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Ultrahigh-Resolution Optical Coherence Tomography in Glaucoma
Abstract
Optical coherence tomography (OCT) has been shown to be a valuable tool in glaucoma assessment. We investigated a new ultrahigh-resolution OCT (UHR-OCT) imaging system in glaucoma patients and compared the findings with those obtained by conventional-resolution OCT.
Retrospective comparative case series.
A normal subject and 4 glaucoma patients representing various stages of glaucomatous damage.
All participants were scanned with StratusOCT (axial resolution of approximately 10 mum) and UHR-OCT (axial resolution of approximately 3 microm) at the same visit.
Comparison of OCT findings detected with StratusOCT and UHR-OCT.
Ultrahigh-resolution OCT provides a detailed cross-sectional view of the scanned retinal area that allows differentiation between retinal layers. These UHR images were markedly better than those obtained by the conventional-resolution OCT.
Ultrahigh-resolution OCT provides high-resolution images of the ocular posterior segment, which improves the ability to detect retinal abnormalities due to glaucoma.
... Según Götzinger et al. (2011) Revisiones sistemáticas con metaanálisis 3 Ávila, 2011;Gonzales et al., 2012;Wanderley, 2011 8 Ensayos clínicos aleatorios 17 Andersson et al., 2011;Atsuya et al., 2013;Borque et al., 2008;Chan et al., 2014;Dimitrios et al., 2011;Garas et al., 2012;Gôtzinger et al., 2011;Hirokazu y Etsuo, 2008;Hwang et al., 2013;Knight et al., 2010;Lee et al., 2010;Méndez, 2008;Mesiwala et al., 2012;Orlev et al., 2008;Toth et al., 2008;Townsend et al., 2010;Zhong et al., 2009 7 Guías de práctica clínica 20 Alías et al., 2008;Bernades y Cunha-vaz., 2012;Bruno y Rispoli, 2012;Carratalá, 2011;Chung y Leung, 2009;Dascalu et al., 2010;Duch y Buchacra, 2012;Fernández et al., 2009;Fingeret, 2009;Goñi y Guarro, 2009;Gupta et al., 2012;Heidelberg, 2009;Heilderberg, 2010;Kotosky et al., 2012;Moreno et al., 2010;Sharma et al., 2010;Suárez, 2011;Vela y Hernecki, 2012;Vizzeri, 2011 6 Estudios de cohorte y de casos y control 9 Álvarez, 2010;Deleon et al., 2013;Egea, 2009;Hermann et al., 2007;Medeiros et al., 2007;Murad, 2007;Sánchez, 2007;Smith et al., 2014;Xiao y Wu, 2010 5 Estudios observacionales (longitudinales o transversales) 16 Alasil et al., 2014;Alencar et al., 2014;Andreou et al., 2007;Balasubramanian, et al., 2011;Bowd et al., 2007;Burgansky et al., 2009;Huijuan et al., 2012;Jung et al., 2013;Lleò et al., 2009;Mederios et al., 2010;Abou-Hinin, 2012;Pablo et al., 2010;Swathy et al., 2009;Xu et al., 2013;Young et al., 2012 4 Casos clínicos o serie de casos 3 Capote et al., 2009;Stone, 2008;Wollstein et al., 2007 3 Investigación básica de laboratorio 0 son (2011), la OCT es un equipo que utiliza una técnica de imagen diagnóstica ocular no invasiva, que a su vez proporciona imágenes en sección transversal con alta resolución de los tejidos. Wollstein et al. (2007) mencionan que numerosos estudios han tratado de establecer las diversas funcionalidades de la OCT, y concluyen que este equipo arroja imágenes de la detección en vivo de los cambios histológicos de la capa de fibras nerviosas de la retina (CFnR) y de las células ganglionares de la retina (CGR). Por otra parte, se ha informado, según evidencia científica, que la OCT puede realizar evaluaciones cualitativas y cuantitativas de los daños netamente estructurales del nervio óptico (nO) y de la CFnR. ...
... Diversos estudios involucrados con la OCT coinciden en la descripción del principio de funcionamiento de esta. Afirman que la tomografía de coherencia óptica utiliza la interferometría de baja coherencia de una fuente de diodo luminiscente (luz infrarroja) con una longitud de onda de 820 nm de centrado y 25 nm de ancho de la banda, a través del cual logra proporcionar imágenes de las estructuras oculares gracias al tiempo de retardo del eco y la magnitud de luz dispersa en las microestructuras de la retina, como la capa de fibras nerviosas, haciendo válido el instrumento para la valoración del glaucoma (Wollstein et al., 2007). ...
... La imagen que resulta de la exploración con OCT tiene una resolución de 10 µm de longitud axial y 20 µm de tejido transversal, con una velocidad de 400 Scan por segundo. Así, la OCT valora el área retinal con un rango de exploración de 3,4 mm y con 6 escaneos lineales en patrón de radio separados por intervalos de 30º (Wollstein et al., 2007). A su vez, Vizzeri et al. (2011) describen que la OCT muestra la imagen artificialmente como un código de colores, traducido por un software que funciona con el principio de reflectividad: a mayor reflectividad, mayor color (amarillo-verde), y a menor reflectividad, menor color (negro-azul). ...
Objetivo: describir y analizar, por medio de una revisión bibliográfica, las tecnologías diagnósticas OCT (tomografía de coherencia óptica), HRT (tomógrafo de Heidelberg) y GDx (analizador de fibras nerviosas) en glaucoma, como un enfoque para la optometría clínica. Materiales y métodos: se realizó una búsqueda sistemática de literatura primaria en bases de datos como Pubmed, Medline, Cochrane y Elsevier; además, se incluyeron textos literarios relacionados con el tema, escritos en inglés, español y portugués. La información seleccionada estuvo dentro de un periodo de publicación comprendido entre 2007 y 2014. Conclusión: la OCT utiliza una longitud de onda de 820 nm, valora la retina y determina la aparición de la enfermedad; el HRT funciona con un láser diodo de 670 nm y genera imágenes en tercera dimensión del nervio óptico, lo que lo convierte en la tecnología diagnóstica más específica para valorar glaucoma; el GDx emplea un láser polarizado de 780 nm y evalúa el nervio óptico, por lo cual es ideal para realizar seguimiento de la enfermedad, ya que determina cambios mínimos. Estos equipos tienen aplicabilidad favorable para la detección y el seguimiento del glaucoma; sin importar cuál instrumento se emplee, es fundamental que el profesional tenga la competencia de interpretar los resultados y realizar una correlación con examen clínico.
... Early studies looking at reproducibility used this 3.4 mm diameter ring, and since neither anatomical recognition software nor eye tracking software existed, focal defects could not be followed precisely over time. 3,[18][19][20] TD-OCT uses RNFL thickness profiles created by retinal segmentation and compares the profiles to normative data to track disease progression. Reproducibility of these scans from visit to visit was found to be reasonable with a standard deviation of 2.5 μm for the mean RFNL thickness. ...
... Reproducibility of these scans from visit to visit was found to be reasonable with a standard deviation of 2.5 μm for the mean RFNL thickness. 3,[18][19][20] Reproducibility of any diagnostic test is important for diagnostic accuracy. Especially in glaucoma, reproducibility of RNFL measurements is critical, if the device is used to monitor progression of the disease. ...
... Developmental tissues such as regeneration and maturation, is always accompanied by formation of new vessels (angiogenesis), and monitoring of this progress can be useful in numerous research and clinical applications (3). Also, some diseases are directly or indirectly related to or influenced by the functional microvasculature, for example stroke and traumatic brain injury (4), diabetes (5), wound healing (6), glaucoma (7) and age-related macular degeneration (8). ...
... Entropy measures the content of an image, with higher values indicating more detailed images. The first-order entropy corresponds to the global entropy and is defined by [7] Where x i is an intensity value, m is the total number of intensity values in the dynamic range and P(x i ) is the probability that a pixel in the image has an intensity value of x i . ...
Optical microangiography is an imaging technology that is capable of providing detailed functional blood flow maps within microcirculatory tissue beds in vivo. Some practical issues however exist when displaying and quantifying the microcirculation that perfuses the scanned tissue volume. These issues include: (I) Probing light is subject to specular reflection when it shines onto sample. The unevenness of the tissue surface makes the light energy entering the tissue not uniform over the entire scanned tissue volume. (II) The biological tissue is heterogeneous in nature, meaning the scattering and absorption properties of tissue would attenuate the probe beam. These physical limitations can result in local contrast degradation and non-uniform micro-angiogram images. In this paper, we propose a post-processing method that uses Rayleigh contrast-limited adaptive histogram equalization to increase the contrast and improve the overall appearance and uniformity of optical micro-angiograms without saturating the vessel intensity and changing the physical meaning of the micro-angiograms. The qualitative and quantitative performance of the proposed method is compared with those of common histogram equalization and contrast enhancement methods. We demonstrate that the proposed method outperforms other existing approaches. The proposed method is not limited to optical microangiography and can be used in other image modalities such as photo-acoustic tomography and scanning laser confocal microscopy.
... The probing wavelength of the SD-OCT system is 840 nm. There are studies in the literature where OCT with a wavelength of about 800 nm has been successfully used to investigate biological tissues, including ocular tissues 21) , and dental tissues 22,23) . The maximum probing depth is 1-2 mm in dental tissue at a wavelength of 850 nm. ...
This study aimed to evaluate the Cirrus high-definition (HD) spectral-domain optical coherence tomography (SD-OCT) for the remineralization of artificial enamel caries and to compare it with the comparison surface microhardness (SMH) analysis. Artificial caries lesions were produced on forty human enamel samples. Then, three different remineralization agents containing casein phosphopeptide amorphous calcium phosphate; casein phosphopeptide amorphous calcium fluoride phosphate; calcium glycerophosphate, magnesium chloride, and xylitol; and remineralization solution (control) were applied with pH cycling for six days. The optical depth of backscattered light and microhardness of enamel were measured using SD-OCT and SMH. All remineralization agents were significantly efficient in reducing optical lesion depth on enamels (p1=0.001, p2=0.002, p3=0.006, p4=0.025), and in increasing the SMH of enamels (p1−3=0.005, p4=0.017). However, the optical lesion depths of the enamel showed no correlation with the SMH in the groups. In conclusion, demineralization and remineralization of artificial lesions can be assessed with both SD-OCT and SMH.
