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Choriocapillary loss is a major cause of neovascular age-related macular degeneration (NV-AMD). Although vascular endothelial growth factor (VEGF) blockade for NV-AMD has shown beneficial outcomes, unmet medical needs for patients refractory or tachyphylactic to anti-VEGF therapy exist. In addition, the treatment could exacerbate choriocapillary rarefaction, necessitating advanced treatment for fundamental recovery from NV-AMD. In this study, Tie2 activation by angiopoietin-2-binding and Tie2-activating antibody (ABTAA) presents a therapeutic strategy for NV-AMD. Conditional Tie2 deletion impeded choriocapillary maintenance, rendering eyes susceptible to NV-AMD development. Moreover, in a NV-AMD mouse model, ABTAA not only suppressed choroidal neovascularization (CNV) and vascular leakage but also regenerated the choriocapillaris and relieved hypoxia. Conversely, VEGF blockade degenerated the choriocapillaris and exacerbated hypoxia, although it suppressed CNV and vascular leakage. Together, we establish that angiopoietin-Tie2 signaling is critical for choriocapillary maintenance and that ABTAA represents an alternative, combinative therapeutic strategy for NV-AMD by alleviating anti-VEGF adverse effects.
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Neovascularización Coroidal/etiología , Neovascularización Coroidal/patología , Degeneración Macular/etiología , Degeneración Macular/patología , Receptor TIE-2/genética , Activación Transcripcional , Factores de Edad , Angiopoyetina 1/genética , Angiopoyetina 1/metabolismo , Animales , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Técnica del Anticuerpo Fluorescente , Eliminación de Gen , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Hipoxia/genética , Hipoxia/metabolismo , Degeneración Macular/metabolismo , Degeneración Macular/fisiopatología , Ratones , Modelos Biológicos , Unión Proteica , Receptor TIE-2/metabolismo , Regeneración , Transducción de Señal , Activación Transcripcional/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Trastornos de la Visión/genética , Trastornos de la Visión/parasitologíaRESUMEN
Functional hyperemia in the rat cortex was investigated using high-speed optical coherence tomography (OCT) angiography and Doppler OCT. OCT angiography (OCTA) was performed to image the hemodynamic stimulus-response over a wide field of view. Temporal changes in vessel diameters in different vessel compartments, which were determined as the diameters of erythrocyte flows in OCT angiograms, were measured in order to monitor localized hemodynamic changes. Our results showed that the dilation of arterioles at the site of activation was accompanied by the dilation of upstream arteries. Relatively negligible dilation was observed in veins. An increase in the OCTA signal was observed during stimulus in multiple capillaries, which may imply that capillary blood flow increases as a result of the expanded arterial blood volume. These results agree with previous observations using two-photon laser scanning microscopy (TPLSM). Doppler OCT was performed to quantitatively measure stimulus-induced blood flow response in pial arteries. The measurement showed small but clear hemodynamic response in upstream arteries with diameters exceeding 100 µm. Our results demonstrate the potential of OCTA and Doppler OCT for the investigation of neurovascular coupling in small animal models.
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Encéfalo/irrigación sanguínea , Acoplamiento Neurovascular , Angiografía/métodos , Animales , Hemodinámica , Masculino , Ratas Sprague-Dawley , Tomografía de Coherencia Óptica/métodosRESUMEN
Purpose: The purpose of this study was to assess the retinal and choroidal vasculatures of an oxygen-induced retinopathy (OIR) rat model using optical coherence tomography angiography (OCTA) as well as to verify the performance of OCTA for visualizing in vivo vascular alterations, longitudinally and quantitatively. Methods: To induce OIR, Sprague Dawley rat pups were incubated in an 80% oxygen chamber from postnatal day 1 (P1) to P11 and returned to room air. OCTA imaging was performed in six eyes at P15, P18, P21, and P24. All eyes were imaged with ex vivo retinal flat mount immunofluorescence microscopy for comparison with OCTA. The areas of the neovascular tufts, retinal vessel tortuosities and diameters, and vessel densities of different retinal and choroidal layers were quantified. Results: The neovascular tufts were observed in two OIR eyes. The tuft areas decreased spontaneously from P18 to P24. The increase in arterial tortuosity and venous dilation were observed in the OIR eyes at P15 and P18. The retardation of vascular developments was observed in the deep vascular plexus and the choroidal layer in the OIR group while the superficial vascular plexus did not show developmental delay. Conclusions: This study demonstrates an application of OCTA for quantitative and longitudinal studies on in vivo vascular alterations, including neovascular tufts, increase in arterial tortuosity, venous dilation, and developmental delay in the OIR rat model.
