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ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 3  |  Page : 104-108

Usefulness of optical coherence tomography angiography in choroidal neovascularization secondary to neovascular age-related macular degeneration


1 Department of VitreoRetina, Retina Institute of Karnataka, Bengaluru, Karnataka, India
2 Department of Ophthalmology, MIMSR Medical College, Latur, Maharashtra, India

Date of Submission11-Mar-2019
Date of Decision08-Jun-2020
Date of Acceptance27-Oct-2020
Date of Web Publication4-Dec-2020

Correspondence Address:
Mayur S Kulkarni
Audumber Niwas, Vivekanand Puram, Near Parimal High School, Latur - 413 512, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcor.jcor_14_19

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  Abstract 


Background: Optical coherence tomography angiography (OCTA) could be a valid tool to detect choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD), allowing the analysis of the type, the morphology, and the extension of CNV in most of the cases. Aim: The aim of the study was to highlight the role of OCTA in the nAMD. Setting and Design: This retrospective, cross-sectional study is done at tertiary eye care center. Materials and Methods: This study enrolled 24 patients (48 eyes). All patients underwent swept-source optical coherence tomography, swept-source OCTA, and fundus fluorescein angiography (FFA). OCTA was used to evaluate neovascular networks in terms of their type, location, and extent of visualization. Sensitivity and specificity of the method were assessed based on FFA diagnosis as the gold standard. Results: In our study, the sensitivity and specificity of OCTA in detecting CNV secondary to neovascular AMD seem to be high which were 85.1% and 80%, respectively. Conclusion: OCTA may be clinically useful to evaluate the CNV activity and response to treatment as well as to differentiate the various types of CNV in neovascular nAMD.

Keywords: Age-related macular degeneration, choroidal neovascularization, optical coherence tomography angiography


How to cite this article:
Kulkarni MS, Bharambe MS, Kulkarni GR. Usefulness of optical coherence tomography angiography in choroidal neovascularization secondary to neovascular age-related macular degeneration. J Clin Ophthalmol Res 2020;8:104-8

How to cite this URL:
Kulkarni MS, Bharambe MS, Kulkarni GR. Usefulness of optical coherence tomography angiography in choroidal neovascularization secondary to neovascular age-related macular degeneration. J Clin Ophthalmol Res [serial online] 2020 [cited 2021 Apr 20];8:104-8. Available from: https://www.jcor.in/text.asp?2020/8/3/104/302194




  Introduction Top


Neovascular age-related macular degeneration (nAMD) also known as wet age-related macular degeneration (AMD), an advanced form of macular degeneration, is the leading cause of visual impairment in older adults related to AMD.[1] The presence of abnormal blood vessels, known as choroidal neovascularization (CNV), can penetrate Bruch’s membrane (BM) and extend into the subretinal pigment epithelial (RPE) or subretinal space. CNV can induce hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and vision loss.[2]

The current gold standard method of determining leakage from CNV is fluorescein angiography (FA), as it can provide dynamic Information (transit time of dye to travel to the eye).[3] In the late phase of the angiogram, leakage of dye is used to diagnose and classify CNV as classic, occult, or combination subtype. However, it is an invasive procedure, requiring intravenous dye injection, which can induce nausea, discomfort, and occasionally anaphylaxis.[4],[5] In addition, this technique is time consuming, taking about 15–20 min to complete, which can limit its routine use in a busy clinical setting.

For these reasons, optical coherence tomography (OCT) was introduced. Nowadays, OCT has become a widely used noninvasive imaging technique to detect the presence and activity of CNV without the use of intravenous dye. It enables visualization of the morphological features of the fibrovascular complex and the exudative consequences of fluid accumulation, which is accompanied by retinal thickening and edema.[6] However, the sensitivity of OCT is only to the backscattering light intensity and cannot distinguish vasculature from fibrous and other surrounding tissues. Due to this limitation, it is very difficult to recognize the precise location and activity of the CNV. Thus, OCT imaging cannot replace but supplement FA in the diagnosis of nAMD.[7]

OCT angiography (OCTA) is a novel imaging modality that allows direct visualization of the retinal and choroidal vasculature in vivo. In OCTA, high-frequency scanning and dense volumetric scanning are applied to detect blood flow by analyzing the signal decorrelation between the scans. Compared with stationary areas of the retina, the movement of erythrocytes within a vessel generates a decorrelated signal.[8] Unlike traditional angiography, OCTA does not require the use of exogenous dyes, thus avoiding potential side effects, such as nausea or other more serious adverse events.

