Purpose To understand the relationship between choroidal thickness and various disease factors in patients with age-related macular degeneration (AMD) using spectral-domain optical coherence ...tomography. Design Cross-sectional, retrospective analysis. Methods Fifty-seven eyes of 47 patients with wet and dry AMD seen between November 2009 and January 2010 at the New England Eye Center, Boston, Massachusetts, were analyzed. Choroidal thickness was measured by 2 independent observers at 11 sites with high-definition horizontal 1-line raster scans through the foveal center. A retrospective chart review was performed to obtain data concerning duration of disease, number of intravitreal anti–vascular endothelial growth factor injections, visual acuity, lens status, and concomitant retinal pathologic features. The Pearson correlation and Student t test were used for statistical analysis for assessment of choroidal thickness changes in wet and dry AMD. Results The choroid in eyes with wet and dry AMD demonstrated a wide range of thicknesses above and below the normal mean (range, 77.5 to 399.5 μm; standard deviation SD, 90.2). Nearly one third (33.3%) of the eyes with AMD measured less than 1 SD below the mean. Eyes with wet AMD demonstrated a mean subfoveal choroidal thickness of 194.6 μm (SD, 88.4; n = 40) compared with 213.4 μm (SD, 92.2; n = 17) in the dry AMD group. The choroidal thickness in eyes with dry AMD was correlated inversely with age ( r = −0.703; P = .002); however, analysis of the number of intravitreal anti–vascular endothelial growth factor injections, number of years of disease, and visual acuity failed to demonstrate any significant correlations with choroidal thickness. Conclusions This study demonstrated that choroidal thickness can be measured by spectral-domain optical coherence tomography and that variable choroidal thickness exists among patients with the clinical diagnosis of wet and dry AMD. However, it is unclear at this time why in some eyes, choroidal thickness either increases or decreases with the disease. Further studies need to be carried out to understand the significance of choroidal thickness with respect to visual function and disease progression over time.
Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography ...(OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.
Significance Retinal vascular diseases are a leading cause of blindness. Optical coherence tomography (OCT) has become the standard imaging modality for evaluating fluid accumulation in these diseases and for guiding treatment. However, fluorescein angiography (FA) is still required for initial evaluation of retinal ischemia and choroidal neovascularization, which are not visible in conventional structural OCT. The limitations of FA include poor penetration of fluorescence through blood and pigment, inability to determine the depth of the pathology due to its two-dimensional nature, and some uncommon but potentially severe complications. As a noninvasive three-dimensional alternative, OCT angiography may be used in routine screening and monitoring to provide new information for clinical diagnosis and management.
Purpose To examine choroidal thickness and area in healthy eyes using spectral-domain optical coherence tomography (SD-OCT). Design Retrospective, observational case series. Methods Thirty-four eyes ...(34 subjects), with no retinal or choroidal disease, underwent high-definition raster scanning using SD-OCT with frame enhancement software. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-μm intervals up to 2500 μm temporal and nasal to the fovea. The central 1-mm area of the choroid was also measured, along with foveal thickness of the retina. All measurements were performed by 2 independent observers. Statistical analysis was used to correlate inter-observer findings, choroidal thickness and area measurements with age, and choroidal thickness with retinal foveal thickness. Results The 34 subjects had a mean age of 51.1 years. Reliable measurements of choroidal thickness were obtainable in 74% of eyes examined. Choroidal thickness and area measurements had strong inter-observer correlation (r = 0.92, P < .0001 and r = 0.93, P < .0001 respectively). Area had a moderate negative correlation with age (r = −0.62, P < .0001) that was comparable to the correlation between mean subfoveal choroidal thickness and age (r = −0.61, P < .0001). Retinal and choroidal thickness were found to be poorly correlated (r = −0.23, P = .18). Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and then thinning again temporally. Mean subfoveal choroidal thickness was found to be 272 μm (SD, ± 81 μm). Conclusions Choroidal thickness can be measured using SD-OCT high-definition raster scans in the majority of eyes. Choroidal thickness across the macula demonstrates a thin choroid nasally, thickest subfoveally, and again thinner temporally, and a trend toward decreasing choroidal thickness with age.
