Characteristics of Polypoidal Choroidal Vasculopathy Evaluated by

Special Issue
Characteristics of Polypoidal Choroidal Vasculopathy
Evaluated by Optical Coherence Tomography Angiography
Taneto Tomiyasu, Miho Nozaki, Munenori Yoshida, and Yuichiro Ogura
Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Correspondence: Miho Nozaki, Department of Ophthalmology and
Visual Science, Nagoya City University Graduate School of Medical
Sciences, 1-Kawasumi, Mizuho-ku,
Nagoya 467-8601, Japan;
nozakim@med.nagoya-cu.ac.jp.
Submitted: December 14, 2015
Accepted: March 15, 2016
Citation: Tomiyasu T, Nozaki M, Yoshida M, Ogura Y. Characteristics of
polypoidal choroidal vasculopathy
evaluated by optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57:OCT324–
OCT330. DOI:10.1167/iovs.15-18898
PURPOSE. The purpose of this study was to compare the angiographic findings of polypoidal
choroidal vasculopathy (PCV) detected by indocyanine green angiography (ICGA) and en face
optical coherence tomography angiography (OCTA).
METHODS. The study design was a retrospective chart review of 20 eyes with a clinical
diagnosis of treatment-naive PCV, seen at Nagoya City University Hospital between December
2014 and January 2016. Indocyanine green angiography was performed with Heidelberg
Retina Angiography 2 and OCTA was performed by using Avanti RTVue XR.
RESULTS. Twenty eyes of 20 patients (18 male, 2 female) were studied. Average age was 71.9
years. Manual segmentation was required to detect the pathologic lesions of PCV in all cases.
The polypoidal lesions were detected in 20 eyes (100%) by ICGA, and in 17 eyes (85%) by
OCTA. The number of polypoidal lesions detected by OCTA averaged 2.6 6 1.9, with an
average of 2.0 6 1.1 by ICGA (P < 0.05). The branching vascular network (BVN) was
detected in 14 eyes (70%) by ICGA and in 14 eyes (70%) by OCTA. All of the BVNs detected by
OCTA were located between the RPE and Bruch’s membrane.
CONCLUSIONS. Despite the manual segmentation required, en face OCTA enabled us to analyze
the angiographic features of PCV combined with longitudinal image (B-scan). En face OCTA
may be useful for understanding the pathogenesis of PCV and managing PCV.
Keywords: polypoidal choroidal vasculopathy, optical coherence tomography angiography,
indocyanine green angiography
olypoidal choroidal vasculopathy (PCV), first described by
Yannuzzi et al.,1 consists of a branching vascular network
(BVN), with polypoidal lesions at its edge, under the retinal
pigment epithelium (RPE).1,2 Polypoidal choroidal vasculopathy is a disease characterized by multiple, recurrent serosanguineous detachments of the RPE and neurosensory retina,
associated with secondary bleeding or leakage from the
polypoidal lesions.3–6
Polypoidal choroidal vasculopathy diagnosis is based on
ophthalmoscopic identification of subretinal reddish orange
spheroidal lesions arising from choroidal vessels.1 Indocyanine
green angiography (ICGA) demonstrates polypoidal dilatations
at the terminals of the BVN.4,7–10
In eyes with PCV, optical coherence tomography (OCT)
shows highly elevated RPE or double reflective layers that
consist of RPE and another highly reflective layer beneath the
RPE (‘‘double-layer sign’’) in the area of the BVN.11
Yannuzzi et al. 1 have described PCV as a primary
abnormality of the choroid. Yuzawa et al.12 have noted that
PCV is caused by inner choroidal vessel abnormalities, not
choroidal neovascularization (CNV). However, recent studies
with high-resolution OCT have demonstrated that polypoidal
lesions exist beneath the RPE, indicating that PCV is a variant
of type 1 neovascularization (NV)13; and Kawamura et al.14
report that there are two types of PCV: polypoidal CNV and
typical PCV, which shows choroidal vessel abnormalities.
Despite a number of these studies, pathogenesis of PCV is not
fully understood.
P
En face OCT angiography (OCTA) is the novel technology
that can visualize chorioretinal microcirculation without
intravenous dye injection.15–24 And OCTA also allows us to
do three-dimensional analysis of the chorioretinal abnormal
lesions.
