|Year : 2019 | Volume
| Issue : 3 | Page : 108-115
Optical coherence tomography angiography in the diagnosis of choroidal neovascular membrane
Tarek A Mohsen, Hanem M Kishk
Department of Ophthalmology, Ophthalmology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||28-Jul-2019|
|Date of Acceptance||01-Aug-2019|
|Date of Web Publication||25-Sep-2019|
MD Tarek A Mohsen
Ophthalmology Center, Faculty of Medicine, Mansoura University, Mansoura, 35516
Source of Support: None, Conflict of Interest: None
Aim To evaluate the ability to diagnose and identify the morphologic features of choroidal neovascular membranes by optical coherence tomography angiography.
Patients and methods Prospective, observational study of patients with Choroidal neovascularization (CNV) attending the outpatient clinic of Mansoura Ophthalmic Center. For all patients fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and swept source optical coherence tomography angiography were done. The results were analyzed and compared.
Results This study included 23 eyes of 23 patients. Seven eyes had age-related CNV and 16 eyes had myopic CNV. Activity was evident in 20 cases with dye leakage in FA and fluid accumulation in SD-OCT, while in the other three cases, no active dye leakage was present in FA in one of them with minimal fluid in structural OCT; in the other cases, structural OCT showed minimal intraretinal fluid in one case and absent intraretinal fluid in the other case. Regarding cases with evident activity in fundus fluorescein angiography (FFA) and OCT, in two cases neovascular network was evident with glomerular appearance. In 18 cases, densely interlaced network of vessels was evident. In three cases without evident activity in other imaging modalities, the membrane appeared as a tangled network with filamentous vessels and loss of small branches.
Conclusion OCT angiography is a noninvasive, safe imaging tool for the diagnosis of CNV which gives information about the accurate size and localization of the membrane. It is a nonexpensive and rapid method that can be used for the diagnosis, screening of patients at risk, differentiate between active and inactive membranes, and follow-up.
Keywords: CNV, OCT, SD-OCT
|How to cite this article:|
Mohsen TA, Kishk HM. Optical coherence tomography angiography in the diagnosis of choroidal neovascular membrane. J Egypt Ophthalmol Soc 2019;112:108-15
|How to cite this URL:|
Mohsen TA, Kishk HM. Optical coherence tomography angiography in the diagnosis of choroidal neovascular membrane. J Egypt Ophthalmol Soc [serial online] 2019 [cited 2020 Feb 21];112:108-15. Available from: http://www.jeos.eg.net/text.asp?2019/112/3/108/267827
| Introduction|| |
Choroidal neovascular membrane is a common cause of vision loss. Its treatment requires accurate diagnosis, localization, and determination of activity. The initial tool used for the diagnosis of Choroidal neovascularization (CNV) was invasive angiography using fluorescent dyes.
Fluorescein angiography (FA) is an invasive method which has been considered the gold standard for imaging the retinal vasculature ,.
It is ideal for the detection of classic choroidal neovascular membranes, but this is not the same in the diagnosis of occult CNV due to the blue-green excitation wavelength that is partially absorbed by different pigments .
Indocyanine green dye uses near-infrared excitation light with more penetration of pigment and the dye remains inside blood vessels with better delineation of CNV. However, it is not depth resolved .
With the introduction of spectral domain OCT, the acquisition time decreased with marked improvement of image resolution. So, it was possible to obtain clinically useful cross-sectional and three-dimensional images of retinal layers ,.
Regarding the diagnosis of CNV, OCT gives information about indirect signs of activity as fluid and altered anatomy of the retina which is of great prognostic value but does not differentiate the membrane from other lesions having the same reflectivity as the fibrous tissue. So, FA and indocyanine green angiography (ICGA) are still needed despite their risk . OCT is limited by its inability to visualize and provide functional information about retinal microcirculation .
Therefore, it was highly needed to develop a noninvasive method to diagnose CNV .
Optical coherence tomography angiography (OCTA) utilizes flow characters within the circulation to give noninvasive images of the vascular network . With OCTA, it is possible to study the spatial relation between vasculature with greater accuracy than invasive techniques .
This study was carried out to evaluate the ability to diagnose and identify the morphologic features of choroidal neovascular membranes by optical coherence tomography angiography and correlate the results with other conventional imaging modalities including FA and OCT B-scans.
| Patients and methods|| |
This study was approved by the Institutional Research Board of Faculty of Medicine, Mansoura University.
A written consent was obtained from each patient enrolled in the study.