25 years is a relatively short period of time for a medical technology to become a standard of care impacting the treatment of millions of people every year. Yet 25 years ago there were no OCT ...companies, no OCT products, no OCT markets, and only one journal article published using the term OCT (optical coherence tomography). OCT has had a tremendous scientific, clinical, and economic impact on society. Today, it is estimated that there are ~30 Million OCT imaging procedures performed worldwide every year and the OCT system market is approaching $1B per year. OCT has helped diagnose patients with retinal disease at early treatable stages, preventing or greatly reducing irreversible vision loss. The technology has facilitated pharmaceutical development and contributed to fundamental understanding of disease mechanisms in multiple fields. The invention and translation of OCT from fundamental research to daily clinical practice would not have been possible without a complex ecosystem involving interaction among physics, engineering, and clinical medicine; government funding of fundamental and clinical research; collaborative and competitive research in the academic sector; entrepreneurship and industry; addressing real clinical needs; harnessing the innovation that occurs at the boundaries of disciplines; and economic and societal impact. This invited review paper discusses the translation of OCT from fundamental research to clinical practice and commercial impact, as well as describes the ecosystem that helped power OCT to where it is today and will continue to drive future advances. While OCT is an example of a technology that has had a powerful impact, there are many biomedical technologies which are poised for translation to clinical practice, and it is our hope that highlighting this ecosystem will help accelerate their translation and clinical impact.
To investigate ultrahigh-speed, swept-source optical coherence tomography (SSOCT) angiography for visualizing vascular changes in eyes with nonexudative age-related macular degeneration (AMD) with ...geographic atrophy (GA).
Observational, prospective, cross-sectional study.
A total of 63 eyes from 32 normal subjects and 12 eyes from 7 patients with nonexudative AMD with GA.
A 1050-nm, 400-kHz A-scan rate SSOCT system was used to perform volumetric optical coherence tomography angiography (OCTA) of the retinal and choriocapillaris (CC) vasculatures in normal subjects and patients with nonexudative AMD with GA. Optical coherence tomography angiography using variable interscan time analysis (VISTA) was performed to assess CC alteration and differentiate varying degrees of CC flow impairment.
Qualitative comparison of retinal and CC vasculatures in normal subjects versus those in patients with a clinical diagnosis of nonexudative AMD with GA.
In all 12 eyes with GA, OCTA showed pronounced CC flow impairment within the region of GA. In 10 of the 12 eyes with GA, OCTA with VISTA showed milder CC flow impairment extending beyond the margin of GA. Of the 5 eyes exhibiting foveal-sparing GA, OCTA showed CC flow within the region of foveal sparing in 4 of the eyes.
The ability of ultrahigh-speed, swept-source OCTA to noninvasively visualize alterations in the retinal and CC vasculatures makes it a promising tool for assessing nonexudative AMD with GA. Optical coherence tomography angiography using VISTA can distinguish varying degrees of CC alteration and flow impairment and may be useful for elucidating disease pathogenesis, progression, and response to therapy.