... Development of ultrabroad bandwidth light sources and high-speed detection techniques has improved the ophthalmic OCT imaging significantly, allowing 3 dimensional ultrahigh-resolution OCT (UHR-OCT) to perform non-invasive optical biopsy of the living human retina [163][164][165]. The improved axial resolution and imaging speed enable high-definition, two-dimensional tomograms, topographic thickness maps of all major intra-retinal layer as well as volumetric quantification of pathologic intra-retinal changes [166][167][168]. Figure 3.7 shows the comparison of the normal optical nerve head imaged by three different OCT systems: Standard OCT system ( 10um axial resolution, 400A − scans/s, Fig. 3.7(a)), UHR OCT using time domain detection ( 3um axial resolution, 150A − scans/s, Fig.3.7(b)), and high-speed UHR OCT using Fourier domain detection ( 2um axial resolution, 25000A − scans/s, figure 3.7(c)). The high-speed UHR OCT not only reduces eye motion artifacts with its fast imaging speed, it also enables better delineation of the intra-retinal layers with its higher axial resolution, smaller speckle size, and increased A-line numbers. ...
This thesis follows the study and development of an adaptive optics full-field optical coherence tomography (AO-FFOCT) system, aiming for high resolution en face human retinal imaging. During the quantification of the effects of geometrical aberrations on the FFOCT system performance, it is shown that, with spatially incoherent illumination, the lateral resolution of FFOCT is insensitive to aberrations, which only cause the FFOCT signal reduction. Since low order aberrations like myopia and astigmatism dominate in human eye, a non-conjugate AO configuration by using transmissive wavefront corrector is suggested and applied for low order aberrations correction to simplify the AO-FFOCT system. Wavefront corrections are done with a wavefront sensorless method by using FFOCT signal level as the metric. Experiments with scattering samples and artificial eye model are conducted to demonstrate the feasibility of the customized AO-FFOCT system for aberration correction. In order to resolve the eye motion effects and employ real-time matching of the optical path lengths of the two interferometric arms in FFOCT, a system combination of traditional spectral-domain OCT (SDOCT) with FFOCT is adopted. With this combined system, high resolution FFOCT cellular retinal imaging is achieved in human eye in vivo for the first time.
... That is, OCT enables depth-resolved visualisation and morphometric analysis of the lamina cribrosa anatomy. [85][86][87][88][89] It has long been thought that the lamina cribrosa is the primary site of injury to retinal ganglion cell axons in glaucoma. The ability to measure its depth, thickness, curvature and other aspects of its shape, as well as microscopic aspects of lamina cribrosa anatomy such as beam thickness, pore size, pore density and pore shape, should offer future insights into pathophysiology and the ability to refine estimates of risk for a given eye, that is, to help determine if an eye is relatively more or less susceptible to develop glaucoma or rapidly progressing disease. ...
Clinical examination of the optic disc is a fundamental component of any ophthalmic evaluation, but it is especially important for diagnosis and management of glaucoma. The purpose of this article is to: (1) review the limitations inherent to clinical examination; (2) outline the rationale for adopting into clinical practice quantitative measures of the optic nerve head neuro‐retinal rim tissue integrity derived from current optical coherence tomography imaging approaches; (3) describe recent developments in this area; and (4) highlight a few avenues of active research that hold promise for future translation to clinical practice.
... OCT is a non invasive method that provides high resolution cross sectional imaging of tissues. 6 Spectral domain OCT, differently from the Time domain OCT, includes a spectrometer. 7 Very high-velocity and high-resolution 2 dimensional images are obtained through the use of SD-OCT. ...
... Optical coherence tomography (OCT) [1,2] is a noninvasive interferometry-based imaging modality that allows for volumetric imaging of the retina. Since its introduction in 1991, it has found widespread use in the diagnosis and management of a variety of ophthalmic disorders in humans [3][4][5][6][7][8][9], as well as in the study of animal models of retinal disease [10][11][12][13]. Traditional ex vivo histological studies of retinal tissues are capable of visualizing structural and morphological changes in high detail; however, artifacts such as shrinkage and retinal detachment [14][15][16][17][18] are difficult to avoid and present challenges for reproducible quantification. ...
The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study. © 2017 Antony et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
... Spectral-domain optical coherence tomography (SDOCT) 1, 2 provides high resolution images of retinal structures and as such has begun to play an important role in clinical practice. Structural changes associated with diseases can now be visualized and quantified in order to better diagnose and monitor a variety of retinal disorders, such as glaucoma 3,4 and age-related macular degeneration. 5,6 In addition to its increasing use in ophthalmology, SDOCT has also begun to find application in neurology to monitor the progression of diseases such as multiple sclerosis (MS), 7,8 Parkinson's disease 9, 10 and Alzhiemer's disease, 11 where retinal thicknesses have been found to correlate with disease severity. ...
Spectral domain optical coherence tomography (SDOCT) is routinely used in the management and diagnosis of a variety of ocular diseases. This imaging modality also finds widespread use in research, where quantitative measurements obtained from the images are used to track disease progression. In recent years, the number of available scanners and imaging protocols grown and there is a distinct absence of a unified tool that is capable of visualizing, segmenting, and analyzing the data. This is especially noteworthy in longitudinal studies, where data from older scanners and/or protocols may need to be analyzed. Here, we present a graphical user interface (GUI) that allows users to visualize and analyze SDOCT images obtained from two commonly used scanners. The retinal surfaces in the scans can be segmented using a previously described method, and the retinal layer thicknesses can be compared to a normative database. If necessary, the segmented surfaces can also be corrected and the changes applied. The interface also allows users to import and export retinal layer thickness data to an SQL database, thereby allowing for the collation of data from a number of collaborating sites. © (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
... Использующийся в UHR OCT фемтосекундный лазер обеспечивает получение изображений с осевым разрешением около 3 мкм [65,66]. Сравнение UHR OCT и обычной OCT показало, что первая позволяет более подробно изучить строение сетчатки и может способствовать расширению клинического применения метода у пациентов с глаукомой [67]. ...
Glaucoma is a chronic optic neuropathy, characterized by ganglion cell loss and specific changes in the optic nerve head (ONH) and retinal nerve fiber layer (RNFL). Early glaucoma detection plays an important role in preventing permanent structural damage development and irreversible vision loss. Glaucoma diagnostics is based on examination of structural damage to the optic nerve and visual functions evaluation. The results of ONH and RNFL clinical evaluation are subjective and can vary to a great extent. As a result, much recent research has been devoted to developing additional objective diagnostic methods, such as the use of confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography for evaluating the OHN status. In order to provide early detection of visual field defects some researchers consider the possibility of replacing standard automated perimetry (SAP) with the selective automated perimetry, that includes the short-wavelength automated perimetry (SWAP) and frequency-doubling technology perimetry (FDT). This article presents a review of modern methods available for glaucoma diagnostics with emphasis on their clinical use.
... As a result, OCT can provide high-resolution images of organs and tissues in a noninvasive manner. This potential has been demonstrated in several biomedical applications including ophthalmology, [3][4][5] cardiology, 6,7 gastroenterology, [8][9][10][11] dermatology, 12 dentistry, 13 urology, 14 and gynecology. 15 In contrast to other forms of noninvasive light microscopy, OCT can image with longer working distances, with improved penetration depth, and without the need for tissue contact. ...
Objectives:
The aging kidney exhibits a progressive decline in renal function with characteristic histopathologic changes and is a risk factor for renal transplant. However, the degree to which the kidney exhibits this decline depends on several factors that vary from one individual to the next. Optical coherence tomography is an evolving noninvasive imaging technology that has recently been used to evaluate acute tubular necrosis of living-human donor kidneys before their transplant. With the increasing use of kidneys from older individuals, it is important to determine whether optical coherence tomography also can distinguish the histopathology associated with aging.
Materials and methods:
In this investigation, we used Munich-Wistar rats to evaluate the ability of optical coherence tomography to detect histopathologic changes associated with aging. Optical coherence tomography observations were correlated with renal function and conventional light microscopic evaluation of these same kidneys.
Results:
With the onset of severe proteinuria at 10 to 12 months of age, optical coherence tomography revealed tubular necrosis/atrophy, interstitial fibrosis, tubular dilation, and glomerulosclerosis. With a further deterioration in kidney function at 16 to 18 months of age (as indicated by rising creatinine levels), optical coherence tomography revealed more extensive interstitial fibrosis and tubular atrophy, increased tubular dilation with cyst formation and more sclerotic glomeruli.
Conclusions:
The foregoing observations suggest that optical coherence tomography can be used to detect the histopathology of progressive nephropathy associated with aging.
... This method can generate 3D images of the object internal structure such as the retina layers with very high axial resolution (3 -12 μm) (Wojtkowski et al 2004 andWollstein et al 2005;Ko et al 2005;Ţălu et al 2009). ...
This paper presents the history and use of optical coherence tomography (OCT) in ophthalmology.
... The axial and transverse resolutions define the image quality, and are important to access information and diagnose any defect in a corresponding species of interest. Age-related macular degeneration (AMD), retinopathy and glaucoma retinal disease [3][4][5][6] can also be diagnosed with this technology. However, the retinal images obtained with OCT are of low quality due to aberrations in the optical system. ...
Adaptive optics plays an important role in the correction of high-order aberrations to enhance lateral resolution. An OCT system coupled with a programmable phase modulator is designed to verify lateral resolution improvement. The Hamamatsu high-resolution, non-pixelized, optically addressed light modulator (PAL-SLM) PPM X7550 series is used to correct aberrations, utilizing a simple method based on phase information from OCT images. The advantages of this method are its high simplicity and low cost. A raster scanning technique is adopted to scan samples covered with scattering suspension. Metal lines covered with scattering suspension are imaged, and a respective correction is applied to remove the aberration. Results demonstrate an improvement in lateral resolution on metal grid samples.
... (Alencar et al., 2008(Alencar et al., , 2005Sharma et al., 2008;Wollstein et al., 2000;Zangwill et al., 2013;Zangwill et al., 2005) Optical coherence tomography (OCT) enables cross-sectional images of ONH and retinal tissue to be acquired in the living eye and thus quantification of individual retinal layer thicknesses, as well as three-dimensional (3D) visualization and quantification of deeper ONH structures such as the lamina cribrosa (LC). (Inoue et al., 2009;Kagemann et al., 2008;Srinivasan et al., 2008;Strouthidis et al., 2009;Wollstein et al., 2005a) Modern OCT systems provide axial resolution of a few micrometers and the addition of adaptive-optics techniques are able to improve lateral (transverse) resolution to the same level. (Hermann et al., 2004;Kocaoglu et al., 2011;Kocaoglu et al., 2014a;Kocaoglu et al., 2014b;Torti et al., 2009;Zawadzki et al., 2009;Zawadzki et al., 2005;Zhang et al., 2005) These most recent developments hold great promise for helping to elucidate directly from studies performed in clinical settings a more precise understanding of glaucoma risk, the susceptibility of individual eyes and even the sequence of events in glaucoma pathogenesis. ...