This prospective, observational study included patients with choroidal neovascular membrane of different etiologies.
For all patients, history taking and ophthalmic examination were done.
Imaging of the fundus was done by FA (except in two cases with a history of severe drug allergy) and spectral domain optical coherence tomography.
Swept source optical coherence tomography angiography (SS-OCTA) was done using the SS-OCT device (Triton; Topcon, Tokyo, Japan).
| Results|| |
This study included 23 eyes of 23 patients, 17 women and six men. Their age ranged between 25 and 66 years (mean age was 46±0.4).
Seven eyes had age-related choroidal neovascular membrane and 16 eyes had myopic choroidal neovascular membrane.
All cases that underwent FA had classic choroidal neovascular membrane.
Activity was evident in 20 cases with dye leakage in FA and fluid accumulation in spectral domain OCT, while in the other three cases, no active dye leakage was present in FA in one of them with minimal fluid in structural OCT. The other two cases in whom FA was contraindicated, structural OCT showed minimal intraretinal fluid in one case and absent intraretinal fluid in the other case.
The results were correlated with OCTA.
Regarding cases with evident activity in fundus fluorescein angiography (FFA) and OCT, in two cases the neovascular network was evident above retinal pigment epithelium (RPE) with glomerular appearance.
In 18 cases, densely interlaced network with hyperintense vessels was evident, the feeder vessel was evident in one case.
In the three cases without evident activity in other imaging modalities, the membrane appeared as tangled network with filamentous vessels and loss of small branches.
Case number 1
|Figure 1 Fluorescein angiography shows myopic classic subfoveal choroidal neovascular membrane with early filling (a) and late leakage (b) of the dye. Spectral domain OCT (c) shows hyperreflective lesion corresponding to choroidal neovascular membrane with posterior shadowing and intraretinal fluid. Swept source optical coherence tomography angiography (SS-OCTA) (d) shows neovascular network above RPE with glomerular appearance.|
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Case number 2
|Figure 2 Fluorescein angiography shows myopic classic subfoveal choroial neovascular membrane with early filling (a) and late leakage (b) of the dye. Spectral domain OCT (c) shows hyperreflective lesion corresponding to choroidal neovascular membrane with posterior shadowing and intraretinal fluid. Swept source optical coherence tomography angiography (SS-OCTA) (d) shows neovascular network above the RPE with glomerular appearance.|
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Case number 3
|Figure 3 Age related choroidal neovascular membrane. Swept source optical coherence tomography angiography (SS-OCTA) showing sharply defined, dense interlacing neovascular network.|
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OCT B-scan shows hyperreflective dome-shaped lesion with hyporreflective subsensory retinal fluid suggestive of active type-2 choroidal neovascular membrane.
Case number 4
|Figure 4 Fluorescein angiography shows age-related classic subfoveal choroial neovascular membrane with early filling (a) and late leakage (b) of the dye. Swept source optical coherence tomography angiography (SS-OCTA) showing sharply defined, dense interlacing neovascular network with tree-like net of vessels. The structural OCT within the printout shows hypereflective lesions with intraretinal fluid.|
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Case number 5
|Figure 5 Swept source optical coherence tomography angiography (SS-OCTA) showing tangled network of filamentous vessels with loosely laced appearance and loss of smaller branches, suggestive of inactive CNV. Structural OCT within the printout shows hyperreflective lesions with minimal intraretinal fluid suggestive of inactive choroidal neovascular membrane.|
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Case number 6
|Figure 6 Swept source optical coherence tomography angiography (SS-OCTA) showing tangled neovascular network with loosely laced appearance of straight thick vessels with loss of smaller branches, suggestive of inactive CNV. Structural OCT within the printout shows hyperreflective lesions with absent intraretinal fluid suggestive of inactive choroidal neovascular membrane.|
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| Discussion|| |
Choroidal neovascular membrane is a common cause of vision loss. Its treatment requires accurate diagnosis, localization, and determination of activity. The initial tool used for the diagnosis of CNV was invasive angiography using fluorescent dyes.
Intravenous dyes have risks ranging from nausea to, in rare cases, anaphylaxis. Invasive techniques are inappropriate for screening. In addition, the technique is time consuming and not suitable in a busy clinical setting .
Fluorescein and indocyanine green angiography are two-dimensional dynamic studies which can detect vascular alterations and vascular leakage. However, they cannot determine the precise margin and anteroposterior location of pathological blood vessels because leakage obscures the vascular details and because these examinations cannot study images in different planes .
