|Year : 2020 | Volume
| Issue : 2 | Page : 29-35
Evaluation of macular vascular changes in Behçet's Disease using optical coherence tomography angiography
Mennatallah G. A. Saleh, Mohamed Tarek Abdelmoneim, Abdelsalam Abdalla, Mohamed Sharaf, Mohamed G. A. Saleh
Department of Ophthalmology, Faculty of Medicine, Assiut University, Assiut, Egypt
|Date of Submission||30-Apr-2020|
|Date of Acceptance||29-Jun-2020|
|Date of Web Publication||1-Feb-2021|
Dr. Mennatallah G. A. Saleh
Department of Ophthalmology, Assiut University Hospital, Assiut 71515
Source of Support: None, Conflict of Interest: None
Purpose: The purpose of the study was to describe macular vascular changes in patients with Behcet's disease (BD) using optical coherence tomography angiography (OCTA) and to compare these findings with those of fluorescein angiography (FA). Patients and Methods: This was a comparative, cross-sectional study. Patients with BD presenting with active uveitis were evaluated using FA and swept-source OCTA. 3 mm × 3 mm and 6 mm × 6 mm en-face images were reviewed and analyzed. Foveal avascular zone (FAZ) areas and vessel densities were also reported. Results: Twenty-five patients (39 eyes) were included. OCTA was superior to FA in showing macular microvascular changes which include areas of retinal capillary hypoperfusion, perifoveal capillary plexuses disruption and capillary abnormalities (including rarefied, dilated, or shunting vessels) were observed more frequently using OCTA than FA. Areas of retinal capillary hypoperfusion were more frequently observed in the deep than in the superficial capillary plexus (SCP). Capillary abnormalities and disorganization of the normal architecture of the capillary network were more frequent in the deep than in the SCP. FAZ area measured in the SCP was significantly larger in eyes with BD than in the control group in both the superficial and the deep capillary plexuses (DCPs). Capillary vessel density measured in the SCP was significantly lower in eyes with BD than in control group in all quadrants of the macula except the nasal sector and the central circle. Conclusion: OCTA allows better identification and description of perifoveal microvascular changes than FA in eyes with active BD. The DCP is more severely involved than the SCP.
Keywords: Behcet's disease; optical coherence angiography tomography; retinal vasculitis
|How to cite this article:|
Saleh MG, Abdelmoneim MT, Abdalla A, Sharaf M, Saleh MG. Evaluation of macular vascular changes in Behçet's Disease using optical coherence tomography angiography. Egypt Retina J 2020;7:29-35
|How to cite this URL:|
Saleh MG, Abdelmoneim MT, Abdalla A, Sharaf M, Saleh MG. Evaluation of macular vascular changes in Behçet's Disease using optical coherence tomography angiography. Egypt Retina J [serial online] 2020 [cited 2022 Dec 3];7:29-35. Available from: https://www.egyptretinaj.com/text.asp?2020/7/2/29/308385
| Introduction|| |
Behçet's disease (BD) is a systemic disease characterized by a relapsing chronic course with recurrent attacks of occlusive and necrotizing vasculitis., Approximately 70% of patients with BD suffer from ocular manifestations. Anterior hypopyon uveitis, retinitis, retinal vasculitis, vitritis, retinal vein occlusion, macular edema, and optic disc edema constitute the major ocular features of this disease. Retinal vasculitis is the sine qua non of posterior segment involvement and main cause of irreversible vision loss in BD. Therefore, fluorescein angiography (FA) has become a gold standard technique for the evaluation of Behçet uveitis (BU). However, only early phase of FA allows the visualization of capillary bed due to dye leakage and it is unable to evaluate the retinal capillary levels separately.,
Optical coherence tomography angiography (OCTA) is a recently developed technology that obtains images of vascular networks at different layers of the retina without the use of dyes. The OCTA acquires sequential B-scans of the same location of the retina, and as a result of erythrocyte movement, changes in the reflected light waves occur. OCTA signal describes those pixel-by-pixel changes, and the machine depicts those variations (called decorrelation) as a flow signal.
A major advantage of OCTA is that it allows the resolution of both the superficial and deeper capillary plexuses networks. The utility of OCTA in imaging retinal microvascular characteristics was shown in some previous studies., Retinal microvascular changes, especially at the foveal region, should be closely monitored in patients with BU, preferably with a noninvasive and effective method. In this study, we aimed to describe microvascular changes in BD patients with using OCTA and comparing those with fundus fluorescein angiography (FFA) findings.
| Patients and Methods|| |
This is a comparative, cross-sectional study where 39 eyes from 25 patients were included in the study. Patients presenting with BD involving the posterior segment at the Department of Ophthalmology, Assiut University Hospital, Egypt, between October 2017 and August 2019, were enrolled in this study. OCTA and FFA imaging was performed at Alforsan eye center (private center) and at the Department of Ophthalmology, Assiut University Hospital. The study was conducted in collaboration with the Department of Rheumatology, Assiut University Hospital, Egypt.