In this study we compared the angiographic features of PCV
detected by ICGA and OCTA, and using B-scan OCTA images,
we also did three-dimensional analysis to find the location of
the polypoidal lesions and the BVN to understand the
pathogenesis of PCV.
METHODS
Patients
This study was a retrospective chart review of patients who had
undergone fundus examination, including OCTA, at Nagoya
City University Hospital between December 2014 and January
2016.
Twenty eyes with a clinical diagnosis of treatment-naive PCV
were evaluated. This study was approved by the Institutional
Review Board of the Nagoya City University Graduate School of
Medical Science and was conducted in accordance with the
ethical standards stated in the 1964 Declaration of Helsinki.
Eyes with poor-quality OCT images due to cataract or poor
fixation were excluded from the study.
The diagnosis of PCV was based on ophthalmoscopic
examinations, ICGA, high-definition (HD) OCT (Cirrus HDOCT; Carl Zeiss Meditec, Dublin, CA, USA), or swept-source
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OCT324
IOVS j Special Issue j Vol. 57 j No. 9 j OCT325
OCTA Versus ICGA in Polypoidal Choroidal Vasculopathy
TABLE. Clinical Characteristics of Patients With PCV and Their ICGA and OCTA Findings
ICGA
No.
Sex
Age, y
Eye
logMAR
VA
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
F
M
M
M
M
F
M
M
M
M
M
M
M
M
M
M
M
M
M
M
80
76
77
82
74
67
72
95
77
70
67
65
67
67
63
62
54
58
81
83
L
L
L
L
L
L
L
R
L
R
L
R
L
L
L
R
L
L
L
L
0.046
0.523
0.079
0.222
0.301
0.176
0.699
0.155
0.046
0.155
0.000
0.079
0.000
0.097
0.097
0.176
0.097
0.000
0.523
0.222
Presence of
Polypoidal
Lesions
(No.)
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
(3)
(1)
(3)
(1)
(1)
(2)
(1)
(1)
(3)
(1)
(1)
(2)
(5)
(2)
(2)
(3)
(1)
(1)
(3)
(2)
OCTA
Presence
of BVN
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
Presence of
Polypoidal
Lesions
(No.)
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
(3)
(1)
(>5)
(1)
(2)
(1)
(3)
(6)
(1)
(2)
(>5)
(5)
(2)
(3)
(2)
(4)
(4)
Relationship in
Location Between
Polypoidal Lesions
and PED
Presence
of BVN
Inside PED
No PED
Inside PED
Margin of PED
Inside PED
Margin of PED
No PED
Inside PED
No PED
No PED
Margin of PED
No PED
No PED
No PED
Margin of PED
Inside PED
Inside PED
Margin of PED
Inside PED
Inside PED
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
Location of BVN
Between
Between
Between
Between
Between
Between
Between
Between
Between
Between
Between
Between
Between
Between
BM
BM
BM
BM
BM
–
–
BM
BM
BM
BM
BM
–
BM
–
BM
BM
–
–
BM
and
and
and
and
and
CC
CC
CC
CC
CC
and
and
and
and
and
CC
CC
CC
CC
CC
and CC
and CC
and CC
and CC
M, male; F, female; VA, visual acuity; L, left; R, right; BVN, branching vascular network; PED, pigment epithelial detachment; BM, Bruch’s
membrane.
OCT (DRI OCT-1 Atlantis; Topcon Medical Systems, Oakland,
NJ, USA) and OCTA. Indocyanine green angiography was
performed by using Heidelberg Retina Angiograph 2 (HRA2;
Heidelberg Engineering, Heidelberg, Germany). Optical coherence tomography angiography was performed by using Avanti
RTVue XR with AngioVue (Optovue, Inc., Fremont, CA, USA).
Optical coherence tomography angiography and ICGA were
performed on the same day.
We counted the number of polypoidal lesions and the BVNs
in each ICG angiogram and OCT angiogram, and the detection
rate for each lesion was compared. Using OCTA, we evaluated
the relationship in the location between polypoidal lesions and
pigment epithelial detachment (PED), and also did threedimensional analysis of the location of the BVN.
