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BJO Online First, published on March 2, 2015 as 10.1136/bjophthalmol-2014-306010 Innovations
Retinal angiography with real-time speckle variance optical coherence tomography Jing Xu,1 Sherry Han,2 Chandrakumar Balaratnasingam,2,3,4 Zaid Mammo,2 Kevin S K Wong,1 Sieun Lee,1 Michelle Cua,1 Mei Young,2 Andrew Kirker,2 David Albiani,2 Farzin Forooghian,2 Paul Mackenzie,2 Andrew Merkur,2 Dao-Yi Yu,3,4 Marinko V Sarunic1 1
School of Engineering Science, Simon Fraser University, Burnaby, British Columbia, Canada 2 Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada 3 Centre for Ophthalmology and Visual Science, Lions Eye Institute, The University of Western Australia, Perth, Western Australia, Australia 4 The ARC Centre of Excellence in Vision Science, The University of Western Australia, Perth, Western Australia, Australia Correspondence to Dr Marinko Sarunic, School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada V5A 1S6; [email protected] Received 17 August 2014 Revised 31 October 2014 Accepted 5 February 2015
ABSTRACT This report describes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for visualising blood flow within human retinal capillary networks. This imaging system uses a custom-built swept source OCT system operating at a line rate of 100 kHz. Real-time processing and visualisation is implemented on a consumer grade graphics processing unit. To investigate the quality of microvascular detail acquired with this device we compared images of human capillary networks acquired with svOCT and fluorescein angiography. We found that the density of capillary microvasculature acquired with this svOCT device was visibly greater than fluorescein angiography. We also found that this svOCT device had the capacity to generate en face images of distinct capillary networks that are morphologically comparable with previously published histological studies. Finally, we found that this svOCT device has the ability to noninvasively illustrate the common manifestations of diabetic retinopathy and retinal vascular occlusion. The results of this study suggest that graphics processing unit accelerated svOCT has the potential to non-invasively provide useful quantitative information about human retinal capillary networks. Therefore svOCT may have clinical and research applications for the management of retinal microvascular diseases, which are a major cause of visual morbidity worldwide.
INTRODUCTION
To cite: Xu J, Han S, Balaratnasingam C, et al. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-306010
Optical coherence tomography (OCT) and fluorescein angiography (FA) are invaluable tools in clinical ophthalmology. Current OCT technology has the capacity to provide high-resolution histologylike anatomical information of different retinal layers. In contrast, FA provides wide-angle information of the retinal circulation and, in particular, is useful for identifying areas of blood-retina-barrier compromise. One of the limitations of FA is the need to inject fluorescein dye which is associated with minor side effects. There is also a small but significant risk of anaphylaxis and death with FA (estimated at 1 in 222 000).1 Furthermore, only limited information concerning depth along the z-axis can be acquired with FA. The ability to acquire en face images of distinct capillary beds with current FA and OCT technology is limited. Recent reports have described adaptations to OCT technology that permit in vivo examination of the human microvasculature.2–6 However, generating images of vascular networks is
computationally intensive and usually requires off-line image processing.7 8 The time to image patients is limited and acquiring usable data without real-time feedback of the vascular network visibility can pose a great challenge. We present a prototype device with hardwareaccelerated processing of speckle variance OCT (svOCT), as first described by Mariampillai et al,4 for real-time visualisation of human microvascular networks. In this study we illustrate the capacity of the device to provide anatomical information of retinal capillary beds without contrast agent administration. The device presented here may therefore have broad clinical application for the management of retinal vascular diseases.
