local divergence of spectral intensities using optical coherence tomography (OCT). This metric was validated in a phantom and applied in a longitudinal study of superoxide dismutase 1 knockout (SOD1-/-) mice, a model for wet and dry age-related macular degeneration. We also examined a new feature of interest in standard OCT image data, the ratio of maximum intensity in the retinal pigment epithelium to that of the choroid (RC ratio). These new biomarkers were supported by polarization-sensitive OCT and histological analysis. Results: SSCoV correlated well with depolarization metrics both in phantom and in vivo with both metrics decreasing more rapidly in SOD1-/- mice with age (P &l...

Investigating the macular choriocapillaris in early primary open-angle glaucoma using swept-source optical coherence tomography angiography

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Introduction: There has been a growing interest in the role of vascular factors in glaucoma. Studies have looked at the characteristics of macular choriocapillaris in patients with glaucoma but with conflicting results. Our study aims to use swept-source optical coherence tomography angiography (SS-OCTA) to evaluate macular choriocapillaris metrics in normal participants and compare them with patients with early primary open-angle glaucoma (POAG) (mean deviation better than -6dB). Methods: In this prospective, observational, cross-sectional study, 104 normal controls (157 eyes) and 100 patients with POAG (144 eyes) underwent 3 mm × 3mm imaging of the macula using the Plex Elite 9000 (Zeiss Meditec, Dublin, CA, USA). Choriocapillaris OCTA images were extracted from the device's built-in review software and were subsequently evaluated for the density and size of choriocapillaris flow deficits. Results: After adjusting for confounding factors, the density of flow deficits was ind...

Optical coherence tomography and OCT angiography characteristics of indocyanine green angiographic plaques in nonexudative age-related macular degeneration

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Purpose: To describe characteristics of indocyanine green (ICG) angiographic plaques in the nonexudative fellow eye of Caucasian patients with unilateral treatment-naïve exudative neovascular age-related macular degeneration (nAMD) through optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: In this retrospective cross-sectional study, nonexudative eyes with ICG angiographic plaques were analyzed by OCT B-scans for the sensitivity of a double-layer sign (DLS), a pigment epithelium detachment (PED), outer retinal atrophy (ORA), hyperreflective dots (HRD) and subretinal hyperreflective material (SRHM). The ICG angiographic plaque was matched with a macular neovascularization (MNV) in OCTA en-face scans and color-coded B-scans. Results: In total, 35 ICG angiographic plaques in 33 of 291 (11%) nonexudative eyes were diagnosed. OCT revealed: 27 DLS (78%), 8 PED (23%), 8 ORA (23%), 8 HRD (23%), 1 SRHM (3%). OCTA confirmed a MNV in 28 plaques (80%): 7 (20%) in en-fa...

Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography

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Breast cancer is a leading cause of death in female patients worldwide. Further research is needed to get a deeper insight into the mechanisms involved in the development of this devastating disease and to find new therapy strategies. The zebrafish is an established animal model, especially in the field of oncology, which has shown to be a promising candidate for pre-clinical research and precision-based medicine. To investigate cancer growth in vivo in zebrafish, one approach is to explore xenograft tumor models. In this article, we present the investigation of a juvenile xenograft zebrafish model using a Jones matrix optical coherence tomography (JM-OCT) prototype. Immunosuppressed wild-type fish at 1-month post-fertilization were injected with human breast cancer cells and control animals with phosphate buffered saline in the tail musculature. In a longitudinal study, the scatter, polarization, and vasculature changes over time were investigated and quantified in control versus t...

Evaluation of Generative Adversarial Networks for High-Resolution Synthetic Image Generation of Circumpapillary Optical Coherence Tomography Images for Glaucoma

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Importance: Deep learning (DL) networks require large data sets for training, which can be challenging to collect clinically. Generative models could be used to generate large numbers of synthetic optical coherence tomography (OCT) images to train such DL networks for glaucoma detection. Objective: To assess whether generative models can synthesize circumpapillary optic nerve head OCT images of normal and glaucomatous eyes and determine the usability of synthetic images for training DL models for glaucoma detection. Design, setting, and participants: Progressively growing generative adversarial network models were trained to generate circumpapillary OCT scans. Image gradeability and authenticity were evaluated on a clinical set of 100 real and 100 synthetic images by 2 clinical experts. DL networks for glaucoma detection were trained with real or synthetic images and evaluated on independent internal and external test data sets of 140 and 300 real images, respectively. Main outcomes...

Predicting treat-and-extend outcomes and treatment intervals in neovascular age-related macular degeneration from retinal optical coherence tomography using artificial intelligence

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Purpose: To predict visual outcomes and treatment needs in a treat & extend (T&E) regimen in neovascular age-related macular degeneration (nAMD) using a machine learning model based on quantitative optical coherence tomography (OCT) imaging biomarkers. Materials and methods: Study eyes of 270 treatment-naïve subjects, randomized to receiving ranibizumab therapy in the T&E arm of a randomized clinical trial were considered. OCT volume scans were processed at baseline and at the first follow-up visit 4 weeks later. Automated image segmentation was performed, where intraretinal (IRF), subretinal (SRF) fluid, pigment epithelial detachment (PED), hyperreflective foci, and the photoreceptor layer were delineated using a convolutional neural network (CNN). A set of respective quantitative imaging biomarkers were computed across an Early Treatment Diabetic Retinopathy Study (ETDRS) grid to describe the retinal pathomorphology spatially and its change after the first injecti...

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