However, the role of OCTA in diagnosing nAMD has not been widely investigated. There are very few clinical studies done by various authors such as Carlo et al.,[9] Ahmed et al.,[10] and Coscas et al.[11] who have evaluated the accuracy of OCTA imaging for the diagnosis of nAMD. Therefore, we did this study to evaluate the efficacy of OCTA in detecting nAMD.


  Materials and Methods Top


The study was approved by the Institutional Ethics Committee and followed the tenets of the Declaration of Helsinki. We retrospectively reviewed 24 consecutive patients (48 eyes) with maculopathy who visited the clinic. We included both treatment-na¨ıve patients and those already treated with intravitreal anti-VEGF. All the patients underwent a comprehensive eye examination, which included slit-lamp biomicroscopy, color fundus photography, swept-source OCT (SS-OCT), SS-OCT using Topcon OCT Triton, and fundus FA (FFA).

The angioretina of the Topcon OCT triton utilizes the OCTARA algorithm. OCTA acquisition protocol in the macular region consisted of a 6 mm × 6 mm area centered onto the fovea. En face OCTA images were segmented into four layers, namely the superficial vascular plexus, deep vascular plexus, outer retina, and choriocapillaries.

The inclusion criteria were (1) patients over 50 years with clinical features of age-related maculopathy, such as soft or hard drusen and pigmentary alterations and (2) macular exudative signs on at least one of the two imaging examinations (FA or OCT)

The exclusion criteria were (1) patients without OCTA or FA results available for analysis, (2) patients with CNV secondary to pathological myopia, angioid streaks, chorioretinitis, central serous chorioretinopathy, tumors, or trauma, (3) media opacities, such as cataracts, preventing detailed imaging, and (4) history of posterior segment surgery or laser photocoagulation within the last 6 months.

For FA, according to the criteria of the Macular Photocoagulation Study,[12],[13] the CNV lesions were graded as classic, occult, and combination. Classic CNV was defined as an area of uniform and early (<30 s) hyperfluorescence leakage throughout the middle and late phases. Occult CNV was identified by fibrovascular pigment epithelial detachment (stippled hyperfluorescence) or late phase leakage of an undetermined source. CNV was graded as combined when it showed the features of both classic and occult CNV.

The appearance of CNV on the OCTA images and coregistered corresponding OCT B-scans was assessed, in addition to the presence of subretinal fluid, intraretinal fluid (IRF), or sub-RPE fluid. OCTA was considered positive if an abnormal flow signal was seen in the outer retina or in the choriocapillaris.

If an eye was determined to have a CNV on FA, an OCTA showing an abnormal neovascular network was considered a true positive; if the CNV was not visualized on OCTA, the examination was taken as a false negative. If the FA did not demonstrate a CNV, an OCTA with no evidence of CNV was considered as a true negative; if a CNV was detected, the examination was considered a false positive.

The sensitivity and the specificity of OCTA for neovascular detection (i.e., new diagnostic tool validity assessment) were estimated in comparison to FA, considered as the gold standard.

All statistical interpretation and analysis of results obtained were carried out using statistical software Statistical Package for the Social Sciences version 22 (SPSS, version 22, SPSS Inc., Chicago, IL, USA) and Microsoft Excel.


  Results Top


We included 24 consecutive patients (48 eyes) affected by AMD. Eleven eyes were excluded because of poor quality images attributable to poor fixation, media opacity, absence of OCTA, or FA results. Thirty-seven eyes of 24 patients were assessed. The patients consisted of 15 men and 9 women were aged between 50 and 85 years with a mean age of 67 years [Table 1]. Two of 24 patients had nausea as an adverse reaction of FFA.
Table 1: Demographic and clinical data of the study patients

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According to FA, 27 eyes were affected by nAMD and lesions were classified as classic in 14 eyes, occult in 11 eyes, and mixed in 2 eyes. Ten eyes with nonexudative AMD acted as negative controls [Table 1]. Among those with nAMD, 8 eyes had previously received anti-VEGF treatment; the remaining 19 eyes were treatment naive.

On OCTA, a CNV was recognized in 25 eyes; 23 were true positives [Table 2]. Occult CNV lesions (Type I on OCT) were best visualized on the SS-OCTA en face projection of the choriocapillaris, whereas classic CNV lesions (Type II on OCT) were best visualized on the SS-OCTA en face projection of the outer retina. Mixed CNV lesions can be seen on the SS-OCTA en face projection of both the outer retina and choriocapillaries layer [Figure 1]. Four cases were evaluated as false negatives [Figure 2].
Table 2: Detection of eyes with neovascular age-related macular degeneration using optical coherence tomography angiography compared to fluorescein angiography

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Figure 1: Multimodal imaging of a mixed choroidal neovascularization, evaluated as a true positive case (a) Fundus of left eye showing yellow lesion at fovea. (b and c) A 6 mm × 6 mm optical coherence tomography angiography slab at the outer retina and at the choriocapillaris showing a well-circumscribed branched choroidal neovascularization. (d) late frame fluorescein angiography (4.28 min) displaying a small area of late leakage (white arrow) in the foveal area. (e) Optical coherence tomography showing cystoid spaces and subretinal hyper-reflective material

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Figure 2: Images of retinal pigment epithelial detachment with subretinal fluid observed in false-negative case on optical coherence tomography angiography. (a) Color fundus photograph of the patient showing retinal pigment epithelial detachment. (b) A 6 mm × 6 mm en face angiogram of choriocapillaries not showing any choroidal neovascularization. (c) Late-frame FA image (3.58 min) displaying big leakage and pooling at the around the macula together with posterior pole pigment epithelium detachment. (d) Spectral-domain optical coherence tomography demonstrating subretinal fluid with the retinal pigment epithelial detachment.

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In eight of the ten controls, both OCTA and FA did not identify any CNV; in the remaining two controls, the OCTA was positive, while FA was negative, i.e., false positive [Figure 3] and [Table 2]. In one of the two patients, the OCT B-scan presented a mild RPE irregularity with no sub- or intraretinal fluid. This clinical feature has been interpreted as quiescent CNV. In the second case, we can speculate that traditional angiography imaging would have been flawed by some masking artifacts hiding the presence of a neovascular network (visualized instead on OCTA). The specificity of OCTA for the detection of CNV was 80%, with a sensitivity of 85.1% and positive and negative predictive values of 92% and 66.6%, respectively.
Figure 3: Images of choroidal neovascularization observed in false-positive case on optical coherence tomography angiography. (a) Fundus photo from a 62-year-old man showing mild retinal pigment epithelial irregularity. (b) A 6 mm × 6 mm en face optical coherence tomography angiogram of the outer retina showing a choroidal neovascularization in the juxtafoveal space (white arrow). (c and d) Early- and late-frame FA (38 s and 150 s, respectively) images of the patient displaying mild hyperfluorescence that is stable throughout the FA in the region of choroidal neovascularization without pooling. (e) Mild retinal pigment epithelial irregularity seen on the spectral-domain optical coherence tomography corresponding to fundus picture

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  Discussion Top


FA can detect dynamic patterns of dye transit and leakage and keeps the current gold standard for diagnosing CNV.[3] However, traditional angiography is invasive and time consuming. Other major limitations are that it provides only a two-dimensional image and cannot directly visualize nascent vessels. SD-OCT is increasingly used in clinical practice to determine both the presence and activity of CNV. However, it cannot replace FA as the gold standard in the diagnosis of nAMD because the reflectivity of CNV tissue and drusenoid material, hemorrhages, and RPE is similar to OCT. Therefore, it is highly desirable to develop a novel method, such as OCTA, for monitoring nAMD. OCTA can simultaneously provide functional (OCT angiograms) and morphological (OCT B-scans) information and may be performed monthly because it is simple, quick, and noninvasive.[14]

The current study aimed to assess the ability of the OCTA technique in detecting active CNV and to determine efficacy (sensitivity and specificity) of SS-OCTA. In our study, OCTA has proved reliable in distinguishing between the two types of CNV: occult and classic, new blood vessels growing beneath or above the RPE, respectively.

During the study, we found a dark halo surrounding active CNV lesions and that was displayed as a hypointense clear zone on SS-OCTA images. This finding is consistent with Jia et al.[15] and Coscas et al.[16] who reported the same sign. An explanation for this dark halo is that CNV tends to develop a region of choriocapillaris alteration caused by impaired flow to compensate for ischemia. The region of choriocapillaris alteration is located underneath the CNV and extends beyond its margins in the form of a ring or halo and appears as hypointense or silent area on SS-OCTA images due to reduced blood flow.[17]

In our study, the sensitivity and specificity of OCTA in detecting the CNV secondary to nAMD were 85.1% and 80%, respectively, almost the same as that of Faridi et al.[18] Four false negative eyes with no decorrelation signal on en face OCTA were due to subretinal hemorrhage. This finding is consistent with other studies, which have reported a decreased ability of OCTA to detect CNV in eyes with subretinal hemorrhage. Moult et al.[19] reported in their series that the single case in which OCTA revealed false-negative results had dense subretinal hemorrhage that caused severe attenuation of the SS-OCT signal. Faridi et al.[18] concluded that sensitivity of en face OCTA improved to 94% if eyes with subretinal hemorrhage were excluded. Jia et al.[15] demonstrated the ability of OCTA to detect and quantify CNV in 10 patients with wet AMD where OCTA provided better visualization of the neovascular network with respect to FA, as images were not obscured by subretinal hemorrhage or other artifacts. De Carlo et al.[20] reported that the sensitivity and specificity of OCTA in detecting CNV secondary to wet AMD were 50% and 91%, respectively. Low sensitivity was due to the small sample size and blockage from large amounts of retinal hemorrhage in some patients. Nikolopoulou et al.[21] reported that the sensitivity and specificity of OCTA in detecting CNV secondary to wet AMD were 88% and 90%, respectively.

In our study, OCTA showed high sensitivity in detecting Type I CNV. This result was partially in discordance with Nikolopoulou et al.[21] who stated that OCTA would display worse sensitivity in naïve CNV due to undetectable flow inside the small peripheral branches of the neovascular complex.

In our study, active CNV on OCTA showed well-defined complexes, dark halo around the lesion, and numerous tiny anastomotic capillaries with thin walls and small diameter. There was excellent level of correlation in treatment decision based on OCTA compared to FFA. This result is consistent with the findings of Coscas et al.[16] and Spaide et al.[22] Coscas et al.[16] had compared the OCTA with traditional multimodal imaging in patients with wet AMD and found that there was high interobserver agreement both for treatment decision in conventional multimodal and for pattern I (active CV) or pattern II (inactive CNV) definition in OCTA imaging analysis.

SS-OCT can provide clues suggesting the presence of CNV, such as the presence of subretinal fluid, IRF, and subretinal hyper-reflective material and allows identification of areas where the RPE is separated from BM.

In our study, the sensitivity of OCT along with en face OCTA in detecting the active CNV secondary to AMD compared to FFA was 85.1% and specificity was 80%.

Our findings demonstrate that OCTA is able to detect the neovascular complex in most of the cases of nAMD, allowing the analysis of the morphology of the CNV in every single patient.

Limitations of the study are retrospective nature and small size of the sample. In fact, we considered patients with different types of CNV and both naive and treated patients. It would be interesting to repeat the same analysis by dividing the patients into separate groups.


  Conclusion Top


OCTA may be clinically useful to evaluate the CNV activity and response to treatment as well as to differentiate the various types of CNV in wet AMD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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