METHODS All subjects were imaged at the Eye Care Centre in Vancouver. We used a Topcon TRC-50DX fundus camera, with 5.0 MP resolution, for standard FA image acquisition, and an OPTOS 200Tx Scanning Laser Ophthalmoscope for ultra-wide-field image acquisition. The clinical prototype svOCT used in this report is based on a 1060 nm swept-source OCT system with 100 kHz A-scan rate. The axial resolution was ∼6 mm in tissue and the estimated focal waist (1/e2 Gaussian radius) was ∼7.3 mm at the retina. For the speckle variance calculation, three repeat acquisitions at each B-scan location were acquired. The scan area was sampled in a 350×300 (×3) grid, which required ∼3.15 s for image acquisition. The real-time svOCT processing and display was performed using our open source software.9 10 The following qualitative assessments were performed in this study: 1. To determine if there was a difference in the morphology and density of capillary networks represented in svOCT and FA images (figure 1). Comparisons were made between macular images from healthy human subjects that were imaged with the two modalities. 2. To determine if the morphology of nerve fibre layer (NFL) peripapillary capillary networks could be imaged with svOCT (figure 1). 3. To determine if svOCT had the capacity to isolate and image distinct capillary networks within the human retina (figure 2). The perifoveal region of a healthy human subject was imaged and manual segmentation of B-scan images was used to generate en face images of different retinal capillary networks. Images were acquired of histologically documented capillary networks including the
Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations
Figure 1 Human macula and peripapillary vasculature. Comparison between fluorescein angiography (FA) (A) and speckle variance optical coherence tomography (svOCT) (B) images captured from the macula of a healthy subject suggests that the density of capillary detail may be greater in the svOCT image. The FA image was acquired with a 40° field of view and cropped to correspond to the region acquired with svOCT. Fluorescein angiogram of the optic disk and peripapillary regions from another healthy human subject is presented in panel C. Insets I–VI are svOCT images that provide anatomical detail of capillary networks in various nerve fibre layer eccentricities (Scale bar=200 μm). NFL network, ganglion cell layer/inner plexiform layer network and outer plexiform layer network (figure 2). 4. To determine if the status of the retinal vasculature in diabetic retinopathy and retinal vein occlusion could be identified using svOCT. Areas of retinal pathology, identified on FA, were imaged using svOCT (figures 3 and 4). Comparisons were made between FA and svOCT images.
RESULTS Capillary density in svOCT images may have been greater than FA (figure 1). We also found that svOCT was able to identify with greater precision the terminal capillaries around the foveal avascular zone. NFL capillary networks in the peripapillary regions were clearly visualised with svOCT. 2
The morphological characteristics of capillary networks in en face images correlated closely with the results of previous histological studies performed on the human retina (figure 2).11 12 We observed that capillaries in the NFL network were longitudinally orientated with a trajectory that was predominantly parallel to the direction of retinal ganglion cell axons in the NFL. In contrast, the capillaries in the ganglion cell layer/inner plexiform layer network demonstrated a complex threedimensional organisation. The capillary network in the outer plexiform layer was found to be planar with multiple closed loops. Colour-coded projection of various capillary network images permitted us to explore important spatial vascular relationships within the retina and also allowed us to identify the change in capillary topography relative to retinal depth (figure 2). Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations
Figure 2 Identification of distinct perifoveal human capillary networks with speckle variance optical coherence tomography (svOCT). Representative B-scan image of the human retina (A) demonstrates various inner retinal layers including nerve fibre layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). Manual segmentation of B-scan images (red, green and blue lines) allows generation of en face OCT images of different capillary networks within, and between, these retinal layers. The morphology of capillary networks within the NFL (B) and networks located between GCL and INL (C) and INL and ONL (D) bear close morphological correlations to previous histological studies of these networks. Superimposing the en face images (E) also provides information on the spatial relationships between various networks. In the merged image, the NFL network is false-coloured red, the GCL-INL network is false-coloured green and the INL-ONL network is false-coloured blue.(Scale bar=200 μm). Figures 3 and 4 illustrate the FA appearance of a patient with proliferative diabetic retinopathy and hemiretinal vein occlusion, respectively. Insets demonstrate in great detail the morphological appearance of the vascular networks at various eccentricities, as examined with svOCT imaging and FA imaging. Optic disk neovascularisation is clearly seen using svOCT as are areas of capillary dropout within and outside the macula.