Patients were diagnosed with BD fulfilling the diagnostic criteria of the international study group for BD with either active or quiescent (controlled by treatment) uveitis. Eyes were considered to have active uveitis in the presence of vitritis, retinal vascular sheathing, retinal vascular leakage on FFA, retinal infiltrates, optic disc edema, or anterior uveitis. Patients were excluded if they show evidence other retinal vascular diseases such as diabetic retinopathy, hypertensive retinopathy, and central serous chorioretinopathy or have media opacities precluding a clear fundus view.
Twenty-two eyes of 11 healthy age-matched subjects were also imaged with OCTA and images were analyzed to serve as a control group.
The study was performed in accordance with the tenets of Helsinki Declaration.
Approval of the study by the Institutional Review Board of the Faculty of Medicine, Assiut University, was obtained prior to the study. All study participants signed written informed consent before enrollment in the study.
All patients underwent detailed ophthalmic examination including measurement of Snellen's best-corrected visual acuity (BCVA), slit-lamp examination, applanation tonometry, and dilated fundus examination.
Investigational workup for all study subjects including serological testing for syphilis, a chest X-ray, and a tuberculin skin test was performed.
Color fundus photography, FFA (Topcon TRC-NW8F plus; Topcon Medical Systems, Inc., Tokyo, Japan), conventional optical coherence tomography (OCT) and OCTA images were also performed for all patients at the same day as FFA using SS-DRI OCT Triton plus; Topcon, Tokyo, Japan. This system operates at 100,000 A-scans per second using a light source of 1050 nm. All scans were acquired over a 3 mm × 3 mm field of view and a 6 mm × 6 mm in about 3 s of total OCT scan time. The OCTA ratio analysis was used to extract OCTA information. This algorithm distinguishes blood flow from static tissue using motion contrast measure, based on a ratio calculation, with a full-spectrum method. Preset parameters were used to segment the capillary bed in the superficial and deep capillary plexuses (DCPs). The en-face images of the superficial capillary plexus (SCP) were obtained with a slab between an inner boundary at 5.6 mm beneath the inner limiting membrane and an outer boundary at 12.6 mm beneath the inner plexiform layer. The en-face images of the DCP were obtained with a slab between the inner and outer boundaries, respectively, at 15.6 and 70.2 mm beneath the inner plexiform layer. Poor-quality OCT angiograms with motion artifacts due to blinking (appearing as straight, white stripes), or fixation loss, were excluded from the evaluation. Qualitative analysis of the 3 × 3 mm OCT angiograms of the SCP and DCP were then independently conducted by two experienced examiners (MS and MGA), at different time points and in different orders, for the following parameters: perifoveal anastomotic capillary arcade disruption in the SCP (when extending over one quadrant of the entire length), capillary changes (including capillary dilatation, telangiectasia, shunting vessels, and areas of rarefied capillaries), areas of capillary nonperfusion/hypoperfusion (presenting as irregular hypointense grayish areas), disorganization of the superficial and deep capillary network (defined as localized or diffuse loss of the normal architecture of capillary network), and intraretinal cystoid spaces (presenting as well-defined black roundish areas without any signal on OCTA). Qualitative analysis of capillary network abnormalities was then compared with FFA and OCT findings. Quantitative analysis of 3 mm × 3 mm OCT angiograms, including foveal avascular zone (FAZ) area and capillary vessel density (CVD) measurement in SCP, was performed using built-in software in the OCT device (IMAGEnet 6 version 220.127.116.1101). FAZ area was manually delineated and measured in square millimeters. The graders performed the assessment independently and were masked to the results of each other. The measurements were averaged to obtain a final value and were compared with those measured in healthy, age-matched controls. CVD was then calculated as percentage of pixels occupying the screen representing flow. Cases with projection artifacts from the SCP were excluded from the analysis of vessel density (VD).