We demonstrate ultrahigh speed spectral / Fourier domain optical coherence tomography (OCT) using an ultrahigh speed CMOS line scan camera at rates of 70,000 - 312,500 axial scans per second. Several ...design configurations are characterized to illustrate trade-offs between acquisition speed, resolution, imaging range, sensitivity and sensitivity roll-off performance. Ultrahigh resolution OCT with 2.5 - 3.0 micron axial image resolution is demonstrated at approximately 100,000 axial scans per second. A high resolution spectrometer design improves sensitivity roll-off and imaging range performance, trading off imaging speed to 70,000 axial scans per second. Ultrahigh speed imaging at >300,000 axial scans per second with standard image resolution is also demonstrated. Ophthalmic OCT imaging of the normal human retina is investigated. The high acquisition speeds enable dense raster scanning to acquire densely sampled volumetric three dimensional OCT (3D-OCT) data sets of the macula and optic disc with minimal motion artifacts. Imaging with approximately 8 - 9 micron axial resolution at 250,000 axial scans per second, a 512 x 512 x 400 voxel volumetric 3D-OCT data set can be acquired in only approximately 1.3 seconds. Orthogonal registration scans are used to register OCT raster scans and remove residual axial eye motion, resulting in 3D-OCT data sets which preserve retinal topography. Rapid repetitive imaging over small volumes can visualize small retinal features without motion induced distortions and enables volume registration to remove eye motion. Cone photoreceptors in some regions of the retina can be visualized without adaptive optics or active eye tracking. Rapid repetitive imaging of 3D volumes also provides dynamic volumetric information (4D-OCT) which is shown to enhance visualization of retinal capillaries and should enable functional imaging. Improvements in the speed and performance of 3D-OCT volumetric imaging promise to enable earlier diagnosis and improved monitoring of disease progression and response to therapy in ophthalmology, as well as have a wide range of research and clinical applications in other areas.
Significance Development of methods for rapid intraoperative assessment of breast pathologies is important for decreasing the rate of surgical reexcisions during breast-conserving therapy. ...Frozen-section analysis is the most widely used method for intraoperative margin assessment but is time consuming, has limited diagnostic accuracy, and produces freezing artifacts. This manuscript demonstrates nonlinear microscopy for rapid assessment of surgical breast specimens without need for fixation, embedding, and sectioning required for conventional histology. Blinded reading of nonlinear microscopy images by three pathologists achieved 95.4% sensitivity, 93.3% specificity, and 94.1% overall accuracy compared with histology for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. The results suggest that nonlinear microscopy is a promising method for intraoperative assessment of breast surgical excision specimens.
Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment.
Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT ...makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.
To investigate swept-source optical coherence tomography (OCT) angiography in the optic nerve head (ONH) and parafoveal regions in patients with multiple sclerosis (MS).
Fifty-two MS eyes and 21 ...healthy control (HC) eyes were included. There were two MS subgroups: 38 MS eyes without an optic neuritis (ON) history (MS -ON), and 14 MS eyes with an ON history (MS +ON). The OCT images were captured by high-speed 1050 nm swept-source OCT. The ONH flow index (FI) and parafoveal FI were quantified from OCT angiograms.
The mean ONH FI was 0.160 ± 0.010 for the HC group, 0.156 ± 0.017 for the MS-ON group, and 0.140 ± 0.020 for the MS+ON group. The ONH FI of the MS+ON group was reduced by 12.5% compared to HC eyes (p=0.004). A higher percentage of MS+ON eyes had abnormal ONH FI compared to HC patients (43% vs 5%, p=0.01). Mean parafoveal FIs were 0.126 ± 0.007, 0.127 ± 0.010, and 0.129 ± 0.005 for the HC, MS-ON, and MS +ON groups, respectively, and did not differ significantly among them. The coefficient of variation (CV) of intravisit repeatability and intervisit reproducibility were 1.03% and 4.53% for ONH FI, and 1.65% and 3.55% for parafoveal FI.
Based on OCT angiography, the FI measurement is feasible, highly repeatable and reproducible, and it is suitable for clinical measurement of ONH and parafoveal perfusion. The ONH FI may be useful in detecting damage from ON and quantifying its severity.
To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller's and Sattler's ...layer thickness in healthy eyes.
Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36°x36° field of view. Haller's and Sattler's layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller's and Sattler's layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidal sublayers.
The coefficients of repeatability for Sattler's and Haller's layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean±SD healthy central submacular field thickness for Sattler's and Haller's was 87±56 µm and 141±50 µm, respectively, with a significant relationship for AL (P<.001).
Automated Sattler's and Haller's thickness segmentation generates rapid 3D measurements with a repeatability corresponding to reported manual segmentation. Sublayers in healthy eyes thinned significantly with increasing AL. In the presence of the thinned Sattler's layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss.
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