For these reasons, a noninvasive imaging technique to detect rapidly and to monitor CNV without the use of intravenous dye is desirable. OCT is a noninvasive tool for detection of CNV which appears as a hyperreflective material .
Spectral domain OCT gives high axial resolution, rapid acquisition time, and excellent penetration of the RPE and choroid, and thus provides invaluable clinical information about retinal thickness, photoreceptor integrity, and response to therapy. However, it cannot differentiate between fibrous and vascular tissues .
OCTA allows noninvasive visualization of the retinal and choroidal vasculature via motion contrast imaging. It maps erythrocyte movement over time by comparing sequential OCT B-scans at a given cross section. Motion correction technology removes motion from patient movement so that the motion between repeated OCT B-scans corresponds to erythrocyte flow and, therefore, vasculature .
There are some limitations of OCTA. One of the main limitations is artifacts including flow projection artifacts which makes interpretation of deeper vasculature more difficult. These artifacts are the results of fluctuating shadow cast by blood in superficial vascular layers that cause variation in OCT signal in deeper layers. The projection artifacts of the retinal circulation can be seen clearly on the bright RPE. This artifact can be removed by software processing .
However, the choriocapillaris is fairly confluent and its projection and shadow artifacts are difficult to remove from deeper choroidal layers .
A second limitation of OCTA is fading of flow signal from large blood vessels due to the interferometric fringe washout effect associated with very fast blood flow. This means that central retinal vessels in the disk and large deep choroidal vessels cannot be visualized . Also, because OCTA depends on the change between two consecutive B-scans, it detects the flow which is higher than the minimal threshold, which depends on the time between the two sequential scans, slower flow lesions cannot be visualized .
Third, the scan area of OCTA is relatively small (3/3 and 6/6 mm) which is a great limitation in practice. Large area angiogram of high quality can be achieved but needs higher speed OCT systems which are not yet commercially available .
In the future, larger fields of view will be essential to evaluate peripheral lesions with unknown pathologies .
Spectral domain optical coherence tomography (SD-OCTA) utilizes 840 nm wavelenghth which is heavily scattered and absorbed by RPE which can affect visualization of CNV while SS-OCTA utilizes a wavelength of around 1000–1200 nm with better penetration of RPE and better visualization of the choroid. This wavelength is also safer for the eye and more laser power can be used to obtain images with improved detection of weak signals from the deep choroid .
Compared with the conventional dye-based angiography techniques, OCTA is rapid, noninvasive, and can be used in every patient visit and is helpful in longitudinal studies. Also, it allows depth-resolved visualization of choroidal and retinal vasculature. Lack of dye leakage allows the study of CNV morphology .
OCTA can help identify the morphologic features of active and inactive membranes.
De Carlo et al.  compared different imaging modalities in diagnosing choroidal neovascular membrane and noted that the neovascular network with long wavy vessels and sea fan appearance was associated with activity while filamentous vessels were associated with inactivity. They reported four false-negative cases, three of them were associated with large subretinal hemorrhage and supposed that this is the cause of failure of visualization of the CNV with OCTA due to the blocking effect of hemorrhage and assumed that the fourth case was due to unexperienced photographer.Bandello et al.  described the CNV in OCTA as interlacing or tangled. Interlacing appearance was associated with activity while tangled appearance with loss of small branches was associated with inactivity.
Lumbroso et al.  reported that the results obtained by OCTA were comparable with invasive angiography.
In this study, OCTA was able to detect all cases of CNV and allowed the study of morphological features and correlated them well with activity. The active membranes were associated with dye leakage in FA intraretinal fluid in OCT, appeared in OCTA as a network of interlacing wavy vessels and numerous small branches in 18 cases and appeared glomerular in two cases, while in the three cases with minimal or no fluid in structural OCT, the vascular network appeared tangled with filamentous vessels and loss of small branches. Moreover, OCTA was of utmost importance in patients for whom fluorescein injection was contraindicated due to a history of severe allergy to multiple drugs.
One of the limitations of this study was the small number of patients and lack of control group.
| Conclusion|| |
OCT angiography is a noninvasive, safe imaging tool for the diagnosis of choroidal neovascular membranes which gives information about accurate size and localization of the membrane. It is not an expensive and rapid method that can be used for diagnosis, screening patients at risk, differentiate between active and inactive membranes, and follow-up of treatment.