Statistical analyses were performed using SPSS software version 25 (SPSS Inc., Chicago, IL, USA). Descriptive statistics (percentages, means, and standard deviation) were computed for demographic and clinical variables. BCVA was converted to the logarithm of the minimum angle resolution for statistical evaluation. Chi-square test was used for qualitative values and independent t-test for quantitative data analysis. Paired sample t-test was used to compare paired data, and Pearson's “r” correlation was measured to analyze the degree of correlation between sets of data. Statistical significance was set at P ≤ 0.05.
| Results|| |
Twenty-five patients were included in the study. Of the 50 eyes examined, 11 eyes were excluded due to poor quality of images because of media haze, poor fixation, and poor pupillary dilatation. Images from the remaining 39 eyes were obtained and analyzed. Twenty-two eyes from 11 age-matched healthy subjects were also included as a control group. The baseline characteristics of the study subjects are summarized in [Table 1].
Clinical and imaging features of the patients are shown in [Table 2]. Qualitative analysis of enface OCTA images of both SCP and DCP of the cases showed three groups of abnormalities as shown in [Figure 1]. The first group includes morphological changes of the retinal capillaries, for example, capillary tortuosity (corkscrew appearance) [Figure 2], increased spaces between capillaries giving the capillary network a rarefied appearance [Figure 3], and dilated and shunt vessels [Figure 4]. The second group was areas of capillary hypoperfusion/nonperfusion appearing as irregular grayish or dark spaces devoid of flow in the enface images [Figure 5]. Furthermore, disruption of the perifoveal capillary arcades with or without enlarged irregular FAZ [Figure 6]. Those findings were looked for in FFA images of the patients. [Table 3] shows a comparison between the frequency of observing the three groups of capillary network abnormalities by OCTA and FFA [Table 2].
|Figure 1: (a) 3 mm × 3 mm optical coherence tomography angiography scan of superficial capillary plexus of right eye of a male patient with Behcet's disease showing telangiectatic capillaries (corkscrew appearance) (yellow dashed circle). (b) 3 mm × 3 mm optical coherence tomography angiography scan of deep capillary plexus showing same finding (more obvious). (c) Optical coherence tomography angiography vessel density map. (d) Color fundus photography of the same patient. (e) Mid phase fundus fluorescein angiography of the same patient showing perifoveal hyperflourescent area. (f and g) Corresponding optical coherence tomography B-scan of the same patient which does not show abnormality|
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|Figure 2: (a) 3 mm × 3 mm optical coherence tomography angiography scan of superficial capillary plexus in the right eye of male patient with Behcet's disease showing areas of hypoperfusion (yellow stars) and rarefaction of capillaries (yellow dashed circle). (b) 3 mm × 3 mm optical coherence tomography angiography scan of the deep capillary plexus showing more extensive ischemic changes. (c) Vessel density map of the same patient. (d) 6 mm × 6 mm optical coherence tomography angiography scan of superficial capillary plexus showing hypointense areas of low/no flow which is more pronounced in deep capillary plexus (e). (f) Color fundus photography of the same patient. (g) Corresponding optical coherence tomography b scan showing epiretinal membrane and showing discontinuity of ellipsoid zone and external limiting membrane|
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|Figure 3: (a) 6 mm × 6 mm optical coherence tomography angiography scan of superficial capillary plexus in the right eye of male patient with Behcet's disease showing extensive ischemic changes shown as dark areas of hypo/nonperfusion (yellow stars). (b) 6 mm × 6 mm optical coherence tomography angiography scan of the deep capillary plexus showing more extensive ischemic changes (yellow stars) and areas of rarefaction of capillaries. (c and f) Vessel density maps. (d and e) 6 mm × 6 mm optical coherence tomography angiography scan of superficial capillary plexus and deep capillary plexus after 1 year showing extensive capillary changes. (g) Fundus photo showing vascular sheathing and retinal hemorrhage. (h and i) Fluorescein angiogram showing blocked fluorescence by haemorrhage|
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|Figure 4: (a) optical coherence tomography b scan of the left eye of patient with Behcet's disease showing epimacular gliosis. (b) Color photography showing an arrow representing the direction of image scanning. (c) 3 mm × 3 mm optical coherence tomography angiography scan of superficial capillary plexus showing hypointense areas of capillary hypoperfusion/no perfusion (yellow stars). (d) 3 mm × 3 mm optical coherence tomography angiography scan of the deep capillary plexus showing more extensive ischemic changes (yellow stars) and areas of rarefaction of capillaries (yellow dashed circle). (e) Vessel density map of the same patient|
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|Figure 5: Scatter plot showing the correlation between foveal avascular zone area in mm and logarithm of the minimum angle resolution best-corrected visual acuity in the cases group|
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|Figure 6: En-face 3 mm × 3 mm optical coherence tomography angiograms of the superficial capillary plexus of two cases with Behcet's disease showing irregular foveal avascular zone without enlargement and enlarged irregular foveal avascular zone|
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|Table 3: Comparison between the frequencies of the three categories of capillary network alterations in patients with Behcet's disease seen by tical coherence tomography angiographyversus fundus fluorescein angiography|
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A comparison between enface images of the SCP and the DCP showed that the DCP is involved to a greater extent than the SCP. [Table 4] shows the differences between SCP and DCP changes seen in 3 mm × 3 mm OCTA in cases group.
