In this paper, we present methods for 3D visualization and quantitative measurements of retinal blood flow in rats by the use of optical microangiography imaging technique (OMAG). We use ultrahigh sensitive OMAG to provide high-quality 3D RBF perfusion maps in the rat eye, from which the Doppler angle, as well as the diameters of blood vessels, are evaluated. Estimation of flow velocity (i.e. axial flow velocity) is achieved by the use of Doppler OMAG, which has its origins in phase-resolved Doppler optical coherence tomography. The measurements of the Doppler angle, vessel size, and the axial velocity lead to the quantitative assessment of the absolute flow velocity and the blood flow rate in selected retinal vessels. We demonstrate the feasibility of OMAG to provide 3D microangiograms and quantitative assessment of retinal blood flow in a rat model subjected to raised intra-ocular pressure (IOP). We show that OMAG is capable of monitoring the longitudinal response of absolute blood velocity and flow rate of retinal blood vessels to increased IOP in the rat, demonstrating its usefulness for ophthalmological research.
(170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging
We present a novel application of optical microangiography (OMAG) imaging technique for
visualization of depth-resolved vascular network within retina and choroid as well as measurement of
total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a
line scan rate of 140 kHz was developed to image the posterior segment of eyes in mice. By applying
an OMAG algorithm to extract the moving blood flow signals out of the background tissue, we are able
to provide true capillary level imaging of the retinal and choroidal vasculature. The microvascular
patterns within different retinal layers are presented. An en face Doppler OCT
approach [Srinivasan et al., Opt Express 18, 2477 (2010)] was adopted for retinal blood
flow measurement. The flow is calculated by integrating the axial blood flow velocity over the
vessel area measured in an en face plane without knowing the blood vessel angle.
Total retinal blood flow can be measured from both retinal arteries and veins. The results indicate
that OMAG has the potential for qualitative and quantitative evaluation of the microcirculation in
posterior eye compartments in mouse models of retinopathy and neovascularization.
(170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging
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.
(170.3880) Medical and biological imaging; (170.4500) Optical coherence tomography
We demonstrate the depth-resolved and detailed ocular perfusion maps within retina and choroid can be obtained from an ultrahigh sensitive optical microangiography (OMAG). As opposed to the conventional OMAG, we apply the OMAG algorithm along the slow scanning axis to achieve the ultrahigh sensitive imaging to the slow flows within capillaries. We use an 840nm system operating at an imaging rate of 400 frames/sec that requires 3 sec to complete one 3D scan of ~3x3 mm2 area on retina. We show the superior imaging performance of OMAG to provide functional images of capillary level microcirculation at different land-marked depths within retina and choroid that correlate well with the standard retinal pathology.
To characterize optic nerve head (ONH) connective tissue deformation following acute (15 or 30 minutes) intraocular pressure (IOP) elevation within six adult normal monkeys using 3-D histomorphometry.
Trephinated ONH and peripapillary sclera from both eyes of six monkeys, each perfusion fixed with one eye at IOP 10 mmHg and the other at IOP 30 or 45 mmHg by anterior chamber manometer were serial sectioned, 3-D reconstructed, 3-D delineated and quantified using standard parameters. For each monkey, inter-eye differences (high IOP eye minus IOP 10 eye) for each parameter were calculated and compared by ANOVA and EPIDmax both overall and regionally. EPIDmax deformations for each parameter were defined to be those statistically significant differences that exceeded the maximum physiologic inter-eye difference within six bilaterally normal monkeys of a previous report.
Regional EPIDmax laminar thinning, posterior bowing of the peripapillary sclera, thinning and expansion of the scleral canal were present in most high IOP eyes and were colocalized in those demonstrating the most deformation. Laminar deformation was minimal and not only posterior but in some cases anterior in the high IOP eyes. No increase in deformation was seen in the IOP-45 versus the IOP-30 eyes.
ONH connective tissue alterations following acute IOP elevation involve regional thinning, stretching and deformation of the lamina cribrosa and peripapillary sclera which are minimal to modest in magnitude. The time-dependent character of these alterations, as well as their compressive, expansile, and shear effects on the contained axons, astrocytes, laminar and posterior ciliary circulations remain to be determined.
