Optical coherence tomography angiography in glaucoma: a mini-review

Kelvin H. Wan; Christopher K. Leung

doi:10.12688/f1000research.11691.1

Home Browse Optical coherence tomography angiography in glaucoma: a mini-review

ALL Metrics

-

Views

-

Downloads

Get PDF

Get XML

Export

▬

✚

Review

Optical coherence tomography angiography in glaucoma: a mini-review

[version 1; peer review: 2 approved]

Kelvin H. Wan^1,2, Christopher K. Leung²

PUBLISHED 14 Sep 2017

Author details Author details

¹ Department of Ophthalmology, Tuen Mun Eye Center and Tuen Mun Hospital, Hong Kong, China
² Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

The advent of optical coherence tomography angiography (OCT-A) provides a new opportunity to visualize the retinal vasculature in a non-invasive and dye-free manner which may help identify vascular abnormalities in glaucoma. While a reduction in retinal and optic nerve head vessel densities and blood flow indexes measured by OCT-A has been demonstrated in patients with glaucoma in many studies, it is unclear whether OCT-A provides additional information for the detection and monitoring of glaucoma compared with OCT measurements such as retinal nerve fiber layer thickness, neuroretinal rim width, and ganglion cell inner plexiform layer thickness. Longitudinal studies are needed to elucidate whether vascular abnormalities detected by OCT-A are a cause or a consequence of optic nerve damage in glaucoma.

Keywords

optical coherence tomography angiography, glaucoma, retina, optic nerve head, vascular abnormalities, optical imaging

Corresponding author: Christopher K. Leung

Competing interests: KW declares that he has no competing interests. CL has received speaker honoraria from Carl Zeiss Meditec and Heidelberg Engineering and research support from Carl Zeiss Meditec.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2017 Wan KH and Leung CK. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Wan KH and Leung CK. Optical coherence tomography angiography in glaucoma: a mini-review [version 1; peer review: 2 approved]. F1000Research 2017, 6(F1000 Faculty Rev):1686 (https://doi.org/10.12688/f1000research.11691.1) First published: 14 Sep 2017, 6(F1000 Faculty Rev):1686 (https://doi.org/10.12688/f1000research.11691.1) Latest published: 14 Sep 2017, 6(F1000 Faculty Rev):1686 (https://doi.org/10.12688/f1000research.11691.1)

Introduction

The recent introduction of optical coherence tomography angiography (OCT-A) has sparked interest in evaluating vascular alterations in the retina and optic nerve head (ONH) for diagnosis, staging, and monitoring in glaucoma. OCT-A is an extension of OCT which allows non-invasive visualization of the retinal vasculature by detecting motion contrast from perfused blood vessels without the use of exogenous dye. In principle, OCT-A compares sequential B-scans acquired at the same location to detect change. As stationary structures would appear static in sequential B-scans, changes detected by OCT-A are largely attributed to erythrocyte movement in the perfused vasculatures. A number of algorithms such as split-spectrum amplitude decorrelation angiography (SSADA), OCT-A ratio analysis, and optical microangiography (OMAG) have been devised to compute blood flow measurements from the sequential B-scans^1,2. Some of these measurements reported in the literature include vessel density (commonly annotated as the percentage of detected vessel area over the imaged area), flow index (a dimension-less parameter between 0 and 1 representing the average decorrelation signal), and blood flux index (the mean flow intensity in the vessel area normalized between 0 and 1 by dividing the full dynamic range of blood flow signal intensity). It is worth noting that these indexes are surrogate measures and their validity for measurement of blood flow remains to be investigated.

