Imaging of Corneal Neovascularization: Optical Coherence Tomography Angiography and Fluorescence Angiography

Brunner, Matthias; Romano, Vito; Steger, Bernhard; Vinciguerra, Riccardo; Lawman, Samuel; Williams, Bryan; Hicks, Nicholas; Czanner, Gabriela; Zheng, Yalin; Willoughby, Colin E.; Kaye, Stephen B.

doi:10.1167/iovs.17-22035

Cited by 53 publications

(46 citation statements)

References 31 publications

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“…UHR-OCT imaging of the ocular surface can now resolve and even measure the thickness of tear film and the major structures, such as the individual corneal layers: the epithelium, the Bowman's membrane, the Stroma, Descemet's membrane and the endothelium [23][24][25][26], which helps clinicians be better in the diagnosis and management of ocular surface pathologies and diseases, including keratitis [23,26], keratoconus [27], ocular surface neoplasia [28], etc.For ocular surface diseases, apart from the physiological structural changes, the microvascular system would also change when the eye is inflamed, as inflammatory mediators would induce a series of vascular changes, including vasodilation, increased permeability and increased blood flow [5,6], which correlates with the severity of the lesion. Techniques like OCT angiography [29,30] have been applied to image the vessels of the anterior segment, but they could only provide morphological information and lack of the function of providing quantitative functional parameters, such as the blood flow velocity. To measure the blood flow velocity in bulbar conjunctival vessels and also evaluate their network complexity, our team has developed functional slit-lamp biomicroscopy to achieve conjunctival vessel network imaging as well as high-resolution conjunctival blood flow videography [10,31].…”

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confidence: 99%

“…For ocular surface diseases, apart from the physiological structural changes, the microvascular system would also change when the eye is inflamed, as inflammatory mediators would induce a series of vascular changes, including vasodilation, increased permeability and increased blood flow [5,6], which correlates with the severity of the lesion. Techniques like OCT angiography [29,30] have been applied to image the vessels of the anterior segment, but they could only provide morphological information and lack of the function of providing quantitative functional parameters, such as the blood flow velocity. To measure the blood flow velocity in bulbar conjunctival vessels and also evaluate their network complexity, our team has developed functional slit-lamp biomicroscopy to achieve conjunctival vessel network imaging as well as high-resolution conjunctival blood flow videography [10,31].…”

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confidence: 99%

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Multi-modal Anterior Eye Imager Combining Ultra-High Resolution OCT and Microvascular Imaging for Structural and Functional Evaluation of the Human Eye

et al. 2020

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To establish complementary information for the diagnosis and evaluation of ocular surface diseases, we developed a multi-modal, non-invasive optical imaging platform by combining ultra-high resolution optical coherence tomography (UHR-OCT) with a microvascular imaging system based on slit-lamp biomicroscopy. Our customized UHR-OCT module achieves an axial resolution of ≈2.9 µm in corneal tissue with a broadband light source and an A-line acquisition rate of 24 kHz with a line array CCD camera. The microvascular imaging module has a lateral resolution of 3.5 µm under maximum magnification of ≈187.5× with an imaging rate of 60 frames/s, which is sufficient to image the conjunctival vessel network and record the movement trajectory of clusters of red blood cells. By combining the imaging optical paths of different modules, our customized multi-modal anterior eye imaging platform is capable of performing real-time cross-sectional UHR-OCT imaging of the anterior eye, conjunctival vessel network imaging, high-resolution conjunctival blood flow videography, fluorescein staining and traditional slit-lamp imaging on a single device. With self-developed software, a conjunctival vessel network image and blood flow videography were further analyzed to acquire quantitative morphological and hemodynamics parameters, including vessel fractal dimensions, blood flow velocity and vessel diameters. The ability of our multi-modal anterior eye imager to provide both structural and functional information for ophthalmic clinical applications was demonstrated on a healthy human subject and a keratitis patient. evaluation of ocular surface diseases, different imaging modalities are usually applied in ophthalmic clinics to provide multi-modal and multi-dimensional images [7,8].Slit-lamp biomicroscopy (SLB) is the gold standard for routine ophthalmic examinations. By shining a thin sheet of light into the eye, an in vivo stereoscopic evaluation of the pathological changes of the cornea, conjunctiva and other anterior segment tissues can be performed by SLB [9]. However, the limited magnification and poor spatial resolution of traditional SLB make it difficult to visualize more detailed pathological structures and perform accurate biometric measurements [10][11][12]. Fluorescein stain could stain stroma while leaving the intact epithelium with a specific fluorescein dye, thereby demarcating the location and area of the epithelial loss in ocular surface diseases, on a relative macro scale as well [13]. Developed in the 1990s, optical coherence tomography (OCT) has revolutionized the field of ophthalmology and vision science with its non-contact, non-invasive and high-resolution nature and become one of the prominent diagnostic tools in offering cross-sectional tissue imaging [14][15][16]. Applications of OCT for in vivo human eye imaging have been widely demonstrated in the literature [17][18][19][20][21][22][23][24][25][26][27][28]. With ever-improving techniques in broadband light sources, ultra-high resolution OCT (UHR-OCT) has achieved m...