A larger study is needed to evaluate sensitivity and specificity of OCTA in CNV and determine whether it can totally replace dye angiography in the diagnosis and follow-up.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Novotny HR, Alvis DL. A method of photographig fluorescence in circulating blood in humen retina. Circulation 1961; 24:82–86.
Lattikainen L. The fluorescein angiography revolution: the breakthrough with sustained impact. Acta Ophthalmol Scand 2004; 82:381–392.
Bischoff P, Flower R. Ten years experience with choroidal angiography using indocyanine green dye: a routine examination or an epilogue? Doc Ophthalmol 1985; 60:235–291.
Zhu L, Zheng Y, von Kerczek CH, Topoleski LD, Flower RW. Feasibility of extracting velocity distribution in choriocapillaris in human eyes from ICG dye angiograms. J Biomech Eng 2005; 128:203–209.
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W et al.
Optical coherence tomography. Science 1991; 254:1178–1181.
Wojtkowski M, Srinivasan V, Fujimoto JG, Ko T, Schuman JS, Kowalczyk A, Duker JS. Three-dimensional retinal imaging with high-speed, ultrahigh-resolution, optical coherence tomography. Ophthalmology 2005; 112:1734–1746.
Mastropasqua R, Antonio LD, Staso SD, Agnifili L, Gregorio AD, Ciancaglini M, Mastropasqua L. Optical coherence tomography angiography in retinal vascular diseases and choroidal neovascularization. J Ophthalmol 2015; 2015:343515.
Jia Y, Bailey ST, Wilson DJ, Tan O, Klein ML, Flaxel CJ et al.
Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology 2014; 121:1435–1444.
Dansingani KK, Naysan J, Freund KB. En face OCT angiography demonstrates flow in early type 3 neovascularization (retinal angiomatous proliferation). Eye 2015; 29:703–706.
Gal-Or O, Balaratnasingam C, Freund KB. Optical coherence tomography angiography findings of choroidal neovasculllaaarization in pseudoxanthoma elasticum. Int J Retina Vitreous 2015; 1:11.
Kwiterovich KA, Maguire MG, Murphy RP, Schachat AP, Bressler NM, Bressler SB, Fine SL et al.
Frequency of adverse systemic reactions after fluorescein angiography. Results of a prospective study. Ophthalmology 1991; 98:1139–1142.
Chen CJ, Wang M, Chen R, Olson M. OCT Angiography Examination of Choroidal Neovascular Membrane in Exudative Age-Related Macular degeneration. In: Clinical OCT Angiography Atlas. First Edition. Jaypee Brothers Medical Publishers. 2015; Ch 8: p42.
De Carlo TE, Bonini Filho MA, Chin AT, Adhi M, Ferrara D, Baumal CR et al.
Spectral-domain optical coherence tomography angiography of choroial neovacularization. Ophthalmology 2015; 122:1228–1238.
Huang D, Jia Y, Gao SS. Principles of optical coherence tomography angiography. In: Clinical OCT angiography Atlas. First edition. Jaypee Brothers Medical Publishers. 2015; Ch1:p5
Hendargo HC, Mc Nabb RP, Dallah AH, Shepherd N, Izatt JA. Doppler velocity detection limitations in spectrometer-based versus swept-source optical coherence tomography. Biomed Opt Express 2011; 2:2175–2188.
Blatter C, Klein T, Grajciar B, Schmoll T, Wieser W, Andre R et al.
Ultrahigh-speed non-invasive widefield angiography. J Biomed Opt 2012; 17:0705051.
Zhang Q, Chen CL, Chu Z, Zheng F, Miller A, Roisman L, Rafael de Oliveira Dias J et al.
Automated quantification of choroidal neovascularization: a comparison study between spectral-domain and swept-source OCT angiograms. Invest Ophthalmol Vis Sci 2017; 58:1506–1513.
Moult E, Choi W, Waheed NK, Adhi M, Lee B, Lu CD et al.
Ultrahigh-speed swept-source OCT angiography in exudative AMD. Ophthalmic Surg Lasers Imaging Retina 2014; 45:496–505.
Bandello F, Souied EH, Querques G. Optical coherence tomography angiography of choroidal neovascularization secondary to pathologic myopia. Dev Ophthalmol 2016; 56:101–106.
Lumbroso B, Huang D, Jia Y, Fujimoto G, Rispoli M. Clinical guide to angio-OCT-noninvasive dyless OCT angiography. New Delhi, India: Jaypee Brothers Medical Publishers. 2015.
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