Glaucoma; Acute IOP elevation; Optic Nerve Head; Neural Canal Offset and Depth; Lamina Cribrosa Position and Thickness; Peripapillary Scleral Position and Thickness; Post-NCO
Optical microangiography (OMAG) is a recently developed volumetric imaging technique that is capable of producing 3D images of dynamic blood perfusion within microcirculatory tissue beds in vivo. The imaging contrast of OMAG image is based on the intrinsic optical scattering signals backscattered by the moving blood cells in patent blood vessels, thus it is a label free imaging technique. In this paper, I will first discuss its recent developments that use a constant modulation frequency introduced in the spectral interferograms to achieve the blood perfusion imaging. I will then introduce its latest development that utilizes the inherent blood flow to modulate the spectral interferograms to realize the blood perfusion imaging. Finally, examples of using OMAG to delineate the dynamic blood perfusion, down to capillary level resolution, within living tissues are given, including cortical blood perfusion in the brain of small animals and blood flow within human retina and choroids.
Optical microangiography; Fourier domain optical coherence tomography; microcirculation; cerebral blood flow; neurological disease models; retinal blood flow
To characterize the hemodynamic features and the association with structural damage in the optic nerve head (ONH) of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys.
In five animals with BOA and nine healthy animals under general anesthesia (pentobarbital), intraocular pressure (IOP) was manometrically controlled. ONH blood flow was measured with a laser speckle flow graph device. Basal blood flow in global and quadrantal sectors was measured with IOP set at 10 mm Hg; autoregulation capacity was assessed by comparing blood flow changes before and after IOP was increased from 10 to 30 mm Hg. Spectral-domain optic coherence tomography was used to measure retinal nerve fiber layer thickness (RNFLT) by peripapillary circular scans.
Compared with control eyes, RNFLT in BOA eyes was significantly less in all sectors (P < 0.001) except the nasal (P = 0.25); the average global and sectoral blood flow in all quadrants was significantly lower (P < 0.001). These blood flow changes were significantly correlated with corresponding sectoral RNFLT (P < 0.01) except the nasal (P = 0.25). After IOP was increased to 30 mm Hg, global blood flow was significantly reduced (P < 0.001), but with no regional preferences despite prominent temporal RNFLT loss; no significant blood flow change was observed in control eyes (P = 0.24).
Basal blood flow and autoregulation capacity in the ONH of BOA were significantly compromised, with a close correlation to structural changes. The hemodynamic changes showed no regional preference across the ONH, which was consistent with postmortem histological observations.
In idiopathic bilateral optic atrophy in the rhesus monkey, basal blood flow and autoregulation capacity in the optic nerve head were compromised and closely correlated with structural damage. The finding suggests that similar changes may develop in other diseases with optic nerve atrophy, such as glaucoma.
This letter presents a useful method that combines the full-range complex Fourier domain optical coherence tomography (OCT) with the ultrahigh sensitive optical microangiography (OMAG) to achieve full range complex imaging of blood flow within microcirculatory tissue beds in vivo. We propose to use the fast scanning axis to realize the full range complex imaging, while using the slow axis to achieve OMAG imaging of blood flow. We demonstrate the proposed method by using a high speed 1310nm OCT/OMAG system running at 92 kHz line scan rate to image the flow phantoms in vitro, and the blood flows in tissue beds in vivo.
To determine whether acutely elevated intraocular pressure (IOP) alters peripapillary retinal thickness, retinal nerve fiber layer thickness (RNFLT) or retardance.
Nine adult non-human primates were studied under isoflurane anesthesia. Retinal and RNFL thicknesses were measured by spectral domain optical coherence tomography 30 min after IOP was set to 10 mmHg and 60 min after IOP was set to 45 mmHg. RNFL retardance was measured by scanning laser polarimetery in 10 min intervals for 30 min while IOP was 10 mmHg, then for 60 min while IOP was 45 mmHg, then for another 30 min after IOP was returned to 10 mmHg.