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Multi-modal Anterior Eye Imager Combining Ultra-High Resolution OCT and Microvascular Imaging for Structural and Functional Evaluation of the Human Eye

et al. 2020

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“…In a comparative analysis by our group, OCTA provided lower-quality images and was less precise in capturing small vessels of neovascular trees compared with ICGA. 27 Current OCTA systems do not provide information on the afferent or efferent quality of CoNV, perfusion velocity, and leakage behavior or maturity of corneal vessels, as does FA/ICGA. 16 Despite its current limitations in image quality OCTA is a feasible tool to assess quantitative information on CoNV.…”

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Functional Staging of Corneal Neovascularization Using Fluorescein and Indocyanine Green Angiography

Palme

Romano

Brunner

et al. 2018

Trans. Vis. Sci. Tech.

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PurposeCorneal neovascularization (CoNV) is a major risk factor for corneal graft rejection and other corneal conditions. The maturity of CoNV is important to guide treatment. This study investigated associations between clinical and angiographic characteristics of CoNV.MethodsIn a prospective cross-sectional study patients with CoNV of variable but known duration and etiology were included. All cases were clinically staged according to a simplified three-grade scale as active, inactive, and regressed and assessed using color photography, anterior-segment optical coherence tomography, and fluorescein and indocyanine green (ICG) angiography. Outcome parameters included age and depth of CoNV, perfusion times and time to leakage of fluorescein and ICG.ResultsForty eyes of 39 patients with CoNV were included, active (14), inactive (22), and regressed CoNV (4). There were significant associations between the time to fluorescein or ICG leakage and clinical staging of CoNV (R2 = 0.24; P = 0.0011, and R2 = 0.3; P = 0.0001). In addition, there was a significant association between the time to fluorescein leakage and the age of CoNV (R2 = 0.32; P = 0.0002). ICG leakage within 10 minutes was observed significantly more frequently in active than the inactive group and was not observed in regressed cases (P < 0.0001).ConclusionsSimplification of the staging of CoNV to active, inactive, and regressed to is significantly associated with the time to extravascular leakage of fluorescein and indocyanine and may be useful to guide the selection of appropriate treatments.Translational RelevanceThe association between clinical and angiographic characteristics of CoNV may provide guidance to the treatment approaches.

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“…The segmentation of a whole CCM image was obtained by combining the segmentations of all its patches using majority voting on the overlap regions. From the image-level segmentation result, further analysis was carried out to derive the clinically relevant variables including the corneal nerve length, branch points, tail points and fractal number [35].…”

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An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy: a development and validation study

et al. 2019

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Aims/hypothesis Corneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics. Methods Our deep learning algorithm, which employs a convolutional neural network with data augmentation, was developed for the automated quantification of the corneal sub-basal nerve plexus for the diagnosis of diabetic neuropathy. The algorithm was trained using a high-end graphics processor unit on 1698 corneal confocal microscopy images; for external validation, it was further tested on 2137 images. The algorithm was developed to identify total nerve fibre length, branch points, tail points, number and length of nerve segments, and fractal numbers. Sensitivity analyses were undertaken to determine the AUC for ACCMetrics and our algorithm for the diagnosis of diabetic neuropathy. Uazman Alam and Yalin Zheng are joint senior authors.

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Imaging of Corneal Neovascularization: Optical Coherence Tomography Angiography and Fluorescence Angiography

Cited by 53 publications

References 31 publications

Multi-modal Anterior Eye Imager Combining Ultra-High Resolution OCT and Microvascular Imaging for Structural and Functional Evaluation of the Human Eye

Multi-modal Anterior Eye Imager Combining Ultra-High Resolution OCT and Microvascular Imaging for Structural and Functional Evaluation of the Human Eye

Functional Staging of Corneal Neovascularization Using Fluorescein and Indocyanine Green Angiography

An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy: a development and validation study

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