Diagnostic performance of OCT-A measurements for glaucoma detection

Jia and colleagues provided the first account of vascular abnormalities at the ONH measured by a swept-source OCT in glaucoma³. They showed that the optic disc flow index was reduced by 25% in glaucomatous eyes (0.161 ± 0.008) compared with healthy eyes (0.121 ± 0.026). Using a cut-off value of 0.1515, they showed that the sensitivity and specificity for the detection of glaucoma were both 100% (the visual field mean deviation in the glaucoma group was −3.28 ± 4.12 dB). The flow index was highly associated with visual field pattern standard deviation (R² = 0.752). The same group then evaluated the peripapillary flow index and the peripapillary vessel density for discrimination between glaucomatous and healthy eyes by using a spectral-domain OCT and reported the area under the receiver operating characteristic curve (AUC) to be 0.892 and 0.938, respectively⁴. It remains controversial whether OCT-A measurements have a higher diagnostic performance for glaucoma detection compared with conventional OCT measurements such as the retinal nerve fiber layer (RNFL) thickness, neuroretinal rim width, and macular ganglion cell and inner plexiform layer thickness. Chen and colleagues demonstrated that the peripapillary blood flux index measured between the internal limiting membrane (ILM) and RNFL using OMAG and circumpapillary RNFL thickness had comparable diagnostic performance for the detection of glaucoma suspect (AUC = 0.76 versus 0.70, respectively) and glaucoma (AUC = 0.93 versus 0.97, respectively)⁵. In a recent study, Rao and colleagues compared the diagnostic performance for glaucoma detection between OCT-A vessel density measurements using SSADA and OCT measurements (circumpapillary RNFL thickness, neuroretinal rim area, and ganglion cell complex [GCC])⁶. All vessel density measurements, including the radial peripapillary capillary (measured between the ILM and RNFL), the ONH segment vessel (measured from 2,000 µm above the ILM to 150 µm below the ILM), and the macular superficial plexus (between the ILM to the inner plexiform layer), were found to have significantly smaller AUCs compared with OCT measurements. Discrepancies among the studies are likely attributed to the different definitions adopted and varying stages of glaucoma patients included in the analysis.

OCT-A abnormality in glaucoma: primary damage or secondary change?

Lee and colleagues hypothesized that if vascular abnormality were a consequence of optic nerve damage, it would be observed only at the area of RNFL defect⁷. Examining 98 primary open-angle glaucoma eyes with a localized RNFL defect, the authors demonstrated that the radial peripapillary capillary vascular abnormality detected by OCT-A using SSADA exactly coincided with the RNFL defect in both the location and the extent, suggesting that vascular change is a consequence of optic nerve damage in glaucoma. On the other hand, Chen and colleagues studied the microvasculature density (excluding the effect of large retinal vessels) and blood flux index between the ILM and RNFL measured using OMAG at the peripapillary region in glaucomatous eyes with single-hemifield visual field defects and reported that the intact visual hemifield showed reduced blood flux index and microvasculature density in eyes with glaucoma compared with healthy eyes but that no significant difference in circumpapillary RNFL thickness between the groups was detected⁸. While significant correlations between blood flow index/circumpapillary RNFL thickness and visual field mean deviation were observed in the normal visual hemifield in eyes with glaucoma, there was no correlation between microvasculature density/blood flux index and visual field mean deviation/circumpapillary RNFL thickness in the abnormal visual hemifield. Yarmohammadi and colleagues showed that while radial peripapillary capillary vessel density, macular superficial vessel density, RNFL thickness, and GCC thickness were all reduced in both the affected and the intact visual hemifields in eyes with glaucoma, the strength of association with visual field sensitivity measures was stronger for vessel density measurements using SSADA compared with RNFL and GCC thicknesses⁹. Longitudinal studies investigating the temporal sequence of OCT-A and ONH/RNFL changes are needed to address whether the vascular changes detected by OCT-A are a cause or a consequence of optic nerve damage in glaucoma.

Limitations of OCT-A

Motion artefacts and projection artefacts are common in OCT-A. A considerable proportion of OCT-A images remain suboptimal in quality for interpretation. For example, in a study evaluating the intra-visit and inter-visit variability of vessel density measurement in primary open-angle glaucoma and ocular hypertension patients, 78.3% of the participants were excluded because of suboptimal SSADA-derived OCT-A image quality¹⁰. Poor-quality OCT-A scans are more common than poor-quality OCT scans. In a study in which both OCT-A and OCT measurements were performed by the same commercially available instrument, 17% and 29% of the OCT-A scans using SSADA were considered to have poor quality at the optic disc and the macula regions, respectively¹¹. By contrast, only 9% of OCT scans at the optic disc region and 3% of OCT scans at the macula were graded as poor quality. With the currently available OCT-A instruments, the scan time typically varies from 3 to 6 seconds for a 3×3 to 6×6 mm² scan¹², which is longer than imaging the ONH or the macula for RNFL and ganglion cell layer/inner plexiform layer analyses. The longer scan time in OCT-A can contribute to a higher incidence of motion artefact.

Summary

Vascular abnormalities detected by OCT-A have been consistently observed in glaucoma. However, it remains unclear whether OCT-A provides additional diagnostic information for the detection of glaucoma compared with conventional OCT measurements such as circumpapillary RNFL thickness, neuroretinal rim width, and ganglion cell inner plexiform form layer thickness. Findings from the literature comparing OCT-A and OCT measurements for the detection of glaucoma and evaluation of structure function association are divergent. The temporal sequence of vascular changes and optic nerve damage in glaucoma remains to be elucidated.