The goal of this review is to summarize the most common imaging methods currently applied for in vivo assessment of ocular structure in animal models of experimental glaucoma with an emphasis on translational relevance to clinical studies of the human disease. The most common techniques in current use include optical coherence tomography and scanning laser ophthalmoscopy. In reviewing the application of these and other imaging modalities to study glaucomatous optic neuropathy, this article is organized into three major sections: 1) imaging the optic nerve head, 2) imaging the retinal nerve fiber layer and 3) imaging retinal ganglion cell soma and dendrites. The article concludes with a brief section on possible future directions.
Copyright © 2015. Published by Elsevier Ltd.
... As a result, OCT can provide very high-resolution images of organs and tissues in a non-invasive manner. This potential has been demonstrated in a number of biomedical applications including ophthalmology [13][14][15], cardiology [16,17], gastroenterology [18][19][20][21], dermatology [22], dentistry [23], urology [24] and gynecology [25], among others. In contrast to other forms of non-invasive light microscopy, OCT can image with longer working distances, improved penetration depth and without the need for tissue contact. ...
... Recently, studies showing that many retinal conditions begin with a loss of neuronal connectivity and consequent damage in the RGC/IPL complex (the combined RGC and inner plexiform layers (IPL)) make identifying such changes by OCT an important goal [5,6]. Work in [7] showed that the light scattering properties of retinal layers affected by retinal neural atrophy can be detected by OCT. Therefore, we hypothesise that the texture of light reflections within the RGC/IPL complex can possibly be used for detecting neuronal changes such as those seen in early glaucoma. ...
This paper presents novel pre-processing image enhancement algorithms for retinal optical coherence tomography (OCT). These images contain a large amount of speckle causing them to be grainy and of very low contrast. To make these images valuable for clinical interpretation, we propose a novel method to remove speckle, while preserving useful information contained in each retinal layer. The process starts with multi-scale despeckling based on a dual-tree complex wavelet transform (DT-CWT). We further enhance the OCT image through a smoothing process that uses a novel adaptive-weighted bilateral filter (AWBF). This offers the desirable property of preserving texture within the OCT image layers. The enhanced OCT image is then segmented to extract inner retinal layers that contain useful information for eye research. Our layer segmentation technique is also performed in the DT-CWT domain. Finally we describe an OCT/fundus image registration algorithm which is helpful when two modalities are used together for diagnosis and for information fusion.
... Ultra-high-resolution (UHR) OCT is a new imaging system that uses broadband light sources and has an axial resolution below 5 μm in tissue. It has been used in several clinical and scientific laboratory research purposes such as evaluation of tear fluid dynamics, etiology of contact lens-associated dry eye, contact lens fitting and imaging of corneal structures [67][68][69][70]. The image qualities of these prototype systems are similar to an optical biopsy. ...
Optical coherence tomography (OCT) is the most promising imaging technique used in ophthalmology today. Noninvasive, noncontact and having quick image acquisition makes OCT a requirement in ophthalmology practice. OCT can be used to gain cross-sectional images of the anterior and posterior segment of the eye. In cornea and refractive surgery anterior segment OCT (AS-OCT) is used in presurgical planning and postsurgical evaluation. AS-OCT is especially needed in phakic intraocular lens implantation, laser-assisted in situ keratomileusis enhancement and lamellar keratoplasty. There are also various promising advancements in AS-OCT imaging, such as intraoperative OCT and ultra-high-resolution OCT. These techniques offer new therapeutic and diagnostic options with increased resolution and improved scanning time.
... Recently, evidence has been presented that many retinal conditions first develop as a loss of neuronal connectivity and damage to the RGC/IPL complex (the combined RGC and inner plexiform layers (IPL)) [6]. The work in [7] shows that the light scattering properties of retinal layers, affected by retinal neural atrophy, can be detected by OCT. Therefore, we hypothesise that texture due to light reflections within given retinal layers can be used for detecting glaucoma. ...
This paper describes a new method for automated texture classification for glaucoma detection using high resolution retinal Optical Coherence Tomography (OCT). OCT is a non-invasive technique that produces cross-sectional imagery of ocular tissue. Here, we exploit information from OCT images, specifically the inner retinal layer thickness and speckle patterns, to detect glaucoma. The proposed method relies on support vector machines (SVM), while principal component analysis (PCA) is also employed to improve classification performance. Results show that texture features can improve classification accuracy over what is achieved using only layer thickness as existing methods currently do.
... UHR OCT technology has been investigated in clinical settings to assess its clinical utility. Cross-sectional studies in ~1,000 eyes with different pathologies demonstrated unprecedented visualization of all major intraretinal layers especially the photoreceptor layer [145,[189][190][191][192][193]. All intraretinal layers, especially the inner and outer photoreceptor segment, are significantly better visualized by UHR OCT (see Figure 4). ...
Biomedical optics is a rapidly emerging field for medical imaging and diagnostics. This paper reviews several biomedical optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging. There representative biomedical applications are also discussed here.
... More recently, ultrahigh resolution OCT technology has enabled unprecedented in vivo sub-cellular and inter-retinal visualization. This novel OCT technology has been used in a clinical environment for in vivo cross section imaging of macular pathologies with high axial resolution of 3μm [5]. To date, commercially available ophthalmic OCT systems have been based on 800nm superluminescent diodes (SLDs) because of their lower cost and low noise levels. ...
1mum light sources are attractive for Fourier domain optical coherence tomography (FD-OCT) applications for ophthalmology. A semiconductor multi-quantum well structure has been designed and grown (based on AlGaAs/GaA material) to reach the 1mum wavelength window. A compact packaged high power (> 30mW) and wide-bandwidth (>100nm) superluminescent light emit diode (SLD) is achieved with catastrophic optical damage (COD) threshold higher than 100mW. The 1mum SLDs are suitable for high-resolution FDOCT and SD-OCT applications. A high gain and high Psat 1050nm semiconductor optical amplifier (SOA) is also achieved. The 1050nm SOA is a suitable gain medium for swept light sources for ultra high resolution OCT and are ideal for in vivo retinal imaging of small choroid blood vessels below the highly reflective and absorbing retinal pigment epithelium (RPE).
... Due to the relative transparent optical properties of human eye, ophthalmology is a perfect application for OCT. OCT has shown promising results in structural and functional imaging of posterior segment of the eye (retina, optic nerve head and choroid) [6][7][8][9], anterior segment of the eye (cornea, iris and lens) [10,11] as well as their mechanical properties [12,13] for diagnosis, monitoring and preventing many eye disease such as glaucoma [14], diabetic retinopathy [15] and age-related macular degeneration [16]. ...
In this paper, we propose a super-resolution spectral estimation technique to quantify microvascular hemodynamics using optical microangiography (OMAG) based on optical coherence tomography (OCT). The proposed OMAG technique uses both amplitude and phase information of the OCT signals which makes it sensitive to the axial and transverse flows. The scanning protocol for the proposed method is identical to three-dimensional ultrahigh sensitive OMAG, and is applicable for in vivo measurements. In contrast to the existing capillary flow quantification methods, the proposed method is less sensitive to tissue motion and does not have aliasing problems due fast flow within large blood vessels. This method is analogous to power Doppler in ultrasonography and estimates the number of red blood cells passing through the beam as opposed to the velocity of the particles. The technique is tested both qualitatively and quantitatively by using OMAG to image microcirculation within mouse ear flap in vivo.
... As the technology has been advanced, various high resolution real-time optical techniques and devices have been used for macular sectional imaging, hoping to detect abnormalities before significant loss of vision. New developments in OCT, with resolution under 10 m , include Spectral-domain OCT (SD-OCT), where the mechanical z-scanning of the TDOCT is replaced with spectral analysis, and swept-source OCT (SS-OCT), where the spectral analysis is replaced with wavelength scanning of the light source [6][7][8][9][10][11][12]. An axial resolution of 1-2 m has been reported using a femtosecond laser 8 . ...
An improved digital interference holography (DIH) technique suitable for fundus images is proposed. This technique incorporates a dispersion compensation algorithm to compensate for the unknown axial length of the eye. Using this instrument we acquired successfully tomographic fundus images in human eye with narrow axial resolution less than 5mum. The optic nerve head together with the surrounding retinal vasculature were constructed. We were able to quantify a depth of 84mum between the retinal fiber and the retinal pigmented epithelium layers. DIH provides high resolution 3D information which could potentially aid in guiding glaucoma diagnosis and treatment.
... Optical coherence tomography (OCT) functions as a type of optical non-invasive non-contact diagnostic technology, offering in vivo imaging of the human retina with unprecedented sensitivity and axial resolution (Drexler et al., 2001;Wollstein et al., 2005). In terms of speed and sensitivity, Fourier-domain OCT (FD-OCT) is superior to the time-domain OCT (TD-OCT) (Leitgeb et al., 2003), and hence there is a tendency for FD-OCT to replace TD-OCT. ...
Fourier-domain rapid scanning optical delay line (RSOD) was introduced for phase modulation and depth scanning in a time-domain
optical coherence tomography (TD-OCT) system. Investigation of parameter optimization of RSOD was conducted. Experiments for
RSOD characterization at different parameters of the groove pitch, focal length, galvomirror size, etc. were performed. By
implementing the optimized RSOD in our established TD-OCT system with a broadband light source centered at 840 nm with 50
nm bandwidth, in vivo retina imaging of a rabbit was presented, demonstrating the feasibility of high-quality TD-OCT imaging
using an RSOD-based phase modulator.