DISCUSSION AND CONCLUSIONS This study highlights the utility of our prototype svOCT device for non-invasive real-time imaging the human retinal vasculature. The Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Figure 3 Comparison between speckle variance optical coherence tomography (svOCT) and fluorescein angiography (FA) for imaging diabetic retinopathy. Wide field FA (A) and a corresponding colour fundus photo (B) of a patient with diabetes demonstrate proliferative retinopathy with marked capillary dropout. Insets provide a magnified view of pathological eccentricities that were imaged with FA (left panel) and svOCT (right panel). In inset I, the morphological characteristics of optic disk neovascular vessels is clearly seen on svOCT while on FA the same region is typified by increased hyperfluorescence, with blurred margins, implicating this region as a site of blood-retina-barrier breakdown. In insets 2 and 3, the anatomical detail of capillary loss is clearly evident on svOCT images while the same regions on FA are marked by a generalised ground glass appearance (Scale bar=500 mm).
results presented suggest that svOCT is complementary to FA, and may be superior in providing retinal capillary detail. Previous work has shown that the anatomical information captured on FA is predominantly that of the innermost retinal capillary networks.13 The en face images of distinct capillary networks illustrated in this report demonstrate that this device 3
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations
Figure 4 Comparison between speckle variance optical coherence tomography (svOCT) and fluorescein angiography (FA) for imaging retinal vein occlusion. FA (A) and a corresponding colour fundus photo (B) of a patient with a superior hemiretinal vein occlusion with associated capillary dropout in the macula. Inset I provides a magnified view of the macula imaged with FA (left panel) and svOCT (right panel). Areas of capillary fallout are clearly seen in the superior macula on the svOCT image (arrow heads) while there is total preservation of the capillary circulation in the inferior hemimacula (Scale bar=500 mm).
has the capability to provide depth-resolved information from the retinal capillary networks. We acknowledge however that further work is required to quantify the detail of anatomical information that is evident on svOCT images. Also, svOCT has the potential to non-invasively identify important pathological manifestations of retinal vascular diseases; ischaemia and proliferation. In patients with compromised renal function, where the administration of fluorescein dye may be contraindicated, this device may be particularly advantageous. In this report we present images with a field of view ranging from 5×5 mm2 and 1×1 mm2. It is possible to acquire images with a wider field of view using a using a system with higher acquisition speed, hardware motion tracking and image mosaicking.14 15 Further quantitative work is required to define the role of svOCT in clinical practice.
acquisition, processing, analysis and clinical correlation. D-YY: Conception of the project, data acquisition, processing, analysis and clinical correlation. MVS: Conception of the project, design of technology, data acquisition, processing and analysis. All of the listed authors were involved in the drafting and revising the work for important intellectual content, have submitted their approval of the final manuscript version being submitted, and are in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Funding Support for this research was provided in part by the Michael Smith Foundation for Health Research, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, and National Health and Medical Research Council of Australia. Competing interests None. Patient consent Obtained. Ethics approval This study was approved by the human ethics committee at the University of British Columbia. Provenance and peer review Not commissioned; externally peer reviewed.
Contributors JX: Conception of the project, design of technology, data acquisition, processing and analysis. SH Conception of the project, data acquisition, processing and analysis. CB: Conception of the project, data acquisition, processing and analysis. ZM: Conception of the project, data acquisition, processing and analysis. KW: Conception of the project, design of technology, data acquisition. SL: Conception of the project, design of technology, data acquisition. MC: Conception of the project, data acquisition, processing and analysis. MY: Data acquisition, processing and analysis. AK: Data processing, analysis and clinical interpretation. DA: Data processing, analysis and clinical interpretation. FF: Data processing, analysis and clinical interpretation. PM: Conception of the project, data acquisition, processing, analysis and clinical correlation. AM: Conception of the project, data 4
REFERENCES 1 2
3
Yannuzzi LA, Rohrer KT, Tindel LJ, et al. Fluorescein angiography complication survey. Ophthalmology 1986;93:611–17. Wang RK, An L, Francis P, et al. Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography. Opt Lett 2010;35:1467–9. Fingler J, Zawadzki RJ, Werner JS, et al. Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique. Opt Express 2009;17:22190–200.
Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
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Mariampillai A, Standish BA, Moriyama EH, et al. Speckle variance detection of microvasculature using swept-source optical coherence tomography. Opt Letters 2008;33(13):1530–1532 Jia Y, Tan O, Tokayer J, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express 2012;20:4710–25. Adhi M, Duker JS. Optical coherence tomography--current and future applications. Curr Opin Ophthalmol 2013;24:213–21. Schwartz DM, Fingler J, Kim DY, et al. Phase-variance optical coherence tomography: a technique for noninvasive angiography. Ophthalmology 2013;121:180–7. Jia Y, Wei E, Wang X, et al. Optical coherence tomography angiography of optic disc perfusion in glaucoma. Ophthalmology 2014;121:1322–32. Xu J, Wong K, Jian Y, et al. Real-time acquisition and display of flow contrast using speckle variance optical coherence tomography in a graphics processing unit. J Biomed Opt 2014;19:026001. Xu J, Wong K, Jian Y, et al. GPU Open Source Code with svOCT Implementation. Secondary GPU Open Source Code with svOCT Implementation. http://borg.ensc.sfu. ca/research/svoct-gpu-code.html (accessed 12 Aug 2014).
Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
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Chan G, Balaratnasingam C, Yu PK, et al. Quantitative morphometry of perifoveal capillary networks in the human retina. Invest Ophthalmol Vis Sci 2012;53:5502–14. Tan PE, Yu PK, Balaratnasingam C, et al. Quantitative confocal imaging of the retinal microvasculature in the human retina. Invest Ophthalmol Vis Sci 2012;53:5728–36. Mendis KR, Balaratnasingam C, Yu P, et al. Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail. Invest Ophthalmol Vis Sci 2010;51: 5864–9. Braaf B, Vienola KV, Sheehy CK, et al. Real-time eye motion correction in phase-resolved OCT angiography with tracking SLO. Biomed Opt Express 2013;4:51–65. Hendargo HC, Estrada R, Chiu SJ, et al. Automated non-rigid registration and mosaicing for robust imaging of distinct retinal capillary beds using speckle variance optical coherence tomography. Biomed Opt Express 2013;4:803–21.
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Retinal angiography with real-time speckle variance optical coherence tomography Jing Xu, Sherry Han, Chandrakumar Balaratnasingam, Zaid Mammo, Kevin S K Wong, Sieun Lee, Michelle Cua, Mei Young, Andrew Kirker, David Albiani, Farzin Forooghian, Paul Mackenzie, Andrew Merkur, Dao-Yi Yu and Marinko V Sarunic Br J Ophthalmol published online March 2, 2015
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BJO Online First, published on March 2, 2015 as 10.1136/bjophthalmol-2014-306010 Innovations
Retinal angiography with real-time speckle variance optical coherence tomography Jing Xu,1 Sherry Han,2 Chandrakumar Balaratnasingam,2,3,4 Zaid Mammo,2 Kevin S K Wong,1 Sieun Lee,1 Michelle Cua,1 Mei Young,2 Andrew Kirker,2 David Albiani,2 Farzin Forooghian,2 Paul Mackenzie,2 Andrew Merkur,2 Dao-Yi Yu,3,4 Marinko V Sarunic1 1
School of Engineering Science, Simon Fraser University, Burnaby, British Columbia, Canada 2 Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada 3 Centre for Ophthalmology and Visual Science, Lions Eye Institute, The University of Western Australia, Perth, Western Australia, Australia 4 The ARC Centre of Excellence in Vision Science, The University of Western Australia, Perth, Western Australia, Australia Correspondence to Dr Marinko Sarunic, School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada V5A 1S6; [email protected] Received 17 August 2014 Revised 31 October 2014 Accepted 5 February 2015
ABSTRACT This report describes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for visualising blood flow within human retinal capillary networks. This imaging system uses a custom-built swept source OCT system operating at a line rate of 100 kHz. Real-time processing and visualisation is implemented on a consumer grade graphics processing unit. To investigate the quality of microvascular detail acquired with this device we compared images of human capillary networks acquired with svOCT and fluorescein angiography. We found that the density of capillary microvasculature acquired with this svOCT device was visibly greater than fluorescein angiography. We also found that this svOCT device had the capacity to generate en face images of distinct capillary networks that are morphologically comparable with previously published histological studies. Finally, we found that this svOCT device has the ability to noninvasively illustrate the common manifestations of diabetic retinopathy and retinal vascular occlusion. The results of this study suggest that graphics processing unit accelerated svOCT has the potential to non-invasively provide useful quantitative information about human retinal capillary networks. Therefore svOCT may have clinical and research applications for the management of retinal microvascular diseases, which are a major cause of visual morbidity worldwide.