En Face OCTA
Optical coherence tomography angiography was performed
with Avanti RTVue XR with AngioVue. AngioVue uses the
split-spectrum amplitude decorrelation angiography (SSADA)
algorithm to detect erythrocytes’ movement, and this
software allows us to visualize noninvasively the retinal and
choroidal vasculature via motion contrast. 25 AngioVue
allowed automatic segmentation into four layers as superficial
capillary plexus layer, deep capillary plexus layer, outer
retinal layer, and choriocapillaris. Superficial capillary plexus
layer images indicate the vasculature from the inner limited
membrane to 15 lm below the inner plexiform layer (IPL);
deep capillary plexus layer images indicate the vasculature
from 15 lm below the IPL to 70 lm below the IPL; and deep
capillary layer images represent both median and deep
capillary plexus layers. In this study, the 6 3 6–mm OCTA
images of the macula were used to evaluate each eye. The
autosegmented images by AngioVue and the images captured
by manual segmentation were compared to see the polypoidal
lesions and the BVN.
In one case treated with anti–vascular endothelial growth
factor (VEGF) therapy, the measuring tool provided from
AngioVue (AngioAnalytics) was used to measure the area and
flow area to follow the size of the polypoidal lesions before and
after treatment.
Statistics
All results are expressed as the mean 6 SD. Data were collected
and analyzed by the paired t-test. For all statistical tests, P < 0.05
was considered as the significance level. Statistical analysis was
performed by using Ekuseru-Toukei 2012 (Social Survey
Research Information Co., Ltd., Tokyo, Japan).
RESULTS
Demographics of patients with PCV are shown in the Table.
Twenty eyes of 20 patients (18 male, 2 female) were evaluated
in this study. Average age was 71.9 6 9.8 years (range, 54–95
years). All eyes had dilated choroidal vessels or thickened
choroid detected by ICGA or swept source (SS)-OCT, and all
cases were considered as typical PCV.14
The polypoidal lesions were detected in 20 eyes (100%) by
ICGA, and in 17 eyes (85%) by OCTA. The number of
polypoidal lesions detected by OCTA averaged 2.6 6 1.9, and
2.0 6 1.1 by ICGA (P < 0.05).
Manual segmentation was required to detect the pathologic
lesions of PCV in all cases. From analysis combined with the
images of OCT longitudinal scan (B-scan) and OCTA, we
determined that polypoidal lesions were located inside
elevated RPE lesions without fluid (six eyes), at the margin
of serous PED (five eyes), or inside of serous PED (nine eyes).
The BVN was detected in 14 eyes (70%) by ICGA and in 14
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OCTA Versus ICGA in Polypoidal Choroidal Vasculopathy
FIGURE 1. Multimodal imaging of the left eye of a 65-year-old man. Color fundus photograph shows the PED (white arrowhead) with subretinal
hemorrhage (A). Early-phase ICGA shows the polypoidal lesion (yellow arrowhead) inside the PED and BVN (yellow circle) (B). Optical coherence
tomography B-scan shows serous retinal detachment and two highly reflective layers consisting of RPE and another reflective layer beneath the RPE
(‘‘double-layer sign’’) (white circle) (C). The polypoidal lesions and the BVN are not detected on OCTA taken by autosegmentation mode (D1, D2).
The polypoidal lesion is clearly seen on OCTA, and the corresponding B-scan taken by manual-segmentation mode shows the polypoidal lesions
(yellow arrowhead) inside the PED detached from Bruch’s membrane (E1, E2). Optical coherence tomography angiography shows the BVN (yellow
circle) clearly, and the corresponding B-scan reveals the BVN between the RPE and above the highly reflective layers, supposedly Bruch’s membrane
(white circle) (F1, F2).
eyes (70%) by OCTA. All of the BVNs detected by OCTA were
located between the RPE and Bruch’s membrane (BM).
Case 1
A 65-year-old man came to our hospital for a distortion in vision
in his left eye of a few weeks’ duration. Visual acuity was 20/20
in both eyes. Fundus examination revealed PED with subretinal
hemorrhage (Fig. 1A). OCT B-scan shows serous retinal
detachment and two highly reflective layers consisting of
RPE and another reflective layer beneath the RPE (Fig. 1C).
Both early-phase ICGA and manual-segmented OCTA detected
the polypoidal lesion and the BVN (Figs. 1B, 1E1, 1E2, 1F1,
1F2), but autosegmented OCTA scan did not identify these
lesions (Fig. 1D1, 1D2).
As in this case, manual segmentation was required to detect
the pathologic lesions of PCV in all cases.
Case 2
A 70-year-old man complained of acute deterioration in his
right vision. Visual acuity was 20/32 in his right eye. Fundus
examination revealed reddish orange nodules with subretinal
hemorrhage (Fig. 2A). Early-phase ICGA showed the BVN
terminating in the polypoidal lesion (Fig. 2B). The polyps and
the BVN were clearly seen on OCTA (Figs. 2C1, 2C2, 2D1). The
BVN was located between the RPE and BM (Fig. 2D2).
Case 3
An 80-year-old woman was referred to our hospital with PCV.
Visual acuity was 20/25 in her left eye. Early-phase ICGA showed
multiple polyps (Fig. 3A). Using OCTA, one polyp was clearly
detected, but the other polyps were poorly identified (Fig. 3C1,
3C2). The BVN was clearly detected on OCTA (Fig. 3D1, 3D2).
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OCTA Versus ICGA in Polypoidal Choroidal Vasculopathy
FIGURE 2. Multimodal imaging of the right eye of a 70-year-old man. Color fundus photograph shows reddish orange nodules (white arrowhead)
with subretinal hemorrhage (white arrow) (A). Early-phase ICGA shows the BVN (yellow circle) terminating in the polypoidal lesion (yellow
arrowhead) (B). The polyps are clearly seen on OCTA (yellow arrowhead) (C1). Corresponding B-scan image provides details about the levels of
the polypoidal lesions (C2). The BVN is clearly seen on OCTA (yellow circle) (D1). The BVN is located between RPE and Bruch’s membrane (white
circle) (D2).
Case 4
DISCUSSION
A 77-year-old man was referred to our clinic with diagnosis of
PCV (Fig. 4A). Visual acuity was 20/25 in his left eye. The size
of the polyp and the flow area inside the polyp lesion was
followed up before and after anti-VEGF treatment. The same
scanning slab was used to analyze the polyp lesion during
follow-up. The size of the polyp lesion was 0.148 mm2 and the
flow area was 0.093 mm2 before treatment. Thirty days after
injection of anti-VEGF agent, the patient’s vision achieved 20/
20, and the size of the same polyp was decreased to 0.076 mm2
with the disappearance of subretinal fluid. The flow area was
also decreased to 0.053 mm2 (Fig. 4B). Four months later after
two injections, the size of the same polyp and the flow area
were increased to 0.118 and 0.074 mm2 (Fig. 4C) with
recurrence of subretinal fluid.
Our current study compared the angiographic features of
PCV detected by ICGA and OCTA. Our results demonstrated
that the detection rate of the polypoidal lesions was
significantly low by OCTA compared with ICGA, but the
BVN was clearly detected by OCTA as well as by ICGA.
Moreover, from combined analysis with OCT B-scan and
OCTA, the BVN was observed to be located between the RPE
and BM in all cases.
Optical coherence tomography angiography is a newly
developed method, which can visualize chorioretinal circulation without dye injection. Optical coherence tomography
angiography has already been applied to various retinal
vascular diseases, and it is reported that OCTA is useful to
detect abnormal vascular lesions.16–18,26 Recently, Inoue et
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OCTA Versus ICGA in Polypoidal Choroidal Vasculopathy
IOVS j Special Issue j Vol. 57 j No. 9 j OCT328
FIGURE 3. Multimodal imaging of an 80-year-old woman. Early-phase ICGA shows multiple polyps (yellow arrowhead) (A). One polyp is clearly
detected (yellow arrowhead) but the others are poorly detected on OCTA (yellow dot circle) (C1). The polyps are located at the level of Bruch’s
membrane on corresponding B-scan (C2). The BVN (yellow circle) is clearly detected on OCTA (D1). Corresponding B-scan shows the BVN located
between the RPE and Bruch’s membrane (white circle) (D2).
al.27 have evaluated the spectrum of PCV by using OCTA. They
have observed case series of seven patients with PCV or
polypoidal CNV, with six of seven patients receiving previous
treatment. They report that OCTA provides anatomic information about the BVN and type 1 NV, which is comparable to
ICGA. However, the polyps are visualized in only three of seven
cases (42.9%) by OCTA. In our current study, the polypoidal
lesions were detected in 17 of 20 eyes (85%) by OCTA, and the
detection rate was higher than that reported by Inoue et al.27
Using OCTA, the polyps were not visualized in some cases,
possibly owing to the poor blood flow in the polyp, since
OCTA can detect the blood flow, but not the vessels
themselves. All our cases included treatment-naı̈ve PCV, and
Inoue et al.27 have included the eyes with previous treatment
in their study. Since anti-VEGF treatment or photodynamic
therapy induces the regression of the polyp, the previous
history of treatment might reduce the detection rate by OCTA.
Another point is that staining or pooling of ICGA dye around
the polyps enhances the visualization of the polyps in ICGA in
the late phase. Miura et al.28 have reported that polypoidal
lesions in the Doppler OCT images are clearly detected at the
corresponding locations of the lesions in the ICGA images, but
the polyps visualized by Doppler OCT are much smaller than
those detected by ICGA, which indicates that the real size of
the polyps is smaller. Since the axial resolution is 5 lm in
OCTA, OCTA might not be able to detect small polyps.
As for the anatomic location of the polyps and the BVN,
Inoue et al.27 have reported that the BVN, type 1 NV, and the
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OCTA Versus ICGA in Polypoidal Choroidal Vasculopathy
FIGURE 4. A 77-year-old man with treatment-naı̈ve PCV (A1, A2). The size of the polyp and flow inside the polyp were followed up before and after
treatment. The scanning slab of the polyp lesion was set at the same depth. The area size of the polyp lesion was 0.148 mm2 and flow area was
0.093 mm2 before treatment. Thirty days after injection of anti-VEGF, the size of the same polyp was decreased to 0.076 mm2 with the resolution of
serous detachment. The flow area was also decreased to 0.053 mm2 (B1, B2). At recurrence 4 months after two injections, the size of the same
polyp and flow area were increased to 0.118 and 0.074 mm2, respectively (C1, C2).
polyps are confined to the anatomic compartment between
the RPE and BM. In our current study, all of the BVNs and the
polyps detected by OCTA were located between the RPE and
BM. Our results are compatible with a previous report by
Inoue et al.,27 and our findings may support the idea that PCV
is a variant of type 1 NV.29 Studies with large numbers of cases
will be required, but with OCTA and OCT B-scan, the
pathophysiology of PCV may be more clearly understood in
the future.
Since ICGA can visualize choroidal vasculature, ICGA has
been the gold standard diagnostic tool for PCV.30–33 Although
ICGA is considered safe, intravenous dye has risks ranging from
discomfort, to nausea, to anaphylaxis in rare cases.34 In
addition, owing to time-consuming issues, performing ICGA
at each clinical visit is not practical in daily practice.
In our study, the size of the polyp and the flow area inside
the polyp lesion were followed up before and after anti-VEGF
treatment with a measuring tool (AngioAnalytics). Because we
can evaluate the polypoidal lesions and the BVN at each
clinical visit, using OCTA without dye injection might be useful
to monitor the progression or recurrence during follow-up.
However, ICGA would still be necessary in diagnosing PCV,
since the detection rate of the polypoidal lesions was
significantly low by OCTA compared with ICGA.
The current study had several limitations. This study was a
retrospective case series with a limited number of patients, so
further study with a prospective study design in a larger
number of patients will be required.
In conclusion, despite the manual segmentation required,
en face OCTA enabled us to analyze the angiographic features
of PCV combined with OCT B-scan. Indocyanine green
angiography will still be necessary to make the diagnosis of
PCV. En face OCTA may be useful for understanding the
pathogenesis of PCV and managing PCV.
Acknowledgments
The authors thank Fumie Shibuya, Yasuyo Matsuda, Ayano
Maruyama, and Sayaka Oshio for their technical assistance.
The authors alone are responsible for the content and writing of
the paper.
Disclosure: T. Tomiyasu, None; M. Nozaki, None; M. Yoshida,
None; Y. Ogura, None
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