Since the introduction of commercial optical coherence tomography (OCT) systems, the ophthalmic imaging modality has rapidly expanded and it has since changed the paradigm of visualization of the retina and revolutionized the management and diagnosis of neuro-retinal diseases, including glaucoma. OCT remains a dynamic and evolving imaging modality, growing from time-domain OCT to the improved spectral-domain OCT, adapting novel image analysis and processing methods, and onto the newer swept-source OCT and the implementation of adaptive optics (AO) into OCT. The incorporation of AO into ophthalmic imaging modalities has enhanced OCT by improving image resolution and quality, particularly in the posterior segment of the eye. Although OCT previously captured in-vivo cross-sectional images with unparalleled high resolution in the axial direction, monochromatic aberrations of the eye limit transverse or lateral resolution to about 15–20 μm and reduce overall image quality. In pairing AO technology with OCT, it is now possible to obtain diffraction-limited resolution images of the optic nerve head and retina in three-dimensions, increasing resolution down to a theoretical 3 μm³. It is now possible to visualize discrete structures within the posterior eye, such as photoreceptors, retinal nerve fiber layer bundles, the lamina cribrosa, and other structures relevant to glaucoma. Despite its limitations and barriers to widespread commercialization, the expanding role of AO in OCT is propelling this technology into clinical trials and onto becoming an invaluable modality in the clinician's arsenal.
Purpose: To investigate the influence of posterior capsular opacification (PCO) and Nd:YAG laser capsulotomy on central macular thickness (CMT) and signal strength (SS) measured with Stratus optical coherence tomography (OCT). Materials and Methods: In this prospective interventional case series, 72 eyes of 69 patients with PCO were enrolled for the study. A complete ophthalmologic examination and measurements of SS and CMT by Stratus OCT before and after Nd:YAG capsulotomy were performed. The patients were classified in two different forms based on PCO score and signal strength (SS) obtained with prelaser OCT scans. Results: The preoperative and postoperative mean CMT were 155±27 ìm and 163±33 ìm, respectively (p=0.019). Mean preoperative SS was 5.6±1.3 which improved to 8.6±1.5 postoperatively (p<0.001). Eyes with preoperative SS less than 6 had significant difierence between prelaser and postlaser CMT (p<0.05). Also, there was a significant increase after laser capsulotomy in CMT in patients with preoperative PCO grade more than 2 (p<0.05). Conclusion: CMT and SS measured by Stratus OCT is influenced by PCO. CMT may be underestimated in eyes with PCO grade more than 2 or in eyes with preoperative SS less than 6.
In this chapter, the emerging applications for OCT in real-time, intraoperative diagnostic imaging and visualization of surgical maneuvers is reviewed, focusing on OCT guidance and evaluation of ophthalmic microsurgery. Three different approaches under development for intraoperative OCT are reviewed, including hand-held OCT imaging during pauses in surgery, microscope-integrated OCT for real-time surgical evaluation and guidance, and intraocular forward-imaging OCT probes. Intraoperative OCT provides surgeons with depth, cross-sectional or three-dimensional visualization in addition to the conventional en face surgical field of view for anterior segment, lens and vitreoretinal surgeries, and may facilitate evaluation of surgical procedures. Such advantages may enable OCT as a vital tool during surgical intervention in addition to its well-known diagnostic capabilities. © Springer-Verlag Berlin Heidelberg 2008 and Springer International Publishing Switzerland 2015.
Aim:
To evaluate the effect of misalignment on the measurements of retinal nerve fiber layer (RNFL) by spectral-domain optical coherence tomography (OCT).
Methods:
A total of 42 eyes from 21 healthy young subjects underwent RNFL measurements with RTVue spectral-domain OCT (Optovue Inc., Fremont, California, USA). Two baseline measurements with perfectly aligned central circle to the borders of the optic nerve and four misaligned measurements which were misaligned towards to four quadrants were taken. The differences in RNFL between the baseline and misaligned measurements were analyzed with a new algorithm called Helvacioglu reproducibility index (HRI) which is designed to measure the reproducibility of the scans by evaluating the RNFL changes in the four main quadrants.
Results:
The average RNFL scores of the first two baseline measurements have good correlation (c=0.930) and good reproducibility scores (0.15±0.07). Superior misaligned measurements had significantly lower superior quadrant score and higher inferior quadrant score, similar nasal and little higher temporal scores (P1, P2<0.001, P3=0.553, P4=0.001). Inferior misaligned measurements had significantly higher superior quadrant score and lower inferior quadrant score with similar temporal and little lower nasal scores (P1, P2<0.001, P3=0.315, P4=0.016). Nasal misaligned measurements had significantly higher temporal quadrant score and lower nasal quadrant score with little lower superior and inferior scores (P1, P2, P4<0.001, P3=0.005). Temporal misaligned measurements had significantly higher nasal quadrant score and lower temporal quadrant score with similar superior and little higher inferior scores (P1, P2<0.001, P3=0.943, P4=0.001).
Conclusion:
Good alignment of the central circle to the borders of optic nerve is crucial to have correct and repeatable RNFL measurements. Misalignment to a quadrant resulted in falsely low readings at that quadrant and falsely high readings at the opposite quadrant.
In this chapter, we review the technology and applications of needle probes for optical coherence tomography (OCT). Needle probes are miniaturized fiber-optic probes that can be mounted inside hypodermic needles, allowing them to be inserted deep into the body during OCT imaging. This overcomes the very limited imaging depth of OCT of only 2–3 mm in biological tissue, enabling access to deep–tissue locations that are beyond the reach of free–space optical scan heads or catheters. This chapter provides an in–depth review of the current state–of–the art in needle probe technology, including optical design and fabrication, scan mechanisms (including three–dimensional scanning), and integration into OCT systems. It also provides an overview of emerging applications of this fascinating new imaging tool in areas such as cancer diagnosis, pulmonary imaging, imaging of the eye and imaging of the brain. Finally, two case studies are presented, illustrating needle–based OCT imaging in breast cancer and lungs. © Springer-Verlag Berlin Heidelberg 2008 and Springer International Publishing Switzerland 2015.
Optical coherence tomography (OCT) is an imaging modality that can generate micrometer resolution, two–dimensional cross–sectional images and three–dimensional volumetric data on the internal structure of optically scattering and reflective tissues and materials. The development of Fourier–domain detection enabled a breakthrough in OCT imaging sensitivity and speed, and the newest generation of OCT is based on wavelength swept light sources (Swept source /Fourier–domain OCT; SS–OCT). We describe high imaging speed and long depth range SS–OCT with an emphasis on SS–OCT technology using MEMS–tunable vertical cavity surface–emitting lasers operating at 1,050 nm and 1,310 nm. We also review representative applications using adjustable high speed and long range SS–OCT including ophthalmic imaging (retinal, anterior segment and full eye length imaging), optical coherence microscopy, endoscopy, ocular biometry, metrology, profilometry and non–destructive material evaluation. © Springer-Verlag Berlin Heidelberg 2008 and Springer International Publishing Switzerland 2015.
End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or “ATN”) induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation. © Springer-Verlag Berlin Heidelberg 2008 and Springer International Publishing Switzerland 2015.
The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of “optical biopsy”, providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.
Based on low-coherence interferometry, a hybrid optical coherence tomography (OCT) system has been built. It coupled time-domain OCT (TD-OCT) and Fourier-domain OCT (FD-OCT) into one system. TD-OCT can take the advantage of a large axial scan range while FD-OCT has superior performance in fast imaging as no axial scan is needed. The two imaging modalities shared a broad bandwidth light source with a centre wavelength of 1550 nm, which is less scattering and can give better penetration depth in the polymer-based material than the shorter wavelength used for biomedical applications. 2D translation stages were incorporated in the system to make cross-sectional and volume imaging available. It can provide larger scan range as well as less image distortion compared with galvo scanners. Finally, we reported on successfully characterized specimens such as polymer coatings and glass-fibre composites. The cross-sectional and volumetric images obtained clearly show the microstructure of the materials. The thickness as well as the defects, e.g. microcrack and delamination can be determined.
In order to prevent major damage to the cardiovascular system, it is of
vital importance to monitor molecular changes in vascular tissues.
Symptoms of cardiovascular diseases frequently do not manifest
themselves until it is too late for effective treatment; therefore,
methodologies that facilitate early detection are crucial.
Atherosclerosis is a major underlying cause of many cardiovascular
diseases; thus, elucidating the mechanisms of atherosclerosis is
essential for shedding light on the initiation and progression of
atherosclerotic lesions. Atherosclerosis includes an inflammatory
process in arterial tissue that involves subintimal accumulation of
lipoproteins particles, mainly low-density lipoprotein and
lipoprotein[a]. Measurement of the permeation rates of these particles
should extend our understanding of this disease and lead to methods for
early disease detection. Over the past decade, optical coherence
tomography (OCT) has become widely used in research and, more recently,
has been used as a high-resolution imaging technique, capable of
quantifying molecular permeability in biological tissues. OCT enables
highly sensitive and accurate measurement of permeability rates of
molecules and particles in vascular tissue. This sensitivity is due to
high in-depth and transverse resolution along with a high dynamic range.
In this chapter, we discuss the permeation of molecules and particles
through human and animal vascular tissue.
The eye is essentially transparent, transmitting light with only minimal optical attenuation and scattering, providing easy
optical access to the anterior segment as well as the retina. For this reason, ophthalmic and especially retinal imaging has
been not only the first, but also most successful clinical application for optical coherence tomography (OCT). This chapter
focuses on the development of OCT technology for retinal imaging. OCT has significantly improved the potential for early diagnosis,
understanding of retinal disease pathogenesis as well as monitoring disease progression and response to therapy. Development
of ultrabroad bandwidth light sources and high speed detection techniques have enabled significant improvements in ophthalmic
OCT imaging performance, demonstrating the potential of three-dimensional, ultrahigh resolution OCT (3D UHR OCT) to perform
noninvasive optical biopsy of the living human retina, i.e., the in vivo visualization of microstructural, intraretinal morphology in situ approaching the resolution of conventional histopathology.
Significant improvements in axial resolution and speed not only enable three-dimensional rendering of retinal volumes, but also high definition, 2D tomograms, topographic
thickness maps of all major intraretinal layers as well as volumetric quantification of pathologic intraretinal changes. These
advances in OCT technology have also been successfully applied in several animal models of retinal pathologies. The development
of light sources emitting at alternative wavelengths, e.g., around ∼l,050 nm, not only enabled three-dimensional OCT imaging
with enhanced choroidal visualization, but also improved OCT performance in cataract patients because of reduced scattering
losses in this wavelength region. Adaptive optics using deformable mirror technology, with unique high stroke to correct higher
order ocular aberrations, with specially designed optics to compensate chromatic aberration of the human eye, in combination
with 3D UHR OCT, recently enabled in vivo cellular resolution retinal imaging.