|Table 4: Capillary changes of superficial capillary plexus versus deep capillary plexus seen in 3×3 en-face images in patients with Behcet's disease|
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Quantitative optical coherence tomography angiography data
The mean VD of all perifoveal quadrants, except nasal quadrant, is significantly lower in patients with BD compared to age-matched controls. Central VD did not show significant changes in cases compared to the control group [Table 5].
|Table 5: Mean quantitative optical coherence tomography angiography parameters in superficial capillary plexus in cases versus controls|
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A weak correlation was found between BCVA and FAZ (R2 = 0.1155).
| Discussion|| |
In the present study, we compared the OCTA images to FA, which is the established gold standard for imaging the retinal vascular diseases. We showed that swept-source OCTA can document microvascular changes at the macula in patients with BD and also quantify those changes. OCTA has many advantages over FFA. First, the image quality is not degraded by dye leakage. Moreover, it can image vasculature at different layers of the retina separately and in larger magnification allowing the depiction of the finest details. Capillary nonperfusion with subsequent FAZ enlargement was the most commonly observed abnormality shown by FFA, while morphologic changes of the capillaries were the most commonly observed finding seen by OCTA (possibly explained by the ability of OCTA to highlight early capillary changes before actual capillary loss). However, the role of FFA cannot be totally discarded. FFA is indispensable in showing the activity of retinal vasculitis in the form of leakage which could not be detected by OCTA. Although it persists for a very long time even after starting treatment and subsidence of vitreous haze and AC cells, it is still the best indicator for monitoring the activity of retinal vasculitis. Another advantage of FFA is the ability to image the far retinal periphery, as far as the ora Serrata using the ultrawide field platforms. By comparing different sectors of the macula, we found that the least involved sectors were the nasal and central quadrants. The nasal quadrant might be less involved because it originally shows rich capillary plexus supplying the papillomacular bundle. Moreover, the central area capillary dropout might be masked by abnormal telangectatic vessels which are interpreted by the device as a blood flow signal. Furthermore, the central circle measurements are partially derived from the nasal quadrant among other quadrants.
Therefore, the VD value should be interpreted carefully and in conjunction with readings of the enface images.
Our results also showed differential involvement of the DCP and SCP. Since, the SCP is closer to the feeding arteries, they are affected to a lesser extent than DCP. Furthermore, DCP lies in a watershed zone of the retina which is more vulnerable to vascular insults. A similar predominance of affection of the DCP has been demonstrated in previous OCTA studies of patients with diabetic retinopathy and other retinal vascular diseases such as sickle cell retinopathy.,
Different study groups investigated different aspects of the utility of OCTA in patients with BD. Most results are consistent with our study. Khairallah et al. showed that OCTA is superior to FFA in delineation of different microvascular changes in BD. They showed that the most commonly encountered finding by OCTA was areas of hypoperfusion followed by capillary morphological abnormalities and disruption of the perifoveal capillary arcade.
Furthermore, Sinan et al. reported areas of capillary nonperfusion to be the most frequently encountered finding followed by perifoveal capillary arcade disruption and least frequent is overall capillary network disorganization.
Accorinti et al. reported that VD of the DCP is more severely reduced in patients with ocular BD (whether active or inactive) compared to healthy controls. Furthermore, VD of the SCP is significantly reduced in patients with active disease compared to inactive disease and controls.
Dan et al. quantified vascular alterations of SCP and DCP in patients with BD compared to normal control group. They reported that VD in all quadrants of the macula except nasal quadrant was reduced in BD patients compared to the control group. We showed similarly relative sparing of the nasal sector which we explained by the rich vascular supply of this area. They also showed a correlation between FAZ alteration and VA similar to our results.
Minghang et al. similarly showed that VD of the SCP and DCP was reduced, and FAZ area was increased in patients with BD compared to controls. Furthermore, they reported consistent reduction of VD involving the quiescent fellow eyes of patients during unilateral uveitis reactivation suggesting that subclinical vascular insult might be ongoing despite apparent quiescence. Raafat Karim et al. also concluded that OCTA findings in patients with non-ocular BD are similar to findings in patients with ocular BD.. Furthermore, quantitative evaluation showed that VDs were significantly lower in patients with nonocular BD than the control group.