INTRODUCTION
To cite: Xu J, Han S, Balaratnasingam C, et al. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-306010
Optical coherence tomography (OCT) and fluorescein angiography (FA) are invaluable tools in clinical ophthalmology. Current OCT technology has the capacity to provide high-resolution histologylike anatomical information of different retinal layers. In contrast, FA provides wide-angle information of the retinal circulation and, in particular, is useful for identifying areas of blood-retina-barrier compromise. One of the limitations of FA is the need to inject fluorescein dye which is associated with minor side effects. There is also a small but significant risk of anaphylaxis and death with FA (estimated at 1 in 222 000).1 Furthermore, only limited information concerning depth along the z-axis can be acquired with FA. The ability to acquire en face images of distinct capillary beds with current FA and OCT technology is limited. Recent reports have described adaptations to OCT technology that permit in vivo examination of the human microvasculature.2–6 However, generating images of vascular networks is
computationally intensive and usually requires off-line image processing.7 8 The time to image patients is limited and acquiring usable data without real-time feedback of the vascular network visibility can pose a great challenge. We present a prototype device with hardwareaccelerated processing of speckle variance OCT (svOCT), as first described by Mariampillai et al,4 for real-time visualisation of human microvascular networks. In this study we illustrate the capacity of the device to provide anatomical information of retinal capillary beds without contrast agent administration. The device presented here may therefore have broad clinical application for the management of retinal vascular diseases.
METHODS All subjects were imaged at the Eye Care Centre in Vancouver. We used a Topcon TRC-50DX fundus camera, with 5.0 MP resolution, for standard FA image acquisition, and an OPTOS 200Tx Scanning Laser Ophthalmoscope for ultra-wide-field image acquisition. The clinical prototype svOCT used in this report is based on a 1060 nm swept-source OCT system with 100 kHz A-scan rate. The axial resolution was ∼6 mm in tissue and the estimated focal waist (1/e2 Gaussian radius) was ∼7.3 mm at the retina. For the speckle variance calculation, three repeat acquisitions at each B-scan location were acquired. The scan area was sampled in a 350×300 (×3) grid, which required ∼3.15 s for image acquisition. The real-time svOCT processing and display was performed using our open source software.9 10 The following qualitative assessments were performed in this study: 1. To determine if there was a difference in the morphology and density of capillary networks represented in svOCT and FA images (figure 1). Comparisons were made between macular images from healthy human subjects that were imaged with the two modalities. 2. To determine if the morphology of nerve fibre layer (NFL) peripapillary capillary networks could be imaged with svOCT (figure 1). 3. To determine if svOCT had the capacity to isolate and image distinct capillary networks within the human retina (figure 2). The perifoveal region of a healthy human subject was imaged and manual segmentation of B-scan images was used to generate en face images of different retinal capillary networks. Images were acquired of histologically documented capillary networks including the
Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations
Figure 1 Human macula and peripapillary vasculature. Comparison between fluorescein angiography (FA) (A) and speckle variance optical coherence tomography (svOCT) (B) images captured from the macula of a healthy subject suggests that the density of capillary detail may be greater in the svOCT image. The FA image was acquired with a 40° field of view and cropped to correspond to the region acquired with svOCT. Fluorescein angiogram of the optic disk and peripapillary regions from another healthy human subject is presented in panel C. Insets I–VI are svOCT images that provide anatomical detail of capillary networks in various nerve fibre layer eccentricities (Scale bar=200 μm). NFL network, ganglion cell layer/inner plexiform layer network and outer plexiform layer network (figure 2). 4. To determine if the status of the retinal vasculature in diabetic retinopathy and retinal vein occlusion could be identified using svOCT. Areas of retinal pathology, identified on FA, were imaged using svOCT (figures 3 and 4). Comparisons were made between FA and svOCT images.