Optical coherence tomography (OCT) is a recently established imaging technique to describe different information about the internal structures of an object and to image various aspects of biological tissues. OCT image segmentation is mostly introduced on retinal OCT to localize the intra-retinal boundaries. Here, we review some of the important image segmentation methods for processing retinal OCT images. We may classify the OCT segmentation approaches into five distinct groups according to the image domain subjected to the segmentation algorithm. Current researches in OCT segmentation are mostly based on improving the accuracy and precision, and on reducing the required processing time. There is no doubt that current 3-D imaging modalities are now moving the research projects toward volume segmentation along with 3-D rendering and visualization. It is also important to develop robust methods capable of dealing with pathologic cases in OCT imaging.
We present three dimensional (3D) imaging of macular diseases and glaucoma with high speed, Fourier domain optical coherence tomography (FD-OCT). Our FD-OCT system allows video rate cross-sectional imaging with 98 dB sensitivity and 4.3 mum depth-resolution in tissue. This performance results in high contrast sectional images that enhance visualization of fine retinal layers including external limiting membrane and of deep structure such as the choroid and optic nerve. Volume rendering of 3D OCT data set taken for 3.5 seconds provides realistic 3D images of macular, optic disc and their pathologic changes. This manuscript will show the methods for three dimensional FD-OCT including a raster scanning protocol for volume rendering and cancellation of the motion artifact of eye balls, and the application of the high contrast three dimensional OCT imaging to macular diseases and glaucoma in clinical examination.
Optical Coherence Tomography is a powerful tool for diagnostic imaging of the ocular posterior chamber. Recent advances in OCT technology have facilitated acquisition of high resolution volumetric images of the retina and optic nerve head. In this report, we investigate optic nerve head imaging in humans using a home-built laboratory grade OCT system in the 800nm wavelength region. We also introduce the development of a computational model of the optic nerve head morphology in order to study physiological changes which may be associated with elevated intra-ocular pressure.
Optical coherence tomography (OCT) is a new non-invasive method to investigate biological tissue. It is particularly suitable for examination of human vocal folds due to its optical penetration depth of around 1.5mm. We developed a modified laryngoscope with an integrated OCT beam path for non-contact imaging of human vocal folds. In vivo studies on awake patients show that synchronous OCT and conventional laryngoscopy works well. For enabling the choice of the appropriate OCT encoding technique for OCT-based laryngoscopy measurements on simulated vibrations were performed with time domain (TD) and fourier domain (FD) OCT devices. The results show that TD-OCT is much more suitable for non-contact imaging than FD-OCT. In studies on porcine and monkey vocal folds the performance of femtosecond laser tissue ablation was analyzed with OCT monitoring. Histopathological sections could be well correlated with the OCT images. In future applications a combined system that uses one femtosecond laser as light source for tissue ablation as well as for OCT imaging is conceivable. In conclusion, OCT can be used as a pre-, intra- and post-operative diagnostic instrument for analysing the vocal fold structure down to the vocalis muscle allowing a more precise indication for potential subsequent invasive procedures. We suggest that OCT should be used in addition to established examination methods for diagnostic evaluation of vocal fold malignancies and functional alterations.
Optical coherence tomography(OCT) is a high resolution imaging system which can image the cross section of microscopic organs in a living tissue with about 1?m resolution. In this paper, we implement OCT system and acquire 2-D images of rat eye and human molar samples especially in the field of opthalmology and dentistry. In terms of 2-D images, we reconstruct 3-D OCT images which give us another inner structural information of target objects. OPEN-GL reduces the 3-D processing time 10 times less than MATLAB.
We used digital interference holography (DIH) for in vitro imaging of human optic nerve head and retina. Samples of peripheral retina, macula, and optic nerve head from two formaldehyde-preserved human eyes were dissected and mounted onto slides. Holograms were captured by a monochrome CCD camera (Sony XC-ST50, with 780 x 640 pixels and pixel size of similar to 9 mu m). Light source was a solid-state pumped dye laser with tunable wavelength range of 560-605 nm. Using about 50 wavelengths in this band, holograms were obtained and numerically reconstructed using custom software based on NI LabView. Tomographic images were produced by superposition of holograms. Holograms of all tissue samples were obtained with a signal-to-noise ratio of approximately 50 dB. Optic nerve head characteristics ( shape, diameter, cup depth, and cup width) were quantified with a few micron resolution (4.06-4.8 mu m). Multiple layers were distinguishable in cross-sectional images of the macula. To our knowledge, this is the first report of DIH use to image human macular and optic nerve tissue. DIH has the potential to become a useful tool for researchers and clinicians in the diagnosis and treatment of many ocular diseases, including glaucoma and a variety of macular diseases.
Glaucomatous damage of the macular area is varied: it can be sector-based or diffused, possibly with peripheral damage. The author has developed an original manual method for mapping the retinal ganglion layer as well as a 1200 μm circular section around the fovea, using a Topcon 3D OCT 1000, which reveals the glaucomatous structural damage of the macula. Several examples show that the most reliable tool for early examination of the condition of the macula is the OCT of the ganglion cell complex at the perifoveolar raised edge. It is much more reliable than the papillary OCT of optical fibers, which does not give significant information on macular damage, and visual field examination, which is often too late. The role of the ganglion cell complex OCT is specified: to confirm visual field defects, if they do exist, and more importantly, to anticipate them; to establish a specified relation between structure and function. Although OCT of the ganglion cell complex is useful in all cases to estimate the severity of glaucoma, this study shows that it has become essential in cases of isolated macular damage. This is the only examination that can detect this in a timely manner and prevent the appearance of a nonreversible juxtafoveolar scotoma and the risk of blindness.
This program, entitled Advanced Technologies for Structural and Functional Optical Coherence Tomography, is a collaborative effort between investigators at the Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics; Dr. David Boas, Associate Professor in Radiology, Harvard Medical School at the Massachusetts General Hospital, Martinos Center for Biomedical Imaging; and Dr. Jay Duker, Director, New England Eye Center, Professor and Chair of Ophthalmology, Tufts University School of Medicine. The objective of this program is to develop and apply advanced optical coherence tomography (OCT) technologies for ultrahigh resolution and functional imaging in biomedical applications.
Purpose:
To measure the inner and outer retinal thicknesses on spectral-domain optical coherence tomography (SD-OCT) and evaluate their association with logMAR after vitrectomy for diabetic macular edema (DME).
Methods:
In this retrospective case series, there were 55 consecutive eyes with DME for which vitrectomy was performed. The total retinal thickness, the inner thickness (from the innermost of the retina to the inner nuclear layer), and the outer thickness (from the outer plexiform layer to the retinal pigment epithelium) in the parafoveal subfields were measured manually, and the association with logMAR was evaluated.
Results:
The total retinal thicknesses in the central, nasal, and inferior subfields were significantly (r = 0.37, P = 0.005; r = 0.29, P = 0.032; r = 0.33, P = 0.015, respectively) associated with the baseline logMAR; no subfield thickness was correlated with the logMAR at the final visit. However, segmentational analysis showed that the outer retinal thickness of the temporal subfield was associated with disruption of the junction between the inner and outer segments at the fovea (P = 0.021 and P = 0.005) and negatively correlated with the logMAR (r = -0.37, P = 0.006 and r = -0.28, P = 0.042) at the 6-month and final visit. The inner thickness of the nasal subfield did not change after vitrectomy compared with the other subfields and the outer thickness of all subfields in the parafoveal area; the baseline nasal total thickness was correlated most significantly with the logMAR (r = 0.40, P = 0.002 and r = 0.37, P = 0.006) at the 6-month and final visits.
Conclusions:
Segmentational analysis provided useful information for considering the prognosis and pathogenesis after vitrectomy for DME.
Commercially-available optical coherence tomography (OCT) systems (e.g., Stratus OCT-3) only segment and provide thickness measurements for the total retina on scans of the macula. Since each intraretinal layer may be affected differently by disease, it is desirable to quantify the properties of each layer separately. Thus, we have developed an automated segmentation approach for the separation of the retina on (anisotropic) 3-D macular OCT scans into five layers. Each macular series consisted of six linear radial scans centered at the fovea. Repeated series (up to six, when available) were acquired for each eye and were first registered and averaged together, resulting in a composite image for each angular location. The six surfaces defining the five layers were then found on each 3-D composite image series by transforming the segmentation task into that of finding a minimum-cost closed set in a geometric graph constructed from edge/regional information and a priori-determined surface smoothness and interaction constraints. The method was applied to the macular OCT scans of 12 patients with unilateral anterior ischemic optic neuropathy (corresponding to 24 3-D composite image series). The boundaries were independently defined by two human experts on one raw scan of each eye. Using the average of the experts' tracings as a reference standard resulted in an overall mean unsigned border positioning error of 6.7 ± 4.0 µm, with five of the six surfaces showing significantly lower mean errors than those computed between the two observers (p < 0.05, pixel size of 50 × 2 µm).
Optical coherence tomography (OCT) is a new imaging modality that has increasingly become an indispensable tool in clinical practice for the diagnosis and management of ocular diseases involving the macula, optic nerve and anterior segment. The instrument is an advanced imaging technique that provides unprecedented high resolution and cross-sectional tomographic images of the ocular microstructure in situ, and in real time. Since its introduction about four years ago, a multitude of advantages has made OCT an essential instrument in ophthalmic imaging. The technique has fast image acquisition speed and non-contact, non-invasive applicability, allowing a non-excisional ‘optical biopsy’ to be performed. The purpose of this paper is to provide an evidence-based review of the increasing role of OCT in the diagnosis and management of ocular disorders, particularly in age-related macular degeneration, diabetic macular oedema, macular hole, epiretinal membrane and glaucoma. Being one of the first users of OCT in Australia, our clinical experiences will be highlighted and clinical examples of various conditions will be presented to provide an overview of the immense implications of OCT in practice. The latest developments of the OCT revolution, in relation to combining OCT with fundus photography and scanning laser ophthalmoscopy, will also be described. New developments of three-dimensional visualisation of tissue morphology with future models of ultra-high speed, ultra-high resolution OCT may further enhance the early diagnosis, monitoring of disease progression and assessment of treatment efficacy, facilitated by this powerful technology.
Since its invention in the late 1980s [1–4] and early 1990s [5–7], the original idea of optical coherence tomography (OCT)
was to enable noninvasive optical biopsy, i.e., the in situ imaging of tissue microstructure with a resolution approaching
that of histology, but without the need for tissue excision and postprocessing. An important advance toward this goal was
the introduction of ultrahigh resolution OCT (UHR OCT). By improving axial OCT resolution by one order of magnitude from the
10–15 μm to the submicrometer region [8–11], UHR OCT enables superior visualization of tissue microstructure, including all
major intraretinal layers in ophthalmic applications as well as cellular resolution OCT imaging in nontransparent tissue.