RNFLT measured 1120 μm from the ONH center decreased from 118.1 ± 9.3 μm at an IOP of 10 mmHg to 116.5 ± 8.4 μm at 45 mmHg, or by 1.4 ± 1.8% (p<0.0001). There was a significant interaction between IOP and eccentricity (p=0.0006). Within 800 μm of the ONH center, the RNFL was 4.9 ± 3.4% thinner 60 min after IOP elevation to 45 mmHg (p<0.001), but unchanged for larger eccentricities. The same pattern was observed for retinal thickness, with 1.1 ± 0.8% thinning overall at 45 mmHg (p<0.0001), and a significant effect of eccentricity (p<0.0001) whereby the retina was 4.8 ± 1.2% thinner (p<0.001) within 800 μm, but unchanged beyond that. Retardance increased by a maximum of 2.2 ± 1.1% 60 min after IOP was increased to 45 mmHg (p=0.0031).
The effects of acute IOP elevation on retinal thickness, RNFL thickness and retardance were minor, limited to the immediate ONH surround and unlikely to have meaningful clinical impact.
retinal ganglion cell; retinal nerve fiber layer; scanning laser polarimetry; optical coherence tomography; intraocular pressure
To compare serial optic nerve head (ONH) histology with interpolated B-scans generated from a three-dimensional (3D) spectral domain OCT (SD-OCT) ONH volume acquired in vivo from the same normal monkey eye.
A 15°, ONH SD-OCT volume was acquired in a normal monkey eye, with IOP controlled at 10 mmHg, using the Heidelberg Spectralis. Following perfusion fixation at 10 mmHg, the ONH was trephined, embedded in a paraffin block and sagittal sections were cut at 4 μm intervals. The location of each section was identified within the optic disc photograph by matching the position of the retinal vessels and of Bruch’s membrane opening. By altering the angles of rotation and incidence, “interpolated” B-scans matching the location of the histologic sections were generated using custom software. Structures identified in the histologic sections were compared to signals identified in matched B-scans.
Close matches between histologic sections and interpolated B-scans were identified throughout the extent of the ONH. SD-OCT identified the neural canal opening as the termination of the Bruch’s membrane/retinal pigment complex and Border Tissue as the innermost termination of the choroidal signal. The anterior lamina cribrosa and its continuity with the prelaminar glial columns were also detected.
Volumetric SD-OCT imaging of the ONH was capable of generating interpolated B-scans which accurately matched serial histologic sections. In this single monkey ONH, SD-OCT captured the anterior laminar surface, which is likely to be a key structure in the detection of early ONH structural damage in ocular hypertension and glaucoma.
AIMS—To study the effects of segmental scleral buckling and encircling procedures on tissue circulation in the human optic nerve head (ONH) and choroid and retina.
METHODS—Using the laser speckle method, the normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 seconds and averaged over three pulses in the optic nerve head (NBONH) and choroid and retina (NBch-ret) in 10 patients with unilateral rhegmatogenous retinal detachment (mean age 52 (SD 17)). NBONH, NBch-ret, and intraocular pressure (IOP) in both eyes, and blood pressure (BP) were measured before, and 1, 4, and 12 weeks after the scleral buckling and encircling procedure.
RESULTS—NBch-ret on the buckled side was significantly reduced after surgery and smaller than that in the unoperated contralateral eye throughout the study period (ANOVA, p<0.0001). NBch-ret on the unbuckled side, in the foveal area, NBONH, IOP, and BP showed no significant change.
CONCLUSIONS—It was indicated that the segmental scleral buckling procedure with encircling elements decreased tissue blood velocity in the choroid and retina on the buckled side but caused no significant change on tissue circulation in other areas of the fundus or ONH.
To characterize optic nerve head (ONH) blood flow (BF) changes in nonhuman primate experimental glaucoma (EG) using laser speckle flowgraphy (LSFG) and the microsphere method and to evaluate the correlation between the two methods.
EG was induced in one eye each of 9 rhesus macaques by laser treatment to the trabecular meshwork. Prior to lasering and following onset of intraocular pressure (IOP) elevation, retinal never fiber layer thickness (RNFLT) and ONH BF were measured biweekly by spectral-domain optical coherence tomography and LSFG, respectively, until RNFLT loss was approximately 40% in the EG eye. Final BF was measured by LSFG and by the microsphere method in the anterior ONH (MS-BFANT), posterior ONH (MS-BFPOST), and peripapillary retina (MS-BFPP).
Baseline RNFLT and LSFG-BF showed no difference between the two eyes (P = 0.69 and P = 0.43, respectively, paired t-test). Mean (±SD) IOP was 30 ± 6 mm Hg in EG eyes and 13 ± 2 mm Hg in control eyes (P < 0.001). EG eye RNFLT and LSFG-BF were reduced by 42 ± 16% (P < 0.0001) and 22 ± 13% (P = 0.003), respectively, at the final time point. EG eye MS-BFANT, MS-BFPOST, and MS-BFPP were reduced by 41 ± 17% (P < 0.001), 22 ± 34% (P = 0.06), and 30 ± 12% (P = 0.001), respectively, compared with the control eyes. Interocular ONH LSFG-BF differences significantly correlated to that measured by the microsphere method (R2 = 0.87, P < 0.001).
Chronic IOP elevation causes significant ONH BF decreases in the EG model. The high correlation between the BF reduction measured by LSFG and the microsphere method provides evidence that the LSFG is capable of assaying BF for a critical deep ONH region.
The blood flow in the anterior optic nerve and retrolaminar is significantly reduced in nonhuman primate experimental glaucoma with chronic IOP elevation demonstrated independently by laser speckle flowgraphy and the microsphere method. The measurements of the two methods are significantly correlated.
A comparison between SD-OCT imaging and serial histology in the same normal optic nerve head identifies potential deep targets for longitudinal glaucoma imaging.
To compare serial optic nerve head (ONH) histology with interpolated B-scans generated from a three-dimensional (3-D) spectral domain (SD)-OCT ONH volume acquired in vivo from the same normal monkey eye.
A 15° ONH SD-OCT volume was acquired in a normal monkey eye, with IOP manometrically controlled at 10 mm Hg. After perfusion fixation at 10 mm Hg, the ONH was trephined, the specimen embedded in a paraffin block, and serial sagittal sections cut at 4-μm intervals. The location of each histologic section was identified within the optic disc photograph by matching the position of the retinal vessels and of Bruch's membrane opening. By altering the angles of rotation and incidence, interpolated B-scans matching the location of the histologic sections were generated with custom software. Structures identified in the histologic sections were compared with signals identified in the matched B-scans.
Close matches between histologic sections and interpolated B-scans were identified throughout the extent of the ONH. SD-OCT identified the neural canal opening as the termination of the Bruch's membrane–retinal pigment complex and border tissue as the innermost termination of the choroidal signal. The anterior lamina cribrosa and its continuity with the prelaminar glial columns were also detected by SD-OCT.
Volumetric SD-OCT imaging of the ONH generates interpolated B-scans that accurately match serial histologic sections. SD-OCT captures the anterior laminar surface, which is likely to be a key structure in the detection of early ONH damage in ocular hypertension and glaucoma.
Diabetic neuropathy (DN) is, at least in part, associated with the functional attenuation of vasa nervorum, the microvascular structure of peripheral nerves. Microvascular imaging options for vasa nervorum still remain limited. In this work, Optical micro-angiography (OMAG), a volumetric, label-free imaging technique is utilized for characterizing, with high resolution, blood perfusion of peripheral nerve in diabetic mice. We demonstrate that OMAG is able to visualize the structure of microvasculature and to quantify the changes of dynamic blood flow and vessel diameters during administration of vessel stimulator in both diabetic and normal mice. The results indicate the potential of OMAG to assess the blood supply of nerve involved in the pathology and treatment of DN.
Vasa nervorum; microcirculation; peripheral nerve; diabetes; optical microangiography
Optical microangiography (OMAG) and Doppler optical microangiography (DOMAG) are two non-invasive techniques capable of determining the tissue microstructural content, microvasculature angiography, and blood flow velocity and direction. These techniques were used to visualize the acute and chronic microvascular and tissue responses upon an injury in vivo. A tissue wound was induced using a 0.5 mm biopsy punch on a mouse pinna. The changes in the microangiography, blood flow velocity and direction were quantified for the acute (<30 min) wound response and the changes in the tissue structure and microangiography were determined for the chronic wound response (30 min–60 days). The initial wound triggered recruitment of peripheral capillaries, as well as redirection of main arterial and venous blood flow within 3 min. The complex vascular networks and new vessel formation were quantified during the chronic response using fractal dimension. The highest rate of wound closure occurred between days 8 and 22. The vessel tortuosity increased during this time suggesting angiogenesis. Taken together, these data signify that OMAG has the capability to track acute and chronic changes in blood flow, microangiography and structure during wound healing. The use of OMAG has great potential to improve our understanding of vascular and tissue responses to injury in order to develop more effective therapeutics.
BACKGROUND/AIMS—Vascular insufficiency due to abnormal autoregulation has been proposed as a major factor in the development of glaucoma. The anterior optic nerve is primarily perfused by the short posterior ciliary arteries. The autoregulatory capacity of these vessels in response to acutely elevated intraocular pressure (IOP) was examined in normal human subjects.
METHODS—Colour Doppler imaging was performed on the short posterior ciliary arteries of 10 normal subjects at baseline and during four incremental IOP elevations. Using a scleral suction cup placed temporally, IOP was elevated to approximately 25, 30, 40, and 50 mm Hg. Additional measurements were performed immediately after pressure release. Systolic and diastolic flow velocities were measured and Pourcelot's resistivity index was calculated.
RESULTS—Systolic and diastolic flow velocities decreased linearly with each incremental increase in IOP (p<0.001). Pourcelot's resistivity index increased linearly with each incremental increase in IOP (p<0.001). Changes in end diastolic velocity, peak systolic velocity, and Pourcelot's resistivity index were linearly related to changes in IOP.
CONCLUSION—The normal healthy eye is not able to autoregulate to maintain PCA blood flow velocities in response to acute large elevations in IOP.
Keywords: blood flow; colour Doppler imaging; posterior ciliary artery; retrobulbar haemodynamics
Several tissue pathologies are correlated with changes in the blood vessel morphology and microcirculation that supplies the tissue. Optical coherence tomography (OCT) is an imaging technique that enables acquiring non-invasive three-dimensional images of biological structures with micrometer resolution. Optical microangiography (OMAG) is a method of processing OCT data which enables visualizing the three-dimensional blood vessel morphology within biological tissues. OMAG has high spatial resolution which allows visualizing single capillary vessels, and does not require the use of contrast agents. The intrinsic optical signals backscattered by the moving blood cells inside blood vessels are used as the contrast for which OMAG images are based on. In this paper, we discuss a brief review of the OMAG theory, and present some examples of applications for this technique.
Fourier domain optical coherence tomography; optical microangiography
Background: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT).
Methods: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude.
Results: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol).
Conclusions: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.
dorzolamide; timolol; ocular blood flow; glaucoma; ocular hypertension
Although the optic nerve head is the likely site of axonal injury in glaucoma, little is known about the initial cellular responses to elevated intraocular pressure exposure. The authors used microarray analysis and their rat glaucoma model to identify cell proliferation and potential interleukin-6 type cytokine signaling as important early nerve head responses.
In glaucoma, the optic nerve head (ONH) is the principal site of initial axonal injury, and elevated intraocular pressure (IOP) is the predominant risk factor. However, the initial responses of the ONH to elevated IOP are unknown. Here the authors use a rat glaucoma model to characterize ONH gene expression changes associated with early optic nerve injury.
Unilateral IOP elevation was produced in rats by episcleral vein injection of hypertonic saline. ONH mRNA was extracted, and retrobulbar optic nerve cross-sections were graded for axonal degeneration. Gene expression was determined by microarray and quantitative PCR (QPCR) analysis. Significantly altered gene expression was determined by multiclass analysis and ANOVA. DAVID gene ontology determined the functional categories of significantly affected genes.
The Early Injury group consisted of ONH from eyes with <15% axon degeneration. By array analysis, 877 genes were significantly regulated in this group. The most significant upregulated gene categories were cell cycle, cytoskeleton, and immune system process, whereas the downregulated categories included glucose and lipid metabolism. QPCR confirmed the upregulation of cell cycle-associated genes and leukemia inhibitory factor (Lif) and revealed alterations in expression of other IL-6–type cytokines and Jak-Stat signaling pathway components, including increased expression of IL-6 (1553%). In contrast, astrocytic glial fibrillary acidic protein (Gfap) message levels were unaltered, and other astrocytic markers were significantly downregulated. Microglial activation and vascular-associated gene responses were identified.
Cell proliferation and IL-6–type cytokine gene expression, rather than astrocyte hypertrophy, characterize early pressure-induced ONH injury.
A multi-functional imaging system capable of determining relative changes in blood flow, hemoglobin concentration, and morphological features of the blood vasculature is demonstrated. The system combines two non-invasive imaging techniques, a dual-wavelength laser speckle contrast imaging (2-LSI) and an optical microangiography (OMAG) system. 2-LSI is used to monitor the changes in the dynamic blood flow and the changes in the concentration of oxygenated (HbO), deoxygenated (Hb) and total hemoglobin (HbT). The OMAG system is used to acquire high resolution images of the functional blood vessel network. The vessel area density (VAD) is used to quantify the blood vessel network morphology, specifically the capillary recruitment. The proposed multi-functional system is employed to assess the blood perfusion status from a mouse pinna before and immediately after a burn injury. To our knowledge, this is the first non-invasive, non-contact and multifunctional imaging modality that can simultaneously measure variations of several blood perfusion parameters.
(170.6930) Tissue; (040.3060) Infrared; (120.6150) Speckle imaging; (170.4500) Optical coherence tomography; (130.3120) Integrated optics devices
Studying the inner ear microvascular dynamics is extremely important to understand the cochlear function and to further advance the diagnosis, prevention and treatment of many otologic disorders. However, there is currently no effective imaging tool available that is able to access the blood flow within the intact cochlea. In this paper, we report the use of an ultrahigh sensitive optical micro angiography (UHS-OMAG) imaging system to image 3D microvascular perfusion within the intact cochlea in living mice. The UHS-OMAG image system used in this study is based on spectral domain optical coherence tomography, which uses a broadband light source centered at 1300nm with an imaging rate of 47,000 A-scans per second, capable of acquiring high-resolution B scans at 300 frames/sec. The technique is sensitive enough to image very slow blood flow velocities, such as those found in capillary networks. The 3D imaging acquisition time for a whole cochlea is ~4.1 sec. We demonstrate that volumetric reconstruction of microvascular flow obtained by UHS-OMAG provides a comprehensive perfusion map of several regions of the cochlea, including the otic capsule, the stria vascularis of the apical and middle turns and the radiating arterioles that emanate from the modiolus.
Biomedical optical imaging; Blood flow measurement; optical interferometry; optical coherence tomography; optical microangiography
Goggles are frequently worn in the sport of swimming and are designed to form a seal around the periorbital tissue orbit. The resultant pressure on the eye may have the potential to affect intraocular pressure and blood flow of the optic nerve head. This study evaluates the influence of wearing swimming goggles on intraocular pressure (IOP) and blood flow of the ocular nerve head (ONH) in normal subjects.
Materials and Methods
Thirty healthy participants took part in this study. The IOP of each participant was measured using a Goldmann tonometer. Measurements were taken immediately before putting on swimming goggles, at 5, 10, 30, and 60 minutes after putting on swimming goggles, and then immediately after taking off the goggles. Blood flow of the ONH was measured using the Heidelberg retinal flowmeter.
The average IOP before, during and after wearing the swimming goggles were 11.88 ± 2.82 mmHg, 14.20 ± 2.81mmHg and 11.78 ± 2.89 mmHg, respectively. The IOP increased immediately after putting on the goggles (p < 0.05) and then returned to normal values immediately after removal (p > 0.05). Blood flow of the ONH was 336.60 ± 89.07 Arbitrary Units (AU) before and 319.18 ± 96.02 AU after the goggles were worn (p < 0.05).
A small but significant IOP elevation was observed immediately after the swimming goggles were put on. This elevated IOP was maintained while the goggles were kept on, and then returned to normal levels as soon as they were taken off. Blood flow of the ONH did not change significantly throughout the experiment. These facts should be considered for safety concerns, especially in advanced glaucoma patients.
Swimming goggles; intraocular pressure; blood flow of optic nerve head
AIMS—To assess the effects of the nitric oxide donor 5-isosorbide mononitrate (ISMO) on blood flow in the optic nerve head (ON flow) and choroid (Ch flow).
METHODS—Laser Doppler flowmetry was used to measure ON flow and Ch flow in 12 normal subjects by aiming the laser beam at the fovea and at the temporal rim, respectively. In a double masked, randomised, crossover design, each subject received orally on separate days either 20 mg of 5-isosorbide mononitrate (ISMO) or placebo. Ch flow and ON flow were determined monocularly at baseline and 1 hour after dosing. In the last six subjects, additional measurements were obtained at 3 hours. Mean arterial blood pressure (BPm), heart rate, and intraocular pressure (IOP) were monitored, and ocular perfusion pressure (PP) was estimated.
RESULTS—No significant changes in ON flow, PP, IOP, or BPm were observed following placebo. Following ISMO, ON flow increased from baseline by 19.8% (SEM 9.3%) at 1 hour (paired t test, p= 0.058) and by 33.1% (7.5%) at 3 hours (p= 0.007). Compared with the changes following placebo, statistically significant increases in ON flow were observed both at 1 (p=0.050) and 3 hours (p=0.041) after ISMO treatment. Compared with placebo, PP decreased significantly 1 hour after ISMO dosing (p=0.039), mainly as a function of reduced BPm. A significant inverse correlation (R=−0.618; p=0.032) was observed between the percentage changes in PP and ON flow 1 hour following ISMO administration, but not after placebo. No significant change in foveal Ch flow was documented.
CONCLUSIONS—These results suggest that, in normal subjects, ISMO increases significantly ON flow but not Ch flow. The inverse correlation observed between PP and ON flow suggests that the same mechanism(s) responsible for systemic vasodilatation and blood pressure decrease may also cause the ON flow increase.
Keywords: choroidal circulation; isosorbide mononitrate; laser Doppler flowmetry; nitric oxide; optic nerve head circulation
Primary open angle glaucoma (OAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and associated visual field loss. OAG is an emerging disease with increasing costs and negative outcomes, yet its fundamental pathophysiology remains largely undetermined. A major treatable risk factor for glaucoma is elevated intraocular pressure (IOP). Despite the medical lowering of IOP, however, some glaucoma patients continue to experience disease progression and subsequent irreversible vision loss. The scientific community continues to accrue evidence suggesting that alterations in ocular blood flow play a prominent role in OAG disease processes. This article develops the thesis that dysfunctional regulation of ocular blood flow may contribute to glaucomatous optic neuropathy. Evidence suggests that impaired vascular autoregulation renders the optic nerve head susceptible to decreases in ocular perfusion pressure, increases in IOP, and/or increased local metabolic demands. Ischemic damage, which likely contributes to further impairment in autoregulation, results in changes to the optic nerve head consistent with glaucoma. Included in this review are discussions of conditions thought to contribute to vascular regulatory dysfunction in OAG, including atherosclerosis, vasospasm, and endothelial dysfunction.
glaucoma; autoregulation; blood flow; atherosclerosis; vasospasm; endothelial dysfunction
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.
(170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging; (170.4470) Ophthalmology