Thanapong et al. compared swept-source OCTA to FFA in patients with ocular BD. They reported that areas of vascular nonperfusion were greater in DCP than SCP and that the greater the ratio of DCP: SCP involvement, the worse the VA. Thus, they concluded that OCTA was more useful to monitor macular ischemia in patients with BD because FFA is incapable of showing the DCP.
| Conclusion|| |
OCTA visualizes and characterizes macular microvascular changes better than FFA in eyes with BD. However, the ability of this technique to determine the activity of inflammation of the vessel wall remains questionable. Thus, OCTA and FFA have complementary roles in evaluation of patients with BD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
France R, Bucanan RN, Wilson MW, Sheldon MB. Relapsing iritis with recurrent ulcers of the mouth and genitalia (Behçet's syndrome): Review: With report of additional case. Medicine 1951;30:335-55.
Deuter CM, Christoph ME, Kötter I, Wallace GR, Murray PI, Stübiger N, Manfred Zierhut. Behçet's disease: Ocular effects and treatment. Progress Retinal Eye Res 2008;27:111-36.
Atmaca LS. Fundus changes associated with Behçet's disease. Graefes Arch Clin Exp Ophthalmol 1989;227:340-4.
Atmaca LS, Sonmez PA. Fluorescein and indocyanine green angiography findings in Behçet's disease. Br J Ophthalmol 2003;87:1466-8.
Khairallah M, Abroug N, Khochtali S, Mahmoud A, Jelliti B, Coscas G, et al
. Optical coherence tomography angiography in patients with Behçet Uveitis. Retina 2017;37:1678-91.
Thanapong Somkijrungroj, Sritatath Vongkulsiri, Wijak Kongwattananon, Peranut Chotcomwongse, Sasivarin Luangpitakchumpol, Korrawan Jaisuekul, “Assessment of Vascular Change Using Swept-Source Optical Coherence Tomography Angiography: A New Theory Explains Central Visual Loss in Behcet's Disease”, Journal of Ophthalmology 2017, Article ID 2180723, 6 pages, 2017. https://doi.org/10.1155/2017/2180723
Shuichi M, Hong Y, Yamanari M, Yatagai T, Yasuno Y. Optical coherence angiography. Optics Express 2006;14:7821-40.
Yali J, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, et al
. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics Express 2012;20:4710-25.
Magrath GN, Say EA, Sioufi K, Ferenczy S, Samara WA, Shields CL. Variability in foveal avascular zone and capillary density using optical coherence tomography angiography machines in healthy eyes. Retina 2017;37:2102-11.
Silman AJ. Criteria for diagnosis of Behcets-disease. Lancet 1990;335:1078-80.
Christian JS, Klufas MA, Sarraf D, Tsui I. Optical coherence tomography angiography of sickle cell maculopathy. Retinal Cases Brief Rep 2015;9:360-2.
Fabio S, Nesper PL, Fawzi AA. Deep retinal capillary nonperfusion is associated with photoreceptor disruption in diabetic macular ischemia. Am J Ophthalmol 2016;168:129-38.
Sinan E, Güven-Yılmaz S, Ulusoy MO, Ateş H. Optical coherence tomography angiography findings in Behcet patients. Int Ophthalmol 2019;39:2391-9.
Accorinti M, Gilardi M, de Geronimo D, Iannetti L, Giannini D, Parravano M. Optical coherence tomography angiography findings in active and inactive ocular Behçet disease. Ocul Immunol Inflamm 2020;28:589-600.
Dan C, Shen M, Zhuang X, Lin D, Dai M, Chen S, et al
. Inner retinal microvasculature damage correlates with outer retinal disruption during remission in Behcet's posterior uveitis by optical coherence tomography angiography. Investig Ophthalmol Visual Sci 2018;59:1295-304.
Minghang P, Zhao C, Gao F, Qu Y, Liang A, Xiao J, et al
. Analysis of parafovealmicrovascular abnormalities in Behcet's uveitis using projection-resolved optical coherence tomographic angiography. Ocular Immunol Inflamma 2019:1-6.
Raafat Karim A, Riham SH, Allam M, Medhat BM. Optical coherence tomography angiography findings in patients with nonocular Behcet disease. Retina 2019;39:1607-12.
Thanapong S, Vongkulsiri S, Kongwattananon W, Chotcomwongse P, Luangpitak Chumpol S, Jaisuekul K. Assessment of vascular change using swept-source optical coherence tomography angiography: A new theory explains central visual loss in Behcet's disease. J Ophthalmol 2017;2017.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]