This chapter reviews the state-of-the-art technology that enables UHR OCT covering the entire wavelength region from 500 to
1,600 nm and discusses fundamental limitations of OCT image resolution.
Optical coherence tomography captures a major role in clinical assessment in eye care. Innovative hardware and software improvements in the technology would further enhance its usefulness. In this review, we present several promising initiatives currently in development or early phase of assessment that we expect to have a future impact on optical coherence tomography.
Optical coherence tomography (OCT) is a three- dimensional optical imaging technique that can be used to identify areas of early caries formation in dental enamel. The OCT signal at 850 nm back-reflected from sound enamel is attenuated stronger than the signal back-reflected from demineralized regions. To quantify this observation, the OCT signal as a function of depth into the enamel (also known as the A-scan intensity), the histogram of the A-scan intensities and three summary parameters derived from the A-scan are defined and their diagnostic potential compared. A total of 754 OCT A-scans were analyzed. The three summary parameters derived from the A-scans, the OCT attenuation coefficient as well as the mean and standard deviation of the lognormal fit to the histogram of the A-scan ensemble show statistically significant differences (p < 0.01) when comparing parameters from sound enamel and caries. Furthermore, these parameters only show a modest correlation. Based on the area under the curve (AUC) of the receiver operating characteristics (ROC) plot, the OCT attenuation coefficient shows higher discriminatory capacity (AUC = 0.98) compared to the parameters derived from the lognormal fit to the histogram of the A-scan. However, direct analysis of the A-scans or the histogram of A-scan intensities using linear support vector machine classification shows diagnostic discrimination (AUC = 0.96) comparable to that achieved using the attenuation coefficient. These findings suggest that either direct analysis of the A-scan, its intensity histogram or the attenuation coefficient derived from the descending slope of the OCT A-scan have high capacity to discriminate between regions of caries and sound enamel.
To establish normative values for Heidelberg Retina Tomograph (HRT3) variables and to develop HRT3-based criteria for glaucomatous optic neuropathy for epidemiological research in a white population.
Consecutive participants in the Rotterdam Study were examined with HRT and simultaneous stereoscopic fundus photography (ImageNet) in addition to other ophthalmic examinations including intraocular pressure (IOP) measurements and perimetry. Normative values for all HRT3 variables were determined in participants who met all the following criteria: no glaucomatous visual field loss (GVFL), an IOP of 21mmHg or less, no IOP lowering treatment, and a negative family history of glaucoma. Sensitivity was determined in participants with glaucomatous visual field loss at a fixed high specificity of 97.5% - a value commonly used in population-based epidemiology.
A total of 2516 participants were included in this study of whom 66 had glaucomatous visual field loss in at least one eye and 1680 fulfilled the criteria for contributing to the normative values. The HRT3 linear cup-disc ratio (LCDR) variable, adjusted for disc area, showed the highest sensitivity, 35%, at the required specificity of 97.5%. The 97.5th percentile of the LCDR was 0.67 for small discs (up to 1.5 mm(2)), 0.71 [corrected] for medium-sized discs and 0.76 [corrected] for large discs (above 2.0 mm(2)).The HRT3 Glaucoma Probability Score and previously published linear discriminant functions showed a lower sensitivity than LCDR at this specificity.
At the high specificity of 97.5% as is commonly used in population-based epidemiology, the sensitivity of the HRT3 is low - albeit not lower than that of the vertical cup-disc ratio as assessed with simultaneous stereoscopic fundus photography and analyzed with the ImageNet software. The LCDR variable, stratified for disc area, seems to be the most suitable variable to develop criteria for glaucomatous optic neuropathy for epidemiological purposes.
A technique called optical coherence tomography (OCT) has been developed
for noninvasive cross-sectional imaging in biological systems. OCT uses
low-coherence interferometry to produce a two-dimensional image of
optical scattering from internal tissue microstructures in a way that is
analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and
lateral spatial resolutions of a few micrometers and can detect
reflected signals as small as ~10-10 of the incident optical
power. Tomographic imaging is demonstrated in vitro in the peripapillary
area of the retina and in the coronary artery, two clinically relevant
examples that are representative of transparent and turbid media,
respectively.
Here we present new technology for optical coherence tomography (OCT) that enables ultrahigh-resolution, non-invasive in vivo ophthalmologic imaging of retinal and corneal morphology with an axial resolution of 2–3 μm. This resolution represents a significant advance in performance over the 10–15-μm resolution currently available in ophthalmic OCT systems and, to our knowledge, is the highest resolution for in vivo ophthalmologic imaging achieved to date. This resolution enables in vivo visualization of intraretinal and intra-corneal architectural morphology that had previously only been possible with histopathology. We demonstrate image processing and segmentation techniques for automatic identification and quantification of retinal morphology. Ultrahigh-resolution OCT promises to enhance early diagnosis and objective measurement for tracking progression of ocular diseases, as well as monitoring the efficacy of therapy.
Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study.
To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG.
A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less.
The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee.
During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication.
Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.
To demonstrate a new generation of ophthalmic optical coherence tomography (OCT) technology with unprecedented axial resolution for enhanced imaging of intraretinal microstructures and to investigate its clinical feasibility to visualize intraretinal morphology of macular pathology.
A clinically viable ultrahigh-resolution ophthalmic OCT system was developed and used in clinical imaging for the first time. Fifty-six eyes of 40 selected patients with different macular diseases including macular hole, macular edema, age-related macular degeneration, central serous chorioretinopathy, epiretinal membranes, and detachment of pigment epithelium and sensory retina were included.
Ultrahigh-resolution tomograms visualizing intraretinal morphologic features in different retinal diseases.
An axial image resolution of approximately 3 micro m was achieved in the eyes examined, nearly 2 orders of magnitude better than conventional ophthalmic ultrasound. Ultrahigh-resolution OCT images provided additional diagnostically important information on intraretinal morphologic features that could not have been obtained by standard techniques.
Ultrahigh-resolution ophthalmic OCT enables unprecedented visualization of intraretinal morphologic features and therefore has the potential to contribute to a better understanding of ocular pathogenesis, as well as to enhance the sensitivity and specificity for early ophthalmic diagnosis and to monitor the efficacy of therapy. This study establishes a baseline for the interpretation of ultrahigh-resolution ophthalmic OCT imaging of macular diseases.
Ultrahigh-resolution optical coherence tomography (OCT) by use of state of the art broad-bandwidth femtosecond laser technology is demonstrated and applied to in vivo subcellular imaging. Imaging is performed with a Kerr-lens mode-locked Ti:sapphire laser with double-chirped mirrors that emits sub-two-cycle pulses with bandwidths of up to 350 nm, centered at 800 nm. Longitudinal resolutions of ~1mum and transverse resolution of 3mum, with a 110-dB dynamic range, are achieved in biological tissue. To overcome depth-of-field limitations we perform zone focusing and image fusion to construct a tomogram with high transverse resolution throughout the image depth. To our knowledge this is the highest longitudinal resolution demonstrated to date for in vivo OCT imaging.
Optical coherence tomography (OCT) enables noninvasive, noncontact, cross-sectional imaging of the eye. OCT is a safe, easy to perform, objective, and reproducible means of quantitatively measuring such parameters as retinal thickness (for macular edema of various etiologies) and nerve fiber layer thickness (for the diagnosis and monitoring of glaucomatous damage). OCT is unique in providing detailed scans of anatomical disorders such as macular hole, epiretinal membrane, and vitreomacular traction. OCT also has the potential for anterior segment imaging, including corneal thickness, anterior chamber depth measurements, and lens opacity grading.
Background
Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study.Objective
To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG.Methods
A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less.Main Outcome Measures
The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee.Results
During the course of the study, the mean ± SD reduction in IOP in the medication group was 22.5% ± 9.9%. The IOP declined by 4.0%± 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication.Conclusions
Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.
• The number and distribution of human optic nerve axons were compared with clinical measurements available in the same eyes, including visual acuity, disc appearance, and visual field studies. Definite loss of axons occurs prior to reproducible visual field defects in some patients suspected of having glaucoma. In glaucoma, the superior and inferior poles of the nerve lose nerve fibers at a selectively greater rate, leading to an hourglass-shaped atrophy. Cavernous degeneration of the retrobulbar optic nerve is rarely observed in chronic glaucoma. The pattern of atrophy in examples of toxic amblyopia, ischemic optic neuropathy, and chronic papilledema differs from that of glaucoma, suggesting different mechanisms of damage in these conditions.
• Standardized perimetry and nerve fiber layer and color fundus photography were performed annually on 1344 eyes with elevated intraocular pressures. In 83 eyes, glaucomatous field defects developed that met rigid criteria on manual kinetic and suprathreshold static perimetry. Individual nerve fiber layer photographs were read by two masked observers. The more sensitive of the two identified nerve fiber layer defects in 88% of readable photographs at the time field loss first occurred; 60% (6/10) of eyes already had nerve fiber layer defects 6 years before field loss. In contrast, the nerve fiber layer was considered abnormal in only 11% (3/27) of normal eyes and 26% (84/327) of hypertensive eyes. The location of nerve fiber layer and field defects closely corresponded, but nerve fiber layer loss was generally more widespread. Examiner experience and severity of optic nerve damage influenced results. Mild focal defects were more readily recognized than more severe diffuse atrophy. Nerve fiber layer defects expanded with time, often by the development and coalescence of adjacent areas of damage.
Objective: To compare the cross-sectional images of primate retinal morphology obtained by optical coherence tomography (OCT) with light microscopy to determine the retinal components represented in OCT images. Methods: Laser pulses were delivered to the retina to create small marker lesions in a Macaca mulatta . These lesions were used to align in vivo OCT scans and ex vivum histologic cross sections for image comparison. Results: The OCT images demonstrated reproducible patterns of retinal morphology that corresponded to the location of retinal layers seen on light microscopic overlays. Layers of relative high reflectivity corresponded to horizontally aligned retinal components such as the nerve fiber layer and plexiform layers, as well as to the retinal pigment epithelium and choroid. In contrast, the nuclear layers and the photoreceptor inner and outer segments demonstrated relative low reflectivity by OCT. Conclusions: Retinal morphology and macular OCT imaging correlate well, with alignment of areas of high and low reflectivity to specific retinal and choroidal elements. Resolution of retinal structures by OCT depends on the contrast in relative reflectivity of adjacent structures. Use of this tool will enable expanded study of retinal morphology, both normal and pathologic, as it evolves in vivo.