Competing interests

KW declares that he has no competing interests. CL has received speaker honoraria from Carl Zeiss Meditec and Heidelberg Engineering and research support from Carl Zeiss Meditec.

Grant information

The author(s) declared that no grants were involved in supporting this work.

F1000 recommended

References

1. Gao SS, Jia Y, Zhang M, et al.: Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2016; 57(9): OCT27–36. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
2. Zhang A, Zhang Q, Chen CL, et al.: Methods and algorithms for optical coherence tomography-based angiography: a review and comparison. J Biomed Opt. 2015; 20(10): 100901. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
3. Jia Y, Wei E, Wang X, et al.: Optical coherence tomography angiography of optic disc perfusion in glaucoma. Ophthalmology. 2014; 121(7): 1322–32. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
4. Liu L, Jia Y, Takusagawa HL, et al.: Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma. JAMA Ophthalmol. 2015; 133(9): 1045–52. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
5. Chen CL, Zhang A, Bojikian KD, et al.: Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography. Invest Ophthalmol Vis Sci. 2016; 57(9): OCT475–85. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
6. Rao HL, Pradhan ZS, Weinreb RN, et al.: A comparison of the diagnostic ability of vessel density and structural measurements of optical coherence tomography in primary open angle glaucoma. PLoS One. 2017; 12(3): e0173930. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
7. Lee EJ, Lee KM, Lee SH, et al.: OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma. Invest Ophthalmol Vis Sci. 2016; 57(14): 6265–70. PubMed Abstract | Publisher Full Text | F1000 Recommendation
8. Chen CL, Bojikian KD, Wen JC, et al.: Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss. JAMA Ophthalmol. 2017; 135(5): 461–8. PubMed Abstract | Publisher Full Text | F1000 Recommendation
9. Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al.: Peripapillary and Macular Vessel Density in Patients with Glaucoma and Single-Hemifield Visual Field Defect. Ophthalmology. 2017; 124(5): 709–19. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
10. Holló G: Intrasession and Between-Visit Variability of Sector Peripapillary Angioflow Vessel Density Values Measured with the Angiovue Optical Coherence Tomograph in Different Retinal Layers in Ocular Hypertension and Glaucoma. PLoS One. 2016; 11(8): e0161631. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation
11. Rao HL, Pradhan ZS, Weinreb RN, et al.: Vessel Density and Structural Measurements of Optical Coherence Tomography in Primary Angle Closure and Primary Angle Closure Glaucoma. Am J Ophthalmol. 2017; 177: 106–15. PubMed Abstract | Publisher Full Text | F1000 Recommendation
12. Chen CL, Wang RK: Optical coherence tomography based angiography [Invited]. Biomed Opt Express. 2017; 8(2): 1056–82. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 14 Sep 2017

Author details Author details

¹ Department of Ophthalmology, Tuen Mun Eye Center and Tuen Mun Hospital, Hong Kong, China
² Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Competing interests

KW declares that he has no competing interests. CL has received speaker honoraria from Carl Zeiss Meditec and Heidelberg Engineering and research support from Carl Zeiss Meditec.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (1)

version 1

Published: 14 Sep 2017, 6:1686

https://doi.org/10.12688/f1000research.11691.1

Copyright

© 2017 Wan KH and Leung CK. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download

Export To

metrics

	Views	Downloads
F1000Research	-	-
PubMed Central Data from PMC are received and updated monthly.	-	-

Citations

0

SEE MORE DETAILS

CITE

how to cite this article

Wan KH and Leung CK. Optical coherence tomography angiography in glaucoma: a mini-review [version 1; peer review: 2 approved] F1000Research 2017, 6(F1000 Faculty Rev):1686 (https://doi.org/10.12688/f1000research.11691.1)

NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.

track

receive updates on this article

Track an article to receive email alerts on any updates to this article.

Open Peer Review

Current Reviewer Status: ?

Key to Reviewer Statuses VIEW HIDE

ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions

Version 1

VERSION 1

PUBLISHED 14 Sep 2017

Views

0

Reviewer Report 14 Sep 2017

Ruikang Wang, Department of Bioengineering & Ophthalmology, University of Washington, Seattle, WA, USA

Approved

https://doi.org/10.5256/f1000research.12631.r25079

I confirm that I have read this submission and believe that I have an ... Continue reading

Competing Interests: No competing interests were disclosed.

Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty, and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Respond or Comment

Views

0

Reviewer Report 14 Sep 2017

Gábor Holló, Department of Ophthalmology, Semmelweis University, Budapest, Hungary

Approved

https://doi.org/10.5256/f1000research.12631.r22908

I confirm that I have read this submission and believe that I have an ... Continue reading

Competing Interests: Gábor Holló is an unpaid consultant of Optovue and Zeiss (both companies produce OCT angiography instruments).

Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty, and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Respond or Comment

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 14 Sep 2017

Open Peer Review

Reviewer Status

Reviewer Reports

	Invited Reviewers
	1	2
Version 1 14 Sep 17	read	read

Gábor Holló, Semmelweis University, Budapest, Hungary
Ruikang Wang, University of Washington, Seattle, USA

Comments on this article

All Comments(0)

Add a comment

Sign up for content alerts

Browse by related subjects

Back to all reports

Reviewer Report

0 Views

14 Sep 2017 | for Version 1

Ruikang Wang, Department of Bioengineering & Ophthalmology, University of Washington, Seattle, WA, USA

0 Views Cite this report Responses(0)

Approved

Competing Interests

No competing interests were disclosed.

Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty, and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

0 Views

14 Sep 2017 | for Version 1

Gábor Holló, Department of Ophthalmology, Semmelweis University, Budapest, Hungary

0 Views Cite this report Responses(0)

Approved

Competing Interests

Gábor Holló is an unpaid consultant of Optovue and Zeiss (both companies produce OCT angiography instruments).

Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty, and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

[1] 1. Gao SS, Jia Y, Zhang M, et al.: Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2016; 57(9): OCT27–36. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[2] 2. Zhang A, Zhang Q, Chen CL, et al.: Methods and algorithms for optical coherence tomography-based angiography: a review and comparison. J Biomed Opt. 2015; 20(10): 100901. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[3] 3. Jia Y, Wei E, Wang X, et al.: Optical coherence tomography angiography of optic disc perfusion in glaucoma. Ophthalmology. 2014; 121(7): 1322–32. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[4] 4. Liu L, Jia Y, Takusagawa HL, et al.: Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma. JAMA Ophthalmol. 2015; 133(9): 1045–52. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[5] 5. Chen CL, Zhang A, Bojikian KD, et al.: Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography. Invest Ophthalmol Vis Sci. 2016; 57(9): OCT475–85. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[6] 6. Rao HL, Pradhan ZS, Weinreb RN, et al.: A comparison of the diagnostic ability of vessel density and structural measurements of optical coherence tomography in primary open angle glaucoma. PLoS One. 2017; 12(3): e0173930. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[7] 7. Lee EJ, Lee KM, Lee SH, et al.: OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma. Invest Ophthalmol Vis Sci. 2016; 57(14): 6265–70. PubMed Abstract | Publisher Full Text | F1000 Recommendation

[8] 8. Chen CL, Bojikian KD, Wen JC, et al.: Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss. JAMA Ophthalmol. 2017; 135(5): 461–8. PubMed Abstract | Publisher Full Text | F1000 Recommendation

[9] 9. Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al.: Peripapillary and Macular Vessel Density in Patients with Glaucoma and Single-Hemifield Visual Field Defect. Ophthalmology. 2017; 124(5): 709–19. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[10] 10. Holló G: Intrasession and Between-Visit Variability of Sector Peripapillary Angioflow Vessel Density Values Measured with the Angiovue Optical Coherence Tomograph in Different Retinal Layers in Ocular Hypertension and Glaucoma. PLoS One. 2016; 11(8): e0161631. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

[11] 11. Rao HL, Pradhan ZS, Weinreb RN, et al.: Vessel Density and Structural Measurements of Optical Coherence Tomography in Primary Angle Closure and Primary Angle Closure Glaucoma. Am J Ophthalmol. 2017; 177: 106–15. PubMed Abstract | Publisher Full Text | F1000 Recommendation

[12] 12. Chen CL, Wang RK: Optical coherence tomography based angiography [Invited]. Biomed Opt Express. 2017; 8(2): 1056–82. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation

Optical coherence tomography angiography in glaucoma: a mini-review

Abstract

Keywords

Introduction

Diagnostic performance of OCT-A measurements for glaucoma detection

OCT-A abnormality in glaucoma: primary damage or secondary change?

Limitations of OCT-A

Summary

Competing interests

Grant information

References

Comments on this article Comments (0)

Open Peer Review

Comments on this article Comments (0)

Open Peer Review

Reviewer Status

Reviewer Reports

Comments on this article

Browse by related subjects

Competing Interests Policy

Stay Updated