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Neovascularización Coroidal/patología , Neovascularización Retiniana/patología , Vasos Retinianos/patología , Retinopatía de la Prematuridad/patología , Animales , Modelos Animales de Enfermedad , Angiografía con Fluoresceína , Oxígeno/farmacología , Ratas , Ratas Sprague-Dawley , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: Longitudinally visualizing relative blood flow speeds within choroidal neovascularization (CNV) may provide valuable information regarding the evolution of CNV and the response to vascular endothelial growth factor (VEGF) inhibitors. DESIGN: Retrospective, longitudinal case series conducted at the New England Eye Center. PARTICIPANTS: Patients with either treatment-naïve or previously treated CNV secondary to neovascular age-related macular degeneration. METHODS: Optical coherence tomography angiography (OCTA) was performed using a 400-kHz, 1050-nm swept-source OCT system with a 5-repeat B-scan protocol. Variable interscan time analysis (VISTA) was used to compute relative flow speeds from pairs of B-scans having 1.5- and 3.0-ms separations; VISTA signals then were mapped to a color space for display. MAIN OUTCOME MEASURES: Quantitative outcomes included OCTA-based area and volume measurements of CNV at initial and follow-up visits. Qualitative outcomes included VISTA OCTA analysis of relative blood flow speeds, along with analysis of contraction, expansion, densification, and rarefication of CNV. RESULTS: Seven eyes of 6 patients (4 women and 2 men) with neovascular age-related macular degeneration were evaluated. Two eyes were treatment naïve at the initial visit. Choroidal neovascularization in all eyes at each visit showed relatively higher flow speeds in the trunk, central, and larger vessels and lower flow speed in the small vessels, which generally were located at the periphery of the CNV complex. Overall, the CNV appeared to expand over time despite retention of good visual acuity in all patients. In the treatment-naïve patients, slower-flow-speed vessels contracted with treatment, whereas the larger vessels with higher flow speed remained constant. CONCLUSIONS: Variable interscan time analysis OCTA allows for longitudinal observations of relative blood flow speeds in CNV treated with anti-VEGF intravitreal injections. A common finding in this study is that the main trunk and larger vessels seem to have relatively faster blood flow speeds compared with the lesions' peripheral vasculature. Moreover, an overall growth of chronically treated CNV was seen despite retention of good visual acuity. The VISTA framework may prove useful for developing clinical end points, as well as for studying hemodynamics, disease pathogenesis, and treatment response.
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PURPOSE: To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). DESIGN: A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. PARTICIPANTS: Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. MAIN OUTCOME MEASURES: A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. RESULTS: Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. CONCLUSIONS: Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images.
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IMPORTANCE: Alterations in ocular blood flow play an important role in the pathogenesis and progression of diabetic retinopathy (DR). However, the measurement of retinal blood flow in clinical studies has been challenging. En face Doppler optical coherence tomography (OCT) provides an effective method for measuring total retinal blood flow (TRBF) in the clinic. OBJECTIVE: To investigate TRBF in eyes with DR of varying severity, with or without diabetic macular edema (DME), using en face Doppler OCT. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted from May 23, 2014, to January 11, 2016, which analyzed 41 eyes with DR from 31 diabetic patients, 20 eyes without DR from 11 diabetic patients, and 16 eyes from 12 healthy age-matched controls, all at the New England Eye Center in Boston, Massachusetts. MAIN OUTCOMES AND MEASURES: Participants were imaged with a high-speed, swept-source OCT prototype at 1050-nm wavelength using repeated en face Doppler OCT raster scans, comprising 600 × 80 axial scans and covering a 1.5 × 2-mm2 area centered at the optic disc. The TRBF was automatically calculated using custom Matlab software. RESULTS: This study included 41 eyes with DR from 31 diabetic patients (mean [SD] age, 62.8 [13.4] years; 12 were female patients), 20 eyes without DR from 11 diabetic patients (mean [SD] age, 58.8 [10.1] years; 5 were female patients), and 16 eyes from 12 healthy age-matched controls (mean [SD] age, 57.9 [8.1] years; 8 were female participants). The mean (SD) TRBF was 28.0 (8.5) µL/min in the eyes with DME, 48.8 (13.4) µL/min in the eyes with DR but without DME, 40.1 (7.7) µL/min in the diabetic eyes without retinopathy, and 44.4 (8.3) µL/min in age-matched healthy eyes. A difference in TRBF between the eyes with DME that were treated and the eyes with DME that were not treated was not identified. The TRBF was consistently low in the eyes with DME regardless of DR severity. The eyes with moderate nonproliferative DR but without DME exhibited a wide range of TRBF from 31.1 to 75.0 µL/min, with the distribution being highly skewed. CONCLUSIONS AND RELEVANCE: High-speed en face Doppler OCT can measure TRBF in healthy and diabetic eyes. Diabetic eyes with DME exhibited lower TRBF than healthy eyes (P ≤ .001). Further longitudinal studies of TRBF in eyes with DR would be helpful to determine whether reduced TRBF is a risk factor for DME.
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Retinopatía Diabética/diagnóstico , Edema Macular/diagnóstico , Flujo Sanguíneo Regional/fisiología , Retina/fisiopatología , Vasos Retinianos/fisiopatología , Tomografía de Coherencia Óptica/métodos , Estudios Transversales , Retinopatía Diabética/complicaciones , Retinopatía Diabética/fisiopatología , Efecto Doppler , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Edema Macular/etiología , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Retina/patología , Vasos Retinianos/diagnóstico por imagen , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
The purpose of this study is to evaluate the suitability of five different anesthetic protocols (isoflurane, isofluranexylazine, pentobarbital, ketaminexylazine, and ketaminexylazinevecuronium) for functional blood flow imaging in the rat eye. Total retinal blood flow was measured at a series of time points using an ultrahigh-speed Doppler OCT system. Additionally, each anesthetic protocol was qualitatively evaluated according to the following criteria: (1) time-stability of blood flow, (2) overall rate of blood flow, (3) ocular immobilization, and (4) simplicity. We observed that different anesthetic protocols produced markedly different blood flows. Different anesthetic protocols also varied with respect to the four evaluated criteria. These findings suggest that the choice of anesthetic protocol should be carefully considered when designing and interpreting functional blood flow studies in the rat eye.
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Anestesia/métodos , Anestésicos , Ojo/irrigación sanguínea , Flujo Sanguíneo Regional/efectos de los fármacos , Animales , Isoflurano , Ketamina , Pentobarbital , Ratas , Retina , Bromuro de Vecuronio , XilazinaRESUMEN
PURPOSE: To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. METHODS: The study was prospective and cross-sectional. A 1,050 nm wavelength, 400 kHz A-scan rate swept source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. RESULTS: Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. CONCLUSION: The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes.
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Capilares , Coroides/irrigación sanguínea , Retinopatía Diabética/fisiopatología , Tomografía de Coherencia Óptica/métodos , Adulto , Anciano , Capilares/diagnóstico por imagen , Capilares/patología , Estudios de Casos y Controles , Coroides/diagnóstico por imagen , Estudios Transversales , Retinopatía Diabética/diagnóstico por imagen , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Microvasos/patología , Persona de Mediana Edad , Estudios Prospectivos , Flujo Sanguíneo Regional , Retina/diagnóstico por imagen , Retina/fisiopatología , Neovascularización Retiniana/diagnóstico por imagen , Neovascularización Retiniana/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Adulto JovenRESUMEN
PURPOSE: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). METHODS: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. RESULTS: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. CONCLUSION: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials.
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Coroides/irrigación sanguínea , Atrofia Geográfica/diagnóstico por imagen , Drusas del Disco Óptico/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Anciano , Artefactos , Angiografía por Tomografía Computarizada/métodos , Femenino , Atrofia Geográfica/etiología , Humanos , Masculino , Drusas del Disco Óptico/complicacionesRESUMEN
PURPOSE: Currently available optical coherence tomography angiography systems provide information about blood flux but only limited information about blood flow speed. The authors develop a method for mapping the previously proposed variable interscan time analysis (VISTA) algorithm into a color display that encodes relative blood flow speed. METHODS: Optical coherence tomography angiography was performed with a 1,050 nm, 400 kHz A-scan rate, swept source optical coherence tomography system using a 5 repeated B-scan protocol. Variable interscan time analysis was used to compute the optical coherence tomography angiography signal from B-scan pairs having 1.5 millisecond and 3.0 milliseconds interscan times. The resulting VISTA data were then mapped to a color space for display. RESULTS: The authors evaluated the VISTA visualization algorithm in normal eyes (n = 2), nonproliferative diabetic retinopathy eyes (n = 6), proliferative diabetic retinopathy eyes (n = 3), geographic atrophy eyes (n = 4), and exudative age-related macular degeneration eyes (n = 2). All eyes showed blood flow speed variations, and all eyes with pathology showed abnormal blood flow speeds compared with controls. CONCLUSION: The authors developed a novel method for mapping VISTA into a color display, allowing visualization of relative blood flow speeds. The method was found useful, in a small case series, for visualizing blood flow speeds in a variety of ocular diseases and serves as a step toward quantitative optical coherence tomography angiography.
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Retinopatía Diabética/fisiopatología , Atrofia Geográfica/fisiopatología , Algoritmos , Velocidad del Flujo Sanguíneo/fisiología , Estudios de Casos y Controles , Coroides/irrigación sanguínea , Angiografía por Tomografía Computarizada/métodos , Retinopatía Diabética/diagnóstico por imagen , Atrofia Geográfica/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Imagen Multimodal , Tomografía de Coherencia Óptica/métodosRESUMEN
PURPOSE: The purpose of this study was to evaluate the performance of optical coherence tomography angiography (OCTA) in visualizing laser-induced choroidal neovascularization (CNV) in the rodent retina. METHODS: Choroidal neovascularization was induced via laser photocoagulation in 2 male Brown Norway rats and 2 male C57BL/6 mice. For qualitative comparison, the animals were imaged in vivo with OCTA, indocyanine green angiography (ICGA), and fluorescein angiography (FA), and ex vivo with immunofluorescence confocal microscopy, 14 days post laser photocoagulation without anti-vascular endothelial growth factor (anti-VEGF) intervention. For longitudinal quantitative analysis, CNV was induced in 6 additional male C57BL/6 mice. Three mice intravitreally received an anti-VEGF agent and the remaining 3 mice phosphate buffered saline (PBS) vehicle 7 days post laser photocoagulation. These animals were imaged using OCTA 6, 14, and 21 days post laser photocoagulation. The area and volume of the laser-induced CNV lesions were measured longitudinally. RESULTS: In both mice and rats, OCTA qualitatively showed high correlation with FA, ICGA, and immunofluorescence imaging. Unlike FA and ICGA, which does not show the microvasculature due to dye leakage, OCTA visualized the CNV microvasculature with resolution and contrast comparable to immunofluorescence images. Longitudinal imaging enabled normalization of the CNV area and volume, reducing inherent variation in the CNV size. By using only 3 mice in each group, statistically significant differences (P < 0.01) in the CNV area and volume could be demonstrated. CONCLUSIONS: Optical coherence tomography angiography enables noninvasive visualization of the laser-induced CNV microvasculature in the rodent retina with high resolution and tissue-lumen contrast, providing quantifiable in vivo measurements for longitudinal analysis.
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Coroides/irrigación sanguínea , Neovascularización Coroidal/diagnóstico , Angiografía con Fluoresceína/métodos , Retina/patología , Tomografía de Coherencia Óptica/métodos , Animales , Coroides/patología , Neovascularización Coroidal/etiología , Modelos Animales de Enfermedad , Fondo de Ojo , Coagulación con Láser/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Ratas , Ratas Endogámicas BN , Epitelio Pigmentado de la Retina/patologíaRESUMEN
PURPOSE: 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). DESIGN: Observational, prospective, cross-sectional study. PARTICIPANTS: A total of 63 eyes from 32 normal subjects and 12 eyes from 7 patients with nonexudative AMD with GA. METHODS: 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. MAIN OUTCOME MEASURES: Qualitative comparison of retinal and CC vasculatures in normal subjects versus those in patients with a clinical diagnosis of nonexudative AMD with GA. RESULTS: 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. CONCLUSIONS: 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.
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Coroides/irrigación sanguínea , Atrofia Geográfica/fisiopatología , Degeneración Macular/fisiopatología , Vasos Retinianos/patología , Adulto , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo , Estudios Transversales , Femenino , Angiografía con Fluoresceína , Atrofia Geográfica/diagnóstico , Humanos , Degeneración Macular/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Flujo Sanguíneo Regional , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To develop and demonstrate a cardiac gating method for repeatable in vivo measurement of total retinal blood flow (TRBF) in humans using en face Doppler optical coherence tomography (OCT) at commercially available imaging speeds. METHODS: A prototype swept-source OCT system operating at 100-kHz axial scan rate was developed and interfaced with a pulse oximeter. Using the plethysmogram measured from the earlobe, Doppler OCT imaging of a 1.5- × 2-mm area at the optic disc at 1.8 volumes/s was synchronized to cardiac cycle to improve sampling of pulsatile blood flow. Postprocessing algorithms were developed to achieve fully automatic calculation of TRBF. We evaluated the repeatability of en face Doppler OCT measurement of TRBF in 10 healthy young subjects using three methods: measurement at 100 kHz with asynchronous acquisition, measurement at 100 kHz with cardiac-gated acquisition, and a control measurement using a 400-kHz instrument with asynchronous acquisition. RESULTS: The median intrasubject coefficients of variation (COV) of the three methods were 8.0%, 4.9%, and 6.1%, respectively. All three methods correlated well, without a significant bias. Mean TRBF measured at 100 kHz with cardiac-gated acquisition was 40.5 ± 8.2 µL/min, and the range was from 26.6 to 55.8 µL/min. CONCLUSIONS: Cardiac-gated en face Doppler OCT can achieve smaller measurement variability than previously reported methods. Although further validation in older subjects and diseased subjects is required, precise measurement of TRBF using cardiac-gated en face Doppler OCT at commercially available imaging speeds should be feasible.
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Velocidad del Flujo Sanguíneo/fisiología , Flujometría por Láser-Doppler/métodos , Flujo Sanguíneo Regional/fisiología , Vasos Retinianos/fisiología , Tomografía de Coherencia Óptica/métodos , Adulto , Algoritmos , Femenino , Humanos , Masculino , Valores de Referencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of conventional OCT and can assess depth-resolved tissue birefringence in addition to intensity. Most existing PS-OCT systems are relatively complex and their clinical translation remains difficult. We present a simple and robust all-fiber PS-OCT system based on swept source technology and polarization depth-encoding. Polarization multiplexing was achieved using a polarization maintaining fiber. Polarization sensitive signals were detected using fiber based polarization beam splitters and polarization controllers were used to remove the polarization ambiguity. A simplified post-processing algorithm was proposed for speckle noise reduction relaxing the demand for phase stability. We demonstrated systems design for both ophthalmic and catheter-based PS-OCT. For ophthalmic imaging, we used an optical clock frequency doubling method to extend the imaging range of a commercially available short cavity light source to improve polarization depth-encoding. For catheter based imaging, we demonstrated 200 kHz PS-OCT imaging using a MEMS-tunable vertical cavity surface emitting laser (VCSEL) and a high speed micromotor imaging catheter. The system was demonstrated in human retina, finger and lip imaging, as well as ex vivo swine esophagus and cardiovascular imaging. The all-fiber PS-OCT is easier to implement and maintain compared to previous PS-OCT systems and can be more easily translated to clinical applications due to its robust design.
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BACKGROUND AND OBJECTIVE: To investigate the potential of ultrahigh-speed swept-source optical coherence tomography angiography (OCTA) to visualize retinal and choroidal vascular changes in patients with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS: Observational, prospective cross-sectional study. An ultrahigh-speed swept-source prototype was used to perform OCTA of the retinal and choriocapillaris microvasculature in 63 eyes of 32 healthy controls and 19 eyes of 15 patients with exudative AMD. MAIN OUTCOME MEASURE: qualitative comparison of the retinal and choriocapillaris microvasculature in the two groups. RESULTS: Choroidal neovascularization (CNV) was clearly visualized in 16 of the 19 eyes with exudative AMD, located above regions of severe choriocapillaris alteration. In 14 of these eyes, the CNV lesions were surrounded by regions of choriocapillaris alteration. CONCLUSION: OCTA may offer noninvasive monitoring of the retinal and choriocapillaris microvasculature in patients with CNV, which may assist in diagnosis and monitoring.
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Angiografía , Coroides/irrigación sanguínea , Neovascularización Coroidal/diagnóstico , Tomografía de Coherencia Óptica , Degeneración Macular Húmeda/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Arterias Ciliares/diagnóstico por imagen , Arterias Ciliares/patología , Estudios Transversales , Exudados y Transudados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Adulto JovenRESUMEN
We used optical coherence tomography (OCT) angiography with a high-speed swept-source OCT system to investigate retinal blood flow changes induced by visual stimulation with a reversing checkerboard pattern. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to quantify blood flow as measured with parafoveal flow index (PFI), which is proportional to the density of blood vessels and the velocity of blood flow in the parafoveal region of the macula. PFI measurements were taken in 15 second intervals during a 4 minute period consisting of 1 minute of baseline, 2 minutes with an 8 Hz reversing checkerboard pattern stimulation, and 1 minute without stimulation. PFI measurements increased 6.1±4.7% (pâ=â.001) during the first minute of stimulation, with the most significant increase in PFI occurring 30 seconds into stimulation (p<0.001). These results suggest that pattern stimulation induces a change to retinal blood flow that can be reliably measured with OCT angiography.
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Mácula Lútea/irrigación sanguínea , Estimulación Luminosa , Vasos Retinianos/diagnóstico por imagen , Tomografía de Coherencia Óptica , Adulto , Angiografía , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Vasos Retinianos/citología , Relación Señal-RuidoRESUMEN
We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in normal human subjects using optical coherence tomography (OCT). An ultrahigh speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan rate is developed for three-dimensional ultrahigh speed imaging of the posterior eye. OCT angiography is used to image three-dimensional vascular structure without the need for exogenous fluorophores by detecting erythrocyte motion contrast between OCT intensity cross-sectional images acquired rapidly and repeatedly from the same location on the retina. En face OCT angiograms of the choriocapillaris and choroidal vasculature are visualized by acquiring cross-sectional OCT angiograms volumetrically via raster scanning and segmenting the three-dimensional angiographic data at multiple depths below the retinal pigment epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as tightly packed networks of feeding arterioles and draining venules, can be visualized at different en face depths. Panoramic ultra-wide field stitched OCT angiograms of the choriocapillaris spanning â¼32 mm on the retina show distinct vascular structures at different fundus locations. Isolated smaller fields at the central fovea and â¼6 mm nasal to the fovea at the depths of the choriocapillaris and Sattler's layer show vasculature structures consistent with established architectural morphology from histological and electron micrograph corrosion casting studies. Choriocapillaris imaging was performed in eight healthy volunteers with OCT angiograms successfully acquired from all subjects. These results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free choriocapillaris and choroidal vasculature imaging, in addition to conventional structural imaging.
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Ojo/patología , Tomografía de Coherencia Óptica/métodos , Adulto , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Despite the challenges in achieving high phase stability, Doppler swept-source/Fourier-domain optical coherence tomography (OCT) has advantages of less fringe washout and faster imaging speeds compared to spectral/Fourier-domain detection. This Letter demonstrates swept-source OCT with a vertical cavity surface-emitting laser light source at 400 kHz sweep rate for phase-sensitive Doppler imaging, measuring pulsatile total retinal blood flow with high sensitivity and phase stability. A robust, simple, and computationally efficient phase stabilization approach for phase-sensitive swept-source imaging is also presented.
Asunto(s)
Retina/patología , Tomografía de Coherencia Óptica/métodos , Algoritmos , Diseño de Equipo , Análisis de Fourier , Humanos , Rayos Láser , Luz , Flujo Sanguíneo Regional , Vasos Retinianos/patología , Sensibilidad y Especificidad , Tomografía de Coherencia Óptica/instrumentaciónRESUMEN
We developed an ultrahigh speed, handheld swept source optical coherence tomography (SS-OCT) ophthalmic instrument using a 2D MEMS mirror. A vertical cavity surface-emitting laser (VCSEL) operating at 1060 nm center wavelength yielded a 350 kHz axial scan rate and 10 µm axial resolution in tissue. The long coherence length of the VCSEL enabled a 3.08 mm imaging range with minimal sensitivity roll-off in tissue. Two different designs with identical optical components were tested to evaluate handheld OCT ergonomics. An iris camera aided in alignment of the OCT beam through the pupil and a manual fixation light selected the imaging region on the retina. Volumetric and high definition scans were obtained from 5 undilated normal subjects. Volumetric OCT data was acquired by scanning the 2.4 mm diameter 2D MEMS mirror sinusoidally in the fast direction and linearly in the orthogonal slow direction. A second volumetric sinusoidal scan was obtained in the orthogonal direction and the two volumes were processed with a software algorithm to generate a merged motion-corrected volume. Motion-corrected standard 6 x 6 mm(2) and wide field 10 x 10 mm(2) volumetric OCT data were generated using two volumetric scans, each obtained in 1.4 seconds. High definition 10 mm and 6 mm B-scans were obtained by averaging and registering 25 B-scans obtained over the same position in 0.57 seconds. One of the advantages of volumetric OCT data is the generation of en face OCT images with arbitrary cross sectional B-scans registered to fundus features. This technology should enable screening applications to identify early retinal disease, before irreversible vision impairment or loss occurs. Handheld OCT technology also promises to enable applications in a wide range of settings outside of the traditional ophthalmology or optometry clinics including pediatrics, intraoperative, primary care, developing countries, and military medicine.
RESUMEN
Optic nerve head (ONH) blood flow may be associated with glaucoma development. A reliable method to quantify ONH blood flow could provide insight into the vascular component of glaucoma pathophysiology. Using ultrahigh-speed optical coherence tomography (OCT), we developed a new 3D angiography algorithm called split-spectrum amplitude-decorrelation angiography (SSADA) for imaging ONH microcirculation. In this study, a method to quantify SSADA results was developed and used to detect ONH perfusion changes in early glaucoma. En face maximum projection was used to obtain 2D disc angiograms, from which the average decorrelation values (flow index) and the percentage area occupied by vessels (vessel density) were computed from the optic disc and a selected region within it. Preperimetric glaucoma patients had significant reductions of ONH perfusion compared to normals. This pilot study indicates OCT angiography can detect the abnormalities of ONH perfusion and has the potential to reveal the ONH blood flow mechanism related to glaucoma.