Objective:
To detect characteristics of persons with ocular hypertension that are associated with a higher risk of future glaucomatous field loss.Methods:
Annual examinations of the optic disc, nerve fiber layer, and visual field in 647 persons with bilateral intraocular pressure higher than 21 mm Hg and initially normal visual field test results with the Goldmann perimeter.Results:
Sixty-eight persons developed a field defect on two consecutive Goldmann visual field tests in at least one eye, while 579 others retained normal fields. Moderate or severe nerve fiber layer atrophy at baseline was associated with a seven to eight times greater risk of development of visual field loss. Attributes that were significantly associated with the incidence of field loss ineluded older age, larger cup-disc ratio, smaller rim—disc area ratio, larger cup asymmetry, presence of disc crescent, and higher intraocular pressure. Characteristics found not to be associated with incidence were gender, race, hypertension, diabetes, refractive error, family history of glaucoma, smoking or alcohol drinking history, and disc area.Conclusions:
Increasing nerve fiber layer atrophy judged by a semiquantitative grading system was associated with increasing risk of development of visual field loss among persons with ocular hypertension. The relationship of the development of field loss to race, myopia, family history of glaucoma, and medical history are more complex than has been presumed.
Summary form only given. Over the past few years, optical coherence tomography (OCT) has been extensively evaluated as a possible diagnostic tool in a variety of medical fields, demonstrating its feasibility as a high speed, non-invasive, high resolution in vivo and in situ imaging modality with the possibility of being easily implemented into different medical diagnostic instruments; e.g., catheters, microscopes, as well as ophthalmoscopes. We demonstrate an ultrahigh, subcellular level resolution OCT system for in vivo and in vitro imaging. It uses a Kerr-lens mode-locked Ti:sapphire laser that emits pulses as short as 5.5 fs with bandwidths up to 350 nm centred at 800 nm with an average power of up to 150 mW, due to broadband controlled dispersion and high reflectivity enabled by low-dispersion prisms and special designed double chirped mirrors. The output spectrum can be shaped by changing the prisms insertions (P1, P2) or by alteration of the prism separation. Appropriate single mode fibers, special broad bandwidth, wavelength flattened 3 dB fiber coupler, as well as special achromatic and catadioptric objectives are used to maintain this ultrabroad bandwidth to achieve subcellular level resolution
Optical coherence tomography (OCT) is a new, noninvasive, high resolution, cross-sectional imaging technology. OCT is useful for both quantitative and qualitative analysis of retinal disease and glaucoma. In retinal disease, OCT can be used in the diagnosis and monitoring of macular holes, macular edema, age-related macular degeneration, and other retinal pathologies. OCT also can be used in glaucoma diagnostics, providing objective, quantitative measurement of nerve fiber layer thickness.
Stereoscopic fundus photographs of 17 abnormal eyes, taken in known temporal relationship to the onset of glaucomatous visual field loss, and 206 eyes of age- and race-matched controls were examined in randomized masked fashion. Width of the narrowest remaining disc rim, size of the vertical and horizontal physical cups, contour of the temporal and nasal slopes (vertical ovalness), and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were all useful for distinguishing patients with impending or established visual field loss. None, however, was as effective as defects in the nerve fiber layer, the only parameter displaying sufficient promise as a clinical screening tool to warrant initiation of large-scale prospective evaluation.
Serial stereoscopic fundus photographs taken in known relationship to the onset of glaucomatous visual field loss on 12 eyes were intermixed with those from 206 age- and race-matched controls and analyzed in randomized masked fashion. Progressive changes in the size, shape, or contour of the disc, and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were readily apparent by the time of onset of glaucomatous field loss in all but two abnormal eyes (one case). In the latter instance, direct comparison of stereophotos indicated progressive pallor of the remaining disc tissue. Serial stereophotographs appear superior to fundus drawings for anticipating glaucomatous field loss.
• Serial fundus photographs of 14 eyes that eventually developed glaucomatous visual field defects and 110 slides from 76 eyes of race- and age-matched controls were reviewed in randomized masked fashion. Each eye that lost visual field demonstrated consistent abnormalities of the nerve fiber layer, beginning as early as 5 years (mean, 1½ years) before it developed glaucomatous visual field defects on routine Goldmann perimetry. Preliminary estimates, based on regression analysis of this small series, suggest that half of these eyes (median) might demonstrate such reproducible abnormalities between four and six years before onset of their visual field defects. Only 9% of the matched controls showed similar nerve fiber layer changes, and in the one instance where analysis was possible, these were inconsistent and nonreproducible. Nerve fiber layer assessment by means of fundus photographs may be the earliest, surest means of distinguishing ocular hypertension from true glaucoma.
(Arch Ophthalmol 95:2149-2156, 1977)
From annual examinations of 813 ocular hypertensive eyes, the authors compared optic disc and nerve fiber layer photographs in 2 age-matched subgroups: 37 eyes that converted to abnormal visual field tests at the end of a 5-year period and 37 control eyes that retained normal field tests. Disc change was detected in only 7 of 37 (19%) converters to field loss and in 1 of 37 (3%) controls. Progressive nerve fiber layer atrophy was observed in 18 of 37 (49%) converters and in 3 of 37 (8%) controls. Serial nerve fiber layer examination was more sensitive than color disc evaluation in the detection of progressive glaucoma damage at this early stage of glaucoma. The evaluation of cup-to-disc ratio or of the nerve fiber layer appearance in the initial photograph taken 5 years before field loss were equally predictive of future field damage. The position of nerve fiber layer defects was highly correlated with the location of subsequent visual field loss.
Standardized perimetry and nerve fiber layer and color fundus photography were performed annually on 1344 eyes with elevated intraocular pressures. In 83 eyes, glaucomatous field defects developed that met rigid criteria on manual kinetic and suprathreshold static perimetry. Individual nerve fiber layer photographs were read by two masked observers. The more sensitive of the two identified nerve fiber layer defects in 88% of readable photographs at the time field loss first occurred; 60% (6/10) of eyes already had nerve fiber layer defects 6 years before field loss. In contrast, the nerve fiber layer was considered abnormal in only 11% (3/27) of normal eyes and 26% (84/327) of hypertensive eyes. The location of nerve fiber layer and field defects closely corresponded, but nerve fiber layer loss was generally more widespread. Examiner experience and severity of optic nerve damage influenced results. Mild focal defects were more readily recognized than more severe diffuse atrophy. Nerve fiber layer defects expanded with time, often by the development and coalescence of adjacent areas of damage.
More than 1,400 eyes with either ocular hypertension glaucomatous visual field loss, or normal pressures and fields (controls) were studied prospectively in standardized, masked fashion. The appearance of the nerve fiber layer was evaluated independently from red-free photographs with the discs blocked-out by two observers. The vast majority of photographs could be evaluated, the proportion varying with the observer and with the age and clinical status of the subject. Sensitivity (proportion of glaucomatous eyes with nerve fiber defects) and specificity (proportion of normal control eyes without defects) averaged 80% to 94%, varying with the observer and with the age, race, and severity of field loss. In two thirds of presumed false-positive eyes, but only 5% of true-positive eyes, the abnormalities were limited to focal slitlike defects. The prevalence of nerve fiber defects in eyes with elevated pressure and normal visual fields was similar to that in control eyes, approximately 10%. However, the proportion of eyes in which these defects included diffuse loss was considerably higher among the hypertensive eyes.
The number and distribution of human optic nerve axons were compared with clinical measurements available the same eyes, including visual acuity, disc appearance, and visual field studies. Definite loss of axons occurs prior to reproducible visual field defects in some patients suspected of having glaucoma. In glaucoma, the superior and inferior poles of the nerve lose nerve fibers at a selectively greater rate, leading to an hourglass-shaped atrophy. Cavernous degeneration of the retrobulbar optic nerve is rarely observed in chronic glaucoma. The pattern of atrophy in examples of toxic amblyopia, ischemic optic neuropathy and chronic papilledema differ from that of glaucoma, suggesting different mechanisms of damage in these conditions.
Serial disc photographs of 259 patients with elevated intraocular pressures were studied retrospectively up to 15 years. Twenty-nine eyes showed progressive enlargement of the optic cup. Early vertical extension of the cup occurred in vertical extension of the cup occurred in five eyes and horizontal extension in one. In 23 eyes, a generalized expansion of the cup (retaining its round appearance) was the first change observed, typically preceding visual field loss by several years. Thus, serial disc photographs are necessary for the earliest detection of optic nerve damage in ocular hypertension. Of 18 eyes with normal visual fields at the time progression of cupping was first noted, typical glaucomatous field loss developed in 50% during a follow-up of one to six years (average, two years). Therefore, treatment is indicated for eyes exhibiting progressive disc cupping, even in the absence of visual field defects.
To detect characteristics of persons with ocular hypertension that are associated with a higher risk of future glaucomatous field loss.
Annual examinations of the optic disc, nerve fiber layer, and visual field in 647 persons with bilateral intraocular pressure higher than 21 mmHg and initially normal visual field test results with the Goldmann perimeter.
Sixty-eight persons developed a field defect on two consecutive Goldmann visual field tests in at least one eye, while 579 others retained normal fields. Moderate or severe nerve fiber layer atrophy at baseline was associated with a seven to eight times greater risk of development of visual field loss. Attributes that were significantly associated with the incidence of field loss included older age, larger cup-disc ratio, smaller rim-disc area ratio, larger cup asymmetry, presence of disc crescent, and higher intraocular pressure. Characteristics found not to be associated with incidence were gender, race, hypertension, diabetes, refractive error, family history of glaucoma, smoking or alcohol drinking history, and disc area.
Increasing nerve fiber layer atrophy judged by a semiquantitative grading system was associated with increasing risk of development of visual field loss among persons with ocular hypertension. The relationship of the development of field loss to race, myopia, family history of glaucoma, and medical history are more complex than has been presumed.
To assess the temporal relationship between visual field progression and optic disc deterioration in early glaucoma, we studied 15 patients with unilateral visual field loss from primary open angle glaucoma. Planimetric optic disc measurements were compared with automated static threshold perimetry during a mean follow-up of 6.1 years. Eight (53%) of 15 eyes with an initially normal visual field showed progression of the disc; six of these eyes did not develop field abnormalities. The mean rates of rim-area loss were 1.7%/y in eyes with initially normal fields and 2.1%/y in eyes with initial field loss. The mean rate of visual field deterioration (change in corrected loss variance) was lower in the eyes with an initially normal field (0.3 dB2/y) than in eyes with initial field loss (3.6 dB2/y; P = .016). This longitudinal study documents progressive disc damage prior to field loss in early glaucoma.