RESULTS Capillary density in svOCT images may have been greater than FA (figure 1). We also found that svOCT was able to identify with greater precision the terminal capillaries around the foveal avascular zone. NFL capillary networks in the peripapillary regions were clearly visualised with svOCT. 2
The morphological characteristics of capillary networks in en face images correlated closely with the results of previous histological studies performed on the human retina (figure 2).11 12 We observed that capillaries in the NFL network were longitudinally orientated with a trajectory that was predominantly parallel to the direction of retinal ganglion cell axons in the NFL. In contrast, the capillaries in the ganglion cell layer/inner plexiform layer network demonstrated a complex threedimensional organisation. The capillary network in the outer plexiform layer was found to be planar with multiple closed loops. Colour-coded projection of various capillary network images permitted us to explore important spatial vascular relationships within the retina and also allowed us to identify the change in capillary topography relative to retinal depth (figure 2). Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations
Figure 2 Identification of distinct perifoveal human capillary networks with speckle variance optical coherence tomography (svOCT). Representative B-scan image of the human retina (A) demonstrates various inner retinal layers including nerve fibre layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). Manual segmentation of B-scan images (red, green and blue lines) allows generation of en face OCT images of different capillary networks within, and between, these retinal layers. The morphology of capillary networks within the NFL (B) and networks located between GCL and INL (C) and INL and ONL (D) bear close morphological correlations to previous histological studies of these networks. Superimposing the en face images (E) also provides information on the spatial relationships between various networks. In the merged image, the NFL network is false-coloured red, the GCL-INL network is false-coloured green and the INL-ONL network is false-coloured blue.(Scale bar=200 μm). Figures 3 and 4 illustrate the FA appearance of a patient with proliferative diabetic retinopathy and hemiretinal vein occlusion, respectively. Insets demonstrate in great detail the morphological appearance of the vascular networks at various eccentricities, as examined with svOCT imaging and FA imaging. Optic disk neovascularisation is clearly seen using svOCT as are areas of capillary dropout within and outside the macula.
DISCUSSION AND CONCLUSIONS This study highlights the utility of our prototype svOCT device for non-invasive real-time imaging the human retinal vasculature. The Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Figure 3 Comparison between speckle variance optical coherence tomography (svOCT) and fluorescein angiography (FA) for imaging diabetic retinopathy. Wide field FA (A) and a corresponding colour fundus photo (B) of a patient with diabetes demonstrate proliferative retinopathy with marked capillary dropout. Insets provide a magnified view of pathological eccentricities that were imaged with FA (left panel) and svOCT (right panel). In inset I, the morphological characteristics of optic disk neovascular vessels is clearly seen on svOCT while on FA the same region is typified by increased hyperfluorescence, with blurred margins, implicating this region as a site of blood-retina-barrier breakdown. In insets 2 and 3, the anatomical detail of capillary loss is clearly evident on svOCT images while the same regions on FA are marked by a generalised ground glass appearance (Scale bar=500 mm).
results presented suggest that svOCT is complementary to FA, and may be superior in providing retinal capillary detail. Previous work has shown that the anatomical information captured on FA is predominantly that of the innermost retinal capillary networks.13 The en face images of distinct capillary networks illustrated in this report demonstrate that this device 3
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations
Figure 4 Comparison between speckle variance optical coherence tomography (svOCT) and fluorescein angiography (FA) for imaging retinal vein occlusion. FA (A) and a corresponding colour fundus photo (B) of a patient with a superior hemiretinal vein occlusion with associated capillary dropout in the macula. Inset I provides a magnified view of the macula imaged with FA (left panel) and svOCT (right panel). Areas of capillary fallout are clearly seen in the superior macula on the svOCT image (arrow heads) while there is total preservation of the capillary circulation in the inferior hemimacula (Scale bar=500 mm).
has the capability to provide depth-resolved information from the retinal capillary networks. We acknowledge however that further work is required to quantify the detail of anatomical information that is evident on svOCT images. Also, svOCT has the potential to non-invasively identify important pathological manifestations of retinal vascular diseases; ischaemia and proliferation. In patients with compromised renal function, where the administration of fluorescein dye may be contraindicated, this device may be particularly advantageous. In this report we present images with a field of view ranging from 5×5 mm2 and 1×1 mm2. It is possible to acquire images with a wider field of view using a using a system with higher acquisition speed, hardware motion tracking and image mosaicking.14 15 Further quantitative work is required to define the role of svOCT in clinical practice.
acquisition, processing, analysis and clinical correlation. D-YY: Conception of the project, data acquisition, processing, analysis and clinical correlation. MVS: Conception of the project, design of technology, data acquisition, processing and analysis. All of the listed authors were involved in the drafting and revising the work for important intellectual content, have submitted their approval of the final manuscript version being submitted, and are in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Funding Support for this research was provided in part by the Michael Smith Foundation for Health Research, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, and National Health and Medical Research Council of Australia. Competing interests None. Patient consent Obtained. Ethics approval This study was approved by the human ethics committee at the University of British Columbia. Provenance and peer review Not commissioned; externally peer reviewed.
Contributors JX: Conception of the project, design of technology, data acquisition, processing and analysis. SH Conception of the project, data acquisition, processing and analysis. CB: Conception of the project, data acquisition, processing and analysis. ZM: Conception of the project, data acquisition, processing and analysis. KW: Conception of the project, design of technology, data acquisition. SL: Conception of the project, design of technology, data acquisition. MC: Conception of the project, data acquisition, processing and analysis. MY: Data acquisition, processing and analysis. AK: Data processing, analysis and clinical interpretation. DA: Data processing, analysis and clinical interpretation. FF: Data processing, analysis and clinical interpretation. PM: Conception of the project, data acquisition, processing, analysis and clinical correlation. AM: Conception of the project, data 4
REFERENCES 1 2
3
Yannuzzi LA, Rohrer KT, Tindel LJ, et al. Fluorescein angiography complication survey. Ophthalmology 1986;93:611–17. Wang RK, An L, Francis P, et al. Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography. Opt Lett 2010;35:1467–9. Fingler J, Zawadzki RJ, Werner JS, et al. Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique. Opt Express 2009;17:22190–200.
Xu J, et al. Br J Ophthalmol 2015;0:1–5. doi:10.1136/bjophthalmol-2014-306010
Downloaded from http://bjo.bmj.com/ on May 7, 2015 - Published by group.bmj.com
Innovations 4
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Retinal angiography with real-time speckle variance optical coherence tomography Jing Xu, Sherry Han, Chandrakumar Balaratnasingam, Zaid Mammo, Kevin S K Wong, Sieun Lee, Michelle Cua, Mei Young, Andrew Kirker, David Albiani, Farzin Forooghian, Paul Mackenzie, Andrew Merkur, Dao-Yi Yu and Marinko V Sarunic Br J Ophthalmol published online March 2, 2015
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