Optical coherence tomography (OCT) is a new technology that uses near-infrared light in an interferometer to produce approximately 10-microns resolution cross-sectional images of the tissue of interest. The authors performed repeated quantitative assessment of nerve fiber layer thickness in individuals with normal and glaucomatous eyes, and they evaluated the reproducibility of these measurements.
The authors studied 21 eyes of 21 subjects by OCT. Each subject underwent five repetitions of a series of scans on five separate occasions within a 1-month period. Each series consisted of three circular scans around the optic nerve head (diameters, 2.9, 3.4, and 4.5 mm). Each series was performed separately using internal (fixation with same eye being studied) and external (fixation with contralateral eye) fixation techniques. The eye studied and the sequence of testing were assigned randomly.
Internal fixation (IF), in general, provides a slightly higher degree of reproducibility than external fixation (EF). Reproducibility was better in a given eye on a given visit than from visit to visit. Reproducibility as measured by intraclass correlation coefficients were as follows: circle diameter (CD), 2.9 mm, 0.51/0.57 (normal/glaucoma) (IF), 0.43/0.54 (EF); CD, 3.4 mm, 0.56/0.52 (IF), 0.43/0.61 (EF); CD, 4.5 mm, 0.53/0.43 (IF), 0.42/0.49 (EF).
Nerve fiber layer thickness can be reproducibly measured using OCT. Internal is superior to external fixation; each circle diameter tested provides adequate reproducibility.
To compare the cross-sectional images of primate retinal morphology obtained by optical coherence tomography (OCT) with light microscopy to determine the retinal components represented in OCT images.
Laser pulses were delivered to the retina to create small marker lesions in a Macaca mulatta. These lesions were used to align in vivo OCT scans and ex vivum histologic cross sections for image comparison.
The OCT images demonstrated reproducible patterns of retinal morphology that corresponded to the location of retinal layers seen on light microscopic overlays. Layers of relative high reflectivity corresponded to horizontally aligned retinal components such as the nerve fiber layer and plexiform layers, as well as to the retinal pigment epithelium and choroid. In contrast, the nuclear layers and the photoreceptor inner and outer segments demonstrated relative low reflectivity by OCT.
Retinal morphology and macular OCT imaging correlate well, with alignment of areas of high and low reflectivity to specific retinal and choroidal elements. Resolution of retinal structures by OCT depends on the contrast in relative reflectivity of adjacent structures. Use of this tool will enable expanded study of retinal morphology, both normal and pathologic, as it evolves in vivo.
To investigate the relationship between ganglion cell losses and visual field defects caused by glaucoma.
Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The ganglion cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of ganglion cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of ganglion cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli.
The relationship between the proportional losses of ganglion cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for ganglion cell losses of less than 30% to 50%, and then with greater amounts of cell loss the visual defects were more systematically related to ganglion cell loss (approximately 0.42 dB/percent cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli.
Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of ganglion cell loss until a substantial proportion have died. The variance in ganglion cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of ganglion cells to injury from glaucoma.
To evaluate the reproducibility of optical coherence tomograph (OCT) retinal nerve fiber layer (RNFL) measurements in normal and glaucomatous eyes by means of the commercially available OCT 2000 instrument (Humphrey Systems, Dublin, CA).
Prospective instrument validation study.
One eye each from 10 normal subjects and 10 glaucoma patients.
Twenty subjects underwent a total of eight scanning sessions during two independent visits. In each session, five circular scans centered on the optic nerve head were performed. The first two sessions were performed by two experienced technicians. Followed by a 30-minute break, a third and a fourth session was completed by the same technicians. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of quadrant and global RNFL measurements were calculated by use of a components of variance model.
RNFL thickness.
The coefficient of variation for the mean RNFL thickness was significantly smaller (P = 0.02) in normal eyes (6.9%) than in glaucoma eyes (11.8%). The estimated root mean squared error based on the statistical model using three scans per patient was 5.8 and 8.0 micrometer for normal and glaucoma eyes, respectively. A components of variance model showed most of the variance (79%) to be due to differences between patients. Only a modest contribution to variability was found for session (1%), visit (5%), and operator (2%).
With the commercially available OCT, our results indicate that the RNFL measurements are reproducible for both normal and glaucomatous eyes.
To assess the reproducibility of retinal thickness measurement using commercially available mapping software of optical coherence tomography (OCT).
Six radial scans, 6 mm long and centered on the fixation point, were performed on 10 eyes of 10 healthy volunteers and 10 eyes of 10 diabetic patients with clinically significant macular edema. Retinal thickness was measured automatically using the mapping software of OCT in the 9 macular Early Treatment Diabetic Retinopathy Study areas and in a central area 500 microm in diameter. Measurement reproducibility was tested by means of 3 series of scans performed by 2 different observers on 2 different days. Results were assessed by their repeatability and intraclass correlation coefficients (ICCs).
In healthy subjects, intraobserver, interobserver, and intervisit reproducibility of retinal thickness measurements were excellent, with a repeatability coefficient of less than 7 microm and ICCs of greater than 0.89. In diabetic patients, the repeatability coefficient was less than 21 microm in all areas of the macula except one, with an ICC of greater than 0.98. Relative variations in measurements were small in both healthy and diabetic subjects, with reproducibilities of +/- 5% and +/- 6%, respectively.
Retinal mapping software of OCT allows reproducible measurement of retinal thickness in both healthy subjects and diabetic patients with macular edema.
To investigate the relationship between optic disc changes measured with scanning laser tomography and those measured with conventional perimetry and optic disc photography.
In a prospective longitudinal study, we followed up 77 patients with early glaucomatous visual field damage. Scanning laser tomography (using the Heidelberg Retina Tomograph) and conventional perimetry (using the Humphrey Field Analyzer) were carried out every 6 months. Disc progression was determined by a procedure recently described by us for scanning laser tomography, with confirmed progression requiring repeatable changes based on probability limits for both the depth (using individual test-retest variability values) and size of change (determined in a group of 37 healthy individuals also followed up prospectively). Field progression was determined with the Statpac Glaucoma Change Probability Analysis. The agreement between scanning laser tomography and conventional disc photography was determined in a subgroup of patients.
Patients were followed up for a median of 5.5 years, with a median of 12 sets of examinations with scanning laser tomography and conventional perimetry. Twenty-one patients (27%) showed no progression with either technique. Thirty-one patients (40%) progressed with scanning laser tomography only, while 3 (4%) progressed with conventional perimetry only. Of the 22 patients (29%) who progressed with both techniques, 10 (45%) progressed with scanning laser tomography first (median, 18 month earlier) and 9 (41%) with conventional perimetry first (median, 12 months earlier), while 3 (14%) progressed at the same time. Of the 16 patients with disc photographs that closely overlapped the follow-up, there was concordance between scanning laser tomography and disc photography in 13 patients (81%).
Glaucomatous disc changes determined with scanning laser tomography occur more frequently than field changes. Most patients with field changes also had disc changes; however, less than half of those with disc changes had field changes.
To compare ultrahigh-resolution optical coherence tomography (UHR-OCT) technology to a standard-resolution OCT instrument for the imaging of macular hole pathology and repair; to identify situations where UHR-OCT provides additional information on disease morphology, pathogenesis, and management; and to use UHR-OCT as a baseline for improving the interpretation of the standard-resolution images.
Observational and interventional case series.
Twenty-nine eyes of 24 patients clinically diagnosed with macular hole in at least one eye.
A UHR-OCT system has been developed and employed in a tertiary-care ophthalmology clinic. Using a femtosecond laser as the low-coherence light source, this new UHR-OCT system can achieve an unprecedented 3-mum axial resolution for retinal OCT imaging. Comparative imaging was performed with UHR-OCT and standard 10-mum resolution OCT in 29 eyes of 24 patients with various stages of macular holes. Imaging was also performed on a subset of the population before and after macular hole surgery.
Ultrahigh- and standard-resolution cross-sectional OCT images of macular hole pathologies.
Both UHR-OCT and standard-resolution OCT exhibited comparable performance in differentiating various stages of macular holes. The UHR-OCT provided improved imaging of finer intraretinal structures, such as the external limiting membrane and photoreceptor inner segment (IS) and outer segment (OS), and identification of the anatomy of successful surgical repair. The improved resolution of UHR-OCT enabled imaging of previously unidentified changes in photoreceptor morphology associated with macular hole pathology and postoperative repair. Visualization of the junction between the photoreceptor IS and OS was found to be an important indicator of photoreceptor integrity for both standard-resolution and UHR-OCT images.
Ultrahigh-resolution optical coherence tomography improves the visualization of the macular hole architectural morphology. The increased resolution of UHR-OCT enables the visualization of photoreceptor morphology associated with macular holes. This promises to lead to a better understanding of the pathogenesis of macular holes, the causes of visual loss secondary to macular holes, the timing of surgical repair, and the evaluation of postsurgical outcome. Ultrahigh-resolution optical coherence tomography imaging of macular holes that correspond to known alterations in retinal morphology can be used to interpret retinal morphology in UHR-OCT images. Comparisons of UHR-OCT images with standard-resolution OCT images can establish a baseline for the better interpretation of clinical standard-resolution OCT images. The ability to visualize photoreceptors and their integrity or impairment is an indicator of macular hole progression and surgical outcome.
1-1993 Safe Use of Lasers
- American
- Standard
American National Standard. ANSI Z136.1-1993. New York: American National Standards Institute; 1993. Safe Use of Lasers.
C, Ultrahigh-resolution optical coherence tomography (OCT) images. Scanning through the NFL defect shows marked thinning surrounded by a normal-thickness NFL. Arrows depict the extent of NFL thinning in the OCT images
- B Stratusoct
B, StratusOCT scans. C, Ultrahigh-resolution optical coherence tomography (OCT) images. Scanning through the NFL defect shows marked thinning surrounded by a normal-thickness NFL. Arrows depict the extent of NFL thinning in the OCT images. Ophthalmology Volume 112, Number 2, February 2005
Ocular Hyper-tension Treatment Study Group. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma
- Kass Ma Dk Heuer
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Kass MA, Heuer DK, Higginbotham EJ, et al. Ocular Hyper-tension Treatment Study Group. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120: 701–13, discussion 829 –30.
Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive
- Ma Kass
- Dk Heuer
- Ej Higginbotham
Kass MA, Heuer DK, Higginbotham EJ, et al. Ocular Hypertension Treatment Study Group. The
Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive